Neuronopathy, distal hereditary motor, autosomal dominant 10

Summary

Neuronopathy, distal hereditary motor, autosomal dominant 10 (MONDO:0859300) is a disease caused by EMILIN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EMILIN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronopathy, distal hereditary motor, autosomal dominant 10
Mondo ID	MONDO:0859300
OMIM	620080
DOID	DOID:0081399
UMLS	C5774234
MedGen	1824007
GARD	0026687
Is cancer (heuristic)	no

Also known as: neuronopathy, distal hereditary motor, type X

Data availability: 4 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 dominant disease › neuronopathy, distal hereditary motor, autosomal dominant › neuronopathy, distal hereditary motor, autosomal dominant 10

Related subtypes (10): neuronopathy, distal hereditary motor, autosomal dominant 1, hereditary spastic paraplegia 17, neuronopathy, distal hereditary motor, autosomal dominant 8, distal hereditary motor neuropathy type 2, distal hereditary motor neuropathy type 7, neuronopathy, distal hereditary motor, type 9, neuronopathy, distal hereditary motor, type 5, neuronopathy, distal hereditary motor, autosomal dominant 11, myopathy, myofibrillar, 13, with rimmed vacuoles, neuronopathy, distal hereditary motor, autosomal dominant 15

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

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1711105	NM_007046.4(EMILIN1):c.748C>T (p.Arg250Cys)	EMILIN1	Pathogenic	no assertion criteria provided
208756	NM_007046.4(EMILIN1):c.64G>A (p.Ala22Thr)	EMILIN1	Uncertain significance	criteria provided, single submitter
3065945	NM_007046.4(EMILIN1):c.1697G>A (p.Arg566Gln)	EMILIN1	Uncertain significance	criteria provided, single submitter
3377015	NM_007046.4(EMILIN1):c.2299A>G (p.Thr767Ala)	EMILIN1	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
EMILIN1	Strong	Autosomal dominant	neuronopathy, distal hereditary motor, autosomal dominant 10	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EMILIN1	Orphanet:485418	EMILIN-1-related connective tissue disease

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
EMILIN1	HGNC:19880	ENSG00000138080	Q9Y6C2	EMILIN-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EMILIN1	EMILIN-1	Involved in elastic and collagen fibers formation.

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)
EMILIN1	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom

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
body of uterus	1
left uterine tube	1
right coronary artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EMILIN1	206	ubiquitous	marker	right coronary artery, body of uterus, left uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EMILIN1	1,254

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EMILIN1	Q9Y6C2	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Molecules associated with elastic fibres	1	308.6×	0.003	EMILIN1

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
negative regulation of cell activation	1	8426.0×	0.002	EMILIN1
negative regulation of collagen fibril organization	1	8426.0×	0.002	EMILIN1
negative regulation of macrophage migration	1	2808.7×	0.002	EMILIN1
positive regulation of defense response to bacterium	1	1872.4×	0.002	EMILIN1
positive regulation of extracellular matrix assembly	1	1872.4×	0.002	EMILIN1
elastic fiber assembly	1	1532.0×	0.002	EMILIN1
negative regulation of vascular endothelial growth factor receptor signaling pathway	1	1296.3×	0.002	EMILIN1
negative regulation of vascular endothelial growth factor signaling pathway	1	1296.3×	0.002	EMILIN1
positive regulation of platelet aggregation	1	1296.3×	0.002	EMILIN1
positive regulation of blood coagulation	1	1123.5×	0.002	EMILIN1
negative regulation of collagen biosynthetic process	1	1123.5×	0.002	EMILIN1
cell adhesion mediated by integrin	1	674.1×	0.003	EMILIN1
negative regulation of SMAD protein signal transduction	1	601.9×	0.004	EMILIN1
positive regulation of cell-substrate adhesion	1	495.6×	0.004	EMILIN1
aortic valve morphogenesis	1	432.1×	0.004	EMILIN1
regulation of blood pressure	1	221.7×	0.008	EMILIN1
negative regulation of ERK1 and ERK2 cascade	1	216.1×	0.008	EMILIN1
negative regulation of transforming growth factor beta receptor signaling pathway	1	173.7×	0.009	EMILIN1
negative regulation of angiogenesis	1	168.5×	0.009	EMILIN1
cell-matrix adhesion	1	163.6×	0.009	EMILIN1
regulation of cell population proliferation	1	115.4×	0.011	EMILIN1
positive regulation of angiogenesis	1	115.4×	0.011	EMILIN1
negative regulation of cell migration	1	111.6×	0.011	EMILIN1
negative regulation of gene expression	1	69.1×	0.017	EMILIN1
cell migration	1	61.5×	0.018	EMILIN1
positive regulation of apoptotic process	1	56.7×	0.019	EMILIN1
positive regulation of gene expression	1	38.7×	0.027	EMILIN1
cell adhesion	1	37.5×	0.027	EMILIN1

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
EMILIN1	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	EMILIN1

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)
EMILIN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.