👪

Inheritance

1

Autosomal Recessive HP:0000007

Homozygous loss-of-function DNMBP variants segregate with cataract in consanguineous families; parents of the Turkish proband were heterozygous carriers.

Autosomal recessive inheritance

Show evidence (2 references)

PMID:30290152 SUPPORT Human Clinical

"Using exome sequencing, we found homozygous loss-of-function variants in DNMBP: nonsense variant c.811C>T (p.Arg271"

Homozygous variants in three consanguineous families, with a LOD score of 5.18 in the largest, establish recessive inheritance.

PMID:37592116 SUPPORT Human Clinical

"In Family 6, a bi-allelic novel nonsense (c.1918C>T; p.R640*) variant was detected in the DNMBP gene in an index case."

Independent homozygous nonsense allele in a child of a first-cousin marriage.

⚙

Pathophysiology

3

DNMBP Loss of Function

All pathogenic alleles reported so far are homozygous nonsense or frameshift variants (p.Arg271*, p.Asp983*, p.Thr951Metfs*41, p.Arg640*) predicted to abolish Tuba, including its central Dbl homology domain, which activates Cdc42 but not Rac or Rho.

DNMBP hgnc:30373

Cdc42 guanine nucleotide exchange factor activity GO:0005085 ↓ DECREASED

Downstream

Epithelial Junction and E-cadherin Disorganization Loss of Tuba-dependent Cdc42 activation at the apical junction alters junctional F-actin and E-cadherin assembly.

Show evidence (2 references)

PMID:30290152 SUPPORT Human Clinical

"frameshift deletion c.2947_2948del (p.Asp983*) in family F372 (two affected individuals), and frameshift variant c.2852_2855del (p.Thr951Metfs"

Two of the three truncating homozygous alleles reported in the founding families are frameshifts.

PMID:14506234 SUPPORT In Vitro

"A Dbl homology domain present in the middle of Tuba upstream of a Bin/amphiphysin/Rvs (BAR) domain activates Cdc42, but not Rac and Rho, and may thus cooperate with the C terminus of the protein in regulating actin assembly."

Biochemical characterization of Tuba as a Cdc42-specific exchange factor, the activity lost with truncating alleles.

Epithelial Junction and E-cadherin Disorganization

In cultured epithelia Tuba depletion leaves cell junctions curved and slack and alters E-cadherin assembly; in the fly eye, knockdown of the ortholog sif disrupts E-cadherin localization in lens-secreting cells and septate junction distribution in neighbouring cone cells. Lens epithelial cells are bound here as the presumed affected cell type in human cataract; no study has examined junctions in a DNMBP-deficient vertebrate lens.

lens epithelial cell CL:0002224

adherens junction organization GO:0034332 ⚠ ABNORMAL tight junction organization GO:0120193 ⚠ ABNORMAL

Animal models

Drosophila sif knockdown Drosophila melanogaster partially recapitulates Knockdown disrupts development of lens-secreting cells, E-cadherin localization and septate junction distribution, and halves electroretinogram amplitudes in young flies.

Downstream

Loss of Lens Transparency Proposed link: E-cadherin is needed for lens vesicle separation and lens epithelial cell survival, so disordered junctional E-cadherin is expected to compromise lens development. Not demonstrated in a vertebrate lens.

Show evidence (2 references)

PMID:17015620 SUPPORT In Vitro

"RNAi-mediated depletion of Tuba altered the geometrical configuration of cell junctions, resulting in a curved and slack appearance."

Junction shape depends on Tuba in cultured epithelia.

PMID:30290152 SUPPORT Model Organism

"RNAi-mediated knockdown of the Drosophila ortholog still life (sif), enriched in lens-secreting cells, affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells"

Fly ortholog knockdown disrupts E-cadherin and junctions in the cells that secrete the compound-eye lens.

Loss of Lens Transparency

Bilateral lens opacity with onset in infancy in every reported affected individual. Morphology was lamellar in both Turkish probands; the morphology in the Pakistani families is not stated in the abstract.

lens fiber cell CL:0011004

maintenance of lens transparency GO:0036438 ↓ DECREASED

Downstream

Developmental cataract

Lamellar cataract

Show evidence (1 reference)

PMID:30290152 SUPPORT Human Clinical

"The phenotypes of all affected individuals include infantile-onset cataracts."

All twelve affected individuals in the three families have infantile-onset cataract.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

2

Developmental cataract 12/12 Ophthalmologic HP:0000519

Show evidence (2 references)

PMID:30290152 SUPPORT Human Clinical

"We identified three consanguineous families affected by bilateral infantile cataracts."

Bilateral infantile cataract defines the founding families.

PMID:30290152 SUPPORT Human Clinical

"The phenotypes of all affected individuals include infantile-onset cataracts."

Basis for the 12/12 frequency (nine, two and one affected individuals per family).

Lamellar cataract Ophthalmologic HP:0007971

Show evidence (1 reference)

PMID:37592116 SUPPORT Human Clinical

"it was found that the index case received the diagnosis of bilateral lamellar"

Family 6 proband, homozygous for DNMBP p.Arg640*.

🧬

Genetic Associations

1

DNMBP (Causative)

Gene: DNMBP hgnc:30373 relationship_type: CAUSATIVE

Show evidence (2 references)

PMID:30290152 SUPPORT Human Clinical

"We therefore conclude that DNMBP loss-of-function variants cause infantile-onset cataracts in humans."

Gene discovery report across three families.

PMID:37592116 SUPPORT Human Clinical

"The present research is the second study in the literature that reports bi-allelic loss-of-function"

Independent replication in a Turkish family.

💊

Medical Actions

1

Cataract Surgery

Action: cataract surgery Ontology label: Cataract Surgery NCIT:C157809

Platform: Surgery

Removal of the opacified lens with optical correction is the standard management of visually significant infantile cataract; both Turkish DNMBP probands underwent surgery at eleven months. No DNMBP-specific therapy exists.

Target Phenotypes: Developmental cataract HP:0000519

Show evidence (1 reference)

PMID:37592116 SUPPORT Human Clinical

"F6 II-1 L 5 month 11 month DNMBP"

Table 1 row (columns: cataract type, age at diagnosis, age at surgery, gene): the homozygous DNMBP proband had lamellar cataract diagnosed at five months and operated at eleven months.

🔬

Diagnosis

1

Exome sequencing

DNMBP cataract is clinically indistinguishable from other inherited infantile cataracts; all reported families were diagnosed by exome sequencing with segregation analysis.

whole exome sequencing NCIT:C101295

Show evidence (2 references)

PMID:30290152 SUPPORT Human Clinical

"Using exome sequencing, we found homozygous loss-of-function variants in DNMBP"

Exome sequencing identified the causal variants.

PMID:37592116 SUPPORT Human Clinical

"WES analysis showed pathogenic/likely pathogenic variant in 7 (58%) of the 12 families"

Exome sequencing diagnostic yield in a congenital cataract cohort that included the DNMBP family.

🐁

Animal Models

1

Drosophila sif knockdown

Species

Drosophila melanogaster

Genotype

RNAi knockdown of still life (sif), the fly ortholog of DNMBP

Publication

PMID:30290152

Pathograph links

Epithelial Junction and E-cadherin Disorganization partially recapitulates fidelity: low observes: cellular Knockdown disrupts development of lens-secreting cells, E-cadherin localization and septate junction distribution, and halves electroretinogram amplitudes in young flies.

Limitations: The insect compound-eye lens is a secreted cuticular structure, not a cellular lens built from crystallin-filled fiber cells, and septate junctions are only functional counterparts of vertebrate tight junctions. The model shows a junctional defect, not lens opacity.

Divergences from the human mechanism

species mismatch qualifying

The fly corneal lens is secreted by cone and pigment cells, so a defect in those cells is not equivalent to opacity of a vertebrate lens built from fiber cells.

Show evidence (1 reference)

PMID:30290152 SUPPORT Model Organism

"RNAi-mediated knockdown of the Drosophila ortholog still life (sif), enriched in lens-secreting cells, affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells"

Fly knockdown phenotype in lens-secreting and cone cells.

{ }

Source YAML

click to show

name: Cataract 48
creation_date: "2026-10-13T00:00:00Z"
category: Mendelian
synonyms:
- CTRCT48
- DNMBP-related cataract
- autosomal recessive infantile cataract, DNMBP-related
description: >-
  Autosomal recessive non-syndromic infantile cataract caused by biallelic
  loss-of-function variants in DNMBP, which encodes Tuba, a multi-SH3 scaffold
  protein whose Dbl homology domain is a Cdc42-specific guanine nucleotide
  exchange factor. Homozygous nonsense and frameshift variants were found in
  three consanguineous Pakistani families with bilateral infantile-onset
  cataract, and a homozygous nonsense variant in a Turkish child with bilateral
  lamellar cataract. In epithelial cells Tuba shapes tight and adherens
  junctions through local Cdc42 activation, and knockdown of the Drosophila
  ortholog disrupts E-cadherin localization in the lens-secreting cells. How
  DNMBP loss causes lens opacity in humans has not been tested in a vertebrate
  lens model.
disease_term:
  preferred_term: cataract 48
  term:
    id: MONDO:0032735
    label: cataract 48
parents:
- Early-onset non-syndromic cataract
inheritance:
- name: Autosomal Recessive
  description: >-
    Homozygous loss-of-function DNMBP variants segregate with cataract in
    consanguineous families; parents of the Turkish proband were heterozygous
    carriers.
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: PMID:30290152
    reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Using exome sequencing, we found homozygous loss-of-function variants in DNMBP: nonsense variant c.811C>T (p.Arg271"
    explanation: >-
      Homozygous variants in three consanguineous families, with a LOD score of
      5.18 in the largest, establish recessive inheritance.
  - reference: PMID:37592116
    reference_title: "Identification of novel variants in Turkish families with non-syndromic congenital cataracts using whole-exome sequencing."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In Family 6, a bi-allelic novel nonsense (c.1918C>T; p.R640*) variant was detected in the DNMBP gene in an index case."
    explanation: Independent homozygous nonsense allele in a child of a first-cousin marriage.
pathophysiology:
- name: DNMBP Loss of Function
  biological_scale: MOLECULAR
  description: >-
    All pathogenic alleles reported so far are homozygous nonsense or
    frameshift variants (p.Arg271*, p.Asp983*, p.Thr951Metfs*41, p.Arg640*)
    predicted to abolish Tuba, including its central Dbl homology domain, which
    activates Cdc42 but not Rac or Rho.
  genes:
  - preferred_term: DNMBP
    term:
      id: hgnc:30373
      label: DNMBP
  molecular_functions:
  - preferred_term: Cdc42 guanine nucleotide exchange factor activity
    term:
      id: GO:0005085
      label: guanyl-nucleotide exchange factor activity
    modifier: DECREASED
  evidence:
  - reference: PMID:30290152
    reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "frameshift deletion c.2947_2948del (p.Asp983*) in family F372 (two affected individuals), and frameshift variant c.2852_2855del (p.Thr951Metfs"
    explanation: Two of the three truncating homozygous alleles reported in the founding families are frameshifts.
  - reference: PMID:14506234
    reference_title: "Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "A Dbl homology domain present in the middle of Tuba upstream of a Bin/amphiphysin/Rvs (BAR) domain activates Cdc42, but not Rac and Rho, and may thus cooperate with the C terminus of the protein in regulating actin assembly."
    explanation: Biochemical characterization of Tuba as a Cdc42-specific exchange factor, the activity lost with truncating alleles.
  downstream:
  - target: Epithelial Junction and E-cadherin Disorganization
    causal_link_type: DIRECT
    description: >-
      Loss of Tuba-dependent Cdc42 activation at the apical junction alters
      junctional F-actin and E-cadherin assembly.
    evidence:
    - reference: PMID:17015620
      reference_title: "Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells."
      supports: SUPPORT
      evidence_source: IN_VITRO
      directness: INDIRECT
      snippet: "At the subcellular level, Tuba inactivation modified the assembly pattern of junctional F-actin and E-cadherin."
      explanation: >-
        Tuba knockdown in cultured simple epithelial cells, not lens cells, so
        the step to lens epithelium is an inference.
    - reference: PMID:17015620
      reference_title: "Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells."
      supports: SUPPORT
      evidence_source: IN_VITRO
      directness: INDIRECT
      snippet: "Suppression of Cdc42 activity or depletion of N-WASP, which is an effector of Cdc42, mimicked the effects of Tuba depletion."
      explanation: Places Cdc42 activation between Tuba and the junctional phenotype.
- name: Epithelial Junction and E-cadherin Disorganization
  biological_scale: CELLULAR
  description: >-
    In cultured epithelia Tuba depletion leaves cell junctions curved and slack
    and alters E-cadherin assembly; in the fly eye, knockdown of the ortholog
    sif disrupts E-cadherin localization in lens-secreting cells and septate
    junction distribution in neighbouring cone cells. Lens epithelial cells are
    bound here as the presumed affected cell type in human cataract; no study
    has examined junctions in a DNMBP-deficient vertebrate lens.
  cell_types:
  - preferred_term: lens epithelial cell
    term:
      id: CL:0002224
      label: lens epithelial cell
  biological_processes:
  - preferred_term: adherens junction organization
    term:
      id: GO:0034332
      label: adherens junction organization
    modifier: ABNORMAL
  - preferred_term: tight junction organization
    term:
      id: GO:0120193
      label: tight junction organization
    modifier: ABNORMAL
  evidence:
  - reference: PMID:17015620
    reference_title: "Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "RNAi-mediated depletion of Tuba altered the geometrical configuration of cell junctions, resulting in a curved and slack appearance."
    explanation: Junction shape depends on Tuba in cultured epithelia.
  - reference: PMID:30290152
    reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "RNAi-mediated knockdown of the Drosophila ortholog still life (sif), enriched in lens-secreting cells, affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells"
    explanation: Fly ortholog knockdown disrupts E-cadherin and junctions in the cells that secrete the compound-eye lens.
  downstream:
  - target: Loss of Lens Transparency
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Proposed link: E-cadherin is needed for lens vesicle separation and lens
      epithelial cell survival, so disordered junctional E-cadherin is
      expected to compromise lens development. Not demonstrated in a
      vertebrate lens.
    evidence:
    - reference: PMID:30290152
      reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: BACKGROUND
      snippet: "E-cadherin has an important role in lens vesicle separation and lens epithelial cell survival in humans."
      explanation: The authors' stated rationale connecting the junctional defect to cataract; background, not a tested result in DNMBP-deficient lens.
- name: Loss of Lens Transparency
  biological_scale: TISSUE
  conforms_to: cataract_lens_opacification#Loss of Lens Refractive Transparency and Light Scattering
  description: >-
    Bilateral lens opacity with onset in infancy in every reported affected
    individual. Morphology was lamellar in both Turkish probands; the
    morphology in the Pakistani families is not stated in the abstract.
  cell_types:
  - preferred_term: lens fiber cell
    term:
      id: CL:0011004
      label: lens fiber cell
  biological_processes:
  - preferred_term: maintenance of lens transparency
    term:
      id: GO:0036438
      label: maintenance of lens transparency
    modifier: DECREASED
  evidence:
  - reference: PMID:30290152
    reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The phenotypes of all affected individuals include infantile-onset cataracts."
    explanation: All twelve affected individuals in the three families have infantile-onset cataract.
  downstream:
  - target: Developmental cataract
    causal_link_type: DIRECT
  - target: Lamellar cataract
    causal_link_type: DIRECT
phenotypes:
- category: Ophthalmologic
  name: Developmental cataract
  frequency: "12/12"
  description: >-
    Bilateral infantile-onset cataract in all twelve affected members of three
    consanguineous Pakistani families (nine, two and one affected).
  phenotype_term:
    preferred_term: Bilateral infantile-onset cataract
    term:
      id: HP:0000519
      label: Developmental cataract
  evidence:
  - reference: PMID:30290152
    reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We identified three consanguineous families affected by bilateral infantile cataracts."
    explanation: Bilateral infantile cataract defines the founding families.
  - reference: PMID:30290152
    reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The phenotypes of all affected individuals include infantile-onset cataracts."
    explanation: Basis for the 12/12 frequency (nine, two and one affected individuals per family).
- category: Ophthalmologic
  name: Lamellar cataract
  description: >-
    Bilateral lamellar cataract diagnosed at five months in the Turkish
    homozygous p.Arg640* proband. A second Turkish child with lamellar
    cataract carried two DNMBP missense variants of uncertain significance and
    is not counted here.
  phenotype_term:
    preferred_term: Bilateral lamellar cataract
    term:
      id: HP:0007971
      label: Lamellar cataract
  evidence:
  - reference: PMID:37592116
    reference_title: "Identification of novel variants in Turkish families with non-syndromic congenital cataracts using whole-exome sequencing."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "it was found that the index case received the diagnosis of bilateral lamellar"
    explanation: Family 6 proband, homozygous for DNMBP p.Arg640*.
genetic:
- name: DNMBP
  gene_term:
    preferred_term: DNMBP
    term:
      id: hgnc:30373
      label: DNMBP
  association: Causative
  relationship_type: CAUSATIVE
  notes: >-
    Reported homozygous alleles: c.811C>T p.(Arg271*) in family F385 (nine
    affected, LOD 5.18), c.2947_2948del p.(Asp983*) in F372, c.2852_2855del
    p.(Thr951Metfs*41) in F3, and c.1918C>T p.(Arg640*) (NM_015221.4) in a
    Turkish family. A non-consanguineous Turkish child with lamellar cataract
    was compound heterozygous for c.395G>A p.(Gly132Glu) and c.960G>T
    p.(Gln320His) (NM_001318326.2), both classified as variants of uncertain
    significance. No ClinGen gene-disease validity classification was found
    in the local cache.
  evidence:
  - reference: PMID:30290152
    reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We therefore conclude that DNMBP loss-of-function variants cause infantile-onset cataracts in humans."
    explanation: Gene discovery report across three families.
  - reference: PMID:37592116
    reference_title: "Identification of novel variants in Turkish families with non-syndromic congenital cataracts using whole-exome sequencing."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The present research is the second study in the literature that reports bi-allelic loss-of-function"
    explanation: Independent replication in a Turkish family.
animal_models:
- name: Drosophila sif knockdown
  species: Drosophila melanogaster
  genotype: RNAi knockdown of still life (sif), the fly ortholog of DNMBP
  publication: PMID:30290152
  modeled_mechanisms:
  - target: Epithelial Junction and E-cadherin Disorganization
    relationship: PARTIALLY_RECAPITULATES
    fidelity: LOW
    model_scale: CELLULAR
    description: >-
      Knockdown disrupts development of lens-secreting cells, E-cadherin
      localization and septate junction distribution, and halves
      electroretinogram amplitudes in young flies.
    limitations: >-
      The insect compound-eye lens is a secreted cuticular structure, not a
      cellular lens built from crystallin-filled fiber cells, and septate
      junctions are only functional counterparts of vertebrate tight
      junctions. The model shows a junctional defect, not lens opacity.
    divergences:
    - divergence_type: SPECIES_MISMATCH
      materiality: QUALIFYING
      description: >-
        The fly corneal lens is secreted by cone and pigment cells, so a defect
        in those cells is not equivalent to opacity of a vertebrate lens built
        from fiber cells.
    evidence:
    - reference: PMID:30290152
      reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "RNAi-mediated knockdown of the Drosophila ortholog still life (sif), enriched in lens-secreting cells, affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells"
      explanation: Fly knockdown phenotype in lens-secreting and cone cells.
diagnosis:
- name: Exome sequencing
  description: >-
    DNMBP cataract is clinically indistinguishable from other inherited
    infantile cataracts; all reported families were diagnosed by exome
    sequencing with segregation analysis.
  diagnosis_term:
    preferred_term: whole exome sequencing
    term:
      id: NCIT:C101295
      label: Whole Exome Sequencing
  evidence:
  - reference: PMID:30290152
    reference_title: "Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Using exome sequencing, we found homozygous loss-of-function variants in DNMBP"
    explanation: Exome sequencing identified the causal variants.
  - reference: PMID:37592116
    reference_title: "Identification of novel variants in Turkish families with non-syndromic congenital cataracts using whole-exome sequencing."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "WES analysis showed pathogenic/likely pathogenic variant in 7 (58%) of the 12 families"
    explanation: Exome sequencing diagnostic yield in a congenital cataract cohort that included the DNMBP family.
treatments:
- name: Cataract Surgery
  description: >-
    Removal of the opacified lens with optical correction is the standard
    management of visually significant infantile cataract; both Turkish
    DNMBP probands underwent surgery at eleven months. No DNMBP-specific
    therapy exists.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: cataract surgery
    term:
      id: NCIT:C157809
      label: Cataract Surgery
  target_phenotypes:
  - preferred_term: Developmental cataract
    term:
      id: HP:0000519
      label: Developmental cataract
  evidence:
  - reference: PMID:37592116
    reference_title: "Identification of novel variants in Turkish families with non-syndromic congenital cataracts using whole-exome sequencing."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "F6 II-1 L 5 month 11 month DNMBP"
    explanation: >-
      Table 1 row (columns: cataract type, age at diagnosis, age at surgery,
      gene): the homozygous DNMBP proband had lamellar cataract diagnosed at
      five months and operated at eleven months.
notes: >-
  No GeneReviews chapter or Orphanet record specific to DNMBP cataract was
  found. A PubMed search for DNMBP (50 records) and a Europe PMC full-text
  search for "DNMBP AND cataract" (29 records) found patient reports only in
  PMID:30290152 and PMID:37592116; the other hits are reviews, gene lists or
  association studies. One exome association study of cataract
  (PMID:40801674) lists DNMBP among nominal gene-based associations and
  reports higher DNMBP expression in lens fibers than in lens epithelium in
  aged human lens datasets; that study concerns cataract susceptibility
  rather than Mendelian infantile cataract and is not used as evidence here. The mechanism linking Tuba loss to lens opacity
  rests on non-lens epithelial cell culture and a Drosophila compound-eye
  model; no vertebrate lens model has been described.

📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Review round 1: Cataract_48 · 2026-10-13T20:21:00Z · View source

Diagnosis rebound from NCIT:C15709 Genetic Testing to NCIT:C101295 Whole Exome Sequencing, since both cited studies used exome sequencing. Loss of Lens Transparency node now binds CL:0011004 lens fiber cell instead of lens epithelial cell. Frameshift snippet on the DNMBP Loss of Function node widened to quote both frameshift alleles, and the Turkish replication snippet trimmed before the PDF word join. references_cache/PMID_37592116.md had NUL bytes from PDF ligature extraction; repaired with scripts/repair_reference_cache_nuls.py --apply (51 ligatures restored, 9 replaced with U+FFFD). Added a claude_code deep-research report (falcon failed authentication twice); it found no further DNMBP families. A PubMed DNMBP search (50 records) and a Europe PMC full-text DNMBP AND cataract search (29 records) also found patient reports only in PMID:30290152 and PMID:37592116, recorded in notes. validate-disorders: 19/19 snippets, 0 issues.

Claude Code ▸

Cataract 48 (CTRCT48; DNMBP-related autosomal recessive infantile cataract): research report

claude-haiku-5-5, claude-opus-5-5 13 citations 2026-10-13T20:18:09.213797

Status: I've read the existing entry and its cached sources, and found OMIM 618415. Running one more search for other DNMBP cataract reports, then I'll write the report.

Cataract 48 (CTRCT48; DNMBP-related autosomal recessive infantile cataract): research report

Scope. Only two publications report human DNMBP cataract: the 2018 gene-discovery paper (PMID:30290152) and one 2023 Turkish exome cohort (PMID:37592116). Web searches for 2024–2026 reports, including Chinese, Indian and Saudi pediatric cataract cohorts, found nothing new. The PubMed search tool was not authorized this session, so I checked abstracts against the local references_cache/ files and web search. A PubMed search filtered to 2024 onward would be the next step to confirm nothing newer exists.

Quotes below are copied from the cached abstracts or full text.

1. Disease information

Definition. A non-syndromic, autosomal recessive cataract with bilateral lens opacity starting in infancy. It is caused by biallelic loss-of-function variants in DNMBP on chromosome 10q24. OMIM-derived records describe it as "characterized by infantile or early-childhood cataracts and visual impairment" (MGI disease page, OMIM:618415).
Identifiers.
MONDO:0032735 (cataract 48)
OMIM 618415
Gene: DNMBP, hgnc:30373
Orphanet: no DNMBP-specific record found. It falls under Orphanet's general early-onset non-syndromic cataract grouping.
ICD-10: Q12.0 (congenital cataract)
MeSH: Cataract / Cataract, congenital
Synonyms. CTRCT48; DNMBP-related cataract; autosomal recessive infantile cataract, DNMBP-related.
Data source. Everything known comes from individual families: 12 affected people in 3 Pakistani families, plus 1 Turkish proband. There is no registry or EHR data.

2. Etiology

Cause. Homozygous truncating DNMBP variants. "We therefore conclude that DNMBP loss-of-function variants cause infantile-onset cataracts in humans" (PMID:30290152).
Genetic risk factor. Consanguinity. Every confirmed homozygous family was consanguineous; the Turkish Family 6 proband was the child of a first-cousin marriage.
Environmental, protective and gene–environment factors. None reported. Not applicable to a fully penetrant Mendelian lens defect as far as the literature shows.

3. Phenotypes

Phenotype	Suggested HPO	Onset	Frequency	Source
Bilateral infantile cataract	HP:0000519 Developmental cataract (or HP:0000518 Cataract; laterality via HP:0012832 Bilateral)	Infancy	12/12 Pakistani; 1/1 Turkish	PMID:30290152 ("The phenotypes of all affected individuals include infantile-onset cataracts."); PMID:37592116
Lamellar cataract	HP:0007971 Lamellar cataract	Diagnosed at 5 months	1/1 homozygous Turkish proband	PMID:37592116 ("…received the diagnosis of bilateral lamellar…")
Visual impairment	HP:0000505 Visual impairment	Infancy	Not quantified	OMIM-derived summary only

Gaps.
The Pakistani abstract does not state the cataract morphology.
No reports of nystagmus, amblyopia or aphakic glaucoma, and no extra-ocular features. The disease is reported as non-syndromic.
Quality of life. No disease-specific data. The general burden is that of infantile cataract: risk of deprivation amblyopia and lifelong optical correction after surgery.

4. Genetics and molecular information

Gene. DNMBP encodes Tuba (dynamin-binding protein). It is a multi-SH3 scaffold with a central Dbl homology (DH) domain and a BAR domain (PMID:14506234).

Reported alleles. All are homozygous unless noted.

Variant	Type	Family / population	Classification
c.811C>T p.(Arg271*)	Nonsense	F385, Pakistani, 9 affected, LOD 5.18 at θ=0	Pathogenic (segregation)
c.2947_2948del p.(Asp983*)	Frameshift → stop	F372, Pakistani, 2 affected	Pathogenic / likely pathogenic
c.2852_2855del p.(Thr951Metfs*41)	Frameshift	F3, Pakistani, 1 affected	Likely pathogenic
c.1918C>T p.(Arg640*) (NM_015221.4)	Nonsense	Turkish Family 6	Novel; reported as LoF ("the second study in the literature that reports bi-allelic loss-of-function")
c.395G>A p.(Gly132Glu) + c.960G>T p.(Gln320His) (NM_001318326.2)	Compound heterozygous missense	Non-consanguineous Turkish child with lamellar cataract	VUS; should not count as confirmed CTRCT48

Variant origin. Germline. Parents were heterozygous carriers.
Functional consequence. Loss of function. The truncations remove the DH (Cdc42 GEF) domain and the C-terminal domains.
Not reported. Modifier genes, epigenetic findings, chromosomal abnormalities and population allele frequencies for these specific variants (check gnomAD per variant).
ClinGen. No gene-disease validity classification was found in the local cache.

5. Environmental information

Not applicable. No environmental, lifestyle or infectious contribution has been reported.

6. Mechanism and pathophysiology

Causal chain. Steps 4 and 5 are inferred, not shown in a lens.

Biallelic truncating DNMBP variants lead to loss of Tuba protein, or of its DH domain at least. Inferred from variant class; no patient protein studies.
Loss of Tuba removes a Cdc42-specific guanine nucleotide exchange factor.
"A Dbl homology domain present in the middle of Tuba … activates Cdc42, but not Rac and Rho" (PMID:14506234, in vitro).
Reduced local Cdc42 / N-WASP activity at the apical junction results in disordered junctional F-actin and E-cadherin assembly, with "curved and slack" junctions.
"At the subcellular level, Tuba inactivation modified the assembly pattern of junctional F-actin and E-cadherin."
"Suppression of Cdc42 activity or depletion of N-WASP … mimicked the effects of Tuba depletion."
Source: PMID:17015620, cultured non-lens epithelial cells.
In the eye, junction disorganization affects the cells that build the lens.
Fly evidence: knockdown of the ortholog sif "affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells," and cuts ERG amplitude by about 50% (PMID:30290152, Drosophila).
Extrapolation to vertebrate lens epithelium is untested.
Disrupted E-cadherin-dependent lens development is proposed to cause loss of lens transparency.
"E-cadherin has an important role in lens vesicle separation and lens epithelial cell survival in humans" (PMID:30290152).
This is the authors' background rationale, not an experimental result.
Loss of lens transparency produces bilateral infantile, sometimes lamellar, cataract and visual impairment.

Ontology suggestions.

Category	Suggested terms
GO	GO:0005085 guanyl-nucleotide exchange factor activity (Cdc42-specific); GO:0034332 adherens junction organization; GO:0120193 tight junction organization; GO:0036438 maintenance of lens transparency; GO:0002088 lens development in camera-type eye
CL	CL:0002224 lens epithelial cell; CL:0011004 lens fiber cell
GO cellular component	apical junction complex; adherens junction; tight junction; actin cortex

Profiling. There are no transcriptomic, proteomic, metabolomic or single-cell studies of DNMBP cataract.

7. Anatomy

Level	Affected structures
Organ / tissue	Lens: UBERON:0000965 lens of camera-type eye; lens epithelium; lens fibers
Subcellular	Cell–cell junctions: adherens and tight junctions
Laterality	Bilateral in all reported cases

There is no secondary organ involvement.

8. Temporal development

Onset. Infantile. The Turkish proband was diagnosed at 5 months and had surgery at 11 months.
Progression. Natural history is not described. As with other developmental cataracts, the opacity is presumed to be stable or slowly progressive.
Critical period. The amblyopia window in the first months of life is when surgery and optical rehabilitation matter most. This is general infantile-cataract knowledge, not DNMBP-specific.

9. Inheritance and population

Inheritance. Autosomal recessive (HP:0000007), with complete penetrance in the families reported.
Prevalence. Unknown. There are 4 confirmed families: 3 Pakistani and 1 Turkish.
Founder effect, carrier frequency and sex ratio. Not reported. Sexes are not separately described in the abstract.
Population pattern. Concentrated in consanguineous populations.

10. Diagnostics

Clinical exam. Slit-lamp examination and red-reflex testing. CTRCT48 cannot be clinically distinguished from other infantile cataracts.
Genetic testing. Exome sequencing or a congenital-cataract gene panel. Confirm DNMBP is included, since it is a rarely tested gene. Follow with segregation analysis.
Suggested NCIT term: NCIT:C101295 Whole Exome Sequencing.
In the Turkish cohort, exome sequencing found a pathogenic or likely pathogenic variant in 7 of 12 families (58%) (PMID:37592116).
Biomarkers. None.
Differential diagnosis. Other autosomal recessive infantile cataracts (e.g., LSS, FYCO1, CRYBB1, GCNT2); dominant crystallin and connexin cataracts; and syndromic or metabolic cataracts, such as galactosemia, which should be excluded biochemically.

11. Outcome and prognosis

Life expectancy is expected to be normal. There are no systemic features.
Visual outcome depends on timely surgery and amblyopia management. No DNMBP-specific outcome data exist.

12. Treatment

Surgery. Lensectomy or cataract extraction (NCIT:C157809 Cataract Surgery), followed by aphakic or IOL optical correction. Both Turkish DNMBP probands had surgery at 11 months.
Rehabilitation. Amblyopia therapy, such as occlusion.
Other therapies. There is no pharmacological, gene-targeted or other DNMBP-specific therapy, and no clinical trials.

13. Prevention

Genetic counseling for consanguineous families, with a 25% recurrence risk for parents who are both carriers.
Carrier testing and prenatal or preimplantation testing are possible once the familial variant is known.
Early detection through newborn red-reflex screening.

14. Other species

No naturally occurring DNMBP cataract is recorded in OMIA from this search.
Drosophila ortholog: still life (sif).

15. Model organisms

Drosophila sif RNAi (PMID:30290152). Knockdown disrupts development of the lens-secreting cells, E-cadherin localization and septate-junction distribution, and roughly halves ERG amplitude in young flies.
Limitation: the insect corneal lens is a secreted cuticular structure, not a crystallin-filled cellular lens. The model shows a junctional defect, not opacity.
Vertebrate models. No vertebrate (mouse or zebrafish) lens model of DNMBP loss has been described. This is the main gap in the evidence for the mechanism.
In vitro. Tuba knockdown in simple epithelial cell lines (PMID:17015620) is the main mechanistic system.

Key evidence gaps

Only 4 confirmed families have been reported.
Cataract morphology in the Pakistani families is not in the abstract.
No vertebrate lens model exists.
There is no ClinGen classification.
Whether the Turkish compound-heterozygous missense variants are pathogenic is unresolved.

Note on the existing knowledge base entry

kb/disorders/Cataract_48.yaml already covers this material: the same 4 alleles, the causal chain marked as inferred, Drosophila model caveats, and surgery evidence. This report found no new primary literature that would change the entry.

Sources - PMID:30290152, Ansar et al., Am J Hum Genet 2018, doi:10.1016/j.ajhg.2018.09.004; PMC6174361 - PMID:37592116, Türkyılmaz et al., Int Ophthalmol 2023, doi:10.1007/s10792-023-02857-1 - PMID:14506234 (Tuba, Cdc42-specific DH domain); PMID:17015620 (Tuba regulates junction configuration) - MGI disease page, OMIM:618415 - FlyBase FBrf0240231 - Texas Children's news release - KTU AVESIS record of the Turkish study - GeneBe DNMBP - Houston Methodist scholars page - EyeSmart, Medical Dialogues, CRST Europe, NZ Optics

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Outcome	Count
References checked	7
Resolved	7
Unresolved (possible confabulation)	0
Unverifiable	0
Quoted claims checked	3
Quoted claims found in source	2
Quoted claims not found in source	1
References weighed for topical relevance	7
On topic	4
Off topic	1

Quotes not found in the cited source

Searched the abstract, any retrieved full text, and the title. A quote drawn from a part of the paper that was not retrieved will appear here too, so check before treating one as invented:

Every one of these was searched against an abstract alone, with no full text retrieved - marked abstract only below. Where full text can be fetched, re-running with it will settle them; where the source publishes only a summary to PubMed, as GeneReviews chapters do, it will not, and the quote has to be checked by hand against the chapter itself.

PMID:14506234 (abstract only): "A Dbl homology domain present in the middle of Tuba … activates Cdc42, but not Rac and Rho"
closest text in source: "A Dbl homology domain present in the middle of Tuba upstream of a Bin/amphiphysin/Rvs (BAR) domain activates Cdc42, but not Rac and Rho, and may thus cooperate with the C terminus of the protein in regulating actin assembly"

References that may not be about this subject

These identifiers resolve, so they are not fabrications, but the records they resolve to share almost none of this report's vocabulary. That is a clue and not a verdict - a paper can be relevant in ways its title and abstract do not spell out - so read them before deciding:

PMID:14506234 (3 mentions) - Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton.
shared terms: tuba

Weighed against this report's own most characteristic terms: cataract, dnmbp, turkish, variant, lens, infantile, found, familie, pakistani, surgery, proband, tuba, affected, bilateral, gene, abstract, amblyopia, autosomal, recessive, visual.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome	Count
Terms checked	18
Resolved	17
Unresolved (possible confabulation)	0
Obsolete	0
Unverifiable	1
Terms whose name was checked	1
Terms named correctly	1
Terms named as a different term	0

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: OMIM.

17 of 18 terms resolved to a current term; the rest could not be looked up either way.

Cataract 48

Ask OpenScientist

OpenScientist Report

Inheritance

Pathophysiology

Pathograph

Phenotypes

Genetic Associations

Medical Actions

Diagnosis

Animal Models

Source YAML

References & Deep Research

Deep Research

Cataract 48 (CTRCT48; DNMBP-related autosomal recessive infantile cataract): research report

1. Disease information

2. Etiology

3. Phenotypes

4. Genetics and molecular information

5. Environmental information

6. Mechanism and pathophysiology

7. Anatomy

8. Temporal development

9. Inheritance and population

10. Diagnostics

11. Outcome and prognosis

12. Treatment

13. Prevention

14. Other species

15. Model organisms

Key evidence gaps

Note on the existing knowledge base entry

Reference Validation

Quotes not found in the cited source

References that may not be about this subject

Term Validation

Prefixes with no resolver