COX10

cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 17:14069489-14231736

Links

ENSG00000006695 ∙ NCBI:1352 ∙ OMIM:602125 ∙ HGNC:2260 ∙ Uniprot:Q12887 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leigh syndrome (Definitive), mode of inheritance: AR
• mitochondrial complex 4 deficiency, nuclear type 3 (Strong), mode of inheritance: AR
• cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex IV deficiency, nuclear type 3	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	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Hematologic; Musculoskeletal; Neurologic	10767350

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX10 gene.

• not provided (177 variants)
• Cytochrome-c oxidase deficiency disease (89 variants)
• Leigh syndrome (89 variants)
• Mitochondrial complex 4 deficiency, nuclear type 3 (34 variants)
• not specified (25 variants)
• Inborn genetic diseases (21 variants)
• Leigh syndrome;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 COX10 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	33	3	38
missense		4	66	3	2	75
nonsense		2				2
start loss						0
frameshift		2				2
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			1	8	1	10
non coding			29	27	36	92
Total	0	8	100	63	41

Highest pathogenic variant AF is 0.0000263

Variants in COX10

This is a list of pathogenic ClinVar variants found in the COX10 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-14069494-G-A		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Benign (Jun 23, 2018)
17-14069497-G-A		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Benign/Likely benign (Jun 14, 2018)
17-14069516-G-T		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 13, 2018)
17-14069517-G-C		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1 • Mitochondrial complex 4 deficiency, nuclear type 3	Uncertain significance (Mar 05, 2022)
17-14069517-G-T		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1 • Mitochondrial complex 4 deficiency, nuclear type 3	Uncertain significance (Apr 20, 2022)
17-14069543-C-T		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Benign/Likely benign (Jan 12, 2018)
17-14069566-G-A		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
17-14069571-A-G		not specified	Likely benign (Nov 23, 2016)
17-14069577-C-A		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
17-14069582-G-A		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Conflicting classifications of pathogenicity (May 30, 2018)
17-14069607-T-C		Mitochondrial complex 4 deficiency, nuclear type 3	Pathogenic (Oct 01, 2004)
17-14069620-G-T		not specified	Likely benign (Mar 22, 2016)
17-14069623-C-T			Likely benign (Apr 22, 2022)
17-14069625-C-G		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
17-14069638-C-T		not specified • Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Benign/Likely benign (Jan 30, 2024)
17-14069639-C-T		Mitochondrial complex 4 deficiency, nuclear type 3	Uncertain significance (Apr 19, 2022)
17-14069658-C-G			Likely benign (Sep 23, 2022)
17-14069660-G-A			Likely benign (Nov 22, 2022)
17-14069814-T-C			Benign (Jun 14, 2018)
17-14069832-G-T			Likely benign (Jul 15, 2018)
17-14074036-G-A			Benign (Jul 31, 2018)
17-14074145-G-A			Benign (Jun 14, 2018)
17-14074261-G-A			Likely benign (Jun 23, 2018)
17-14074320-T-C		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
17-14074321-A-G			Uncertain significance (Nov 27, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX10	protein_coding	protein_coding	ENST00000261643	7	139182

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0840	0.914	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.180	266	258	1.03	0.0000156	2814
Missense in Polyphen		100	116.2	0.86062		1207
Synonymous	-1.02	124	110	1.12	0.00000707	944
Loss of Function	2.73	5	17.2	0.290	8.04e-7	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000530	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts protoheme IX and farnesyl diphosphate to heme O. {ECO:0000250}.
• Disease: DISEASE: Mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome. {ECO:0000269|PubMed:10767350, ECO:0000269|PubMed:12928484, ECO:0000269|PubMed:26741492}. Note=The disease is caused by mutations affecting the gene represented in this entry.; 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. 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;Heme biosynthesis;Metabolism of porphyrins;Metabolism (Consensus)

Recessive Scores

• pRec: 0.195

Intolerance Scores

• loftool: 0.109
• rvis_EVS: 0.76
• rvis_percentile_EVS: 86.75

Haploinsufficiency Scores

• pHI: 0.0347
• hipred: Y
• hipred_score: 0.683
• ghis: 0.442

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.909

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Cox10
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: mitochondrial fission;mitochondrial electron transport, cytochrome c to oxygen;heme biosynthetic process;heme a biosynthetic process;respiratory chain complex IV assembly;cellular respiration;heme O biosynthetic process;proton transmembrane transport
• Cellular component: nucleolus;mitochondrion;mitochondrial inner membrane;cytosol;integral component of membrane;cytochrome complex
• Molecular function: cytochrome-c oxidase activity;farnesyltranstransferase activity;protoheme IX farnesyltransferase activity