COX6A2

cytochrome c oxidase subunit 6A2, the group of Mitochondrial complex IV: cytochrome c oxidase subunits

Basic information

Region (hg38): 16:31427731-31428360

Links

ENSG00000156885 ∙ NCBI:1339 ∙ OMIM:602009 ∙ HGNC:2279 ∙ Uniprot:Q02221 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 4 deficiency, nuclear type 18 (Limited), mode of inheritance: AR
• cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
• mitochondrial complex 4 deficiency, nuclear type 18 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex IV deficiency, nuclear type 18	AR	General	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	Biochemical; Cardiovascular; Craniofacial; Musculoskeletal	31155743

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX6A2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX6A2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense		2	11			13
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	2	12	0	0

Variants in COX6A2

This is a list of pathogenic ClinVar variants found in the COX6A2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-31427787-T-C		not specified	Uncertain significance (Jun 05, 2023)
16-31427793-G-A		not specified	Uncertain significance (Jan 01, 2025)
16-31427803-G-A		not specified	Uncertain significance (Nov 18, 2022)
16-31427810-G-C		not specified	Uncertain significance (Feb 04, 2025)
16-31427813-G-A		COX6A2-related disorder	Likely benign (Nov 01, 2019)
16-31427814-C-T		not specified	Uncertain significance (Apr 14, 2022)
16-31427827-G-C			Uncertain significance (Jan 01, 2024)
16-31427829-G-A		not specified	Uncertain significance (Jan 23, 2024)
16-31427834-G-C		not specified	Uncertain significance (Jul 06, 2021)
16-31427846-C-A		not specified	Uncertain significance (Dec 29, 2024)
16-31427849-G-A		COX6A2-related disorder	Benign (Dec 09, 2019)
16-31428022-C-T		not specified	Uncertain significance (Dec 04, 2024)
16-31428047-G-A		not specified	Uncertain significance (Mar 29, 2024)
16-31428064-C-A		not specified	Uncertain significance (Feb 21, 2024)
16-31428071-C-T		not specified	Uncertain significance (Apr 18, 2023)
16-31428098-A-G		Mitochondrial complex 4 deficiency, nuclear type 18	Conflicting classifications of pathogenicity (Jan 01, 2025)
16-31428108-G-T		Mitochondrial complex 4 deficiency, nuclear type 18	Likely pathogenic (Dec 04, 2020)
16-31428113-G-A		not specified	Uncertain significance (Feb 19, 2025)
16-31428146-T-A		not specified	Uncertain significance (May 24, 2024)
16-31428292-A-C		COX6A2-related disorder	Conflicting classifications of pathogenicity (Jan 01, 2025)
16-31428324-A-G		not specified	Uncertain significance (Nov 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX6A2	protein_coding	protein_coding	ENST00000287490	3	916

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.189	0.658	108120	0	1	108121	0.00000462

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.235	41	45.5	0.902	0.00000276	577
Missense in Polyphen		20	21.582	0.9267		280
Synonymous	0.353	19	21.1	0.902	0.00000143	206
Loss of Function	0.928	1	2.62	0.382	1.11e-7	40

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000325	0.0000325
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: 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);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Electron Transport Chain (Consensus)

Recessive Scores

• pRec: 0.125

Intolerance Scores

• loftool: 0.296
• rvis_EVS: 0.26
• rvis_percentile_EVS: 69.83

Haploinsufficiency Scores

• pHI: 0.142
• hipred: N
• hipred_score: 0.245
• ghis: 0.454

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.438

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cox6a2
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: generation of precursor metabolites and energy;mitochondrial electron transport, cytochrome c to oxygen;aerobic respiration;regulation of catalytic activity;proton transmembrane transport
• Molecular function: cytochrome-c oxidase activity;enzyme regulator activity