Dystonia 37, early-onset, with striatal lesions

Summary

Dystonia 37, early-onset, with striatal lesions (MONDO:0957385) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dystonia 37, early-onset, with striatal lesions
Mondo ID	MONDO:0957385
OMIM	620427
DOID	DOID:0060956
UMLS	C5830592
MedGen	1841228
GARD	0026819
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › extrapyramidal and movement disease › dystonic disorder › inherited dystonia › dystonia 37, early-onset, with striatal lesions

Related subtypes (23): lymphatic malformation 5, Woodhouse-Sakati syndrome, severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome, torsion dystonia 7, developmental malformations-deafness-dystonia syndrome, dopa-responsive dystonia due to sepiapterin reductase deficiency, ataxia - oculomotor apraxia type 4, striatonigral degeneration, childhood-onset, dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, dystonia 28, childhood-onset, isolated dystonia, combined dystonia, dystonia 30, dystonia 31, dystonia 32, dystonia 33, dystonia 34, myoclonic, dystonia 35, childhood-onset, familial idiopathic torsion dystonia, dystonia, focal, task-specific, dystonia 22, juvenile-onset, dystonia 22, adult-onset, autosomal dominant dopa-responsive dystonia

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:

4 pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2506594	NM_017426.4(NUP54):c.[1414G>A;1420C>T]		Pathogenic	no assertion criteria provided
2506591	NM_017426.4(NUP54):c.1073T>G (p.Ile358Ser)	NUP54	Pathogenic	no assertion criteria provided
2506592	NM_017426.4(NUP54):c.1126A>G (p.Lys376Glu)	NUP54	Pathogenic	no assertion criteria provided
2506593	NM_017426.4(NUP54):c.1404ACA[2] (p.Gln471del)	NUP54	Pathogenic	no assertion criteria provided
3067935	NM_017426.4(NUP54):c.17G>T (p.Gly6Val)	LOC129992689	Uncertain significance	criteria provided, single submitter
3775866	NM_017426.4(NUP54):c.1121A>C (p.Gln374Pro)	NUP54	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
NUP54	Moderate	Autosomal recessive	dystonia 37, early-onset, with striatal lesions	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NUP54	Orphanet:225154	Familial infantile bilateral striatal necrosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NUP54	HGNC:17359	ENSG00000138750	Q7Z3B4	Nucleoporin p54	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NUP54	Nucleoporin p54	Component of the nuclear pore complex, a complex required for the trafficking across the nuclear membrane.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NUP54	Other/Unknown	no		Nup54/Nup57/Nup44, Nup54_alpha-helical_dom, Nup54_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
mucosa of paranasal sinus	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NUP54	288	ubiquitous	marker	calcaneal tendon, oocyte, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUP54	2,441

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NUP54	Q7Z3B4	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Postmitotic nuclear pore complex (NPC) reformation	1	407.9×	0.006	NUP54
IPs transport between nucleus and cytosol	1	380.7×	0.006	NUP54
IP3 and IP4 transport between cytosol and nucleus	1	380.7×	0.006	NUP54
IP6 and IP7 transport between cytosol and nucleus	1	380.7×	0.006	NUP54
Transport of Ribonucleoproteins into the Host Nucleus	1	356.9×	0.006	NUP54
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	356.9×	0.006	NUP54
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	356.9×	0.006	NUP54
NEP/NS2 Interacts with the Cellular Export Machinery	1	346.1×	0.006	NUP54
Nuclear import of Rev protein	1	335.9×	0.006	NUP54
Vpr-mediated nuclear import of PICs	1	335.9×	0.006	NUP54
Transport of the SLBP independent Mature mRNA	1	326.3×	0.006	NUP54
SUMOylation of SUMOylation proteins	1	326.3×	0.006	NUP54
Transport of the SLBP Dependant Mature mRNA	1	317.2×	0.006	NUP54
Rev-mediated nuclear export of HIV RNA	1	317.2×	0.006	NUP54
Nuclear Pore Complex (NPC) Disassembly	1	308.6×	0.006	NUP54
SUMOylation of ubiquitinylation proteins	1	292.8×	0.006	NUP54
NS1 Mediated Effects on Host Pathways	1	285.5×	0.006	NUP54
Transport of Mature mRNA Derived from an Intronless Transcript	1	271.9×	0.006	NUP54
Viral Messenger RNA Synthesis	1	259.6×	0.006	NUP54
SUMOylation of DNA replication proteins	1	248.3×	0.006	NUP54
SUMOylation of RNA binding proteins	1	237.9×	0.006	NUP54
snRNP Assembly	1	211.5×	0.007	NUP54
tRNA processing in the nucleus	1	196.9×	0.007	NUP54
SUMOylation of chromatin organization proteins	1	158.6×	0.008	NUP54
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	152.3×	0.008	NUP54
ISG15 antiviral mechanism	1	150.3×	0.008	NUP54
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.008	NUP54
Regulation of HSF1-mediated heat shock response	1	139.3×	0.008	NUP54
HCMV Late Events	1	98.5×	0.011	NUP54
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.012	NUP54

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to nuclear inner membrane	1	4213.0×	0.001	NUP54
nuclear pore organization	1	2106.5×	0.001	NUP54
NLS-bearing protein import into nucleus	1	802.5×	0.002	NUP54
nucleocytoplasmic transport	1	391.9×	0.003	NUP54
mRNA transport	1	263.3×	0.004	NUP54

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NUP54	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	NUP54

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NUP54	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.