COX20

cytochrome c oxidase assembly factor COX20, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 1:244835616-244845057

Previous symbols: [ "FAM36A" ]

Links

ENSG00000203667 ∙ NCBI:116228 ∙ OMIM:614698 ∙ HGNC:26970 ∙ Uniprot:Q5RI15 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR
• mitochondrial complex 4 deficiency, nuclear type 11 (Strong), mode of inheritance: AR
• mitochondrial complex 4 deficiency, nuclear type 11 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex IV deficiency, nuclear type 11	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	23125284; 24202787

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX20 gene.

• COX20-related disorder (1 variants)
• Mitochondrial complex 4 deficiency, nuclear type 11 (1 variants)
• not provided (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX20 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				20	2	22
missense	1		47	1	1	50
nonsense		1	2			3
start loss			1			1
frameshift		3	2			5
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)		3				3
splice region		1	3	3	3	10
non coding			1	21	8	30
Total	1	8	56	42	11

Highest pathogenic variant AF is 0.0000470

Variants in COX20

This is a list of pathogenic ClinVar variants found in the COX20 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-244835676-C-G		not specified	Likely benign (Mar 02, 2016)
1-244835677-C-T			Likely benign (Jan 15, 2021)
1-244835705-A-T		not specified	Likely benign (Jun 21, 2016)
1-244835716-T-C		Mitochondrial complex 4 deficiency, nuclear type 11	Uncertain significance (Jul 30, 2024)
1-244835718-G-A		Mitochondrial complex 4 deficiency, nuclear type 11	Uncertain significance (Feb 04, 2024)
1-244835720-C-T			Likely benign (Jun 11, 2024)
1-244835721-G-A		Inborn genetic diseases • Mitochondrial complex 4 deficiency, nuclear type 11	Uncertain significance (Mar 08, 2024)
1-244835721-G-T		not specified • Mitochondrial complex 4 deficiency, nuclear type 11	Benign/Likely benign (Jan 27, 2025)
1-244835722-C-T		Mitochondrial complex 4 deficiency, nuclear type 11	Uncertain significance (Apr 22, 2024)
1-244835723-C-G			Likely benign (Jun 07, 2022)
1-244835723-C-T		COX20-related disorder	Likely benign (Apr 11, 2024)
1-244835724-C-T		Mitochondrial complex 4 deficiency, nuclear type 11	Uncertain significance (Apr 01, 2024)
1-244835727-C-T			Uncertain significance (May 24, 2024)
1-244835730-G-T		Mitochondrial complex 4 deficiency, nuclear type 11	Likely pathogenic (Jan 24, 2024)
1-244835729-G-GGAGCCCGGTGAGCCC			Uncertain significance (Apr 04, 2022)
1-244835732-G-A			Likely benign (Apr 01, 2022)
1-244835733-C-T		Mitochondrial complex 4 deficiency, nuclear type 11	Uncertain significance (Jan 28, 2024)
1-244835736-G-A			Uncertain significance (Nov 04, 2024)
1-244835738-T-C		Mitochondrial complex 4 deficiency, nuclear type 11	Likely benign (Aug 13, 2024)
1-244835739-G-A			Uncertain significance (Apr 22, 2022)
1-244835741-G-C		Mitochondrial complex 4 deficiency, nuclear type 11	Uncertain significance (Jan 28, 2024)
1-244835744-C-G		not specified	Likely benign (Mar 31, 2017)
1-244835745-G-A		Mitochondrial complex 4 deficiency, nuclear type 11	Uncertain significance (Oct 24, 2024)
1-244835747-G-T		Mitochondrial complex 4 deficiency, nuclear type 11	Uncertain significance (Mar 07, 2024)
1-244835755-A-G		Mitochondrial complex 4 deficiency, nuclear type 11 • COX20-related disorder • Inborn genetic diseases	Pathogenic (Oct 09, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX20	protein_coding	protein_coding	ENST00000411948	4	9736

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0201	0.759	125696	0	25	125721	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.293	51	57.2	0.891	0.00000283	749
Missense in Polyphen		20	23.148	0.86401		293
Synonymous	-1.01	25	19.4	1.29	9.24e-7	208
Loss of Function	0.852	3	5.07	0.592	2.10e-7	84

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000334	0.0000334
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000452	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.000492	0.000490
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase (PubMed:23125284). Acts as a chaperone in the early steps of cytochrome c oxidase subunit II (MT-CO2/COX2) maturation, stabilizing the newly synthesized protein and presenting it to metallochaperones SCO1/2 which in turn facilitates the incorporation of the mature MT-CO2/COX2 into the assembling CIV holoenzyme (PubMed:24403053). {ECO:0000269|PubMed:23125284, ECO:0000269|PubMed:24403053}.
• 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:23125284, ECO:0000269|PubMed:24202787, ECO:0000269|PubMed:29154948}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human);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)

Intolerance Scores

• rvis_EVS: 0.08
• rvis_percentile_EVS: 59.76

Haploinsufficiency Scores

• pHI: 0.156
• hipred: N
• hipred_score: 0.177
• ghis: 0.474

Essentials

• essential_gene_CRISPR: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cox20

Gene ontology

• Biological process: aerobic respiration;mitochondrial respiratory chain complex IV assembly
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane
• Molecular function: protein binding