COX14

cytochrome c oxidase assembly factor COX14, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 12:50112082-50120457

Previous symbols: [ "C12orf62" ]

Links

ENSG00000178449 ∙ NCBI:84987 ∙ OMIM:614478 ∙ HGNC:28216 ∙ Uniprot:Q96I36 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cytochrome-c oxidase deficiency disease (Limited), mode of inheritance: AR
• cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
• cytochrome-c oxidase deficiency disease (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 10	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	Cardiovascular; Biochemical; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	22243966

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX14 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX14 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				5		5
missense			11			11
nonsense			1			1
start loss			1			1
frameshift		1	2			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				5	5	10
Total	0	1	15	10	5

Variants in COX14

This is a list of pathogenic ClinVar variants found in the COX14 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-50112104-A-C			Likely benign (Mar 17, 2021)
12-50112316-A-G		not specified	Likely benign (Aug 31, 2016)
12-50118417-T-C			Benign (Jun 29, 2018)
12-50118510-G-A			Benign (Jun 29, 2018)
12-50118583-C-T			Likely benign (Apr 18, 2019)
12-50118849-T-C			Benign (Apr 18, 2019)
12-50119736-G-T			Benign (Jun 26, 2018)
12-50119904-C-T			Benign (Jun 23, 2018)
12-50120022-A-G		not specified • Mitochondrial complex 4 deficiency, nuclear type 10	Likely benign (Aug 20, 2021)
12-50120046-G-A			Uncertain significance (Dec 18, 2023)
12-50120066-C-G		not specified	Uncertain significance (Dec 06, 2022)
12-50120075-G-C			Uncertain significance (Nov 27, 2023)
12-50120085-C-T			Likely benign (Oct 15, 2023)
12-50120092-A-C		not specified	Uncertain significance (May 30, 2024)
12-50120100-G-A		Mitochondrial complex 4 deficiency, nuclear type 10	Pathogenic (Jan 13, 2012)
12-50120111-C-T			Uncertain significance (Jun 12, 2021)
12-50120117-A-G		Mitochondrial complex 4 deficiency, nuclear type 10	Uncertain significance (Dec 11, 2023)
12-50120118-T-TG			Likely pathogenic (Jan 20, 2015)
12-50120124-G-A			Likely benign (Aug 27, 2023)
12-50120124-GT-G		not specified	Uncertain significance (Jun 11, 2024)
12-50120141-G-A		not specified	Uncertain significance (Feb 16, 2023)
12-50120150-AC-A			Uncertain significance (Oct 05, 2023)
12-50120159-A-G		not specified	Uncertain significance (Dec 03, 2024)
12-50120164-C-T		not specified	Uncertain significance (Dec 30, 2023)
12-50120165-G-A			Uncertain significance (Nov 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX14	protein_coding	protein_coding	ENST00000550487	1	8479

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.357	0.493	125732	0	12	125744	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0597	35	34.0	1.03	0.00000195	363
Missense in Polyphen		10	10.713	0.93343		134
Synonymous	0.513	10	12.3	0.814	6.15e-7	113
Loss of Function	0.769	0	0.689	0.00	2.85e-8	10

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000173	0.000173
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000527	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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. Requires for coordination of the early steps of cytochrome c oxidase assembly with the synthesis of MT-CO1. {ECO:0000269|PubMed:22243966, ECO:0000269|PubMed:22356826}.
• Disease: DISEASE: Note=Defects in COX14 may be a cause of a mitochondrial disorder presenting with severe congenital lactic acidosis and dysmorphic features associated with a COX assembly defect. Other features include brain hypertrophy, diffuse alteration of the white-matter myelination, and numerous cavities in the parieto- occipital region, brainstem, and cerebellum, as well as hepatomegaly, hypertrophic cardiomyopathy, renal hypoplasia, and adrenal-gland hyperplasia. {ECO:0000269|PubMed:22243966}.
• 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: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• pHI: 0.0876
• hipred: N
• hipred_score: 0.253
• ghis: 0.574

Essentials

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

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cox14

Gene ontology

• Biological process: mitochondrial respiratory chain complex IV assembly
• Cellular component: mitochondrion;integral component of membrane;mitochondrial membrane