Infantile bilateral striatal necrosis

Summary

Infantile bilateral striatal necrosis (MONDO:0015518) is a disease with 2 cohort genes.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 6

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	infantile bilateral striatal necrosis
Mondo ID	MONDO:0015518
Orphanet	1576
ICD-11	1947032348
SNOMED CT	718174008
UMLS	C0795996
MedGen	167090
GARD	0005040
Is cancer (heuristic)	no

Also known as: IBSN · infantile bilateral striatal necrosis · infantile striatonigral degeneration · infantile striatonigral necrosis · SNDI · striatal degeneration familial · striatonigral degeneration infantile

Data availability: 6 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › infantile bilateral striatal necrosis

Related subtypes (21): synucleinopathy, eyelid degenerative disorder, senile degeneration of brain, olivopontocerebellar atrophy, neuroaxonal dystrophy, demyelinating disease, choroidal sclerosis, tauopathy, secondary Parkinson disease, Marchiafava-Bignami disease, superficial siderosis, primary progressive apraxia of speech, human prion disease, primary progressive freezing gait, primary progressive aphasia, motor neuron disorder, brachial amyotrophic diplegia, cerebellar degeneration, inherited neurodegenerative disorder, cerebral degeneration, hypertrophic olivary degeneration

Subtypes (2): familial infantile bilateral striatal necrosis, sporadic infantile bilateral striatal necrosis

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

3 benign, 2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4752	NM_016553.5(NUP62):c.1172A>C (p.Gln391Pro)	IL4I1	Pathogenic	no assertion criteria provided
1031240	NM_016553.5(NUP62):c.700A>G (p.Thr234Ala)	IL4I1	Uncertain significance	criteria provided, multiple submitters, no conflicts
800771	NM_016553.5(NUP62):c.548C>T (p.Thr183Met)	IL4I1	Uncertain significance	criteria provided, multiple submitters, no conflicts
129846	NM_016553.5(NUP62):c.1323T>C (p.Asp441=)	IL4I1	Benign	criteria provided, multiple submitters, no conflicts
129849	NM_016553.5(NUP62):c.848G>C (p.Ser283Thr)	IL4I1	Benign	criteria provided, multiple submitters, no conflicts
129848	NM_016553.5(NUP62):c.648C>T (p.Ser216=)	NUP62	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NUP62	Orphanet:225154	Familial infantile bilateral striatal necrosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IL4I1	HGNC:19094	ENSG00000104951	Q96RQ9	L-amino-acid oxidase	clinvar
NUP62	HGNC:8066	ENSG00000213024	P37198	Nuclear pore glycoprotein p62	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL4I1	L-amino-acid oxidase	Secreted L-amino-acid oxidase that acts as a key immunoregulator.
NUP62	Nuclear pore glycoprotein p62	Essential component of the nuclear pore complex.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IL4I1	Other/Unknown	no		Flavin_amine_oxidase, Amino_oxidase, FAD/NAD-bd_sf
NUP62	Other/Unknown	no		Nucleoporin_NSP1_C, NSP1/NUP62

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	2
male germ line stem cell (sensu Vertebrata) in testis	1
vermiform appendix	1
granulocyte	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL4I1	160	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, left testis, vermiform appendix
NUP62	278	ubiquitous	marker	right testis, left testis, granulocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUP62	2,560
IL4I1	1,428

Intra-cohort edges

A	B	Sources
IL4I1	NUP62	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NUP62	P37198	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IL4I1	Q96RQ9	86.80

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Phenylalanine metabolism	1	951.7×	0.012	IL4I1
Postmitotic nuclear pore complex (NPC) reformation	1	203.9×	0.012	NUP62
IPs transport between nucleus and cytosol	1	190.3×	0.012	NUP62
IP3 and IP4 transport between cytosol and nucleus	1	190.3×	0.012	NUP62
IP6 and IP7 transport between cytosol and nucleus	1	190.3×	0.012	NUP62
Transport of Ribonucleoproteins into the Host Nucleus	1	178.4×	0.012	NUP62
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	178.4×	0.012	NUP62
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	178.4×	0.012	NUP62
NEP/NS2 Interacts with the Cellular Export Machinery	1	173.0×	0.012	NUP62
Nuclear import of Rev protein	1	167.9×	0.012	NUP62
Vpr-mediated nuclear import of PICs	1	167.9×	0.012	NUP62
Transport of the SLBP independent Mature mRNA	1	163.1×	0.012	NUP62
SUMOylation of SUMOylation proteins	1	163.1×	0.012	NUP62
Transport of the SLBP Dependant Mature mRNA	1	158.6×	0.012	NUP62
Rev-mediated nuclear export of HIV RNA	1	158.6×	0.012	NUP62
Nuclear Pore Complex (NPC) Disassembly	1	154.3×	0.012	NUP62
SUMOylation of ubiquitinylation proteins	1	146.4×	0.012	NUP62
NS1 Mediated Effects on Host Pathways	1	142.8×	0.012	NUP62
Transport of Mature mRNA Derived from an Intronless Transcript	1	135.9×	0.012	NUP62
Viral Messenger RNA Synthesis	1	129.8×	0.012	NUP62
SUMOylation of DNA replication proteins	1	124.1×	0.012	NUP62
SUMOylation of RNA binding proteins	1	119.0×	0.012	NUP62
snRNP Assembly	1	105.7×	0.013	NUP62
tRNA processing in the nucleus	1	98.5×	0.014	NUP62
SUMOylation of chromatin organization proteins	1	79.3×	0.016	NUP62
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	76.1×	0.016	NUP62
ISG15 antiviral mechanism	1	75.1×	0.016	NUP62
SUMOylation of DNA damage response and repair proteins	1	73.2×	0.016	NUP62
Regulation of HSF1-mediated heat shock response	1	69.6×	0.016	NUP62
HCMV Late Events	1	49.2×	0.022	NUP62

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete L-tryptophan catabolic process to indole-3-acetate	1	8426.0×	0.003	IL4I1
positive regulation of centriole replication	1	1685.2×	0.003	NUP62
L-tryptophan catabolic process	1	1404.3×	0.003	IL4I1
L-tyrosine catabolic process	1	1404.3×	0.003	IL4I1
mitotic centrosome separation	1	1404.3×	0.003	NUP62
amino acid catabolic process	1	1404.3×	0.003	IL4I1
centriole assembly	1	1404.3×	0.003	NUP62
positive regulation of protein localization to centrosome	1	1203.7×	0.003	NUP62
negative regulation of T cell mediated immune response to tumor cell	1	1053.2×	0.003	IL4I1
L-phenylalanine catabolic process	1	1053.2×	0.003	IL4I1
positive regulation of mitotic cytokinetic process	1	1053.2×	0.003	NUP62
regulation of adaptive immune response	1	936.2×	0.003	IL4I1
regulation of Ras protein signal transduction	1	936.2×	0.003	NUP62
regulation of B cell differentiation	1	648.1×	0.004	IL4I1
RNA export from nucleus	1	468.1×	0.005	NUP62
positive regulation of regulatory T cell differentiation	1	468.1×	0.005	IL4I1
regulation of mitotic spindle organization	1	421.3×	0.005	NUP62
negative regulation of epidermal growth factor receptor signaling pathway	1	383.0×	0.005	NUP62
negative regulation of programmed cell death	1	366.4×	0.005	NUP62
negative regulation of Ras protein signal transduction	1	337.0×	0.006	NUP62
positive regulation of mitotic nuclear division	1	271.8×	0.007	NUP62
negative regulation of T cell activation	1	263.3×	0.007	IL4I1
positive regulation of epidermal growth factor receptor signaling pathway	1	247.8×	0.007	NUP62
nucleocytoplasmic transport	1	195.9×	0.008	NUP62
mitotic metaphase chromosome alignment	1	191.5×	0.008	NUP62
centrosome cycle	1	168.5×	0.009	NUP62
negative regulation of T cell proliferation	1	165.2×	0.009	IL4I1
cellular senescence	1	147.8×	0.009	NUP62
regulation of signal transduction	1	133.8×	0.010	NUP62
mRNA transport	1	131.7×	0.010	NUP62

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IL4I1	0	0
NUP62	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
IL4I1	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	IL4I1, NUP62

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
IL4I1	2	—
NUP62	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.