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

Caenorhabditis elegans: tomm-40
Danio rerio: tomm40l
Danio rerio: tomm40
Drosophila melanogaster: Tom40
Drosophila melanogaster: tomboy40
Mus musculus: Tomm40
Rattus norvegicus: Tomm40
Saccharomyces cerevisiae: TOM40

In other databases

CellAge gene expression

This gene is present as 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

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

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

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

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

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

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