COX8A

cytochrome c oxidase subunit 8A, the group of Mitochondrial complex IV: cytochrome c oxidase subunits

Basic information

Region (hg38): 11:63974619-63976543

Previous symbols: [ "COX8" ]

Links

ENSG00000176340 ∙ NCBI:1351 ∙ OMIM:123870 ∙ HGNC:2294 ∙ Uniprot:P10176 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 4 deficiency, nuclear type 15 (Limited), mode of inheritance: AR
• cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
• cytochrome-c oxidase deficiency disease (Limited), mode of inheritance: Unknown
• Leigh syndrome (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 15	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; Musculoskeletal; Neurologic	26685157

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX8A gene.

• not provided (19 variants)
• Mitochondrial complex 4 deficiency, nuclear type 15 (4 variants)
• Cytochrome-c oxidase deficiency disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX8A 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				7	1	8
missense			6	1		7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				3	2	5
Total	0	0	6	11	3

Variants in COX8A

This is a list of pathogenic ClinVar variants found in the COX8A region.

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

Position	Type	Phenotype	Significance	ClinVar
11-63974686-C-T			Likely benign (Jan 29, 2024)
11-63974702-C-T		COX8A-related disorder	Benign (Jan 22, 2024)
11-63974706-T-A			Uncertain significance (Jul 07, 2023)
11-63974736-T-C			Uncertain significance (Sep 01, 2022)
11-63974747-C-T			Benign/Likely benign (Oct 03, 2023)
11-63974773-G-T		Mitochondrial complex 4 deficiency, nuclear type 15	Likely benign (Aug 01, 2023)
11-63974791-C-A		Mitochondrial complex 4 deficiency, nuclear type 15	Benign/Likely benign (Jan 24, 2024)
11-63974806-G-A			Likely benign (Aug 06, 2023)
11-63974811-G-A		Mitochondrial complex 4 deficiency, nuclear type 15	Likely benign (Mar 18, 2023)
11-63974814-G-A			Likely benign (Aug 24, 2023)
11-63975081-T-G			Benign (Jun 14, 2018)
11-63975948-A-C			Likely benign (Oct 16, 2018)
11-63975948-A-G			Benign (Jun 14, 2018)
11-63976224-G-C		Mitochondrial complex IV deficiency, nuclear type 1	Pathogenic (Oct 23, 2020)
11-63976234-G-A			Uncertain significance (Jun 10, 2022)
11-63976234-G-T			Uncertain significance (Jan 12, 2024)
11-63976263-C-T			Likely benign (Jul 21, 2022)
11-63976281-G-T		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Feb 22, 2018)
11-63976284-C-A		Mitochondrial complex 4 deficiency, nuclear type 15 • COX8A-related disorder	Benign/Likely benign (Jan 19, 2024)
11-63976292-A-G			Uncertain significance (Jan 04, 2022)
11-63976299-G-A			Likely benign (Jul 07, 2023)
11-63976314-A-G			Likely benign (Dec 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX8A	protein_coding	protein_coding	ENST00000314133	2	1937

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.116	0.619	117625	0	1	117626	0.00000425

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.154	35	37.7	0.929	0.00000194	412
Missense in Polyphen		9	11.364	0.79198		104
Synonymous	0.859	15	19.9	0.755	0.00000109	166
Loss of Function	0.368	1	1.48	0.674	6.21e-8	22

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000303	0.0000303
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;Arachidonate Epoxygenase - Epoxide Hydrolase;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• rvis_EVS: 0.26
• rvis_percentile_EVS: 69.83

Haploinsufficiency Scores

• pHI: 0.0418
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.429

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cox8a

Gene ontology

• Biological process: generation of precursor metabolites and energy;electron transport chain;proton transmembrane transport
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane;respiratory chain complex IV
• Molecular function: cytochrome-c oxidase activity;protein binding