COX5A

cytochrome c oxidase subunit 5A, the group of Mitochondrial complex IV: cytochrome c oxidase subunits

Basic information

Region (hg38): 15:74919791-74938083

Links

ENSG00000178741 ∙ NCBI:9377 ∙ OMIM:603773 ∙ HGNC:2267 ∙ Uniprot:P20674 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
• mitochondrial complex 4 deficiency, nuclear type 20 (Limited), mode of inheritance: AR
• mitochondrial complex 4 deficiency, nuclear type 20 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex IV deficiency, nuclear type 20	AR	General	Among other findings, the condition may involve pulmonary artery hypertension, and awareness may allow early management	Biochemical; Cardiovascular; Neurologic	28247525

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX5A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX5A 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				2		2
missense			13	2		15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	13	4	0

Variants in COX5A

This is a list of pathogenic ClinVar variants found in the COX5A region.

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

Position	Type	Phenotype	Significance	ClinVar
15-74923695-T-G		not specified	Uncertain significance (Jun 19, 2024)
15-74926786-G-A		Mitochondrial complex 4 deficiency, nuclear type 20	Pathogenic (Mar 07, 2024)
15-74926786-G-T		not specified	Uncertain significance (Jun 10, 2024)
15-74926789-C-T		not specified	Uncertain significance (Jun 23, 2023)
15-74926791-G-A		not specified	Uncertain significance (Mar 22, 2023)
15-74926835-A-G			Likely benign (Apr 23, 2018)
15-74926839-A-C		Mitochondrial complex 4 deficiency, nuclear type 20	Pathogenic (Mar 07, 2024)
15-74926883-T-C		not specified	Likely benign (Sep 29, 2022)
15-74929172-G-C		not specified	Uncertain significance (Nov 08, 2022)
15-74929188-C-G		not specified	Uncertain significance (Dec 13, 2021)
15-74929196-T-C		not specified	Uncertain significance (Dec 19, 2022)
15-74929199-G-A		not specified	Uncertain significance (Sep 20, 2023)
15-74929205-T-C		not specified	Uncertain significance (Nov 27, 2023)
15-74937920-G-T		not specified	Uncertain significance (Aug 12, 2021)
15-74937921-C-T		not specified	Uncertain significance (Aug 12, 2021)
15-74937926-C-T		not specified	Uncertain significance (Feb 27, 2023)
15-74937941-G-C		COX5A-related disorder	Likely benign (Dec 31, 2019)
15-74937950-A-T		not specified	Uncertain significance (Jun 26, 2023)
15-74937959-G-C			Uncertain significance (Aug 01, 2023)
15-74937979-G-A			Likely benign (Oct 01, 2024)
15-74937999-G-A		not specified	Uncertain significance (Jun 18, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX5A	protein_coding	protein_coding	ENST00000322347	4	18378

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.494	0.487	125135	0	1	125136	0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.246	65	70.8	0.918	0.00000409	946
Missense in Polyphen		23	26.057	0.88267		311
Synonymous	0.0737	23	23.5	0.981	0.00000109	313
Loss of Function	1.89	1	6.00	0.167	2.51e-7	88

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000882	0.00000882
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This is the heme A-containing chain of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
• Disease: DISEASE: Note=Mitochondrial complex IV deficiency is a rare condition caused by mutation in COX5A that lead to pulmonary arterial hypertension (PAH), failure to thrive and lactic acidemia. {ECO:0000269|PubMed:28247525}.
• 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: 0.288

Intolerance Scores

• loftool: 0.137
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• pHI: 0.125
• hipred: Y
• hipred_score: 0.600
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0872

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cox5a

Zebrafish Information Network

• Gene name: cox5aa
• Affected structure: secondary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: mitochondrial electron transport, cytochrome c to oxygen;proton transmembrane transport
• Cellular component: mitochondrial inner membrane;mitochondrial respiratory chain complex IV
• Molecular function: cytochrome-c oxidase activity;protein binding;electron transfer activity;metal ion binding