COX16

cytochrome c oxidase assembly factor COX16, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 14:70325081-70416984

Previous symbols: [ "C14orf112" ]

Links

ENSG00000133983 ∙ NCBI:51241 ∙ OMIM:618064 ∙ HGNC:20213 ∙ Uniprot:Q9P0S2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex IV deficiency, nuclear type 22 (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 22	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; Gastrointestinal; Neurologic	33169484

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX16 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX16 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				2		2
missense			11			11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	11	2	0

Variants in COX16

This is a list of pathogenic ClinVar variants found in the COX16 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-70326403-G-A		not specified	Uncertain significance (Apr 12, 2022)
14-70326410-G-A		Mitochondrial complex IV deficiency, nuclear type 22	Pathogenic (Jun 04, 2022)
14-70326416-T-C		not specified	Uncertain significance (May 23, 2023)
14-70326444-G-A			Likely benign (Apr 01, 2024)
14-70326444-G-C		not specified	Uncertain significance (Jun 24, 2022)
14-70326449-T-C		not specified	Uncertain significance (Dec 05, 2022)
14-70329183-C-T		not specified	Likely benign (Jan 03, 2024)
14-70329184-G-A		not specified	Uncertain significance (Aug 16, 2021)
14-70329194-A-G		not specified	Uncertain significance (Aug 01, 2023)
14-70329212-G-T		not specified	Uncertain significance (Oct 27, 2021)
14-70342698-C-T		not specified	Uncertain significance (Apr 04, 2023)
14-70359530-C-T		not specified	Uncertain significance (Jun 06, 2023)
14-70359539-C-T		not specified	Uncertain significance (Jan 24, 2024)
14-70359547-T-G		not specified	Uncertain significance (Dec 03, 2021)
14-70373005-G-A		not specified	Uncertain significance (Dec 27, 2022)
14-70373031-A-G		not specified	Uncertain significance (Aug 21, 2023)
14-70375717-G-A		not specified	Uncertain significance (Aug 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX16	protein_coding	protein_coding	ENST00000389912	4	34651

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000187	0.278	125703	0	42	125745	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.254	48	53.2	0.902	0.00000265	689
Missense in Polyphen		12	19.161	0.62627		263
Synonymous	-0.455	20	17.6	1.14	8.45e-7	193
Loss of Function	-0.0959	7	6.73	1.04	4.25e-7	77

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000248	0.000245
Ashkenazi Jewish	0.000109	0.0000992
East Asian	0.000169	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000253	0.000246
Middle Eastern	0.000169	0.000163
South Asian	0.0000997	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase (PubMed:29355485, PubMed:29381136). Promotes the insertion of copper into the active site of cytochrome c oxidase subunit II (MT-CO2/COX2) (PubMed:29355485, PubMed:29381136). Interacts specifically with newly synthesized MT-CO2/COX and its copper center-forming metallochaperones SCO1, SCO2 and COA6 (PubMed:29381136). Probably facilitates MT-CO2/COX2 association with the MITRAC assembly intermediate containing MT-CO1/COX1, thereby participating in merging the MT-CO1/COX1 and MT-CO2/COX2 assembly lines (PubMed:29381136). {ECO:0000269|PubMed:29355485, ECO:0000269|PubMed:29381136}.
• 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

• loftool: 0.489
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.173
• hipred: N
• hipred_score: 0.231
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.603

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cox16

Gene ontology

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