Neuronopathy, distal hereditary motor, autosomal recessive 7

Summary

Neuronopathy, distal hereditary motor, autosomal recessive 7 (MONDO:0030977) is a disease caused by VWA1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: VWA1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronopathy, distal hereditary motor, autosomal recessive 7
Mondo ID	MONDO:0030977
OMIM	619216
DOID	DOID:0081426
UMLS	C5543119
MedGen	1786836
GARD	0018444
Is cancer (heuristic)	no

Also known as: HMNMYO · neuropathy, hereditary motor, with myopathic features

Data availability: 20 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › neuronopathy, distal hereditary motor, autosomal recessive › neuronopathy, distal hereditary motor, autosomal recessive 7

Related subtypes (11): autosomal recessive distal spinal muscular atrophy 1, autosomal recessive distal spinal muscular atrophy 2, neuronopathy, distal hereditary motor, autosomal recessive 3, neuronopathy, distal hereditary motor, autosomal recessive 4, neuronopathy, distal hereditary motor, autosomal recessive 5, neuronopathy, distal hereditary motor, autosomal recessive 8, early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome, spinal muscular atrophy, distal, autosomal recessive, 6, neuronopathy, distal hereditary motor, autosomal recessive 9, neuronopathy, distal hereditary motor, autosomal recessive 10, neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity

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

20 retrieved; paginated sample, class counts are floors:

6 likely pathogenic, 4 conflicting classifications of pathogenicity, 4 uncertain significance, 3 pathogenic/likely pathogenic, 2 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3065995	NM_022834.5(VWA1):c.462del (p.Met155fs)	VWA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
830324	NM_022834.5(VWA1):c.62_71del (p.Gly21fs)	VWA1	Pathogenic	criteria provided, multiple submitters, no conflicts
830325	NM_022834.5(VWA1):c.252del (p.Glu85fs)	VWA1	Pathogenic	criteria provided, multiple submitters, no conflicts
830327	NM_022834.5(VWA1):c.62_71dup (p.Gly25fs)	VWA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
830328	NM_022834.5(VWA1):c.879del (p.Arg293fs)	VWA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2584513	NM_022834.5(VWA1):c.1169_1217del (p.Leu390fs)	VWA1	Likely pathogenic	criteria provided, single submitter
2664084	NM_022834.5(VWA1):c.662dup (p.Glu222fs)	VWA1	Likely pathogenic	criteria provided, single submitter
3383311	NM_022834.5(VWA1):c.763del (p.Ala255fs)	VWA1	Likely pathogenic	criteria provided, single submitter
4293587	NM_022834.5(VWA1):c.462dup (p.Met155fs)	VWA1	Likely pathogenic	criteria provided, single submitter
4294047	NM_022834.5(VWA1):c.1127_1128insA (p.Gln377fs)	VWA1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
830326	NM_022834.5(VWA1):c.94C>T (p.Arg32Ter)	VWA1	Likely pathogenic	criteria provided, single submitter
1675331	NM_022834.5(VWA1):c.1088_1091dup (p.Tyr364Ter)	VWA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2572417	NM_022834.5(VWA1):c.558C>T (p.Ala186=)	VWA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2920806	NM_022834.5(VWA1):c.1312C>A (p.Pro438Thr)	VWA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3237466	NM_022834.5(VWA1):c.161G>C (p.Arg54Pro)	VWA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1878315	NM_022834.5(VWA1):c.1275GCGCCC[3] (p.Pro431_Val432insArgPro)	VWA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065720	NM_022834.5(VWA1):c.1121G>A (p.Gly374Glu)	VWA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3780791	NM_022834.5(VWA1):c.1083_1089del (p.Leu362fs)	VWA1	Uncertain significance	criteria provided, single submitter
3892864	NM_022834.5(VWA1):c.1261_1274del (p.Thr421fs)	VWA1	Uncertain significance	criteria provided, single submitter
1280635	NM_022834.5(VWA1):c.1005A>G (p.Pro335=)	VWA1	Benign	criteria provided, multiple submitters, no conflicts

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
VWA1	Strong	Autosomal recessive	neuronopathy, distal hereditary motor, autosomal recessive 7	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VWA1	Orphanet:314485	Young adult-onset distal hereditary motor neuropathy

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
VWA1	HGNC:30910	ENSG00000179403	Q6PCB0	von Willebrand factor A domain-containing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VWA1	von Willebrand factor A domain-containing protein 1	Promotes matrix assembly.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VWA1	Antibody/Immunoglobulin	yes		VWF_A, FN3_dom, Ig-like_fold

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
C1 segment of cervical spinal cord	1
lower esophagus muscularis layer	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VWA1	240	ubiquitous	marker	tibial nerve, C1 segment of cervical spinal cord, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VWA1	1,184

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
VWA1	Q6PCB0	79.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Post-translational protein phosphorylation	1	100.2×	0.012	VWA1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	VWA1

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
behavioral response to pain	1	887.0×	0.003	VWA1
extracellular matrix organization	1	122.1×	0.008	VWA1
protein homooligomerization	1	122.1×	0.008	VWA1

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
VWA1	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	1	VWA1
E	Difficult family or no structure, no drug	0

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)
VWA1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.