COA3

cytochrome c oxidase assembly factor 3, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 17:42795146-42798704

Previous symbols: [ "CCDC56" ]

Links

ENSG00000183978 ∙ NCBI:28958 ∙ OMIM:614775 ∙ HGNC:24990 ∙ Uniprot:Q9Y2R0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
• mitochondrial complex 4 deficiency, nuclear type 14 (Limited), mode of inheritance: Unknown
• mitochondrial disease (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 14	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; Craniofacial; Musculoskeletal; Neurologic	25604084

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COA3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COA3 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				3		3
missense			15	1		16
nonsense						0
start loss						0
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1		1
Total	0	0	18	5	0

Variants in COA3

This is a list of pathogenic ClinVar variants found in the COA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-42795167-C-T		Inborn genetic diseases	Uncertain significance (Jul 27, 2022)
17-42795168-C-T		Inborn genetic diseases	Uncertain significance (May 14, 2024)
17-42795175-C-A			Likely benign (Dec 01, 2023)
17-42795228-C-T			Uncertain significance (Dec 20, 2023)
17-42795235-C-G		Pseudohypoaldosteronism type 2B	Uncertain significance (Jan 13, 2018)
17-42795244-G-A		Pseudohypoaldosteronism type 2B	Uncertain significance (Jan 13, 2018)
17-42795250-C-T		WNK4-related disorder	Likely benign (Jun 22, 2021)
17-42795258-C-G		Pseudohypoaldosteronism type 2A • Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 30, 2021)
17-42795260-G-A		Inborn genetic diseases	Uncertain significance (Apr 24, 2023)
17-42795263-C-A		Pseudohypoaldosteronism type 2B	Benign (Jan 13, 2018)
17-42795275-TCTC-T			Uncertain significance (Sep 04, 2023)
17-42795281-C-T		Pseudohypoaldosteronism type 2B	Uncertain significance (Jan 13, 2018)
17-42795302-C-T		Pseudohypoaldosteronism type 2B	Benign (Jan 28, 2024)
17-42795306-G-C		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
17-42795314-C-T			Benign (Nov 27, 2023)
17-42795321-C-G		Pseudohypoaldosteronism type 2B	Uncertain significance (Jan 13, 2018)
17-42795323-C-G		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
17-42795326-G-A		Inborn genetic diseases	Uncertain significance (Aug 26, 2022)
17-42795422-C-T			Benign (May 20, 2021)
17-42795479-C-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
17-42795480-G-A		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
17-42795508-G-A			Benign (Jun 22, 2022)
17-42795524-A-G		Pseudohypoaldosteronism type 2B	Benign (Jan 13, 2018)
17-42795608-T-C			Likely benign (Apr 26, 2023)
17-42795616-G-A		WNK4-related disorder	Benign/Likely benign (Apr 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COA3	protein_coding	protein_coding	ENST00000328434	2	3558

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0648	0.743	125733	0	7	125740	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.189	71	66.7	1.07	0.00000327	649
Missense in Polyphen		22	26.647	0.82562		275
Synonymous	1.47	20	30.3	0.660	0.00000154	252
Loss of Function	0.873	2	3.85	0.520	1.63e-7	40

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. MITRAC complexes regulate both translation of mitochondrial encoded components and assembly of nuclear-encoded components imported in mitochondrion. Required for efficient translation of MT-CO1 and mitochondrial respiratory chain complex IV assembly. {ECO:0000269|PubMed:23260140}.
• Pathway: Thermogenesis - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0929

Intolerance Scores

• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.79

Haploinsufficiency Scores

• pHI: 0.368
• hipred: N
• hipred_score: 0.250
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Coa3

Gene ontology

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