LongevityMap Gene

Gene details

HGNC symbol
UCP3 
Aliases
SLC25A9 
Common name
uncoupling protein 3 
Description
Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. The different UCPs have tissue-specific expression; this gene is primarily expressed in skeletal muscle. This gene's protein product is postulated to protect mitochondria against lipid-induced oxidative stress. Expression levels of this gene increase when fatty acid supplies to mitochondria exceed their oxidation capacity and the protein enables the export of fatty acids from mitochondria. UCPs contain the three solcar protein domains typically found in MACPs. Two splice variants have been found for this gene.[provided by RefSeq, Nov 2008]
Cytogenetic Location
11q13.4
UCSC Genome Browser
View 11q13.4 on the UCSC genome browser
OMIM
602044
Ensembl
ENSG00000175564
UniProt/Swiss-Prot
A0A0S2Z4G5_HUMAN
Entrez Gene
7352
UniGene
101337
1000 Genomes
1000 Genomes

Homologs in model organisms

Mus musculus
Ucp3
Rattus norvegicus
Ucp3

In other databases

GenAge human genes
  • This gene is present as UCP3

Studies (4)

Significant/Non-significant: 3/1

Study 1

Longevity Association
Significant
Population
Danish
Study Design
Two cohorts of middle aged (N = 708; 356 males and 352 females) and oldest old individuals (N = 908; 265 males and 643 females) were genotyped for UCP3 polymorphisms, hand grip performance and survival at old age
Conclusions
The study showed that after 10 years from the start of the project, a significant effect on survival chances was observed for rs11235972 and rs3781907. Carriers of the A allele at rs11235972 and carriers of the G allele at rs3781907 showed a reduced survival chance. Interestingly, the rs11235972-A variation was also associated with a decreased in hand grip performance in this cohort. The rs3781907 variant displayed only a borderline association with hand grip performance.
Indentifier
rs11235972
Reference

    Study 2

    Longevity Association
    Significant
    Population
    Italian (Southern)
    Study Design
    A total of 598 subjects (293 men and 305 women, age range 64–105 years; mean ages 82.74 and 85.23 years, respectively) were analyzed for genetic variability in Uncoupling Proteins (UCPs). The set was divided into two age classes. The separation threshold for these two classes was 88 years for men and 91 years for women.
    Conclusions
    The genetic variability of UCP2, UCP3 and UCP4 affects the individual’s chances of surviving up to a very old age. Using the minor allele for each SNP as reference and after adjusting for BMI and sex, the dominant model for the rs660339 (UCP2) and the rs1800849 (UCP3) resulted to be significantly associated with the longevity phenotype (p = 0.001 in both cases), while the recessive model was the most likely for SNPs rs15763 (UCP3), rs9472817 (UCP4) and rs2235800 (UCP5) (p < 0.05). After adjusting for multiple testing, all the previous associations remained statistically significant, except those for rs2235800 of the UCP5 gene (p= 0.058).
    Indentifier
    rs1800849
    Reference

      Study 3

      Longevity Association
      Significant
      Population
      Danish
      Study Design
      38 genes (311 SNPs) belonging to pro-antioxidant pathways were investigated for the association with physical and cognitive performances in a Cohort of 1089 Danish nonagenarians. For each gene analyzed in the pro-antioxidant pathway, the influence on longitudinal survival was tested.
      Conclusions
      NDUFS1, TXNRD1, SOD2 and UCP3 were found significantly associated with lifespan in the female cohort. This result is consistent with their associations with physical functioning and suggests that the variability of genes in the pro-antioxidant pathway can influence survival through an effect on physical performances, at least in the analyzed cohort.
      Indentifier
      rs11235972
      Reference

        Study 4

        Longevity Association
        Non-significant
        Population
        Danish
        Study Design
        Two cohorts of middle aged (N = 708; 356 males and 352 females) and oldest old individuals (N = 908; 265 males and 643 females) were genotyped for UCP3 polymorphisms, hand grip performance and survival at old age
        Conclusions
        The study showed that after 10 years from the start of the project, a significant effect on survival chances was observed for rs11235972 and rs3781907, but not for rs1685354 or rs647126.
        Indentifier
        rs1685354
        Reference