UCP1 Gene: Uncoupling Protein 1 (Thermogenin) - Function, Disease Associations, and Expression
Comprehensive biomedical resource on UCP1, including gene structure, protein function, tissue expression, mutations, and clinical significance.
Gene Information Card
| Symbol | UCP1 |
|---|---|
| Full Name | Uncoupling Protein 1 (Mitochondrial, Proton Carrier) |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.1 (GRCh38) |
| NCBI Gene ID | 7350 ncbi.nlm.nih.gov/gene/7350 |
| Ensembl ID | ENSG00000109424 |
| UniProt ID | P25874 |
| OMIM ID | 113730 |
| HGNC ID | 12518 |
| Aliases | UCP, SLC25A7, UCP1 (thermogenin) |
Description
The UCP1 gene encodes uncoupling protein 1 (UCP1), also known as thermogenin, a mitochondrial carrier protein predominantly expressed in brown adipose tissue (BAT). UCP1 dissipates the proton gradient across the inner mitochondrial membrane, uncoupling oxidative phosphorylation from ATP synthesis and generating heat (non-shivering thermogenesis). This process is critical for thermoregulation in cold environments and energy metabolism. UCP1 is a key regulator of energy expenditure and has been implicated in obesity, type 2 diabetes, and metabolic disorders. Its expression is induced by cold exposure and β-adrenergic signaling, and it is a target for anti-obesity therapies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | Reduced UCP1 expression or function in brown adipose tissue leads to decreased thermogenesis and energy expenditure, contributing to positive energy balance and obesity. | Association studies and animal models (e.g., UCP1 knockout mice) show increased susceptibility to diet-induced obesity; human studies link UCP1 polymorphisms (e.g., A-3826G) with obesity risk (ClinVar, OMIM). |
| Type 2 Diabetes | UCP1-mediated thermogenesis influences insulin sensitivity and glucose metabolism; reduced UCP1 activity may impair metabolic health. | Genetic variants in UCP1 are associated with type 2 diabetes and insulin resistance in some populations (OMIM, ClinVar). |
| Hyperthermia / Hypothermia | Dysregulation of UCP1 activity can impair thermoregulation, leading to abnormal body temperature responses. | UCP1 knockout mice exhibit cold intolerance; human mutations affecting UCP1 function are rare but may cause thermoregulatory defects (OMIM). |
| Cancer (potential) | UCP1 expression in certain tumors may alter mitochondrial metabolism, affecting tumor growth or response to therapy. | COSMIC lists UCP1 mutations in various cancers, but functional significance is not fully established; research ongoing. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brown Adipose Tissue | High (nTPM ~ 500-1000) | High |
| Subcutaneous Adipose Tissue | Low (nTPM < 10) | Low |
| Visceral Adipose Tissue | Low (nTPM < 5) | Low |
| Skeletal Muscle | Very low (nTPM < 1) | Not detected |
| Heart | Very low (nTPM < 1) | Not detected |
| Liver | Very low (nTPM < 1) | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Brown Adipocytes (differentiated) | High (nTPM > 100) | Primary brown adipocytes show high UCP1 expression upon differentiation. |
| Beige/Brite Adipocytes | Moderate (nTPM 10-50) | Inducible by cold or β-adrenergic stimulation. |
| White Adipocytes | Low (nTPM < 5) | Minimal expression under basal conditions. |
| HeLa (cervical cancer) | Not detected | No significant expression. |
| HepG2 (liver cancer) | Not detected | No significant expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| A-3826G (rs1800592) | SNP (promoter) | ~30% in some populations | Associated with reduced UCP1 expression and increased obesity risk. |
| Met229Leu (rs45539933) | Missense | Rare (<1%) | May affect protein stability or function; clinical significance uncertain. |
| Ala64Val (rs45565935) | Missense | Rare (<1%) | Potential impact on mitochondrial targeting; not well characterized. |
| COSMIC mutations (various) | Somatic | Low frequency in cancers | Found in melanoma, lung, and colorectal cancers; functional impact unknown. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in UCP1 (e.g., complete knockout or severe missense) impair thermogenesis, leading to cold intolerance and increased susceptibility to obesity in animal models. In humans, such mutations are rare and may cause metabolic dysfunction.
Gain of Function (GOF)
Gain-of-function mutations that increase UCP1 activity could enhance energy expenditure and protect against obesity, but such variants are not well-documented. Overexpression of UCP1 in mice increases thermogenesis and resistance to diet-induced obesity.
Dominant Negative (DN)
Dominant-negative effects are not clearly established for UCP1. Since UCP1 functions as a dimer, some missense mutations might interfere with dimerization, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • Mitochondrial inner membrane | • Uncoupling protein activity |
| • Proton transmembrane transporter activity | • Mitochondrial transport |
| • Thermogenesis | • Cellular response to cold |
| • Oxidative phosphorylation uncoupling | • Fatty acid binding |
Pathways
• Thermogenesis (Reactome: R-HSA-163685)
• Brown fat cell differentiation (KEGG: hsa04931)
• PPAR signaling pathway (KEGG: hsa03320)
• cAMP signaling pathway (KEGG: hsa04024)
• AMPK signaling pathway (KEGG: hsa04152)
Protein Summary
UCP1 is a 307-amino acid protein (32 kDa) localized to the inner mitochondrial membrane. It belongs to the mitochondrial carrier family (SLC25) and functions as a dimer. UCP1 transports protons across the inner membrane, bypassing ATP synthase, thereby dissipating the proton gradient as heat. Its activity is activated by free fatty acids and inhibited by purine nucleotides (e.g., GDP). UCP1 is essential for non-shivering thermogenesis in brown adipose tissue. The protein has six transmembrane domains and a nucleotide-binding domain. Post-translational modifications include phosphorylation, which may regulate activity. UCP1 expression is controlled by transcription factors such as PPARγ, PGC-1α, and PRDM16.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UCP1 Knockout HEK293 Cell Line | EDJ-KQ1453 | Human | 7350 | Details Get a Quote |
| UCP1 Knockout HeLa Cell Line | EDJ-KQ54721 | Human | 7350 | Details Get a Quote |
| UCP1 Knockout A-549 Cell Line | EDJ-KQ63212 | Human | 7350 | Details Get a Quote |
| UCP1 Knockout HCT 116 Cell Line | EDJ-KQ71678 | Human | 7350 | Details Get a Quote |
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