COX4I1

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

Basic information

Region (hg38): 16:85798632-85807068

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 4 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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex IV deficiency, nuclear type 16	AR	Biochemical	Treatment with coenzyme Q has been described as resulting in mild clinical improvement	Biochemical; Craniofacial; Musculoskeletal; Neurologic	28766551; 31290619

ClinVar

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

• Inborn genetic diseases (10 variants)
• not provided (4 variants)
• Mitochondrial complex 4 deficiency, nuclear type 16 (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.

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	1	2
missense			11	1		12
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	1

Variants in COX4I1

This is a list of pathogenic ClinVar variants found in the COX4I1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-85799139-G-A		not specified	Uncertain significance (Oct 26, 2022)
16-85799141-G-A		not specified	Uncertain significance (Dec 19, 2023)
16-85799157-G-A		not specified	Uncertain significance (Aug 13, 2021)
16-85799187-G-A		not specified	Uncertain significance (Mar 07, 2024)
16-85801212-G-A		COX4I1-related disorder	Benign (Oct 16, 2019)
16-85801230-C-G		not specified	Uncertain significance (Nov 18, 2022)
16-85801248-A-G		not specified	Uncertain significance (Sep 26, 2023)
16-85801270-G-A		not specified	Uncertain significance (Feb 23, 2023)
16-85804985-G-A			Likely benign (Nov 01, 2022)
16-85804987-C-T		not specified	Uncertain significance (Jun 02, 2023)
16-85805003-C-T		not specified	Uncertain significance (Jan 04, 2022)
16-85805022-G-A		COX4I1-related disorder	Benign (Dec 11, 2023)
16-85805041-A-G		not specified	Uncertain significance (Mar 06, 2023)
16-85805091-T-C		Mitochondrial complex 4 deficiency, nuclear type 16 • COX4I1-related disorder	Benign/Likely benign (Feb 15, 2022)
16-85805094-G-C		not specified	Uncertain significance (Jun 29, 2023)
16-85805103-G-C			Uncertain significance (Oct 01, 2023)
16-85805734-G-A		COX4I1-related disorder	Likely benign (Dec 30, 2020)
16-85805794-GA-TT		Mitochondrial complex IV deficiency, nuclear type 1	Pathogenic (Apr 07, 2020)
16-85806743-G-A		not specified	Uncertain significance (Dec 13, 2022)
16-85806792-A-G		not specified	Uncertain significance (Feb 06, 2023)
16-85806818-C-A		Mitochondrial complex 4 deficiency, nuclear type 16	Pathogenic (Oct 23, 2020)
16-85806818-C-T		not specified	Uncertain significance (Jan 22, 2024)
16-85806851-G-A		not specified	Uncertain significance (Aug 05, 2023)
16-85806860-G-A		not specified	Uncertain significance (Jun 29, 2023)
16-85806868-G-A		COX4I1-related disorder	Benign (Jul 23, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX4I1	protein_coding	protein_coding	ENST00000562336	4	8412

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.394	0.597	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.174	112	107	1.05	0.00000641	1131
Missense in Polyphen		26	35.416	0.73414		384
Synonymous	-0.539	47	42.5	1.11	0.00000312	291
Loss of Function	2.21	2	9.26	0.216	5.76e-7	92

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
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.
• 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

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

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