LongevityMap Gene

Gene details

HGNC symbol
TOMM40 
Aliases
TOM40; PEREC1; C19orf1; PER-EC1; D19S1177E 
Common name
translocase of outer mitochondrial membrane 40 
Description
The protein encoded by this gene is localized in the outer membrane of the mitochondria. It is the channel-forming subunit of the translocase of the mitochondrial outer membrane (TOM) complex that is essential for import of protein precursors into mitochondria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]
Cytogenetic Location
19q13.32
UCSC Genome Browser
View 19q13.32 on the UCSC genome browser
OMIM
608061
Ensembl
ENSG00000130204
UniProt/Swiss-Prot
TOM40_HUMAN
Entrez Gene
10452
UniGene
655909
1000 Genomes
1000 Genomes

Homologs in model organisms

Danio rerio
tomm40l
Mus musculus
Tomm40
Rattus norvegicus
Tomm40

Studies (7)

Significant/Non-significant: 7/0

Study 1

Longevity Association
Significant
Population
American (Caucasian)
Study Design
Genome-wide association study in 801 centenarians and 914 healthy controls
Conclusions
rs2075650, in a TOMM40 intron but a proxy of SNPs defining APOE alleles, was highly significant for exceptional longevity
Indentifier
rs2075650
Reference

    Study 2

    Longevity Association
    Significant
    Population
    Polish
    Study Design
    The impact of TOMM40 poly-T tracts on late-onset Alzheimer's disease (LOAD) incidence, age of onset, and longevity were investigated in of 414 LOAD patients (64.3% female, 74.64 ± 5.60 y), 173 centenarians (83.81% females, 98.45 ± 1.72, 105 with LOAD) and 305 neurologically healthy individuals (72.8% females, 70.36 ± 5.88 y)
    Conclusions
    TOMM40 allelic variants were significantly associated with LOAD risk. L allele, as well as genotypes (S/L, V/L) and haplotypes (L-E3, L-E4) comprising L, significantly reduce the likelihood of living up to 100 years ( P < 0.001).
    Indentifier
    rs10524523
    Reference

      Study 3

      Longevity Association
      Significant
      Population
      Danish, American
      Study Design
      Generalized estimating equations were used to compare the likelihood of carrying risk alleles in offspring (n = 2307) and spouse controls (n = 764) of long-lived families, adjusting for age, sex, level of education, and family membership
      Conclusions
      The likelihood of carrying an APOE ɛ4 allele or a G allele in rs2075650 was lower (odds ratio [OR], 0.75; p = 0.005 and OR, 0.70; p = 0.002) and the likelihood of carrying an APOE ɛ2 allele was higher (OR, 1.5; p = 0.007) among family members in the offspring generation than among their spouse controls. Both reduction in the frequency of the ε4 allele and increase in the frequency of the ε2 allele contribute to longevity.
      Indentifier
      rs2075650
      Reference

        Study 4

        Longevity Association
        Significant
        Population
        American, English, Irish
        Study Design
        10 late-onset Alzheimer's disease genes were tested for association with human aging in a dataset with 1385 samples with documented age at death (age range: 58–108 years; mean age at death: 80.2 years) using the most significant SNPs found in the previous studies
        Conclusions
        APOE locus (rs2075650) showed compelling evidence of association with human life span (p = 5.27 × 10−4)
        Indentifier
        rs2075650
        Reference

          Study 5

          Longevity Association
          Significant
          Population
          German
          Study Design
          Genome-wide association study comparing 664,472 autosomal SNPs in 763 long-lived individuals (mean age: 99.7 years) and 1085 controls (mean age: 60.2 years). Top SNPs from the GWAS were further investigated in an independent German sample comprised of 754 long-lived individuals (mean age: 96.9 years) and 860 controls (mean age: 67.3 years).
          Conclusions
          Only one SNP (rs4420638 near APOC1) was significantly associated with longevity after correcting for multiple hypothesis testing in the GWAS. This SNP was replicated in an independent German sample and can be explained by linkage disequilibrium with APOE allelic variants. rs2075650, also in LD with APOE alleles, was also associated with longevity.
          Indentifier
          rs2075650
          Reference

            Study 6

            Longevity Association
            Significant
            Population
            Dutch
            Study Design
            Genome-wide association study in 403 unrelated nonagenarians from long-living families and 1670 younger controls. Strongest candidates were then investigated in a meta-analysis of 4149 nonagenarian cases and 7582 younger controls.
            Conclusions
            No SNP reached significance in the GWAS but 62 SNPs had an indicative association with survival into old age. Of these 62 SNPs then studied in the meta-analysis, only one was significant: rs2075650 located in TOMM40 and close to APOE. This association may be due to linkage disequilibrium with rs429358 and rs7412 in APOE; both rs429358 and rs7412 were associated with longevity in the meta-analysis.
            Indentifier
            rs2075650
            Reference

              Study 7

              Longevity Association
              Significant
              Population
              American (Caucasian)
              Study Design
              Genome-wide association study in 801 centenarians and 914 healthy controls
              Conclusions
              281 SNPs were found to discriminate between cases and controls
              Indentifier
              rs2075650
              Reference