COX6C

protein-coding

cytochrome c oxidase subunit 6C, the group of Mitochondrial complex IV: cytochrome c oxidase subunits

Gene summary

Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIc, which has 77% amino acid sequence identity with mouse subunit VIc. This gene is up-regulated in prostate cancer cells. A pseudogene has been found on chromosomes 16p12. [provided by RefSeq, Jul 2010]

MANE transcript

NM_004374.4

Inheritance

—

ClinVar variants

U:18B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr8:99,873,200-99,893,707

External References & Databases

Ensembl (ENSG00000164919)

Transcript & Mutation Effects

hg38 • Region Span ~20.5 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 COX6C variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004374.4. 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			2 clinvar			2
missense			14 clinvar	1 clinvar		15
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	18	1	0	19

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004374.4	RefSeq	NP_004365.1	2	MANE Select
ENST00000520468.7	Ensembl	ENSP00000428895.1	2	MANE Select
ENST00000297564.6	Ensembl	ENSP00000297564.2	2	Standard
ENST00000297564.7	Ensembl	ENSP00000297564.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cardiac muscle contraction - Homo sapiens (human)
Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
Alzheimer,s disease - Homo sapiens (human)
Huntington,s disease - Homo sapiens (human)
Thermogenesis - Homo sapiens (human)

Biological Process

generation of precursor metabolites and energy
electron transport chain
proton transmembrane transport

Molecular Function

cytochrome-c oxidase activity

Cellular Component

mitochondrion
mitochondrial inner membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000520468
Coding exons: 2
Length: 20863
Individuals with no LoFs: 125428
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125431
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0822	45	46.6	0.966	0.00000296	485
Missense (PolyPhen)		8	9.3148	0.85885		155
Synonymous	1.57	7	14.6	0.478	7.83e-7	146
Loss of Function	0.642	2	3.25	0.616	2.21e-7	36

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	0.000056	0.000055	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.;

Recessive Scores

pRec: 0.0800

Intolerance Scores

LoFtool: 0.472
RVIS EVS: 0.17
RVIS percentile EVS: 65.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.920

Gene Damage Prediction

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