GeneBe

COX4I1

cytochrome c oxidase subunit 4I1, the group of Mitochondrial complex IV: cytochrome c oxidase subunits

Basic information

Region (hg38): 16:85798633-85807068

Previous symbols: [ "COX4" ]

Links

ENSG00000131143 ∙ NCBI:1327 ∙ OMIM:123864 ∙ HGNC:2265 ∙ Uniprot:P13073 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • mitochondrial complex IV deficiency, nuclear type 16 (Limited), mode of inheritance: AR
  • cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
  • Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Mitochondrial complex IV deficiency, nuclear type 16ARBiochemicalTreatment with coenzyme Q has been described as resulting in mild clinical improvementBiochemical; Craniofacial; Musculoskeletal; Neurologic28766551; 31290619

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX4I1 gene.

  • not_specified (25 variants)
  • not_provided (4 variants)
  • COX4I1-related_disorder (4 variants)
  • Mitochondrial_complex_IV_deficiency,_nuclear_type_16 (3 variants)
  • Mitochondrial_complex_IV_deficiency,_nuclear_type_1 (1 variants)
  • Mitochondrial_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX4I1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001861.6. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
2
clinvar
 5
missense
2
clinvar
25
clinvar
2
clinvar
 29
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total 2 0 26 4 2
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
COX4I1protein_codingprotein_codingENST00000562336 48412
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.3940.597125742061257480.0000239
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.1741121071.050.000006411131
Missense in Polyphen2635.4160.73414384
Synonymous-0.5394742.51.110.00000312291
Loss of Function2.2129.260.2165.76e-792

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00005780.0000578
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00001760.0000176
Middle Eastern0.00005440.0000544
South Asian0.00003270.0000327
Other0.000.00

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.;
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
0.189

Intolerance Scores

loftool
0.602
rvis_EVS
-0.07
rvis_percentile_EVS
48.12

Haploinsufficiency Scores

pHI
0.129
hipred
Y
hipred_score
0.825
ghis
0.508

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
K
gene_indispensability_pred
E
gene_indispensability_score
0.994

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Cox4i1
Phenotype
integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype;

Gene ontology

Biological process
generation of precursor metabolites and energy;mitochondrial electron transport, cytochrome c to oxygen;response to nutrient;proton transmembrane transport
Cellular component
nucleus;mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex IV;membrane
Molecular function
cytochrome-c oxidase activity;protein binding