COA4

protein-coding

cytochrome c oxidase assembly factor 4 homolog, the group of Mitochondrial respiratory chain complex assembly factors|Coiled-coil-helix-coiled-coil-helix domain containing proteins

Gene summary

Predicted to be involved in mitochondrial respiratory chain complex IV assembly. Located in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

CHCHD8

MANE transcript

NM_016565.3

Inheritance

—

ClinVar variants

U:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr11:73,869,846-73,876,901

External References & Databases

Ensembl (ENSG00000181924)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COA4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016565.3. 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						0
missense			11 clinvar			11
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	12	0	0	12

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016565.3	RefSeq	NP_057649.2	1	MANE Select
ENST00000355693.5	Ensembl	ENSP00000347919.4	1	MANE Select
ENST00000537289.1	Ensembl	ENSP00000437772.1	1	Standard
ENST00000537289.2	Ensembl	ENSP00000437772.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thermogenesis - Homo sapiens (human)
Metabolism of proteins
Mitochondrial protein import

Biological Process

mitochondrial respiratory chain complex IV assembly

Cellular Component

mitochondrion
mitochondrial intermembrane space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355693
Coding exons: 1
Length: 4322
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125700
p: 0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.294	48	54.1	0.887	0.00000333	574
Missense (PolyPhen)		19	21.744	0.87379		235
Synonymous	0.595	19	22.6	0.841	0.00000142	158
Loss of Function	1.05	1	2.95	0.339	1.29e-7	27

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Putative COX assembly factor. {ECO:0000250}.;

Recessive Scores

pRec: 0.0293

Intolerance Scores

RVIS EVS: 0.5
RVIS percentile EVS: 79.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): K

Gene Damage Prediction

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