COX4I2

cytochrome c oxidase subunit 4I2, the group of Mitochondrial complex IV: cytochrome c oxidase subunits

Basic information

Region (hg38): 20:31637912-31645006

Previous symbols: [ "COX4L2" ]

Links

ENSG00000131055 ∙ NCBI:84701 ∙ OMIM:607976 ∙ HGNC:16232 ∙ Uniprot:Q96KJ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pancreatic insufficiency-anemia-hyperostosis syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis	AR	Gastrointestinal	Pancreatic enzyme supplementation has been reported to improve psychomotor development, as well as direct sequelae such as steatorrhea	Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	19268275

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COX4I2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COX4I2 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				10		10
missense			25	2	1	28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				4	11	15
Total	0	0	25	16	12

Variants in COX4I2

This is a list of pathogenic ClinVar variants found in the COX4I2 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-31637923-G-A			Likely benign (Apr 26, 2018)
20-31637989-C-T			Benign (Jun 23, 2018)
20-31638740-C-G			Benign (Jun 18, 2021)
20-31638887-G-A			Benign (Jun 23, 2018)
20-31638961-G-C			Benign (Jun 23, 2018)
20-31639012-C-T			Likely benign (Mar 01, 2024)
20-31639045-G-A		Pancreatic insufficiency-anemia-hyperostosis syndrome	Uncertain significance (Dec 07, 2021)
20-31639092-A-C		not specified	Uncertain significance (Dec 13, 2021)
20-31639105-A-ACCTGGACT			Likely benign (Aug 13, 2021)
20-31639114-C-T			Likely benign (Jan 09, 2023)
20-31639836-A-G			Benign (Jun 23, 2018)
20-31639921-TTG-T		Pancreatic insufficiency-anemia-hyperostosis syndrome	Conflicting classifications of pathogenicity (Jan 09, 2024)
20-31639923-G-T			Benign (Jan 25, 2024)
20-31639936-G-A			Uncertain significance (Dec 18, 2023)
20-31639938-G-C		Pancreatic insufficiency-anemia-hyperostosis syndrome	Benign/Likely benign (Jan 25, 2024)
20-31639941-G-A		not specified	Uncertain significance (Apr 20, 2023)
20-31639941-G-C		not specified	Uncertain significance (Dec 14, 2022)
20-31639964-C-T		not specified • COX4I2-related disorder	Likely benign (Aug 17, 2023)
20-31639968-T-C		not specified	Uncertain significance (Dec 01, 2022)
20-31640004-C-T			Uncertain significance (Dec 11, 2023)
20-31640005-C-A			Uncertain significance (Mar 08, 2023)
20-31640024-C-T		COX4I2-related disorder	Likely benign (Jun 26, 2019)
20-31640025-G-C		Pancreatic insufficiency-anemia-hyperostosis syndrome	Conflicting classifications of pathogenicity (Dec 15, 2023)
20-31640081-C-T			Likely benign (Aug 04, 2023)
20-31640084-C-T		not specified	Likely benign (Dec 27, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COX4I2	protein_coding	protein_coding	ENST00000376075	4	7119

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000140	0.665	125678	0	69	125747	0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0669	105	103	1.02	0.00000681	1106
Missense in Polyphen		42	38.128	1.1016		444
Synonymous	-0.405	41	37.8	1.08	0.00000237	312
Loss of Function	0.824	7	9.78	0.716	5.21e-7	104

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000474	0.000472
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00143	0.00143
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000218	0.000217
South Asian	0.0000670	0.0000653
Other	0.000815	0.000815

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) (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.807
• rvis_EVS: 0.86
• rvis_percentile_EVS: 88.62

Haploinsufficiency Scores

• pHI: 0.0899
• hipred: N
• hipred_score: 0.244

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cox4i2
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype

Gene ontology

• Biological process: generation of precursor metabolites and energy;mitochondrial electron transport, cytochrome c to oxygen;cellular respiration;oxidation-reduction process;cellular response to hypoxia;proton transmembrane transport
• Cellular component: mitochondrial respiratory chain complex IV
• Molecular function: cytochrome-c oxidase activity