COA5

cytochrome c oxidase assembly factor 5, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 2:98599314-98608515

Previous symbols: [ "C2orf64" ]

Links

ENSG00000183513 ∙ NCBI:493753 ∙ OMIM:613920 ∙ HGNC:33848 ∙ Uniprot:Q86WW8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cytochrome-c oxidase deficiency disease (Limited), mode of inheritance: AR
• cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3 (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 9	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	21457908
Manifestations include lethal neonatal hypertrophic cardiomyopathy

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COA5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COA5 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				4		4
missense			3	1		4
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				8	4	12
Total	0	0	3	13	4

Variants in COA5

This is a list of pathogenic ClinVar variants found in the COA5 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-98600749-G-C			Conflicting classifications of pathogenicity (Jul 08, 2015)
2-98600780-G-A		not specified	Uncertain significance (Oct 11, 2023)
2-98601088-C-T			Benign (Jun 14, 2018)
2-98603948-C-T			Likely benign (Nov 09, 2018)
2-98604134-C-G		Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3	Pathogenic (Apr 08, 2011)
2-98604134-C-T			Uncertain significance (Dec 22, 2023)
2-98604175-C-T		not specified	Uncertain significance (Aug 13, 2021)
2-98604178-G-A		not specified	Uncertain significance (Mar 20, 2024)
2-98604194-A-G			Uncertain significance (Nov 01, 2023)
2-98604244-T-C			Benign (Jun 14, 2018)
2-98604359-G-GA			Likely benign (Aug 15, 2019)
2-98604430-T-C			Benign (Jul 15, 2018)
2-98608123-A-G			Likely benign (Jun 16, 2018)
2-98608129-A-G			Likely benign (Jul 07, 2018)
2-98608279-C-T			Benign (Jul 15, 2018)
2-98608322-C-G			Likely benign (Mar 20, 2023)
2-98608343-C-G			Likely benign (Dec 28, 2023)
2-98608357-G-T		not specified	Uncertain significance (Jul 25, 2024)
2-98608379-C-A			Likely benign (Nov 06, 2023)
2-98608380-G-A			Likely benign (Oct 03, 2023)
2-98608382-C-T			Likely benign (Sep 11, 2023)
2-98608428-G-A		not specified	Likely benign (Jun 07, 2017)
2-98608437-T-C			Likely benign (Jun 01, 2018)
2-98608474-G-C			Likely benign (Jun 23, 2018)
2-98608476-G-A			Likely benign (Aug 03, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COA5	protein_coding	protein_coding	ENST00000328709	3	9206

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0183	0.743	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.383	33	39.8	0.829	0.00000195	461
Missense in Polyphen		8	13.362	0.59872		173
Synonymous	0.202	16	17.1	0.938	8.97e-7	132
Loss of Function	0.790	3	4.88	0.614	2.04e-7	64

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000457	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.0000552	0.0000527
Middle Eastern	0.000457	0.000435
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in an early step of the mitochondrial complex IV assembly process. {ECO:0000269|PubMed:21457908}.
• Disease: DISEASE: Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3 (CEMCOX3) [MIM:616500]: An infantile disorder with a fatal course in the first weeks of life, characterized by hypertrophic cardiomyopathy and mitochondrial complex IV deficiency. Postmortem microscopic investigations show accumulation of lipid droplets in cardiomyocytes and mitochondrial proliferation. {ECO:0000269|PubMed:21457908}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human) (Consensus)

Intolerance Scores

• rvis_EVS: 0.06
• rvis_percentile_EVS: 58

Haploinsufficiency Scores

• pHI: 0.118
• hipred: N
• hipred_score: 0.400
• ghis: 0.661

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Coa5
• Phenotype: endocrine/exocrine gland 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region 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); limbs/digits/tail phenotype; skeleton phenotype; embryo phenotype

Gene ontology

• Biological process: mitochondrial respiratory chain complex IV assembly
• Cellular component: mitochondrion
• Molecular function: protein binding