UCP2

uncoupling protein 2, the group of Solute carrier family 25

Basic information

Region (hg38): 11:73974061-73982843

Previous symbols: [ "BMIQ4" ]

Links

ENSG00000175567 ∙ NCBI:7351 ∙ OMIM:601693 ∙ HGNC:12518 ∙ Uniprot:P55851 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperinsulinism due to UCP2 deficiency (Supportive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UCP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UCP2 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	4	1	6
missense			39	5	1	45
nonsense			3			3
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1			1
non coding			4	3	3	10
Total	0	0	48	12	5

Variants in UCP2

This is a list of pathogenic ClinVar variants found in the UCP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-73975005-G-C		not specified	Uncertain significance (Jun 01, 2020)
11-73975073-G-A		not specified	Likely benign (Aug 06, 2022)
11-73975084-C-T		not specified	Uncertain significance (Jul 05, 2022)
11-73975123-T-C		not specified	Uncertain significance (Aug 05, 2022)
11-73975131-A-C			Likely benign (Apr 16, 2018)
11-73975136-T-A			Benign (Oct 04, 2022)
11-73975137-C-T			Likely benign (Sep 15, 2022)
11-73975488-C-A			Uncertain significance (Aug 07, 2023)
11-73975498-A-G		not specified	Uncertain significance (Jul 12, 2023)
11-73975500-A-G		not specified	Uncertain significance (Mar 01, 2023)
11-73975503-G-C		not specified • Body mass index quantitative trait locus 4	Likely benign (Jun 21, 2023)
11-73975506-C-T		not specified	Uncertain significance (Dec 19, 2022)
11-73975507-G-A		not specified • Body mass index quantitative trait locus 4	Uncertain significance (Mar 22, 2022)
11-73975512-C-A		not specified	Uncertain significance (Dec 14, 2023)
11-73975556-G-A		not specified • Body mass index quantitative trait locus 4	Benign/Likely benign (Nov 29, 2023)
11-73975593-A-T		not specified	Uncertain significance (Mar 13, 2023)
11-73975618-C-G		not specified	Uncertain significance (Nov 07, 2022)
11-73975621-T-C		Maturity-onset diabetes of the young type 2	Likely benign (-)
11-73975680-G-C			Uncertain significance (Dec 09, 2023)
11-73975814-ACTT-A			Benign (Jun 19, 2021)
11-73976623-G-A			Benign (Oct 09, 2023)
11-73976652-T-C		not specified	Uncertain significance (Jan 10, 2022)
11-73976680-G-A		not specified	Uncertain significance (Jan 30, 2023)
11-73976693-C-T		not specified	Benign (Jan 22, 2024)
11-73976706-T-C		not specified	Uncertain significance (Feb 13, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UCP2	protein_coding	protein_coding	ENST00000310473	6	8641

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.55e-10	0.0596	125629	1	118	125748	0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00251	197	197	1.00	0.0000124	1985
Missense in Polyphen		60	66.092	0.90783		639
Synonymous	0.960	64	74.5	0.859	0.00000442	677
Loss of Function	-0.0391	15	14.8	1.01	0.00000109	132

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000774	0.000774
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.000592	0.000580
Middle Eastern	0.000435	0.000435
South Asian	0.000784	0.000752
Other	0.000330	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: UCP are mitochondrial transporter proteins that create proton leaks across the inner mitochondrial membrane, thus uncoupling oxidative phosphorylation from ATP synthesis. As a result, energy is dissipated in the form of heat.
• Pathway: Electron Transport Chain;Energy Metabolism;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;The fatty acid cycling model;The proton buffering model;Mitochondrial Uncoupling Proteins;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.618

Intolerance Scores

• loftool: 0.609
• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.91

Haploinsufficiency Scores

• pHI: 0.168
• hipred: Y
• hipred_score: 0.612
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.573

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ucp2
• Phenotype: homeostasis/metabolism phenotype; cellular 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system 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); hematopoietic system phenotype; 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)

Gene ontology

• Biological process: response to superoxide;response to hypoxia;female pregnancy;aging;response to cold;positive regulation of cell death;cellular response to insulin stimulus;cellular response to amino acid starvation;negative regulation of apoptotic process;regulation of mitochondrial membrane potential;negative regulation of insulin secretion involved in cellular response to glucose stimulus;response to fatty acid;cellular response to glucose stimulus;liver regeneration;positive regulation of cold-induced thermogenesis;proton transmembrane transport;mitochondrial transmembrane transport;adaptive thermogenesis
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane
• Molecular function: protein binding;oxidative phosphorylation uncoupler activity