LongevityMap Gene

Gene details

HGNC symbol: AKT1
Aliases: AKT; PKB; RAC; CWS6; PRKBA; PKB-ALPHA; RAC-ALPHA
Common name: AKT serine/threonine kinase 1
Description: The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mutations in this gene have been associated with the Proteus syndrome. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2011]
Cytogenetic Location: 14q32.33
UCSC Genome Browser: View 14q32.33 on the UCSC genome browser
OMIM: 164730
Ensembl: ENSG00000142208
UniProt/Swiss-Prot: AKT1_HUMAN
Entrez Gene: 207
UniGene: 525622
1000 Genomes: 1000 Genomes

Homologs in model organisms

Caenorhabditis elegans: akt-2
Caenorhabditis elegans: akt-1
Danio rerio: AKT1
Drosophila melanogaster: Akt1
Mus musculus: Akt1
Rattus norvegicus: Akt1
Saccharomyces cerevisiae: SCH9
Saccharomyces cerevisiae: YPK1
Saccharomyces cerevisiae: YPK2

In other databases

GenAge model organism genes

A homolog of this gene for Caenorhabditis elegans is present as akt-1
A homolog of this gene for Saccharomyces cerevisiae is present as SCH9
A homolog of this gene for Drosophila melanogaster is present as Akt1
A homolog of this gene for Saccharomyces cerevisiae is present as YPK1
A homolog of this gene for Mus musculus is present as Akt1

GenAge human genes

This gene is present as AKT1

GenDR gene manipulations

A homolog of this gene for Saccharomyces cerevisiae is present as SCH9

CellAge

This gene is present as AKT1

Studies (6)

Significant/Non-significant: 4/2

Study 1

Longevity Association: Significant
Population: American (Caucasian)
Study Design: 291 SNPs in 30 genes in the insulin/IGF1 signaling pathway were evaluated in 293 long-lived cases and 603 average-lifespan controls (all female), then replicated the candidate genes in two independent cohorts: 279 cases (47% male vs 797 controls(52.6% male) and 383 cases (25.2% male) vs 363 controls (42.7 % male)
Conclusions: rs3803304 in AKT1 was significantly associated with longevity from a meta-analysis result (odds ratio (OR)=0.78 (95% confidence interval (CI)=0.68-0.89), adjusted p=0.043)
Indentifier

Study 2

Longevity Association: Significant
Population: Danish, German
Study Design: Seven SNPs were examined in 2996 long-lived individuals (1383 Danish cases, 92-93 y, 70.7% female; 1613 German cases, 95-110y, 73% female) and 1840 younger controls (736 Danish controls, 46-55 y, 73% female; 1104 German controls, 60-75 y, 74.4% female)
Conclusions: A disadvantageous effect of rs3803304 was significantly associated with longevity in Danish men (P=0.03), and this indication was supported when applying genotypic (P=0.02) and dominant models (P=0.01).
Indentifier

Study 3

Longevity Association

Population

Study Design

Studied genetic variation in the insulin/insulin-like growth factor signaling (IIS) pathway and in the telomere maintenance pathway for associations with longevity in 403 unrelated nonagenarians and 1,670 younger controls

Conclusions

SNP sets in both pathways were associated with longevity with the association of the IIS pathway defined by several genes (AKT1, AKT3, FOXO4, IGF2, INS, PIK3CA, SGK, SGK2, and YWHAG), while the telomere maintenance pathway seemed to be mainly determined by POT1 since only these genes showed an association with longevity

Indentifier

Reference

Study 4

Longevity Association

Population

Study Design

1,018 SNPs within a 10-kb window around 40 mTOR signalling genes were studied for differences in variation between 417 unrelated nonagenarian participants and 476 younger controls

Conclusions

As a whole, there was a significant association of genetic variation in the mTOR pathway and familial longevity, though no individual gene was significant after correcting for multiple hypothesis testing

Indentifier

Reference

Study 5

Longevity Association: Non-significant
Population: Danish, German
Study Design: Seven SNPs were examined in 2996 long-lived individuals (1383 Danish cases, 92-93 y, 70.7% female; 1613 German cases, 95-110y, 73% female) and 1840 younger controls (736 Danish controls, 46-55 y, 73% female; 1104 German controls, 60-75 y, 74.4% female)
Conclusions: Six SNPs of AKT1 variations (rs2494731, rs2494732, rs2494732, rs2494738, rs2494748, rs1130214) were not associated with longevity
Indentifier

Study 6

Longevity Association: Non-significant
Population: Italian (Southern)
Study Design: A two-stage case-control study was performed to identify the association between longevity and variation of in homeostasis regulation pathway genes. 317 SNPs in 104 genes were analyzed in 78 cases (≥90 years, median age 98 years, 42 females) and 71 controls (<90 years, median age 67 years, 32 females) in stage 1. Then, 31 candidate SNPs identified in stage 1 (π markers = 0.1) were analyzed in an independent sample composed by 288 cases (≥90 years, median age 92 years, 163 females) and 554 controls (<90 years, median age 67 years, 277 females).
Conclusions: After adjustment for multiple testing, no significant association was identified between various SNPs and longevity.
Indentifier