COX6A1

cytochrome c oxidase subunit 6A1, the group of Mitochondrial complex IV: cytochrome c oxidase subunits

Basic information

Region (hg38): 12:120438090-120440737

Previous symbols: [ "COX6A" ]

Links

ENSG00000111775 ∙ NCBI:1337 ∙ OMIM:602072 ∙ HGNC:2277 ∙ Uniprot:P12074 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease recessive intermediate D (Limited), mode of inheritance: AR
• Charcot-Marie-Tooth disease recessive intermediate D (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease recessive intermediate D (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, recessive intermediate D	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	Musculoskeletal; Neurologic	25152455

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX6A1 gene.

• not provided (1 variants)
• Charcot-Marie-Tooth disease recessive intermediate D (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX6A1 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				25		25
missense			38	1		39
nonsense			1			1
start loss			2			2
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region	1			3	1	5
non coding				10	4	14
Total	0	0	45	36	4

Highest pathogenic variant AF is 0.0000854

Variants in COX6A1

This is a list of pathogenic ClinVar variants found in the COX6A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-120438129-G-A			Uncertain significance (Sep 26, 2021)
12-120438129-G-T			Uncertain significance (Mar 31, 2022)
12-120438130-G-T			Uncertain significance (May 15, 2022)
12-120438131-C-T			Uncertain significance (Aug 25, 2023)
12-120438132-G-A			Likely benign (Jun 20, 2023)
12-120438134-T-C			Uncertain significance (Aug 26, 2021)
12-120438135-A-G			Likely benign (Dec 27, 2022)
12-120438136-G-T		not specified	Uncertain significance (May 18, 2022)
12-120438137-T-G			Uncertain significance (Aug 13, 2022)
12-120438140-G-T			Uncertain significance (Aug 20, 2021)
12-120438145-T-A			Uncertain significance (Aug 30, 2024)
12-120438146-C-G		not specified	Uncertain significance (Aug 15, 2023)
12-120438146-C-T		not specified	Uncertain significance (Nov 15, 2023)
12-120438153-T-G			Likely benign (Nov 07, 2022)
12-120438155-C-G		not specified	Uncertain significance (Jun 26, 2024)
12-120438158-G-C			Uncertain significance (Sep 04, 2021)
12-120438162-G-C			Likely benign (Oct 18, 2023)
12-120438166-G-A		not specified	Uncertain significance (Dec 05, 2022)
12-120438170-G-A			Uncertain significance (May 12, 2022)
12-120438173-C-T			Uncertain significance (Sep 24, 2021)
12-120438174-C-T			Likely benign (Mar 13, 2022)
12-120438176-G-A			Uncertain significance (Aug 03, 2022)
12-120438190-C-T			Uncertain significance (Apr 28, 2022)
12-120438196-A-G		COX6A1-related disorder	Likely benign (Jun 06, 2023)
12-120438207-C-A			Likely benign (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX6A1	protein_coding	protein_coding	ENST00000229379	3	2653

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00231	0.548	125725	0	22	125747	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.42	99	66.5	1.49	0.00000312	696
Missense in Polyphen		22	16.847	1.3059		220
Synonymous	-1.93	41	28.0	1.46	0.00000139	233
Loss of Function	0.247	4	4.57	0.875	1.96e-7	48

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.0000472	0.0000462
European (Non-Finnish)	0.000143	0.000141
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000982	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
• Disease: DISEASE: Charcot-Marie-Tooth disease, recessive, intermediate type, D (CMTRID) [MIM:616039]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. {ECO:0000269|PubMed:25152455}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cardiac muscle contraction - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Electron Transport Chain;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)

Recessive Scores

• pRec: 0.0899

Intolerance Scores

• loftool: 0.356
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.453
• hipred: N
• hipred_score: 0.166
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.575

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cox6a1
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; muscle phenotype

Gene ontology

• Biological process: generation of precursor metabolites and energy;mitochondrial electron transport, cytochrome c to oxygen;aerobic respiration;regulation of catalytic activity;proton transmembrane transport
• Cellular component: mitochondrion;mitochondrial inner membrane
• Molecular function: cytochrome-c oxidase activity;enzyme regulator activity