UCP1

uncoupling protein 1, the group of Solute carrier family 25

Basic information

Region (hg38): 4:140559430-140568961

Previous symbols: [ "UCP" ]

Links

ENSG00000109424 ∙ NCBI:7350 ∙ OMIM:113730 ∙ HGNC:12517 ∙ Uniprot:P25874 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UCP1 gene.

• Inborn genetic diseases (14 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UCP1 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			14	1	2	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	0	14	2	5

Variants in UCP1

This is a list of pathogenic ClinVar variants found in the UCP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-140559973-C-T		not specified	Uncertain significance (Jul 13, 2021)
4-140562289-G-T		not specified	Uncertain significance (Feb 06, 2023)
4-140562307-G-A		not specified	Uncertain significance (Dec 16, 2022)
4-140562322-G-A			Benign (Jun 15, 2018)
4-140562326-C-T		not specified	Likely benign (Mar 16, 2022)
4-140562581-A-C			Benign (Nov 12, 2018)
4-140563152-C-T		not specified	Uncertain significance (Sep 17, 2021)
4-140563186-A-G			Likely benign (Dec 13, 2017)
4-140563339-C-T		not specified	Uncertain significance (Dec 19, 2023)
4-140563342-C-T		not specified	Uncertain significance (Apr 25, 2022)
4-140563380-G-A		not specified	Uncertain significance (Aug 14, 2023)
4-140563395-A-T		not specified	Uncertain significance (Nov 10, 2021)
4-140563446-G-C		not specified	Uncertain significance (Mar 07, 2024)
4-140563476-G-C		not specified	Uncertain significance (Jun 24, 2022)
4-140563479-G-A			Uncertain significance (Feb 15, 2023)
4-140563611-AT-A			Benign (Jun 19, 2021)
4-140567837-G-A			Benign (Jan 05, 2018)
4-140567842-A-C		not specified	Uncertain significance (Jun 29, 2023)
4-140567904-T-C		not specified	Uncertain significance (Dec 28, 2022)
4-140567934-C-G		not specified	Uncertain significance (Jun 29, 2022)
4-140567973-T-C		not specified	Uncertain significance (Dec 17, 2021)
4-140567977-C-A		not specified	Uncertain significance (Mar 07, 2024)
4-140568612-G-A			Benign (Mar 05, 2018)
4-140568647-T-C		not specified	Uncertain significance (Feb 28, 2024)
4-140568653-A-G		not specified	Uncertain significance (Jan 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UCP1	protein_coding	protein_coding	ENST00000262999	6	9372

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.69e-11	0.0164	125668	0	80	125748	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.222	165	173	0.952	0.00000932	1957
Missense in Polyphen		61	64.203	0.95011		776
Synonymous	-0.422	78	73.4	1.06	0.00000476	653
Loss of Function	-0.697	15	12.4	1.21	6.15e-7	150

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00126	0.00126
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.000217	0.000217
South Asian	0.00102	0.000915
Other	0.000341	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates to non-shivering adaptive thermogenesis to temperature and diet variations and more generally to the regulation of energy balance (By similarity). Functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane (PubMed:24196960). However, LCFAs remaining associated with the transporter via their hydrophobic tails, it results in an apparent transport of protons activated by LCFAs. Thereby, dissipates the mitochondrial proton gradient and converts the energy of substrate oxydation into heat instead of ATP. Regulates the production of reactive oxygen species/ROS by mitochondria (By similarity). {ECO:0000250|UniProtKB:P12242, ECO:0000269|PubMed:24196960}.
• Pathway: Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Electron Transport Chain;Adipogenesis;FTO Obesity Variant Mechanism;PPAR signaling pathway;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. (Consensus)

Recessive Scores

• pRec: 0.588

Intolerance Scores

• loftool: 0.644
• rvis_EVS: 0.2
• rvis_percentile_EVS: 67.19

Haploinsufficiency Scores

• pHI: 0.177
• hipred: N
• hipred_score: 0.275
• ghis: 0.405

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.654

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ucp1
• 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); cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: diet induced thermogenesis;regulation of transcription by RNA polymerase II;response to temperature stimulus;response to cold;response to nutrient levels;cellular response to hormone stimulus;cellular response to reactive oxygen species;brown fat cell differentiation;cellular response to fatty acid;positive regulation of cold-induced thermogenesis;proton transmembrane transport;regulation of reactive oxygen species biosynthetic process;mitochondrial transmembrane transport;adaptive thermogenesis
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane
• Molecular function: oxidative phosphorylation uncoupler activity;transmembrane transporter activity;purine ribonucleotide binding;long-chain fatty acid binding;cardiolipin binding