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 IV deficiency, nuclear type 20 (Limited), mode of inheritance: AR
mitochondrial complex IV 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.

not_specified (21 variants)
not_provided (4 variants)
Mitochondrial_complex_IV_deficiency,_nuclear_type_20 (3 variants)
COX5A-related_disorder (1 variants)

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. These statistics are base on transcript: NM_000004255.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense	2 clinvar		22 clinvar	2 clinvar		26
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	0	22	4	0

Highest pathogenic variant AF is 0.0000013695122

Loading clinvar variants...

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
Phenotype

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