UCP3

uncoupling protein 3, the group of Solute carrier family 25

Basic information

Region (hg38): 11:74000277-74009085

Links

ENSG00000175564 ∙ NCBI:7352 ∙ OMIM:602044 ∙ HGNC:12519 ∙ Uniprot:P55916 ∙ 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 UCP3 gene.

• UCP3-related_disorder (149 variants)
• not_provided (60 variants)
• not_specified (56 variants)
• Obesity (10 variants)
• Inherited_obesity (6 variants)
• Obesity,_severe,_and_type_II_diabetes (3 variants)
• Morbid_obesity (1 variants)
• UCP3_POLYMORPHISM_G/A (1 variants)
• UCP3_POLYMORPHISM,_EXON_6_SPLICE_DONOR_JUNCTION (1 variants)
• Short-rib_thoracic_dysplasia_13_with_or_without_polydactyly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UCP3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003356.4. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	47	1	49
missense			117	6	2	125
nonsense				1		1
start loss			1			1
frameshift			6			6
splice donor/acceptor (+/-2bp)			2		1	3
Total	0	0	127	54	4

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UCP3	protein_coding	protein_coding	ENST00000314032	6	9155

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.55e-10	0.0471	124047	54	1647	125748	0.00679

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.306	218	206	1.06	0.0000130	2015
Missense in Polyphen		79	75.707	1.0435		672
Synonymous	-1.29	101	85.8	1.18	0.00000595	655
Loss of Function	-0.407	13	11.5	1.13	5.73e-7	140

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0964	0.0950
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000553	0.000536
Middle Eastern	0.000109	0.000109
South Asian	0.000880	0.000850
Other	0.00519	0.00473

dbNSFP

Source: dbNSFP

• Function: FUNCTION: UCP are mitochondrial transporter proteins that create proton leaks across the inner mitochondrial membrane, thus uncoupling oxidative phosphorylation. As a result, energy is dissipated in the form of heat. May play a role in the modulation of tissue respiratory control. Participates in thermogenesis and energy balance.
• Pathway: Electron Transport Chain;Energy Metabolism;Exercise-induced Circadian Regulation;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: 0.329

Intolerance Scores

• loftool: 0.358
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.61

Haploinsufficiency Scores

• pHI: 0.0893
• hipred: N
• hipred_score: 0.219
• ghis: 0.543

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.979

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ucp3
• Phenotype: 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)

Gene ontology

• Biological process: response to superoxide;response to hypoxia;lipid metabolic process;fatty acid metabolic process;aging;response to nutrient;respiratory gaseous exchange;response to cold;response to activity;response to insulin;cellular response to hormone stimulus;response to glucocorticoid;proton transmembrane transport;mitochondrial transmembrane transport;adaptive thermogenesis
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane
• Molecular function: transporter activity;protein binding;oxidative phosphorylation uncoupler activity