Spastic ataxia 10, autosomal recessive

Summary

Spastic ataxia 10, autosomal recessive (MONDO:0958009) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spastic ataxia 10, autosomal recessive
Mondo ID	MONDO:0958009
OMIM	620666
UMLS	C5882738
MedGen	1851662
GARD	0026908
Is cancer (heuristic)	no

Data availability: 22 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › atactic disorder › hereditary ataxia › spastic ataxia › spastic ataxia 10, autosomal recessive

Related subtypes (5): spastic ataxia 2, spasticity-ataxia-gait anomalies syndrome, autosomal dominant spastic ataxia, autosomal recessive spastic ataxia, spastic ataxia 9, autosomal recessive

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

22 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
189201	NM_016035.5(COQ4):c.718C>T (p.Arg240Cys)	COQ4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2158634	NM_016035.5(COQ4):c.613C>T (p.Arg205Ter)	COQ4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2686020	NM_016035.5(COQ4):c.434G>A (p.Arg145His)	COQ4	Pathogenic	no assertion criteria provided
2686021	NM_016035.5(COQ4):c.719G>A (p.Arg240His)	COQ4	Pathogenic	no assertion criteria provided
2686023	NM_016035.5(COQ4):c.87dup (p.Arg30Ter)	COQ4	Pathogenic	no assertion criteria provided
280320	NM_016035.5(COQ4):c.23_33del (p.Val8fs)	COQ4	Pathogenic	criteria provided, multiple submitters, no conflicts
379740	NM_016035.5(COQ4):c.402+1G>C	COQ4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
476179	NM_016035.5(COQ4):c.370G>A (p.Gly124Ser)	COQ4	Pathogenic	criteria provided, multiple submitters, no conflicts
915899	NM_016035.5(COQ4):c.305G>A (p.Arg102His)	COQ4	Pathogenic	criteria provided, single submitter
3596460	NM_016035.5(COQ4):c.627-1G>A	COQ4	Likely pathogenic	criteria provided, single submitter
4293681	NM_016035.5(COQ4):c.409dup (p.Ser137fs)	COQ4	Likely pathogenic	criteria provided, single submitter
1033389	NM_016035.5(COQ4):c.1A>G (p.Met1Val)	COQ4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1518505	NM_016035.5(COQ4):c.202+4A>C	COQ4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
488488	NM_016035.5(COQ4):c.469C>A (p.Gln157Lys)	COQ4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
634502	NM_016035.5(COQ4):c.304C>T (p.Arg102Cys)	COQ4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1333992	NM_016035.5(COQ4):c.533G>A (p.Gly178Glu)	COQ4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1449250	NM_016035.5(COQ4):c.473G>A (p.Arg158Gln)	COQ4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2686019	NM_016035.5(COQ4):c.745C>T (p.Arg249Trp)	COQ4	Uncertain significance	criteria provided, single submitter
2686024	NM_016035.5(COQ4):c.433C>T (p.Arg145Cys)	COQ4	Uncertain significance	criteria provided, single submitter
3899276	NM_016035.5(COQ4):c.164G>T (p.Gly55Val)	COQ4	Uncertain significance	criteria provided, single submitter
4293247	NM_016035.5(COQ4):c.595G>A (p.Ala199Thr)	COQ4	Uncertain significance	criteria provided, single submitter
647378	NM_016035.5(COQ4):c.376G>A (p.Glu126Lys)	COQ4	Uncertain significance	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
COQ4	Orphanet:457185	Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome

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
COQ4	HGNC:19693	ENSG00000167113	Q9Y3A0	Ubiquinone biosynthesis protein COQ4 homolog, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COQ4	Ubiquinone biosynthesis protein COQ4 homolog, mitochondrial	Lyase that catalyzes the C1-decarboxylation of 4-hydroxy-3-methoxy-5-(all-trans-decaprenyl)benzoic acid into 2-methoxy-6-(all-trans-decaprenyl)phenol during ubiquinone biosynthesis.

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)
COQ4	Other/Unknown	no		Coq4, Coq4_euk

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
adenohypophysis	1
olfactory segment of nasal mucosa	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COQ4	254	ubiquitous	marker	right uterine tube, olfactory segment of nasal mucosa, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COQ4	953

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COQ4	Q9Y3A0	88.56

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	COQ4

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×	0.001	COQ4

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
COQ4	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	COQ4

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)
COQ4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.