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

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

not_provided (40 variants)
Mitochondrial_complex_IV_deficiency,_nuclear_type_7 (12 variants)
Inborn_genetic_diseases (10 variants)
Mitochondrial_complex_IV_deficiency,_nuclear_type_1 (6 variants)
not_specified (4 variants)

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. These statistics are base on transcript: NM_000001863.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				10 clinvar		10
missense		2 clinvar	17 clinvar	2 clinvar		21
nonsense						0
start loss			1			1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	2	18	12	0

Highest pathogenic variant AF is 0.00000547264

Loading clinvar variants...

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
Phenotype

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