Neuronopathy, distal hereditary motor, autosomal recessive 9

Summary

Neuronopathy, distal hereditary motor, autosomal recessive 9 (MONDO:0957874) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		12	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronopathy, distal hereditary motor, autosomal recessive 9
Mondo ID	MONDO:0957874
OMIM	620402
Orphanet	658778
DOID	DOID:0081428
UMLS	C5882672, C5925143
MedGen	1850177, 1863922
GARD	0026888, 0026944
Is cancer (heuristic)	no

Also known as: COQ7-related distal hereditary motor neuropathy · HMNR9

Data availability: 9 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › coenzyme Q10 deficiency › primary coenzyme Q10 deficiency 8 › neuronopathy, distal hereditary motor, autosomal recessive 9

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

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 3 conflicting classifications of pathogenicity, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2584639	NM_016138.5(COQ7):c.1A>G (p.Met1Val)	COQ7	Pathogenic	no assertion criteria provided
2584640	NM_016138.5(COQ7):c.253-2A>T	COQ7	Pathogenic	no assertion criteria provided
2584641	NM_016138.5(COQ7):c.467T>A (p.Leu156Gln)	COQ7	Pathogenic	no assertion criteria provided
2584643	NM_016138.5(COQ7):c.467T>G (p.Leu156Arg)	COQ7	Pathogenic	no assertion criteria provided
1463095	NM_016138.5(COQ7):c.3G>T (p.Met1Ile)	COQ7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
587428	NM_016138.5(COQ7):c.161G>A (p.Arg54Gln)	COQ7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
929475	NM_016138.5(COQ7):c.319C>T (p.Arg107Trp)	COQ7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1396906	NM_016138.5(COQ7):c.446A>G (p.Tyr149Cys)	COQ7	Uncertain significance	criteria provided, single submitter
2580230	NM_016138.5(COQ7):c.160C>T (p.Arg54Trp)	COQ7	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COQ7	Orphanet:319678	Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome
COQ7	Orphanet:658778	COQ7-related 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
COQ7	HGNC:2244	ENSG00000167186	Q99807	NADPH-dependent 3-demethoxyubiquinone 3-hydroxylase, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COQ7	NADPH-dependent 3-demethoxyubiquinone 3-hydroxylase, mitochondrial	Catalyzes the hydroxylation of the 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone at the C6 position and participates in the biosynthesis of ubiquinone.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COQ7	Enzyme (other)	yes	1.14.99.60	Ferritin-like_SF, Ubq_synth_Coq7

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
hindlimb stylopod muscle	1
muscle of leg	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COQ7	236	ubiquitous	marker	primordial germ cell in gonad, hindlimb stylopod muscle, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COQ7	1,137

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COQ7	Q99807	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
Ubiquinol biosynthesis	1	878.5×	0.001	COQ7

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
ubiquinone biosynthetic process	1	936.2×	0.004	COQ7
regulation of reactive oxygen species metabolic process	1	732.7×	0.004	COQ7
determination of adult lifespan	1	432.1×	0.005	COQ7
regulation of gene expression	1	83.4×	0.018	COQ7
negative regulation of transcription by RNA polymerase II	1	17.7×	0.067	COQ7
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	COQ7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COQ7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
COQ7	16	Binding:16

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
COQ7	1.14.99.60	3-demethoxyubiquinol 3-hydroxylase

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	1	COQ7
D	Druggable family + AlphaFold only, no drug	0
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)
COQ7	16	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.