COA6

cytochrome c oxidase assembly factor 6, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 1:234373456-234385080

Previous symbols: [ "C1orf31" ]

Links

ENSG00000168275 ∙ NCBI:388753 ∙ OMIM:614772 ∙ HGNC:18025 ∙ Uniprot:Q5JTJ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 (Strong), mode of inheritance: Unknown
• cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 (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 13	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; Neurologic	22277967; 24549041; 25339201
Manifestations include lethal neonatal hypertrophic cardiomyopathy

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COA6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COA6 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				11		11
missense			8	1	3	12
nonsense			1			1
start loss			1			1
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	2	4
non coding		1	1	7	11	20
Total	0	2	11	19	14

Variants in COA6

This is a list of pathogenic ClinVar variants found in the COA6 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-234373505-C-A			Likely benign (Feb 01, 2024)
1-234373511-G-A		COA6-related disorder	Likely benign (Mar 09, 2020)
1-234373513-G-C		not specified • Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4	Benign (Jul 22, 2021)
1-234373513-G-T			Uncertain significance (Sep 01, 2023)
1-234373538-T-C		not specified	Likely benign (Feb 08, 2018)
1-234373556-G-A		not specified	Likely benign (May 01, 2022)
1-234373657-C-G		not specified • COA6-related disorder	Benign (Nov 22, 2017)
1-234373707-C-T		not specified	Likely benign (Jul 05, 2017)
1-234373726-C-T		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
1-234373728-G-A		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
1-234373744-C-T			Uncertain significance (Apr 22, 2022)
1-234373748-G-T			Likely benign (May 23, 2023)
1-234373754-C-A		not specified	Likely benign (Oct 14, 2023)
1-234373792-G-T		Inborn genetic diseases	Uncertain significance (Nov 13, 2024)
1-234373822-C-G			Benign (Jan 23, 2024)
1-234373832-A-G		not specified	Likely benign (Jun 21, 2022)
1-234373840-G-A		not specified • Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4	Benign/Likely benign (Dec 22, 2023)
1-234373841-G-A		See cases	Likely pathogenic (Nov 13, 2020)
1-234373854-C-T			Likely benign (Nov 18, 2022)
1-234374112-GT-G			Benign (Sep 08, 2019)
1-234374112-GTT-G			Likely benign (Oct 20, 2020)
1-234374112-GTTTTTTT-G			Likely benign (Oct 02, 2019)
1-234374119-T-G			Benign (Aug 06, 2019)
1-234374125-T-G			Likely benign (Aug 11, 2019)
1-234374226-A-G		not specified	Benign (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COA6	protein_coding	protein_coding	ENST00000366613	3	10594

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00569	0.738	125723	0	24	125747	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.720	50	66.5	0.752	0.00000306	810
Missense in Polyphen		16	20.088	0.79648		281
Synonymous	-0.0162	26	25.9	1.00	0.00000124	227
Loss of Function	0.811	4	6.18	0.648	2.61e-7	79

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000671	0.0000671
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the maturation of the mitochondrial respiratory chain complex IV subunit MT-CO2/COX2. Thereby, may regulate early steps of complex IV assembly. Mitochondrial respiratory chain complex IV or cytochrome c oxidase is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane space cytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis. May also be required for efficient formation of respiratory supercomplexes comprised of complexes III and IV. {ECO:0000269|PubMed:24549041, ECO:0000269|PubMed:25959673, ECO:0000269|PubMed:26160915}.
• Disease: DISEASE: Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 (CEMCOX4) [MIM:616501]: An infantile disorder with a fatal course in the first weeks of life, characterized by hypertrophic cardiomyopathy, left ventricular non-compaction, lactic acidosis, metabolic hypotonia, and mitochondrial complex IV deficiency. {ECO:0000269|PubMed:24549041, ECO:0000269|PubMed:25339201, ECO:0000269|PubMed:25959673}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human);Metabolism of proteins;Mitochondrial protein import (Consensus)

Intolerance Scores

• rvis_EVS: 0.37
• rvis_percentile_EVS: 74.95

Haploinsufficiency Scores

• pHI: 0.0590
• hipred: N
• hipred_score: 0.153
• ghis: 0.469

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Coa6

Zebrafish Information Network

• Gene name: coa6
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: respiratory chain complex IV assembly;plasma membrane ATP synthesis coupled electron transport
• Cellular component: mitochondrion;mitochondrial intermembrane space;plasma membrane
• Molecular function: RNA binding;copper ion binding;protein binding