COX15

cytochrome c oxidase assembly homolog COX15, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 10:99710868-99732127

Links

ENSG00000014919

∙ NCBI:1355 ∙ OMIM:603646 ∙ HGNC:2263 ∙ Uniprot:Q7KZN9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 (Moderate), mode of inheritance: AR
Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 (Strong), mode of inheritance: AR
cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 (Definitive), mode of inheritance: AR
mitochondrial disease (Definitive), mode of inheritance: AR
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 6	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; Musculoskeletal; Neurologic	2175025; 12474143; 15235026; 15863660; 21412973

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX15 gene.

not_provided (322 variants)
Inborn_genetic_diseases (43 variants)
Cardioencephalomyopathy,_fatal_infantile,_due_to_cytochrome_c_oxidase_deficiency_2 (29 variants)
Leigh_syndrome (27 variants)
not_specified (27 variants)
COX15-related_disorder (7 variants)
Mitochondrial_complex_IV_deficiency,_nuclear_type_1 (1 variants)
Cardiomyopathy (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX15 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000078470.6. 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		1 clinvar	3 clinvar	107 clinvar	1 clinvar	112
missense	1 clinvar	6 clinvar	94 clinvar	11 clinvar		112
nonsense	8 clinvar	6 clinvar				14
start loss						0
frameshift	11 clinvar	5 clinvar	1 clinvar			17
splice donor/acceptor (+/-2bp)		14 clinvar				14
Total	20	32	98	118	1

Highest pathogenic variant AF is 0.0003302203

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX15	protein_coding	protein_coding	ENST00000016171	9	20257

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.10e-13	0.0429	125617	0	131	125748	0.000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.262	208	219	0.950	0.0000123	2603
Missense in Polyphen		72	80.559	0.89375		967
Synonymous	-0.177	87	84.9	1.02	0.00000448	870
Loss of Function	0.348	21	22.8	0.921	0.00000128	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000945	0.000944
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000687	0.000686
Middle Eastern	0.000326	0.000326
South Asian	0.000393	0.000392
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

Function: FUNCTION: May be involved in the biosynthesis of heme A. {ECO:0000269|PubMed:12474143}.;
Disease: DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:15235026, ECO:0000269|PubMed:15863660}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Porphyrin and chlorophyll metabolism - Homo sapiens (human);Hereditary Coproporphyria (HCP);Porphyria Variegata (PV);Congenital Erythropoietic Porphyria (CEP) or Gunther Disease;Acute Intermittent Porphyria;Porphyrin Metabolism;Electron Transport Chain;Heme biosynthesis;Metabolism of porphyrins;Metabolism (Consensus)

Recessive Scores

pRec: 0.147

Intolerance Scores

loftool: 0.167
rvis_EVS: -0.25
rvis_percentile_EVS: 36.07

Haploinsufficiency Scores

pHI: 0.407
hipred: N
hipred_score: 0.326
ghis: 0.566

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.990

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cox15
Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); 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: mitochondrial electron transport, cytochrome c to oxygen;heme biosynthetic process;heme a biosynthetic process;respiratory gaseous exchange;respiratory chain complex IV assembly;cellular respiration;oxidation-reduction process;proton transmembrane transport
Cellular component: nucleus;mitochondrion;mitochondrial inner membrane;mitochondrial respirasome;integral component of membrane;cytochrome complex
Molecular function: cytochrome-c oxidase activity;protein binding;oxidoreductase activity, acting on the CH-CH group of donors;oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor