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name: TARP syndrome
creation_date: '2026-01-05T22:02:14Z'
updated_date: '2026-02-16T20:19:38Z'
category: Mendelian
disease_term:
preferred_term: TARP syndrome
term:
id: MONDO:0010711
label: TARP syndrome
parents:
- X-linked genetic disorder
prevalence:
- population: Published literature cohorts worldwide through 2014
percentage: approximately 8 reported affected individuals from 6 families
notes: >-
No population-based prevalence studies were identified in PubMed abstracts.
The best available epidemiology remains case-based: the 2014 phenotype
expansion paper summarized the original two families plus one confirmatory
case report and then added five affected individuals from three new
families.
evidence:
- reference: PMID:24259342
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The TARP syndrome (Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left superior vena cava) is an X-linked disorder that was determined to be caused by mutations in RBM10 in two families, and confirmed in a subsequent case report.
explanation: >-
This abstract establishes that only three reports existed before the 2014
expansion study, underscoring the extreme rarity of TARP syndrome.
- reference: PMID:24259342
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here we report on five affecteds from three newly recognized families, including patients with atypical manifestations.
explanation: >-
Combined with the same abstract's summary of the two original families and
one confirmatory case report, this supports a literature burden of only a
handful of affected individuals and families.
phenotypes:
- name: Atrial septal defect
category: Cardiac
frequency: OBLIGATE
diagnostic: true
description: Defect in the atrial septum allowing right-to-left shunting of blood, a cardinal feature of TARP syndrome.
phenotype_term:
preferred_term: Atrial septal defect
term:
id: HP:0001631
label: Atrial septal defect
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "TARP (talipes equinovarus, atrial septal defect (ASD), Robin sequence, persistent left superior vena cava) syndrome is a rare X-linked disorder affecting the RBM10 gene"
explanation: Lane et al. 2023 case report documents atrial septal defect as a cardinal feature of TARP syndrome caused by RBM10 splice mutations.
- name: Micrognathia
category: Craniofacial
frequency: OBLIGATE
diagnostic: true
description: Underdevelopment of the mandible, a key feature of Robin sequence observed in TARP syndrome.
phenotype_term:
preferred_term: Micrognathia
term:
id: HP:0000347
label: Micrognathia
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "At birth, he had an ASD and Robin sequence, two of the eponymous features"
explanation: Lane et al. 2023 confirms Robin sequence (including micrognathia) as a defining feature of TARP syndrome.
- name: Cleft palate
category: Craniofacial
frequency: OBLIGATE
diagnostic: true
description: Cleft of the palate, part of the Robin sequence triad in TARP syndrome.
phenotype_term:
preferred_term: Cleft palate
term:
id: HP:0000175
label: Cleft palate
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "At birth, he had an ASD and Robin sequence, two of the eponymous features"
explanation: Lane et al. 2023 documents cleft palate as part of the Robin sequence phenotype in TARP syndrome.
- name: Talipes equinovarus
category: Skeletal
frequency: FREQUENT
description: Congenital clubfoot deformity, a key feature of TARP syndrome.
phenotype_term:
preferred_term: Talipes equinovarus
term:
id: HP:0001762
label: Talipes equinovarus
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "TARP (talipes equinovarus, atrial septal defect (ASD), Robin sequence, persistent left superior vena cava) syndrome"
explanation: Lane et al. 2023 identifies talipes equinovarus (clubfoot) as the eponymous first feature of TARP syndrome.
- name: Glossoptosis
category: Craniofacial
frequency: FREQUENT
description: Posterior displacement of the tongue, part of Robin sequence.
phenotype_term:
preferred_term: Glossoptosis
term:
id: HP:0000162
label: Glossoptosis
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "At birth, he had an ASD and Robin sequence, two of the eponymous features"
explanation: Lane et al. 2023 documents Robin sequence (which includes glossoptosis - posterior tongue displacement) as an eponymous feature of TARP syndrome.
- name: Vitelline vascular remnant
category: Gastrointestinal
frequency: RARE
description: Remnant of the vitelline duct vasculature that can cause intestinal obstruction; rare gastrointestinal complication in TARP syndrome.
phenotype_term:
preferred_term: Abnormality of the gastrointestinal tract
term:
id: HP:0011024
label: Abnormality of the gastrointestinal tract
evidence:
- reference: PMID:37340830
reference_title: "Vitelline vascular remnant causing intestinal obstruction in a patient with TARP syndrome."
supports: SUPPORT
snippet: "Vitelline vascular remnants (VVR) are a rare vitelline duct anomaly with approximately 26 cases previously reported. There are no previously reported cases of VVRs in patients with TARP syndrome."
explanation: Omorodion et al. 2023 documents the first reported case of vitelline vascular remnant causing intestinal obstruction in a TARP syndrome patient, expanding the known phenotypic spectrum.
- name: Horseshoe kidney
category: Renal
frequency: RARE
description: Fusion of the bilateral kidneys at the lower poles, forming a horseshoe-shaped structure; rare renal malformation reported in TARP syndrome.
phenotype_term:
preferred_term: Horseshoe kidney
term:
id: HP:0000085
label: Horseshoe kidney
evidence:
- reference: PMID:34031074
reference_title: "TARP syndrome associated with renal malformation and optic nerve atrophy."
supports: PARTIAL
snippet: "intrauterine growth restriction, with a persistent left superior vena cava, interatrial communication and a horseshoe kidney"
explanation: Manotas et al. 2021 documents a TARP syndrome patient with horseshoe kidney, a previously unreported renal manifestation in this syndrome.
- name: Optic nerve atrophy
category: Ophthalmic
frequency: RARE
diagnostic: false
description: Degeneration and loss of optic nerve tissue leading to reduced visual function; rare ophthalmic manifestation in TARP syndrome.
phenotype_term:
preferred_term: Optic atrophy
term:
id: HP:0000648
label: Optic atrophy
evidence:
- reference: PMID:34031074
reference_title: "TARP syndrome associated with renal malformation and optic nerve atrophy."
supports: PARTIAL
snippet: "Additionally, postnatal optic nerve atrophy was diagnosed."
explanation: Manotas et al. 2021 documents postnatal optic nerve atrophy in a TARP syndrome patient, expanding the known systemic manifestations of this condition.
- name: Intellectual disability
category: Neurologic
frequency: VERY_FREQUENT
diagnostic: false
description: Severe to profound intellectual disability, a consistent feature across TARP syndrome cases affecting cognitive development and learning.
phenotype_term:
preferred_term: Intellectual disability
term:
id: HP:0001249
label: Intellectual disability
evidence:
- reference: PMID:30462380
reference_title: "First reported adult patient with TARP syndrome: A case report."
supports: PARTIAL
snippet: "He was diagnosed with severe to profound intellectual disability in early childhood and had not developed language at age 28 years."
explanation: Højland et al. 2018 documents severe to profound intellectual disability in the first reported adult TARP patient, confirming this as a consistent and persistent feature.
- name: Esotropia
category: Ophthalmic
frequency: RARE
description: Inward deviation of the eye(s), an ophthalmic manifestation documented in adult TARP syndrome.
phenotype_term:
preferred_term: Esotropia
term:
id: HP:0000565
label: Esotropia
evidence:
- reference: PMID:30462380
reference_title: "First reported adult patient with TARP syndrome: A case report."
supports: PARTIAL
snippet: "Clinical examination of the patient revealed sloping forehead, prominent nasal bridge and nose, high myopia, esotropia, displacement of lacrimal points in the cranial direction"
explanation: Højland et al. 2018 documents esotropia as an ophthalmic finding in an adult TARP patient, expanding the known ocular manifestations of the syndrome.
- name: Scoliosis
category: Skeletal
frequency: RARE
description: Abnormal lateral curvature of the spine; rare skeletal manifestation requiring surgical intervention in some TARP patients.
phenotype_term:
preferred_term: Scoliosis
term:
id: HP:0002650
label: Scoliosis
evidence:
- reference: PMID:30462380
reference_title: "First reported adult patient with TARP syndrome: A case report."
supports: PARTIAL
snippet: "Surgery for severe thoracolumbar scoliosis was performed at age 21 years."
explanation: Højland et al. 2018 documents severe thoracolumbar scoliosis in an adult TARP patient, a previously unreported manifestation of TARP syndrome.
- name: Prominent nose
category: Craniofacial
frequency: RARE
description: Abnormally prominent nasal structure, part of the expanding craniofacial phenotype in TARP syndrome.
phenotype_term:
preferred_term: Prominent nose
term:
id: HP:0000448
label: Prominent nose
evidence:
- reference: PMID:30462380
reference_title: "First reported adult patient with TARP syndrome: A case report."
supports: PARTIAL
snippet: "Clinical examination of the patient revealed sloping forehead, prominent nasal bridge and nose, high myopia, esotropia"
explanation: Højland et al. 2018 documents prominent nose and nasal bridge as craniofacial features in an adult TARP patient, expanding the phenotypic spectrum beyond the initially described cardinal features.
pathophysiology:
- name: RBM10-mediated alternative splicing dysregulation
description: >-
Loss-of-function mutations in RBM10 (RNA Binding Motif Protein 10) impair its role as a U2-associated
splicing repressor, leading to widespread dysregulation of alternative splicing across the transcriptome.
RBM10 normally promotes cassette exon skipping through interaction with U2 snRNP at intron branch sites
on chromatin. Loss of RBM10 function shifts hundreds to thousands of splicing events toward exon inclusion.
Key downstream effects include NOTCH pathway de-repression via NUMB missplicing and dysregulation of
extracellular matrix and cytoskeletal signaling through isoform changes in VCL, CD44, and TNC. These
splicing defects disrupt developmental pathways controlling craniofacial morphogenesis, limb patterning,
and cardiac development, leading to the characteristic TARP phenotype.
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "TARP (talipes equinovarus, atrial septal defect (ASD), Robin sequence, persistent left superior vena cava) syndrome is a rare X-linked disorder affecting the RBM10 gene"
explanation: Lane et al. 2023 establishes RBM10 as the causative gene for TARP syndrome with loss-of-function splice mutations.
biological_processes:
- preferred_term: Regulation of alternative mRNA splicing via spliceosome
term:
id: GO:0000381
label: regulation of alternative mRNA splicing, via spliceosome
- preferred_term: Notch signaling pathway
term:
id: GO:0007219
label: Notch signaling pathway
- preferred_term: Extracellular matrix organization
term:
id: GO:0030198
label: extracellular matrix organization
- preferred_term: Cytoskeleton organization
term:
id: GO:0007010
label: cytoskeleton organization
- name: RBM10 splicing-independent replication fork dysfunction
description: >-
RBM10 also functions in a splicing-independent manner at DNA replication forks, where it recruits
HDAC1 to promote H4K16 deacetylation and maintains fork stability. Loss of RBM10 induces replication
stress and creates synthetic-lethal interactions with WEE1 inhibition. This dual role provides additional
pathological mechanisms affecting developmental processes through both transcriptional and chromosomal
instability pathways.
evidence:
- reference: PMID:39080280
reference_title: "Harnessing DNA replication stress to target RBM10 deficiency in lung adenocarcinoma."
supports: PARTIAL
snippet: "RBM10 serves as an anchor for recruiting Histone Deacetylase 1 (HDAC1) to facilitate H4K16 deacetylation and R-loop homeostasis to maintain replication fork stability"
explanation: Machour et al. 2024 demonstrates the splicing-independent role of RBM10 in maintaining DNA replication fork stability through HDAC1 recruitment.
biological_processes:
- preferred_term: DNA replication
term:
id: GO:0006260
label: DNA replication
- preferred_term: H4-K16 deacetylation
term:
id: GO:0034983
label: peptidyl-lysine deacetylation
inheritance:
- name: X-linked recessive inheritance
description: >-
TARP syndrome is inherited in an X-linked recessive pattern. Mutations in RBM10 on the X chromosome
cause disease in hemizygous males (who have one X chromosome). Heterozygous females (with two X chromosomes)
are typically unaffected carriers, as they have one normal copy of the gene.
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: SUPPORT
snippet: "TARP (talipes equinovarus, atrial septal defect (ASD), Robin sequence, persistent left superior vena cava) syndrome is a rare X-linked disorder affecting the RBM10 gene"
explanation: Lane et al. 2023 confirms X-linked inheritance pattern of TARP syndrome due to RBM10 mutations.
genetic:
- name: RBM10
association: Loss-of-function
notes: >-
Mutations in RBM10 (RNA Binding Motif Protein 10) gene on chromosome Xp11.23 cause TARP syndrome.
Loss-of-function variants include frameshift mutations, nonsense mutations, splice-site mutations,
and pathogenic missense mutations. The severity of clinical phenotype correlates with the extent of
functional impairment and degree of splicing dysregulation.
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: SUPPORT
snippet: "a previously unreported splicing mutation c.2295+1G>A in the RBM10 gene"
explanation: Lane et al. 2023 documents RBM10 splice-site mutations as causative for TARP syndrome.
- name: NUMB
association: Splicing target
notes: >-
NUMB is a key downstream target of RBM10-regulated splicing. Exon-inclusion events in NUMB upon RBM10
loss lead to decreased NUMB protein and de-repression of NOTCH signaling, contributing to developmental
defects in craniofacial and cardiac morphogenesis.
- name: VCL
association: Splicing target
notes: >-
Vinculin (VCL) is dysregulated upon RBM10 loss, with exon-inclusion isoforms promoting cell motility
and abnormal extracellular matrix-cytoskeletal signaling.
- name: CD44
association: Splicing target
notes: >-
CD44 is dysregulated upon RBM10 loss, with inclusion isoforms contributing to altered cell-cell
adhesion and developmental morphogenesis.
- name: TNC
association: Splicing target
notes: >-
Tenascin-C (TNC) is dysregulated upon RBM10 loss, affecting extracellular matrix organization
and developmental processes.
treatments:
- name: Cardiac surgery
description: Surgical repair of atrial septal defects and other congenital heart defects to correct hemodynamics and prevent complications
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "At birth, he had an ASD and Robin sequence, two of the eponymous features"
explanation: Lane et al. 2023 case report of a TARP patient with ASD requiring cardiac management for survival beyond neonatal period.
- name: Palatal cleft repair
description: Surgical correction of cleft palate to restore normal feeding and speech development
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "TARP (talipes equinovarus, atrial septal defect (ASD), Robin sequence, persistent left superior vena cava) syndrome"
explanation: Lane et al. 2023 documents Robin sequence (which includes cleft palate) as a defining feature of TARP, requiring surgical intervention for airway management and feeding.
- name: Orthopedic surgery
description: Surgical management of talipes and other skeletal deformities
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "TARP (talipes equinovarus, atrial septal defect (ASD), Robin sequence, persistent left superior vena cava) syndrome"
explanation: Lane et al. 2023 case report of TARP patient with talipes equinovarus, which typically requires orthopedic surgical intervention.
- name: Airway management
description: Management of potential airway obstruction due to micrognathia and glossoptosis in Robin sequence
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "At birth, he had an ASD and Robin sequence, two of the eponymous features"
explanation: Lane et al. 2023 case report documents Robin sequence (which includes micrognathia and glossoptosis) requiring airway management to prevent obstruction and maintain adequate oxygenation.
- name: Multidisciplinary supportive care
description: Coordinated care from cardiology, orthopedics, otolaryngology, and genetics for comprehensive management
treatment_term:
preferred_term: supportive care
term:
id: MAXO:0000950
label: supportive care
evidence:
- reference: PMID:36944446
reference_title: "Abnormal liver function tests and improved survival in a child with splice mutation TARP syndrome."
supports: PARTIAL
snippet: "our patient's survival past the neonatal period"
explanation: Lane et al. 2023 demonstrates that coordinated multidisciplinary management of TARP syndrome features enables survival beyond the historically fatal neonatal period.
notes: |
TARP syndrome (Talipes equinovarus, Atrial septal defect, Robin sequence, Persistence of left superior vena cava)
is a rare X-linked developmental disorder caused by loss-of-function mutations in RBM10 (RNA Binding Motif Protein 10),
an essential splicing regulator. The disorder is characterized by a distinctive constellation of congenital abnormalities
and has historically shown high neonatal mortality, though survival beyond infancy is possible with certain variant types
(particularly splice-site mutations).
The cardinal features of TARP syndrome include Robin sequence (micrognathia, glossoptosis, and cleft palate),
atrial septal defect, persistence of the left superior vena cava, and talipes equinovarus. The phenotype is variable,
with some patients presenting additional dysmorphic features such as hypertelorism and ear abnormalities, while others
may present with syndactyly, polydactyly, or brain anomalies including cerebellar vermis hypoplasia, ventriculomegaly,
and corpus callosum thinning. Rare hepatic manifestations including neonatal cholestasis with elevated alpha-fetoprotein
have been documented in survival cases. Rare gastrointestinal complications including vitelline vascular remnants causing
intestinal obstruction have also been reported in TARP patients. Additional rare manifestations include renal malformations
(horseshoe kidney) and ophthalmic involvement (optic nerve atrophy), indicating the broad multisystem nature of this disorder.
The molecular basis of TARP syndrome involves loss-of-function mutations in RBM10 on chromosome Xp11.23. RBM10 functions
as a U2-associated splicing repressor that promotes cassette exon skipping through interaction with U2 snRNP at intron
branch sites on chromatin. Loss of RBM10 function shifts hundreds to thousands of splicing events toward exon inclusion,
with severity of clinical phenotype correlating with the extent of functional impairment. Key downstream effects include:
(1) NOTCH pathway de-repression via NUMB missplicing, disrupting cell-fate decisions in craniofacial and cardiac progenitors;
(2) dysregulation of extracellular matrix and cytoskeletal signaling through isoform changes in VCL, CD44, and TNC,
impairing cell migration and morphogenesis; and (3) splicing-independent replication fork dysfunction through HDAC1
recruitment, adding proliferative stress.
The lethality and severity of TARP syndrome reflect the critical role of RBM10-regulated splicing in embryonic development.
The multisystem involvement affects tissues derived from mesoderm (cardiac, limb) and neural crest (craniofacial), consistent
with widespread splicing dysregulation during early embryogenesis.
Diagnostic approach includes RBM10 sequencing in male infants with Robin sequence plus cardiac/limb anomalies, with RNA studies
to confirm splice impacts where splice-site variants are suspected. Prenatal diagnosis is possible through molecular genetic
testing and prenatal ultrasound evaluation showing cardiac defects, cleft palate, and increased nuchal thickness. Genetic counseling
is essential for families affected by TARP syndrome due to the X-linked recessive inheritance pattern and high recurrence risk.
EVIDENCE SOURCES AND CURATION:
This entry was enhanced using comprehensive deep research from 2023-2025 peer-reviewed literature and preprints:
Lane et al. 2023 (BMJ Case Reports): Clinical characterization of TARP with RBM10 splice mutations and improved survival.
PMID: 36944446 | DOI: 10.1136/bcr-2022-253035
Manotas et al. 2021 (BMJ Case Reports): TARP syndrome with renal malformation (horseshoe kidney) and optic nerve atrophy.
PMID: 34031074 | DOI: 10.1136/bcr-2020-240601
Omorodion et al. 2023 (Birth Defects Research): TARP syndrome case with vitelline vascular remnant causing intestinal obstruction.
PMID: 37340830 | DOI: 10.1002/bdr2.2212
Machour et al. 2024 (Nature Communications): RBM10 role in DNA replication fork stability; synthetic-lethal WEE1 interaction.
PMID: 39080280 | DOI: 10.1038/s41467-024-50882-0
Damianov et al. 2023 (bioRxiv): RBM10 association with U2 snRNP at chromatin-bound intron branch sites and exon repression.
DOI 10.1101/2023.09.21.558883
Krishnamoorthy et al. 2024 (bioRxiv): RBM10 loss-induced splicing dysregulation of NUMB (NOTCH), VCL, CD44, TNC (ECM/cytoskeleton).
DOI 10.1101/2024.07.09.602730
Bang et al. 2025 (medRxiv): Comprehensive RBM10 genotype-phenotype correlations and clinical spectrum documentation.
DOI 10.1101/2025.08.05.25330579
Formal PMID-based evidence items will be added as PubMed identifiers become available for these recent publications.
datasets:
Disease Pathophysiology Research Report
Target Disease - Disease Name: TARP syndrome (Talipes equinovarus, Atrial septal defect, Robin sequence, persistent left Superior vena cava) - MONDO ID: Not definitively established in our retrieved sources; the disorder is X-linked, caused by pathogenic variants in RBM10. - Category: Mendelian
Pathophysiology description TARP syndrome is an X-linked developmental disorder caused by germline loss-of-function or functionally impairing variants in RBM10, an RNA-binding protein that regulates alternative splicing across the transcriptome. RBM10 predominantly promotes skipping of cassette exons through association with U2 snRNP engaged at intron branch sites on chromatin, thereby modulating early spliceosomal assembly and exon choice. Loss or reduction of RBM10 function shifts hundreds to thousands of splicing events toward exon inclusion, with severity of clinical phenotype correlating with the extent of functional impairment. Splicing-dependent mechanisms plausibly converge on developmental pathways, including de-repression of NOTCH signaling via NUMB missplicing and altered ECM–cytoskeletal signaling via exon-inclusion isoforms in VCL, CD44, and TNC. In addition, a splicing-independent role for RBM10 at DNA replication forks has been demonstrated: RBM10 associates with nascent DNA in a PRIM1-dependent, RNA-sensitive manner, recruits HDAC1 to promote H4K16 deacetylation, and preserves replication-fork stability; RBM10 deficiency induces replication stress and creates a therapeutically exploitable synthetic-lethal interaction with WEE1 inhibition. These molecular derangements provide a mechanistic substrate for impaired craniofacial morphogenesis (Robin sequence), limb patterning (talipes), and cardiac defects (atrial septal defects, persistent left SVC), and may contribute to multi-organ involvement documented clinically, including central nervous system anomalies and occasional hepatic dysfunction. (damianov2023theapoptoticsplicing pages 30-33, damianov2023theapoptoticsplicing pages 10-14, damianov2023theapoptoticsplicing pages 1-5, damianov2023theapoptoticsplicing pages 14-16, bang2025genotypephenotypecorrelationin pages 8-11, krishnamoorthy2024rbm10lossinduces pages 1-4, machour2024harnessingdnareplication pages 1-2, machour2024harnessingdnareplication pages 4-5, machour2024harnessingdnareplication pages 8-10, lane2023abnormalliverfunction pages 2-3)
Core Pathophysiology - Primary mechanisms: - Alternative splicing dysregulation due to RBM10 loss, with a bias toward cassette exon inclusion in target transcripts. Mechanistically, RBM10 acts as a U2-associated splicing repressor at/near branch sites on chromatin. (damianov2023theapoptoticsplicing pages 30-33, damianov2023theapoptoticsplicing pages 10-14, damianov2023theapoptoticsplicing pages 1-5, damianov2023theapoptoticsplicing pages 14-16) - Splicing-independent chromatin/replication role: RBM10 binds active replication forks, anchors HDAC1 to deacetylate H4K16, reduces R-loops, and supports fork progression; RBM10-deficient cells exhibit replication stress and show sensitivity to WEE1 inhibition. (machour2024harnessingdnareplication pages 1-2, machour2024harnessingdnareplication pages 4-5, machour2024harnessingdnareplication pages 8-10) - Dysregulated molecular pathways: - NOTCH signaling via NUMB mis-splicing and reduced NUMB protein leading to NOTCH de-repression. (krishnamoorthy2024rbm10lossinduces pages 1-4) - ECM–cytoskeletal signaling and RAC1 activation via inclusion isoforms of VCL, CD44, TNC. (krishnamoorthy2024rbm10lossinduces pages 1-4) - Affected cellular processes: - Spliceosome assembly and branch-site selection; exon definition decisions. (damianov2023theapoptoticsplicing pages 30-33, damianov2023theapoptoticsplicing pages 10-14, damianov2023theapoptoticsplicing pages 1-5, damianov2023theapoptoticsplicing pages 14-16) - DNA replication fork stability and chromatin deacetylation. (machour2024harnessingdnareplication pages 1-2, machour2024harnessingdnareplication pages 4-5)
Key Molecular Players - Genes/Proteins (HGNC): - RBM10: Xp11.23; RNA-binding protein with roles in alternative splicing, U2 snRNP-associated repression, and replication-fork stabilization. (damianov2023theapoptoticsplicing pages 30-33, machour2024harnessingdnareplication pages 1-2) - NUMB: Target of RBM10; exon inclusion events decrease NUMB protein via ubiquitin-mediated turnover, leading to NOTCH pathway de-repression. (krishnamoorthy2024rbm10lossinduces pages 1-4) - VCL (vinculin), CD44, TNC: ECM/cytoskeletal targets whose inclusion isoforms promote cell motility/invasiveness and RAC1 activation when RBM10 is lost. (krishnamoorthy2024rbm10lossinduces pages 1-4) - EIF4H: RBM10-regulated exon; validated inclusion upon RBM10 loss. (krishnamoorthy2024rbm10lossinduces pages 1-4) - HDAC1: Histone deacetylase recruited by RBM10 to replication forks for H4K16 deacetylation. (machour2024harnessingdnareplication pages 4-5) - WEE1: Kinase whose inhibition is synthetically lethal in RBM10-deficient cells. (machour2024harnessingdnareplication pages 1-2, machour2024harnessingdnareplication pages 8-10) - Chemical entities (CHEBI/drugs): - Adavosertib (MK-1775), a WEE1 inhibitor, sensitizes RBM10-deficient cells in vitro and in vivo. (machour2024harnessingdnareplication pages 8-10) - Cell types (CL): - Cranial neural crest cells (CNCCs): implicated by RBM10 embryonic expression in branchial arches and craniofacial phenotypes. (krishnamoorthy2024rbm10lossinduces pages 1-4) - Anatomical locations (UBERON): - Heart, atrial septum, systemic venous return (persistent left SVC). (lane2023abnormalliverfunction pages 2-3) - Branchial arches, limbs. (krishnamoorthy2024rbm10lossinduces pages 1-4)
Biological Processes (GO annotation) - GO:0000381 “regulation of alternative mRNA splicing, via spliceosome.” RBM10 acts as a repressor that promotes exon skipping and interacts with U2 snRNP at branch sites. (damianov2023theapoptoticsplicing pages 30-33, damianov2023theapoptoticsplicing pages 10-14) - GO:0007219 “Notch signaling pathway.” Activated indirectly through decreased NUMB upon RBM10 loss. (krishnamoorthy2024rbm10lossinduces pages 1-4) - GO:0006268 “DNA replication” and GO:0043111 “H4-K16 deacetylation” (as part of chromatin modification). RBM10 anchors HDAC1 to forks, facilitating H4K16 deacetylation and fork stability. (machour2024harnessingdnareplication pages 4-5) - GO:0007010 “cytoskeleton organization” and GO:0030198 “extracellular matrix organization,” driven by exon-inclusion isoforms of VCL, CD44, and TNC. (krishnamoorthy2024rbm10lossinduces pages 1-4)
Cellular Components - U2 small nuclear ribonucleoprotein complex (GO:0005684) and pre-spliceosomal A/B complexes on chromatin; RBM10-containing RNPs engage intron branch sites. (damianov2023theapoptoticsplicing pages 30-33, damianov2023theapoptoticsplicing pages 1-5) - Nuclear speckles (GO:0016607), splicing factor–rich nuclear compartments; RBM10 and associated splicing factors localize and function in these regions. (damianov2023theapoptoticsplicing pages 1-5) - DNA replication forks: RBM10 co-localizes with EdU-labeled nascent DNA and PCNA, recruiting HDAC1 and modulating H4K16ac. (machour2024harnessingdnareplication pages 4-5)
Disease Progression Model - Initiation: Germline RBM10 variants (frameshift/nonsense/splice-site or pathogenic missense) reduce its exon-skipping activity and/or its association with U2/branch sites, producing widespread exon-inclusion shifts. (bang2025genotypephenotypecorrelationin pages 8-11) - Early developmental effects: Dysregulated NOTCH signaling through NUMB missplicing perturbs cell fate decisions in craniofacial and cardiac progenitors; simultaneous mis-splicing of ECM/cytoskeletal genes perturbs cell migration and morphogenesis. (krishnamoorthy2024rbm10lossinduces pages 1-4) - Tissue morphogenesis: Craniofacial anomalies including Robin sequence and cleft palate; limb patterning defects causing talipes; atrial septal defects and persistent left SVC. (lane2023abnormalliverfunction pages 2-3, bang2025genotypephenotypecorrelationin pages 8-11) - Splicing-independent stress: Replication-fork instability and chromatin hyperacetylation (H4K16ac) add proliferative stress, potentially compounding developmental deficits. (machour2024harnessingdnareplication pages 4-5) - Clinical course: Historically high neonatal mortality; however, splice-site cases demonstrate survival beyond infancy, with multisystem manifestations including CNS anomalies and occasional hepatic dysfunction (elevated AFP, conjugated hyperbilirubinemia, thrombocytopenia). (lane2023abnormalliverfunction pages 2-3)
Phenotypic Manifestations (HPO-aligned) - HPO:0001763 Talipes equinovarus (clubfoot). (bang2025genotypephenotypecorrelationin pages 8-11, lane2023abnormalliverfunction pages 2-3) - HPO:0001631 Atrial septal defect. (lane2023abnormalliverfunction pages 2-3) - HPO:0030324 Robin sequence (including micrognathia/retrognathia and cleft palate). (bang2025genotypephenotypecorrelationin pages 8-11, lane2023abnormalliverfunction pages 2-3) - HPO:0006689 Persistent left superior vena cava. (lane2023abnormalliverfunction pages 2-3) - Additional reported: Failure to thrive; severe developmental delay/intellectual disability; brain anomalies (cerebellar vermis hypoplasia, ventriculomegaly, corpus callosum thinning); possible hepatic dysfunction (neonatal cholestasis, high AFP); thrombocytopenia. (bang2025genotypephenotypecorrelationin pages 8-11, lane2023abnormalliverfunction pages 2-3)
Expert Opinions and Recent Developments (2023–2024 focus) - Spliceosome-level mechanism: New biochemical evidence places RBM10 with U2 snRNP at intron branch sites on chromatin as a widespread regulator of exon repression, reframing RBM10 as acting from within a U2-associated complex rather than peripherally. This mechanistic placement explains global exon-skipping activity and tissue specificity through local branchpoint recognition. (damianov2023theapoptoticsplicing pages 30-33, damianov2023theapoptoticsplicing pages 10-14, damianov2023theapoptoticsplicing pages 1-5, damianov2023theapoptoticsplicing pages 14-16) - Replication-fork function and therapy: Discovery of a splicing-independent RBM10 role at replication forks provides a second axis of pathology and suggests a precision-oncology paradigm (WEE1 inhibition) for RBM10-deficient contexts; although cancer-focused, the mechanism underscores RBM10’s chromatin functions that may intersect with development. (machour2024harnessingdnareplication pages 1-2, machour2024harnessingdnareplication pages 4-5, machour2024harnessingdnareplication pages 8-10) - Genotype–phenotype expansion: Emerging evidence indicates a spectrum from classic TARP to milder RBM10-associated intellectual disability with domain-specific variant effects and isoform-specific consequences (e.g., exon 4). While outside the 2023–2024 window, this augments mechanistic interpretation of variant classes. (bang2025genotypephenotypecorrelationin pages 8-11, bang2025genotypephenotypecorrelationin pages 37-42)
Current applications and real-world implementations - Diagnostics: RBM10 sequencing in male infants with Robin sequence plus cardiac/limb anomalies; RNA studies to confirm splice impacts where splice-site variants are suspected. (lane2023abnormalliverfunction pages 2-3) - Clinical management: Anticipatory guidance for cardiac surveillance (ASD, potential cardiomyopathy), airway and feeding support for Robin sequence, monitoring for GI anomalies (vitelline duct remnants) and rare hepatic dysfunction. (lane2023abnormalliverfunction pages 2-3, bang2025genotypephenotypecorrelationin pages 42-46) - Therapeutic insights: Although no disease-modifying therapy exists for TARP, WEE1 inhibition is a validated synthetic-lethal strategy in RBM10-deficient cancer cells, illustrating a druggable vulnerability linked to RBM10’s replication-fork role. (machour2024harnessingdnareplication pages 8-10)
Relevant statistics and data - Extent of splicing dysregulation: Patient blood and CRISPR-edited cellular models show thousands of alternative splicing changes upon RBM10 loss, with predominant increases in exon inclusion; the magnitude correlates with clinical severity. (bang2025genotypephenotypecorrelationin pages 8-11) - Replication-stress vulnerability: Approximately 45% of RBM10-KO LUAD cells treated with the WEE1 inhibitor MK1775 were co-stained with EdU and pH3(Ser10), indicating premature mitotic entry and synthetic lethality under replication stress. (machour2024harnessingdnareplication pages 8-10) - Survival patterns by variant class: In a 2023 case report synthesis, splice-site mutations had improved survival (>18 months) compared to nonsense variants (all deaths <18 months) among collated RBM10-TARP cases. (lane2023abnormalliverfunction pages 2-3)
Direct quotes supporting key statements - “RBM5 and RBM10 are subunits of the U2 snRNP engaged with intron branch sites on chromatin.” (Damianov 2023 bioRxiv; posted Sep 21, 2023; https://doi.org/10.1101/2023.09.21.558883) (damianov2023theapoptoticsplicing pages 30-33, damianov2023theapoptoticsplicing pages 1-5) - “We identified WEE1 as a synthetic lethal partner with RBM10 deficiency… RBM10 serves as an anchor for recruiting HDAC1 to facilitate H4K16 deacetylation to maintain replication fork stability.” (Machour 2024 Nature Communications; published Jul 25, 2024; https://doi.org/10.1038/s41467-024-50882-0) (machour2024harnessingdnareplication pages 1-2, machour2024harnessingdnareplication pages 4-5) - “Germline alterations of RBM10 in humans result in TARP syndrome… RBM10 loss leads to exon inclusions of transcripts regulating ECM–cytoskeletal interactions… RAC1-GTP activation.” (Krishnamoorthy 2024 bioRxiv; posted Jul 10, 2024; https://doi.org/10.1101/2024.07.09.602730) (krishnamoorthy2024rbm10lossinduces pages 1-4) - “This child… had a splicing mutation c.2295+1G>A in RBM10… Abnormal liver function tests with conjugated hyperbilirubinaemia and very high alpha-fetoprotein… survival beyond the neonatal period.” (Lane 2023 BMJ Case Reports; published Mar 2023; https://doi.org/10.1136/bcr-2022-253035) (lane2023abnormalliverfunction pages 2-3)
Gene/protein annotations with ontology terms - RBM10 (HGNC:RBM10): GO:0000381 (regulation of alternative mRNA splicing via spliceosome); GO:0006268 (DNA replication) involvement; GO:0043111 (histone H4-K16 deacetylation) via HDAC1 recruitment; CC: GO:0005684 (U2 snRNP), GO:0016607 (nuclear speckle), GO:0005654 (nucleoplasm), replication fork association. (damianov2023theapoptoticsplicing pages 30-33, machour2024harnessingdnareplication pages 4-5) - NUMB (HGNC:NUMB): GO:0007219 (Notch signaling), alternative splicing target of RBM10; reduced NUMB leads to NOTCH de-repression. (krishnamoorthy2024rbm10lossinduces pages 1-4) - VCL/CD44/TNC/EIF4H: GO processes in cytoskeleton/ECM organization and translation initiation regulation; RBM10-sensitive cassette exons. (krishnamoorthy2024rbm10lossinduces pages 1-4)
Phenotype associations (HPO) - HPO:0001763 Talipes equinovarus; HPO:0001631 Atrial septal defect; HPO:0030324 Robin sequence; HPO:0006689 Persistent left superior vena cava; HPO:0001531 Failure to thrive; HPO:0001249 Intellectual disability; HPO:0001321 Cerebellar vermis hypoplasia; HPO:0002119 Ventriculomegaly; HPO:0001274 Thin corpus callosum; HPO:0002904 Conjugated hyperbilirubinemia (rare). (bang2025genotypephenotypecorrelationin pages 8-11, lane2023abnormalliverfunction pages 2-3)
Cell type involvement (CL) and anatomical locations (UBERON) - CL: cranial neural crest cell involvement inferred from craniofacial defects and RBM10 embryonic expression in branchial arches; UBERON:0002315 branchial arch; UBERON:0002101 limb; UBERON:0000948 heart. (krishnamoorthy2024rbm10lossinduces pages 1-4, lane2023abnormalliverfunction pages 2-3)
Chemical entities (CHEBI) with relevance - CHEBI: Adavosertib (MK-1775), a WEE1 inhibitor with synthetic-lethal efficacy in RBM10-deficient models. (machour2024harnessingdnareplication pages 8-10)
Evidence items with URLs and publication dates - Damianov et al. 2023 (bioRxiv preprint posted Sep 21, 2023): https://doi.org/10.1101/2023.09.21.558883 (U2 snRNP association, branch-site engagement). (damianov2023theapoptoticsplicing pages 30-33, damianov2023theapoptoticsplicing pages 10-14, damianov2023theapoptoticsplicing pages 1-5, damianov2023theapoptoticsplicing pages 14-16) - Machour et al. 2024 (Nature Communications; published Jul 25, 2024): https://doi.org/10.1038/s41467-024-50882-0 (replication forks, HDAC1/H4K16ac, WEE1 synthetic lethality). (machour2024harnessingdnareplication pages 1-2, machour2024harnessingdnareplication pages 4-5, machour2024harnessingdnareplication pages 8-10) - Krishnamoorthy et al. 2024 (bioRxiv; posted Jul 10, 2024): https://doi.org/10.1101/2024.07.09.602730 (NUMB/NOTCH, ECM/cytoskeleton isoforms, RAC1). (krishnamoorthy2024rbm10lossinduces pages 1-4) - Lane et al. 2023 (BMJ Case Reports; published Mar 2023): https://doi.org/10.1136/bcr-2022-253035 (clinical features including survival and hepatic involvement). (lane2023abnormalliverfunction pages 2-3) - RBM10 genotype–phenotype spectrum (medRxiv; posted Aug 5, 2025): https://doi.org/10.1101/2025.08.05.25330579 (broader context and statistics; used sparingly as a preprint outside target window but informative). (bang2025genotypephenotypecorrelationin pages 8-11, bang2025genotypephenotypecorrelationin pages 37-42, bang2025genotypephenotypecorrelationin pages 42-46, bang2025genotypephenotypecorrelationin pages 1-4)
Embedded artifact summary table | Category | Entity (Symbol/Name) | Ontology ID (HGNC/GO/CL/UBERON/HPO/CHEBI) | Mechanistic relevance in TARP | Key evidence (short) | Source (URL, year) | |---|---|---|---|---|---| | Gene / Protein | RBM10 | HGNC:RBM10 | RNA-binding splicing regulator that promotes cassette-exon exclusion; also reported splicing-independent roles in replication-fork stability and transcriptional/3'UTR control | Loss-of-function → increased exon inclusion and multisystem TARP phenotypes (severity correlates with degree of LOF) (krishnamoorthy2024rbm10lossinduces pages 1-4, bang2025genotypephenotypecorrelationin pages 4-8) | https://doi.org/10.1101/2024.07.09.602730 (2024), https://doi.org/10.1101/2025.08.05.25330579 (2025) | | Gene / Protein | NUMB | HGNC:NUMB | Alternative splicing target of RBM10; altered splicing → decreased NUMB protein and de-repression of NOTCH signaling during development | Validated exon inclusion changes and downstream NOTCH de-repression in RBM10 loss models (krishnamoorthy2024rbm10lossinduces pages 1-4) | https://doi.org/10.1101/2024.07.09.602730 (2024) | | Pathway | NOTCH signaling | GO:0007219 (Notch signaling pathway) | Developmental cell-fate pathway indirectly activated by RBM10 loss via NUMB missplicing; implicated in craniofacial/cardiac development defects | Mechanistic link: NUMB mis-splicing → NOTCH de-repression; developmental relevance discussed in RBM10 literature (krishnamoorthy2024rbm10lossinduces pages 1-4, bang2025genotypephenotypecorrelationin pages 37-42) | https://doi.org/10.1101/2024.07.09.602730 (2024), https://doi.org/10.1101/2025.08.05.25330579 (2025) | | Gene / Protein | VCL (vinculin) | HGNC:VCL | Cytoskeletal gene whose exon-inclusion isoform increases cell motility and ECM–cytoskeleton signaling when RBM10 is lost | Exon-inclusion events in VCL contribute to increased cell velocity in RBM10-null cells (krishnamoorthy2024rbm10lossinduces pages 1-4) | https://doi.org/10.1101/2024.07.09.602730 (2024) | | Gene / Protein | CD44 | HGNC:CD44 | ECM/cell-adhesion transcript with RBM10-sensitive isoforms that promote invasiveness when mis-spliced | Inclusion isoforms increase invasiveness in RBM10-deficient models (krishnamoorthy2024rbm10lossinduces pages 1-4) | https://doi.org/10.1101/2024.07.09.602730 (2024) | | Gene / Protein | TNC (tenascin-C) | HGNC:TNC | Extracellular matrix glycoprotein with RBM10-regulated exon usage affecting invasiveness/ECM interactions | TNC exon-inclusion isoforms contribute to invasiveness in RBM10 loss (krishnamoorthy2024rbm10lossinduces pages 1-4) | https://doi.org/10.1101/2024.07.09.602730 (2024) | | Gene / Protein | EIF4H | HGNC:EIF4H | Translation-initiation factor with RBM10-regulated exon (e.g., exon 5) validated as an RBM10 splicing target | EIF4H exon inclusion validated in RBM10-deficient models (krishnamoorthy2024rbm10lossinduces pages 1-4) | https://doi.org/10.1101/2024.07.09.602730 (2024) | | Complex / Machinery | U2 snRNP (pre-spliceosome) | GO:0005684 (U2 snRNP) | RBM10 associates with pre-spliceosomal complexes and binds intronic regions near branch sites, modulating A/B complex activity and exon choice | RBM10 interacts with U2-engaged complexes on chromatin and influences branch-site-associated splicing outcomes (bang2025genotypephenotypecorrelationin pages 4-8) | https://doi.org/10.1101/2025.08.05.25330579 (2025) | | Cellular component | Nuclear speckles | GO:0016607 (nuclear speckle) | Subnuclear splicing factor-rich compartments where RBM10/splicing regulators localize, informing tissue-specific splicing dynamics | RBM-family splicing regulators work within chromatin-associated splicing complexes and speckle-related compartments (bang2025genotypephenotypecorrelationin pages 4-8) | https://doi.org/10.1101/2025.08.05.25330579 (2025) | | Cellular component / Function | DNA replication forks | GO (replication fork) / molecular function | RBM10 reported to play a replication-associated role: associates with active forks, recruits HDAC1 and modulates H4K16 deacetylation to maintain fork progression (splicing-independent) | Splicing-independent RBM10 role in replication-fork progression and synthetic-lethal interactions (WEE1) in RBM10-deficient cells (krishnamoorthy2024rbm10lossinduces pages 1-4) | Nature Commun. article (DOI listed in retrieved set), reported 2024 (krishnamoorthy2024rbm10lossinduces pages 1-4) | | Cell type (CL) | Cranial neural crest cells (CNCCs) | CL:cranial neural crest cell | Embryonic cell population contributing to craniofacial structures; RBM10 expression in branchial arches implicates CNCCs in TARP craniofacial defects | Embryonic expression in branchial arches/limb buds and craniofacial phenotypes reported in RBM10 models and human cases (krishnamoorthy2024rbm10lossinduces pages 1-4, bang2025genotypephenotypecorrelationin pages 4-8) | https://doi.org/10.1101/2024.07.09.602730 (2024), https://doi.org/10.1101/2025.08.05.25330579 (2025) | | Anatomy (UBERON) | Heart (cardiac atria/ASD) | UBERON:0000948 (heart) | Atrial septal defects (ASD) are a canonical structural cardiac manifestation in TARP; RBM10 perturbation affects cardiac development | ASD and other cardiac anomalies commonly reported in TARP cohorts and case reports (lane2023abnormalliverfunction pages 2-3, bang2025genotypephenotypecorrelationin pages 4-8) | https://doi.org/10.1136/bcr-2022-253035 (2023), https://doi.org/10.1101/2025.08.05.25330579 (2025) | | Phenotype (HPO) | Talipes equinovarus (clubfoot) | HPO:0001763 | Classic limb phenotype in TARP; likely reflects disrupted musculoskeletal/limb development downstream of splicing defects in developmental programs | Talipes is a defining clinical feature in case series and cohort descriptions of RBM10-related TARP (lane2023abnormalliverfunction pages 2-3, bang2025genotypephenotypecorrelationin pages 4-8) | https://doi.org/10.1136/bcr-2022-253035 (2023), https://doi.org/10.1101/2025.08.05.25330579 (2025) |
Table: Compact reference table mapping key genes, pathways, cellular components, cell types, anatomical sites, and canonical phenotypes for TARP syndrome (RBM10-related), with concise mechanistic notes and primary evidence citations (context IDs) useful for disease knowledge-base curation.
Limitations - Some mechanistic sources are preprints (2023–2024) and should be interpreted with caution until peer-reviewed versions are available; nevertheless, their claims align with orthogonal data (e.g., replication-fork association is peer-reviewed in 2024). The 2025 medRxiv genotype–phenotype dataset extends beyond the requested 2023–2024 focus and is cited to provide breadth; where possible, 2023–2024 peer-reviewed sources were prioritized. (machour2024harnessingdnareplication pages 1-2, damianov2023theapoptoticsplicing pages 30-33, krishnamoorthy2024rbm10lossinduces pages 1-4, lane2023abnormalliverfunction pages 2-3)
References
(damianov2023theapoptoticsplicing pages 30-33): Andrey Damianov, Chia-Ho Lin, Jeffrey Huang, Lin Zhou, Yasaman Jami-Alahmadi, James Wohlschlegel, and Douglas L. Black. The apoptotic splicing regulators rbm5 and rbm10 are subunits of the u2 snrnp engaged with intron branch sites on chromatin. bioRxiv, Sep 2023. URL: https://doi.org/10.1101/2023.09.21.558883, doi:10.1101/2023.09.21.558883. This article has 4 citations and is from a poor quality or predatory journal.
(damianov2023theapoptoticsplicing pages 10-14): Andrey Damianov, Chia-Ho Lin, Jeffrey Huang, Lin Zhou, Yasaman Jami-Alahmadi, James Wohlschlegel, and Douglas L. Black. The apoptotic splicing regulators rbm5 and rbm10 are subunits of the u2 snrnp engaged with intron branch sites on chromatin. bioRxiv, Sep 2023. URL: https://doi.org/10.1101/2023.09.21.558883, doi:10.1101/2023.09.21.558883. This article has 4 citations and is from a poor quality or predatory journal.
(damianov2023theapoptoticsplicing pages 1-5): Andrey Damianov, Chia-Ho Lin, Jeffrey Huang, Lin Zhou, Yasaman Jami-Alahmadi, James Wohlschlegel, and Douglas L. Black. The apoptotic splicing regulators rbm5 and rbm10 are subunits of the u2 snrnp engaged with intron branch sites on chromatin. bioRxiv, Sep 2023. URL: https://doi.org/10.1101/2023.09.21.558883, doi:10.1101/2023.09.21.558883. This article has 4 citations and is from a poor quality or predatory journal.
(damianov2023theapoptoticsplicing pages 14-16): Andrey Damianov, Chia-Ho Lin, Jeffrey Huang, Lin Zhou, Yasaman Jami-Alahmadi, James Wohlschlegel, and Douglas L. Black. The apoptotic splicing regulators rbm5 and rbm10 are subunits of the u2 snrnp engaged with intron branch sites on chromatin. bioRxiv, Sep 2023. URL: https://doi.org/10.1101/2023.09.21.558883, doi:10.1101/2023.09.21.558883. This article has 4 citations and is from a poor quality or predatory journal.
(bang2025genotypephenotypecorrelationin pages 8-11): J. M. V. Bang, C. Fagerberg, T. K. Doktor, Mia M. Rosenlund, Santiago M. Lumbreras, Mark Burton, Klaus Brusgaard, Ángel Guerra-Moreno, Sofie Høi, Lenet W. Skovstrøm, Nikolaj A. Nielsen, Qin Hao, Carolina Alves, Lars K. Hansen, Melissa Lees, P. Suwannarat, Connie Stumpel, M. Sinnema, A. Stegmann, H. Esch, Chiara De Luca, Christine Van Mol, Andrew Green, Dagmar Wieczorek, Jonathan Rodgers, Julie McGaughran, Véronique Duboc, Khaoula Zaafrane-Khachnaoui, Jill Mad-den, Pankaj B. Agrawal, P. Rump, B. Gener, María Jesús Martínez-González, J. Good, G. Vitiello, F. Passaretti, A. Lolascon, Michael Field, El-lenore M. Martin, B. Keren, Martine Doco-Fenzy, Tony Yammine, K. Steindl, Anita Rauch, A. Begemann, Gregory Costain, Zhuo Shao, Diana Carli, G. B. Ferrero, I. Valenzuela, M. Codina-Solà, Bárbara Masotto, Laura Trujillano, C. Kumps, Olivier Vanakker, Anand Vasudevan, M. Passos-Bueno, Erasmo Ca-sella, Fernarnda Bonilla Colomé, L. Faivre, C. Philippe, Marlin Touma, Lee-Kai Wang, Stanley F. Nelson, M. Scala, Vincenzo Nigro, V. Capra, Kris-ten Truxal, Valentina Caceres, Jonathan Lévy, V. Kalscheuer, A. Delahaye-Duriez, Juan Valcárcel, Michael Sattler, and Brage Storstein Andresen. Genotype-phenotype correlation in rbm10-associated syndromes. how variant function shapes a broad phenotypic landscape. MedRxiv, Aug 2025. URL: https://doi.org/10.1101/2025.08.05.25330579, doi:10.1101/2025.08.05.25330579. This article has 0 citations.
(krishnamoorthy2024rbm10lossinduces pages 1-4): Gnana P. Krishnamoorthy, Anthony R. Glover, Brian R. Untch, Nickole Sigcha-Coello, Bin Xu, Dina Vukel, Yi Liu, Vera Tiedje, Katherine Berman, Prasanna P. Tamarapu, Adrian Acuña-Ruiz, Mahesh Saqcena, Elisa de Stanchina, Laura Boucai, Ronald A. Ghossein, Jeffrey A. Knauf, Omar Abdel-Wahab, Robert K. Bradley, and James A. Fagin. Rbm10 loss induces aberrant splicing of cytoskeletal and extracellular matrix mrnas and promotes metastatic fitness. bioRxiv, Jul 2024. URL: https://doi.org/10.1101/2024.07.09.602730, doi:10.1101/2024.07.09.602730. This article has 2 citations and is from a poor quality or predatory journal.
(machour2024harnessingdnareplication pages 1-2): Feras E. Machour, Enas R. Abu-Zhayia, Joyce Kamar, Alma Sophia Barisaac, Itamar Simon, and Nabieh Ayoub. Harnessing dna replication stress to target rbm10 deficiency in lung adenocarcinoma. Nature Communications, Jul 2024. URL: https://doi.org/10.1038/s41467-024-50882-0, doi:10.1038/s41467-024-50882-0. This article has 12 citations and is from a highest quality peer-reviewed journal.
(machour2024harnessingdnareplication pages 4-5): Feras E. Machour, Enas R. Abu-Zhayia, Joyce Kamar, Alma Sophia Barisaac, Itamar Simon, and Nabieh Ayoub. Harnessing dna replication stress to target rbm10 deficiency in lung adenocarcinoma. Nature Communications, Jul 2024. URL: https://doi.org/10.1038/s41467-024-50882-0, doi:10.1038/s41467-024-50882-0. This article has 12 citations and is from a highest quality peer-reviewed journal.
(machour2024harnessingdnareplication pages 8-10): Feras E. Machour, Enas R. Abu-Zhayia, Joyce Kamar, Alma Sophia Barisaac, Itamar Simon, and Nabieh Ayoub. Harnessing dna replication stress to target rbm10 deficiency in lung adenocarcinoma. Nature Communications, Jul 2024. URL: https://doi.org/10.1038/s41467-024-50882-0, doi:10.1038/s41467-024-50882-0. This article has 12 citations and is from a highest quality peer-reviewed journal.
(lane2023abnormalliverfunction pages 2-3): Michael Lane, Nicholas M Allen, and Johannes Letshwiti. Abnormal liver function tests and improved survival in a child with splice mutation tarp syndrome. BMJ Case Reports, 16:e253035, Mar 2023. URL: https://doi.org/10.1136/bcr-2022-253035, doi:10.1136/bcr-2022-253035. This article has 3 citations and is from a peer-reviewed journal.
(bang2025genotypephenotypecorrelationin pages 37-42): J. M. V. Bang, C. Fagerberg, T. K. Doktor, Mia M. Rosenlund, Santiago M. Lumbreras, Mark Burton, Klaus Brusgaard, Ángel Guerra-Moreno, Sofie Høi, Lenet W. Skovstrøm, Nikolaj A. Nielsen, Qin Hao, Carolina Alves, Lars K. Hansen, Melissa Lees, P. Suwannarat, Connie Stumpel, M. Sinnema, A. Stegmann, H. Esch, Chiara De Luca, Christine Van Mol, Andrew Green, Dagmar Wieczorek, Jonathan Rodgers, Julie McGaughran, Véronique Duboc, Khaoula Zaafrane-Khachnaoui, Jill Mad-den, Pankaj B. Agrawal, P. Rump, B. Gener, María Jesús Martínez-González, J. Good, G. Vitiello, F. Passaretti, A. Lolascon, Michael Field, El-lenore M. Martin, B. Keren, Martine Doco-Fenzy, Tony Yammine, K. Steindl, Anita Rauch, A. Begemann, Gregory Costain, Zhuo Shao, Diana Carli, G. B. Ferrero, I. Valenzuela, M. Codina-Solà, Bárbara Masotto, Laura Trujillano, C. Kumps, Olivier Vanakker, Anand Vasudevan, M. Passos-Bueno, Erasmo Ca-sella, Fernarnda Bonilla Colomé, L. Faivre, C. Philippe, Marlin Touma, Lee-Kai Wang, Stanley F. Nelson, M. Scala, Vincenzo Nigro, V. Capra, Kris-ten Truxal, Valentina Caceres, Jonathan Lévy, V. Kalscheuer, A. Delahaye-Duriez, Juan Valcárcel, Michael Sattler, and Brage Storstein Andresen. Genotype-phenotype correlation in rbm10-associated syndromes. how variant function shapes a broad phenotypic landscape. MedRxiv, Aug 2025. URL: https://doi.org/10.1101/2025.08.05.25330579, doi:10.1101/2025.08.05.25330579. This article has 0 citations.
(bang2025genotypephenotypecorrelationin pages 42-46): J. M. V. Bang, C. Fagerberg, T. K. Doktor, Mia M. Rosenlund, Santiago M. Lumbreras, Mark Burton, Klaus Brusgaard, Ángel Guerra-Moreno, Sofie Høi, Lenet W. Skovstrøm, Nikolaj A. Nielsen, Qin Hao, Carolina Alves, Lars K. Hansen, Melissa Lees, P. Suwannarat, Connie Stumpel, M. Sinnema, A. Stegmann, H. Esch, Chiara De Luca, Christine Van Mol, Andrew Green, Dagmar Wieczorek, Jonathan Rodgers, Julie McGaughran, Véronique Duboc, Khaoula Zaafrane-Khachnaoui, Jill Mad-den, Pankaj B. Agrawal, P. Rump, B. Gener, María Jesús Martínez-González, J. Good, G. Vitiello, F. Passaretti, A. Lolascon, Michael Field, El-lenore M. Martin, B. Keren, Martine Doco-Fenzy, Tony Yammine, K. Steindl, Anita Rauch, A. Begemann, Gregory Costain, Zhuo Shao, Diana Carli, G. B. Ferrero, I. Valenzuela, M. Codina-Solà, Bárbara Masotto, Laura Trujillano, C. Kumps, Olivier Vanakker, Anand Vasudevan, M. Passos-Bueno, Erasmo Ca-sella, Fernarnda Bonilla Colomé, L. Faivre, C. Philippe, Marlin Touma, Lee-Kai Wang, Stanley F. Nelson, M. Scala, Vincenzo Nigro, V. Capra, Kris-ten Truxal, Valentina Caceres, Jonathan Lévy, V. Kalscheuer, A. Delahaye-Duriez, Juan Valcárcel, Michael Sattler, and Brage Storstein Andresen. Genotype-phenotype correlation in rbm10-associated syndromes. how variant function shapes a broad phenotypic landscape. MedRxiv, Aug 2025. URL: https://doi.org/10.1101/2025.08.05.25330579, doi:10.1101/2025.08.05.25330579. This article has 0 citations.
(bang2025genotypephenotypecorrelationin pages 1-4): J. M. V. Bang, C. Fagerberg, T. K. Doktor, Mia M. Rosenlund, Santiago M. Lumbreras, Mark Burton, Klaus Brusgaard, Ángel Guerra-Moreno, Sofie Høi, Lenet W. Skovstrøm, Nikolaj A. Nielsen, Qin Hao, Carolina Alves, Lars K. Hansen, Melissa Lees, P. Suwannarat, Connie Stumpel, M. Sinnema, A. Stegmann, H. Esch, Chiara De Luca, Christine Van Mol, Andrew Green, Dagmar Wieczorek, Jonathan Rodgers, Julie McGaughran, Véronique Duboc, Khaoula Zaafrane-Khachnaoui, Jill Mad-den, Pankaj B. Agrawal, P. Rump, B. Gener, María Jesús Martínez-González, J. Good, G. Vitiello, F. Passaretti, A. Lolascon, Michael Field, El-lenore M. Martin, B. Keren, Martine Doco-Fenzy, Tony Yammine, K. Steindl, Anita Rauch, A. Begemann, Gregory Costain, Zhuo Shao, Diana Carli, G. B. Ferrero, I. Valenzuela, M. Codina-Solà, Bárbara Masotto, Laura Trujillano, C. Kumps, Olivier Vanakker, Anand Vasudevan, M. Passos-Bueno, Erasmo Ca-sella, Fernarnda Bonilla Colomé, L. Faivre, C. Philippe, Marlin Touma, Lee-Kai Wang, Stanley F. Nelson, M. Scala, Vincenzo Nigro, V. Capra, Kris-ten Truxal, Valentina Caceres, Jonathan Lévy, V. Kalscheuer, A. Delahaye-Duriez, Juan Valcárcel, Michael Sattler, and Brage Storstein Andresen. Genotype-phenotype correlation in rbm10-associated syndromes. how variant function shapes a broad phenotypic landscape. MedRxiv, Aug 2025. URL: https://doi.org/10.1101/2025.08.05.25330579, doi:10.1101/2025.08.05.25330579. This article has 0 citations.
(bang2025genotypephenotypecorrelationin pages 4-8): J. M. V. Bang, C. Fagerberg, T. K. Doktor, Mia M. Rosenlund, Santiago M. Lumbreras, Mark Burton, Klaus Brusgaard, Ángel Guerra-Moreno, Sofie Høi, Lenet W. Skovstrøm, Nikolaj A. Nielsen, Qin Hao, Carolina Alves, Lars K. Hansen, Melissa Lees, P. Suwannarat, Connie Stumpel, M. Sinnema, A. Stegmann, H. Esch, Chiara De Luca, Christine Van Mol, Andrew Green, Dagmar Wieczorek, Jonathan Rodgers, Julie McGaughran, Véronique Duboc, Khaoula Zaafrane-Khachnaoui, Jill Mad-den, Pankaj B. Agrawal, P. Rump, B. Gener, María Jesús Martínez-González, J. Good, G. Vitiello, F. Passaretti, A. Lolascon, Michael Field, El-lenore M. Martin, B. Keren, Martine Doco-Fenzy, Tony Yammine, K. Steindl, Anita Rauch, A. Begemann, Gregory Costain, Zhuo Shao, Diana Carli, G. B. Ferrero, I. Valenzuela, M. Codina-Solà, Bárbara Masotto, Laura Trujillano, C. Kumps, Olivier Vanakker, Anand Vasudevan, M. Passos-Bueno, Erasmo Ca-sella, Fernarnda Bonilla Colomé, L. Faivre, C. Philippe, Marlin Touma, Lee-Kai Wang, Stanley F. Nelson, M. Scala, Vincenzo Nigro, V. Capra, Kris-ten Truxal, Valentina Caceres, Jonathan Lévy, V. Kalscheuer, A. Delahaye-Duriez, Juan Valcárcel, Michael Sattler, and Brage Storstein Andresen. Genotype-phenotype correlation in rbm10-associated syndromes. how variant function shapes a broad phenotypic landscape. MedRxiv, Aug 2025. URL: https://doi.org/10.1101/2025.08.05.25330579, doi:10.1101/2025.08.05.25330579. This article has 0 citations.