NUP62-Related Infantile Bilateral Striatal Necrosis

Mendelian MONDO:0010080 Pathograph 8 Show in embeddings browser Neurodegenerative Disease Movement Disorder

NUP62-related infantile bilateral striatal necrosis is an autosomal recessive neurodegenerative disorder caused by pathogenic germline variation in NUP62, which encodes nucleoporin 62, a component of the central transport channel of the nuclear pore complex. The best-established familial form was mapped to 19q13.33 and associated with homozygous NUP62 p.Q391P. The curated mechanism is a nuclear pore / nucleocytoplasmic-transport defect with selective basal ganglia vulnerability, producing severe basal ganglia atrophy or degeneration and infantile developmental arrest with choreoathetosis, dysphagia, and later nystagmus.

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1
Mappings
1
Inheritance
3
Pathophys.
5
Phenotypes
8
Pathograph
1
Genes
🏷

Classifications

ICIMD (Inherited Metabolic Disorders)
ectonucleotides and nucleic acids
🔗

Mappings

MONDO
MONDO:0015518 infantile bilateral striatal necrosis Not Yet Curated
skos:broadMatch MONDO
👪

Inheritance

1
Autosomal recessive HP:0000007
The NUP62-linked familial IBSN kindred and mapped disease series support autosomal recessive inheritance.
Autosomal recessive inheritance
Show evidence (2 references)
PMID:16786527 SUPPORT Human Clinical
"The objective of this study was to identify the gene causing autosomal recessive infantile bilateral striatal necrosis."
The NUP62 discovery study frames the mapped condition as autosomal recessive IBSN.
PMID:12374138 SUPPORT Human Clinical
"Inheritance was apparently autosomal recessive."
The earlier familial IBSN clinical series supports recessive inheritance for the same Bedouin kindred later mapped to NUP62.
⚙

Pathophysiology

3
NUP62 p.Q391P Germline Variant
Homozygous NUP62 p.Q391P changes a highly conserved glutamine in the nucleoporin 62 protein and is the primary gene lesion in the reported familial autosomal recessive IBSN series.
NUP62 hgnc:8066 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves NUP62 (hgnc:8066). hgnc:8066 is a gene from the HUGO Gene Nomenclature Committee.
nuclear pore GO:0005643 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves nuclear pore (GO:0005643). GO:0005643 is a cellular component from the Gene Ontology.
Downstream
Central Nuclear Pore Transport Channel Disruption
Show evidence (1 reference)
PMID:16786527 SUPPORT Human Clinical
"Sequencing of the nup62 gene showed a missense mutation causing a change from glutamine to proline (Q391P) in all the patients, producing a substitution from a polar, hydrophilic residue to a nonpolar, neutral residue."
The discovery paper identifies the shared NUP62 Q391P missense variant in affected patients.
Central Nuclear Pore Transport Channel Disruption
NUP62 is a central channel nucleoporin in the nuclear pore complex. The disease-specific NUP62 lesion is therefore modeled as disruption of the Nup62-dependent nucleocytoplasmic transport channel, with the exact cell-type-selective transport defect still incompletely resolved.
NUP62 hgnc:8066 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves NUP62 (hgnc:8066). hgnc:8066 is a gene from the HUGO Gene Nomenclature Committee.
nucleocytoplasmic transport GO:0006913 ⚠ ABNORMAL Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal nucleocytoplasmic transport (GO:0006913). GO:0006913 is a biological process from the Gene Ontology.
nuclear pore GO:0005643 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves nuclear pore (GO:0005643). GO:0005643 is a cellular component from the Gene Ontology.
Downstream
Basal Ganglia Neuronal Degeneration
Show evidence (2 references)
PMID:22036567 SUPPORT In Vitro
"The nuclear pore complex encloses a central channel for nucleocytoplasmic transport, which is thought to consist of three nucleoporins, Nup54, Nup58, and Nup62."
Structural work places Nup62 in the central nuclear-pore transport channel.
PMID:19552648 SUPPORT In Vitro
"Nucleoporin Nup62 localizes at the central channel of the nuclear pore complex and is essential for nucleocytoplasmic transport."
Cell-biological evidence supports Nup62 as an essential nucleocytoplasmic transport-channel component.
Basal Ganglia Neuronal Degeneration
The cellular/tissue lesion is selective degeneration of basal ganglia structures, including severe atrophy of lenticular nuclei with gliosis and neuronal loss. This node bridges the nuclear-pore defect to the movement and developmental phenotype.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology.
basal ganglion UBERON:0002420 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in basal ganglion (UBERON:0002420). UBERON:0002420 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Developmental Arrest
Choreoathetosis
Dysphagia
Nystagmus
Show evidence (2 references)
PMID:12374138 SUPPORT Human Clinical
"MRI, performed at various stages of the disease, showed severe basal ganglia atrophy."
Human neuroimaging in familial IBSN documents severe basal ganglia atrophy.
PMID:12374138 SUPPORT Human Clinical
"Postmortem study in one patient showed severe atrophy of the lenticular nuclei with gliosis and loss of neurons."
Human pathology demonstrates neuronal loss in basal ganglia nuclei.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for NUP62-Related Infantile Bilateral Striatal Necrosis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Digestive 1
Dysphagia HP:0002015 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dysphagia (HP:0002015). HP:0002015 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12374138 SUPPORT Human Clinical
"Clinical features included developmental arrest, dysphagia, and choreoathetosis."
The clinical series names dysphagia among the core clinical features.
Eye 1
Nystagmus HP:0000639 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pendular nystagmus, annotated with Nystagmus (HP:0000639). HP:0000639 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12374138 SUPPORT Human Clinical
"Pendular nystagmus appeared at a late stage."
The clinical series documents late-stage pendular nystagmus.
Nervous System 3
Basal Ganglia Atrophy Abnormal basal ganglia morphology HP:0002134 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Basal ganglia atrophy, annotated with Abnormal basal ganglia morphology (HP:0002134). HP:0002134 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12374138 SUPPORT Human Clinical
"MRI, performed at various stages of the disease, showed severe basal ganglia atrophy."
MRI showed severe basal ganglia atrophy in familial IBSN.
Developmental Arrest Global developmental delay HP:0001263 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Developmental arrest, annotated with Global developmental delay (HP:0001263). HP:0001263 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12374138 SUPPORT Human Clinical
"The untreated children had a similar clinical picture including developmental arrest beginning at the age of 7 to 15 months, choreoathetosis, and dysphagia."
The familial clinical series reports developmental arrest as a core infantile feature.
Choreoathetosis HP:0001266 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Choreoathetosis (HP:0001266). HP:0001266 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12374138 SUPPORT Human Clinical
"Clinical features included developmental arrest, dysphagia, and choreoathetosis."
The clinical series names choreoathetosis among the core clinical features.
🧬

Genetic Associations

1
NUP62 pathogenic germline variant (Causative)
Gene: NUP62 hgnc:8066 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is NUP62 (hgnc:8066). hgnc:8066 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE variant_origin: GERMLINE
Show evidence (1 reference)
PMID:16786527 SUPPORT Human Clinical
"Sequencing of the nup62 gene showed a missense mutation causing a change from glutamine to proline (Q391P) in all the patients"
Sequencing identified the causal NUP62 missense variant in affected patients.
{ }

Source YAML

click to show 
name: NUP62-Related Infantile Bilateral Striatal Necrosis
creation_date: '2026-07-06T03:59:09Z'
category: Mendelian
synonyms:
- Nucleoporin 62 deficiency
- NUP62-related nucleoporin 62 deficiency
- Infantile striatonigral degeneration
- SNDI
- IBSN
- Familial infantile bilateral striatal necrosis
description: >-
  NUP62-related infantile bilateral striatal necrosis is an autosomal recessive
  neurodegenerative disorder caused by pathogenic germline variation in NUP62,
  which encodes nucleoporin 62, a component of the central transport channel of
  the nuclear pore complex. The best-established familial form was mapped to
  19q13.33 and associated with homozygous NUP62 p.Q391P. The curated mechanism
  is a nuclear pore / nucleocytoplasmic-transport defect with selective basal
  ganglia vulnerability, producing severe basal ganglia atrophy or degeneration
  and infantile developmental arrest with choreoathetosis, dysphagia, and later
  nystagmus.
classifications:
  icimd_category:
  - classification_value: ectonucleotides_and_nucleic_acids
    notes: >-
      WP-047 code 16.4.46.01. The NUP62 entry is kept as a nucleic-acid
      transport / nuclear-pore disorder rather than a tRNA-modification disorder.
disease_term:
  preferred_term: NUP62-related infantile bilateral striatal necrosis
  term:
    id: MONDO:0010080
    label: familial infantile bilateral striatal necrosis
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0015518
      label: infantile bilateral striatal necrosis
    mapping_predicate: skos:broadMatch
    mapping_source: MONDO
    notes: >-
      The clinical umbrella this entry was previously anchored to. Its own
      definition describes "several syndromes" of bilateral striatal degeneration
      and it asserts no causal gene, so it is broader than the gene-defined form
      this entry models.
parents:
- Neurodegenerative Disease
- Movement Disorder
notes: >-
  Term note. `disease_term` binds MONDO:0010080 familial infantile bilateral
  striatal necrosis, whose OWL axioms record hgnc:8066 NUP62 as the causal gene
  and which MONDO files as a child of the clinical umbrella MONDO:0015518. The
  umbrella is retained in `mappings.mondo_mappings` as a broad match: its own
  definition describes "several syndromes" of bilateral striatal degeneration and
  asserts no gene, so binding it as `disease_term` had this gene-defined entry
  asserting identity with a multi-cause class. This entry is curated as the
  gene-defined NUP62 mechanism requested by WP-047; OMIM 271930 is represented in
  source text as infantile bilateral striatal necrosis / infantile striatonigral
  degeneration.
inheritance:
- name: Autosomal recessive
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    The NUP62-linked familial IBSN kindred and mapped disease series support
    autosomal recessive inheritance.
  evidence:
  - reference: PMID:16786527
    reference_title: Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The objective of this study was to identify the gene causing autosomal recessive infantile bilateral striatal necrosis."
    explanation: The NUP62 discovery study frames the mapped condition as autosomal recessive IBSN.
  - reference: PMID:12374138
    reference_title: "Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Inheritance was apparently autosomal recessive."
    explanation: The earlier familial IBSN clinical series supports recessive inheritance for the same Bedouin kindred later mapped to NUP62.
pathophysiology:
- name: NUP62 p.Q391P Germline Variant
  description: >-
    Homozygous NUP62 p.Q391P changes a highly conserved glutamine in the
    nucleoporin 62 protein and is the primary gene lesion in the reported
    familial autosomal recessive IBSN series.
  genes:
  - preferred_term: NUP62
    term:
      id: hgnc:8066
      label: NUP62
  cellular_components:
  - preferred_term: nuclear pore
    term:
      id: GO:0005643
      label: nuclear pore
  evidence:
  - reference: PMID:16786527
    reference_title: Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Sequencing of the nup62 gene showed a missense mutation causing a change
      from glutamine to proline (Q391P) in all the patients, producing a
      substitution from a polar, hydrophilic residue to a nonpolar, neutral
      residue.
    explanation: The discovery paper identifies the shared NUP62 Q391P missense variant in affected patients.
  downstream:
  - target: Central Nuclear Pore Transport Channel Disruption
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - altered nucleoporin 62 protein function in the Nup62/Nup54/Nup58 channel
    evidence:
    - reference: PMID:16786527
      reference_title: Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "This is the second example of a nuclear pore complex protein causing mendelian disease in humans"
      explanation: The human genetic study links the NUP62 lesion to nuclear pore complex protein disease.
- name: Central Nuclear Pore Transport Channel Disruption
  description: >-
    NUP62 is a central channel nucleoporin in the nuclear pore complex. The
    disease-specific NUP62 lesion is therefore modeled as disruption of the
    Nup62-dependent nucleocytoplasmic transport channel, with the exact
    cell-type-selective transport defect still incompletely resolved.
  genes:
  - preferred_term: NUP62
    term:
      id: hgnc:8066
      label: NUP62
  biological_processes:
  - preferred_term: nucleocytoplasmic transport
    term:
      id: GO:0006913
      label: nucleocytoplasmic transport
    modifier: ABNORMAL
  cellular_components:
  - preferred_term: nuclear pore
    term:
      id: GO:0005643
      label: nuclear pore
  evidence:
  - reference: PMID:22036567
    reference_title: Molecular architecture of the transport channel of the nuclear pore complex.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The nuclear pore complex encloses a central channel for nucleocytoplasmic
      transport, which is thought to consist of three nucleoporins, Nup54,
      Nup58, and Nup62.
    explanation: Structural work places Nup62 in the central nuclear-pore transport channel.
  - reference: PMID:19552648
    reference_title: Exo70-mediated recruitment of nucleoporin Nup62 at the leading edge of migrating cells is required for cell migration.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Nucleoporin Nup62 localizes at the central channel of the nuclear pore complex and is essential for nucleocytoplasmic transport."
    explanation: Cell-biological evidence supports Nup62 as an essential nucleocytoplasmic transport-channel component.
  downstream:
  - target: Basal Ganglia Neuronal Degeneration
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:16786527
      reference_title: Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Our findings suggest that p62 has a cell type-specific role and is important in the degeneration of the basal ganglia in humans."
      explanation: The disease-gene paper supports a selective basal-ganglia degeneration consequence of NUP62 dysfunction.
- name: Basal Ganglia Neuronal Degeneration
  description: >-
    The cellular/tissue lesion is selective degeneration of basal ganglia
    structures, including severe atrophy of lenticular nuclei with gliosis and
    neuronal loss. This node bridges the nuclear-pore defect to the movement and
    developmental phenotype.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  locations:
  - preferred_term: basal ganglion
    term:
      id: UBERON:0002420
      label: basal ganglion
  evidence:
  - reference: PMID:12374138
    reference_title: "Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MRI, performed at various stages of the disease, showed severe basal ganglia atrophy."
    explanation: Human neuroimaging in familial IBSN documents severe basal ganglia atrophy.
  - reference: PMID:12374138
    reference_title: "Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Postmortem study in one patient showed severe atrophy of the lenticular nuclei with gliosis and loss of neurons."
    explanation: Human pathology demonstrates neuronal loss in basal ganglia nuclei.
  downstream:
  - target: Developmental Arrest
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Choreoathetosis
    causal_link_type: DIRECT
  - target: Dysphagia
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Nystagmus
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
phenotypes:
- category: Radiologic
  name: Basal Ganglia Atrophy
  description: >-
    Severe basal ganglia atrophy is the defining neuroimaging expression of the
    bilateral striatal necrosis lesion.
  phenotype_term:
    preferred_term: Basal ganglia atrophy
    term:
      id: HP:0002134
      label: Abnormal basal ganglia morphology
  evidence:
  - reference: PMID:12374138
    reference_title: "Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MRI, performed at various stages of the disease, showed severe basal ganglia atrophy."
    explanation: MRI showed severe basal ganglia atrophy in familial IBSN.
- category: Clinical
  name: Developmental Arrest
  description: Developmental arrest begins in infancy in the untreated familial IBSN course.
  phenotype_term:
    preferred_term: Developmental arrest
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:12374138
    reference_title: "Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The untreated children had a similar clinical picture including developmental arrest beginning at the age of 7 to 15 months, choreoathetosis, and dysphagia."
    explanation: The familial clinical series reports developmental arrest as a core infantile feature.
- category: Clinical
  name: Choreoathetosis
  description: Choreoathetosis is a prominent movement phenotype downstream of basal ganglia degeneration.
  phenotype_term:
    preferred_term: Choreoathetosis
    term:
      id: HP:0001266
      label: Choreoathetosis
  evidence:
  - reference: PMID:12374138
    reference_title: "Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clinical features included developmental arrest, dysphagia, and choreoathetosis."
    explanation: The clinical series names choreoathetosis among the core clinical features.
- category: Clinical
  name: Dysphagia
  description: Dysphagia occurs with the infantile neurodegenerative movement disorder.
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:12374138
    reference_title: "Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clinical features included developmental arrest, dysphagia, and choreoathetosis."
    explanation: The clinical series names dysphagia among the core clinical features.
- category: Clinical
  name: Nystagmus
  description: Pendular nystagmus can appear later in the disease course.
  phenotype_term:
    preferred_term: Pendular nystagmus
    term:
      id: HP:0000639
      label: Nystagmus
  evidence:
  - reference: PMID:12374138
    reference_title: "Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pendular nystagmus appeared at a late stage."
    explanation: The clinical series documents late-stage pendular nystagmus.
genetic:
- name: NUP62 pathogenic germline variant
  association: Causative
  relationship_type: CAUSATIVE
  gene_term:
    preferred_term: NUP62
    term:
      id: hgnc:8066
      label: NUP62
  variant_origin: GERMLINE
  notes: >-
    The reported familial NUP62-related IBSN cohort shared homozygous p.Q391P.
  evidence:
  - reference: PMID:16786527
    reference_title: Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Sequencing of the nup62 gene showed a missense mutation causing a change
      from glutamine to proline (Q391P) in all the patients
    explanation: Sequencing identified the causal NUP62 missense variant in affected patients.