COA7

protein-coding

cytochrome c oxidase assembly factor 7, the group of Mitochondrial respiratory chain complex assembly factors

Gene summary

Enables protein-disulfide reductase activity. Involved in mitochondrial respiratory chain complex IV assembly. Located in mitochondrion. Is active in mitochondrial intermembrane space. Implicated in autosomal recessive spinocerebellar ataxia with axonal neuropathy 3. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C1orf163
SELRC1

MANE transcript

NM_023077.3

Inheritance

ClinVar variants

P:9U:34B:20

Top phenotype

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr1:52,684,449-52,698,347

External References & Databases

Ensembl (ENSG00000162377)

Transcript & Mutation Effects

hg38 • Region Span ~13.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0020770

Submitter: Ambry Genetics

mitochondrial diseaseDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: ClinGen

The relationship between *COA7* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of August 22, 2024. The *COA7* gene encodes an assembly factor for complex IV of the mitochondrial respiratory chain. The COA7 protein also acts as a heme binding protein with disulfide reductase activity. *COA7* was first reported in relation to autosomal recessive primary mitochondrial disease in 2016 (PMID: 27683825). While various names could be given to the constellation of features seen in those with *COA7*-related disorders, pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the COA7 phenotype has been lumped into one disease entity according to the ClinGen Lumping and Splitting Framework. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included 12 variants [nine missense variants including a founder variant, NM_023077.3:c.17A>G (p.Asp6Gly), one nonsense variant, one frameshift variant, and one splicing variant) in eight probands from six publications (PMIDs: 29718187, 35603692, 37264311, 37750949, 34322155, 27683825). Clinical features in affected individuals include leukodystrophy, spinocerebellar ataxia, Parkinsonism, neuropathy, tremor, weakness, ataxia, dysarthria, and cardiomyopathy. Onset ranges from childhood to adulthood. Mild elevations of lactate and creatine kinase have been reported. The mechanism of disease is loss of function This gene-disease association is also supported by its known biochemical function of the COA7 protein in the assembly of complex IV, functional alteration in patient cells and non-patient cells, rescue studies performed in HEK293T cells, and a *Drosophila* model (PMIDs: 29718187, 24333015, 29718187, 35210360). In summary, there is definitive evidence to support the relationship between *COA7* and primary mitochondrial disease. This relationship has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on August 22, 2024 (SOP Version 10).

spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020770

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27683825; 29718187

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COA7 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 52

Inborn genetic diseasesTotal: 15

not specifiedTotal: 10

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3Total: 7

COA7-related disorderTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_023077.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				19 clinvar		19
missense	3 clinvar	1 clinvar	34 clinvar	1 clinvar		39
nonsense						0
start loss						0
frameshift	1 clinvar	2 clinvar				3
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar				2
Total	5	4	34	20	0	63

Highest pathogenic variant AF is 0.000016727505

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_023077.3	RefSeq	NP_075565.2	3	MANE Select
ENST00000371538.5	Ensembl	ENSP00000360593.3	3	MANE Select
ENST00000939652.1	Ensembl	ENSP00000609711.1	2	Standard
ENST00000939652.2	Ensembl	ENSP00000609711.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thermogenesis - Homo sapiens (human)

Cellular Component

nucleus
mitochondrion
mitochondrial intermembrane space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371538
Coding exons: 3
Length: 11531
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125747
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.672	106	127	0.832	0.00000626	1533
Missense (PolyPhen)		40	41.299	0.96855		506
Synonymous	0.0262	50	50.2	0.995	0.00000256	412
Loss of Function	1.55	3	7.60	0.395	3.17e-7	113

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for assembly of mitochondrial respiratory chain complex I and complex IV. {ECO:0000269|PubMed:24333015}.;

Intolerance Scores

RVIS EVS: 0.24
RVIS percentile EVS: 68.98

Essentials

Essential (gene trap): K

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium