COA7

Chr 1

cytochrome c oxidase assembly factor 7

Also known as: C1orf163, RESA1, SCAN3, SELRC1

NCBI Gene: 65260 ENSG00000162377 UniProt: Q96BR5

The protein enables protein-disulfide reductase activity and is involved in respiratory chain complex IV assembly in the mitochondrial intermembrane space. Mutations cause spinocerebellar ataxia with axonal neuropathy type 3, inherited in an autosomal recessive pattern. The pathogenic mechanism involves disrupted complex IV assembly leading to mitochondrial respiratory dysfunction.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Enables protein-disulfide reductase activity. Involved in respiratory chain complex IV assembly. Located in mitochondrion and nucleoplasm. Is active in mitochondrial intermembrane space. Implicated in spinocerebellar ataxia with axonal neuropathy type 3. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.02

Clinical Summary— COA7

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 34 VUS of 80 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.060

Z-score 1.55

OE 0.39 (0.18–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.67Z-score

OE missense 0.83 (0.71–0.98)

106 obs / 127.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.18–1.02)

0≤0.351.4

Missense OE?0.83 (0.71–0.98)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 3 / 7.6Missense obs/exp: 106 / 127.4Syn Z: 0.03

This gene — mechanism propensity

0.76top 25%

GOF

0.75top 25%

LOF

0.1993th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

80 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic6

VUS34

Likely Benign29

Benign7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	0	0	4
Likely Pathogenic	4	2	0	0	6
VUS	0	33	1	0	34
Likely Benign	0	1	9	19	29
Benign	0	1	6	0	7
Total	6	39	16	19	80

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap COA7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →