COX6B1

cytochrome c oxidase subunit 6B1, the group of Mitochondrial complex IV: cytochrome c oxidase subunits

Basic information

Region (hg38): 19:35648323-35658782

Previous symbols: [ "COX6B" ]

Links

ENSG00000126267 ∙ NCBI:1340 ∙ OMIM:124089 ∙ HGNC:2280 ∙ Uniprot:P14854 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cytochrome-c oxidase deficiency disease (Definitive), mode of inheritance: AR
• mitochondrial complex 4 deficiency, nuclear type 7 (Strong), mode of inheritance: AR
• cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex IV deficiency, nuclear type 7	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; Musculoskeletal; Neurologic; Ophthalmologic	18499082

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX6B1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX6B1 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			1	7	1	9
missense		1	14			15
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			2	11	4	17
Total	0	1	18	18	5

Variants in COX6B1

This is a list of pathogenic ClinVar variants found in the COX6B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-35648368-A-G		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
19-35648373-G-A		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
19-35648379-C-G		not specified	Likely benign (Mar 21, 2017)
19-35651137-A-G			Likely benign (Aug 03, 2018)
19-35651225-G-A		not specified • Mitochondrial complex 4 deficiency, nuclear type 7	Likely benign (May 11, 2022)
19-35651244-A-G			Uncertain significance (Jun 01, 2022)
19-35651249-G-A			Likely benign (Dec 14, 2017)
19-35651256-A-C		Inborn genetic diseases	Uncertain significance (Jul 17, 2022)
19-35651256-A-G			Uncertain significance (Oct 22, 2023)
19-35651261-G-C		Mitochondrial complex 4 deficiency, nuclear type 7	Uncertain significance (Mar 21, 2024)
19-35651285-C-T		not specified • Mitochondrial complex IV deficiency, nuclear type 1 • COX6B1-related disorder	Benign (Jan 31, 2024)
19-35651301-C-T		Mitochondrial complex IV deficiency, nuclear type 1	Likely pathogenic (Nov 05, 2019)
19-35651302-G-A		Mitochondrial complex IV deficiency, nuclear type 1 • Mitochondrial complex 4 deficiency, nuclear type 7	Likely pathogenic (May 31, 2024)
19-35651303-C-T			Likely benign (Feb 20, 2022)
19-35651334-T-C			Uncertain significance (May 27, 2022)
19-35651345-C-T		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
19-35651360-C-T			Likely benign (Jun 27, 2022)
19-35651362-T-C			Likely benign (Nov 20, 2023)
19-35651363-T-C			Likely benign (Oct 02, 2020)
19-35651394-G-A			Benign (Jun 16, 2018)
19-35654377-T-C			Benign (Jun 26, 2018)
19-35654507-CA-C			Likely benign (May 05, 2020)
19-35654526-G-A			Benign (Jul 09, 2018)
19-35654555-A-G		not specified • Mitochondrial complex 4 deficiency, nuclear type 7	Benign/Likely benign (Jan 18, 2024)
19-35654590-G-A			Conflicting classifications of pathogenicity (Apr 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX6B1	protein_coding	protein_coding	ENST00000246554	3	10639

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.121	0.788	125746	0	2	125748	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.748	40	55.7	0.718	0.00000370	576
Missense in Polyphen		4	13.266	0.30152		183
Synonymous	0.756	16	20.3	0.787	0.00000142	140
Loss of Function	1.34	2	5.35	0.374	2.30e-7	56

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000176	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Connects the two COX monomers into the physiological dimeric form. {ECO:0000250}.
• Disease: DISEASE: Mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome. {ECO:0000269|PubMed:18499082}. 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: 0.142

Intolerance Scores

• loftool: 0.433
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• pHI: 0.113
• hipred: Y
• hipred_score: 0.709
• ghis: 0.528

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.855

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cox6b1

Gene ontology

• Biological process: substantia nigra development;electron transport chain;proton transmembrane transport
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial intermembrane space;respiratory chain complex IV
• Molecular function: cytochrome-c oxidase activity;protein binding