LongevityMap variant group

Entry Details

Longevity Association
Significant
Population
Dutch
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

Variants (10)

AKT1

1.
Identifier
AKT1
In Other Studies (IDs)
1093
Cytogenetic Location
14q32.33
UCSC Genome Browser
View 14q32.33 on the UCSC genome browser

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]
Other longevity studies of this gene
9
OMIM
164730
Ensembl
ENSG00000142208
UniProt/Swiss-Prot
AKT1_HUMAN
Entrez Gene
207
UniGene
525622
HapMap
View on HapMap

Homologs in model organisms

Mus musculus
Akt1
Rattus norvegicus
Akt1

In other databases

GenAge model organism genes
  • A homolog of this gene for Mus musculus is present as Akt1
GenAge human genes
  • This gene is present as AKT1
CellAge
  • This gene is present as AKT1

AKT3

1.
Identifier
AKT3
Cytogenetic Location
1q43-q44
UCSC Genome Browser
View 1q43-q44 on the UCSC genome browser

Gene details

HGNC symbol
AKT3
Aliases
MPPH; PKBG; MPPH2; PRKBG; STK-2; PKB-GAMMA; RAC-gamma; RAC-PK-gamma 
Common name
AKT serine/threonine kinase 3 
Description
The protein encoded by this gene is a member of the AKT, also called PKB, serine/threonine protein kinase family. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
OMIM
611223
Ensembl
ENSG00000117020
UniProt/Swiss-Prot
AKT3_HUMAN
Entrez Gene
10000
UniGene
498292
HapMap
View on HapMap

Homologs in model organisms

Caenorhabditis elegans
akt-2
Danio rerio
akt3a
Mus musculus
Akt3
Rattus norvegicus
Akt3

In other databases

CellAge
  • This gene is present as AKT3

FOXO4

1.
Identifier
FOXO4
Cytogenetic Location
Xq13.1
UCSC Genome Browser
View Xq13.1 on the UCSC genome browser

Gene details

HGNC symbol
FOXO4
Aliases
AFX; AFX1; MLLT7 
Common name
forkhead box O4 
Description
This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded by this class are regulated by factors involved in growth and differentiation indicating they play a role in these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax gene, encoding a DNA binding protein, located on chromosome 11 is associated with leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]
Other longevity studies of this gene
5
OMIM
300033
Ensembl
ENSG00000184481
UniProt/Swiss-Prot
FOXO4_HUMAN
Entrez Gene
4303
UniGene
584654
HapMap
View on HapMap

Homologs in model organisms

Danio rerio
LOC563719
Drosophila melanogaster
foxo
Mus musculus
Foxo4
Rattus norvegicus
Foxo4
Saccharomyces cerevisiae
FHL1
Schizosaccharomyces pombe
sep1

In other databases

GenAge model organism genes
  • A homolog of this gene for Drosophila melanogaster is present as foxo
GenAge human genes
  • This gene is present as FOXO4
GenDR gene manipulations
  • A homolog of this gene for Drosophila melanogaster is present as foxo
CellAge
  • This gene is present as FOXO4

IGF2

1.
Identifier
IGF2
In Other Studies (IDs)
73 1151
Cytogenetic Location
11p15.5
UCSC Genome Browser
View 11p15.5 on the UCSC genome browser

Gene details

HGNC symbol
IGF2
Aliases
GRDF; IGF-II; PP9974; C11orf43 
Common name
insulin like growth factor 2 
Description
This gene encodes a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. A read-through INS-IGF2 gene exists, whose 5' region overlaps the INS gene and the 3' region overlaps this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]
Other longevity studies of this gene
6
OMIM
147470
Ensembl
ENSG00000167244
UniProt/Swiss-Prot
E3UN46_HUMAN
Entrez Gene
3481
UniGene
272259
HapMap
View on HapMap

Homologs in model organisms

Danio rerio
igf2a
Mus musculus
Igf2
Rattus norvegicus
Igf2

In other databases

GenAge human genes
  • This gene is present as IGF2

INS

1.
Identifier
INS
In Other Studies (IDs)
181 1154
Cytogenetic Location
11p15.5
UCSC Genome Browser
View 11p15.5 on the UCSC genome browser

Gene details

HGNC symbol
INS
Aliases
IDDM; ILPR; IRDN; IDDM1; IDDM2; MODY10 
Common name
insulin 
Description
After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. A multitude of mutant alleles with phenotypic effects have been identified. There is a read-through gene, INS-IGF2, which overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]
Other longevity studies of this gene
5
OMIM
176730
Ensembl
ENSG00000254647
UniProt/Swiss-Prot
I3WAC9_HUMAN
Entrez Gene
3630
UniGene
272259
HapMap
View on HapMap

Homologs in model organisms

Danio rerio
ins
Mus musculus
Ins1
Rattus norvegicus
Ins1

In other databases

GenAge human genes
  • This gene is present as INS

PIK3CA

1.
Identifier
PIK3CA
Cytogenetic Location
3q26.32
UCSC Genome Browser
View 3q26.32 on the UCSC genome browser

Gene details

HGNC symbol
PIK3CA
Aliases
MCM; CWS5; MCAP; PI3K; CLOVE; MCMTC; PI3K-alpha; p110-alpha 
Common name
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha 
Description
Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]
Other longevity studies of this gene
3
OMIM
171834
Ensembl
ENSG00000121879
UniProt/Swiss-Prot
PK3CA_HUMAN
Entrez Gene
5290
UniGene
553498
HapMap
View on HapMap

Homologs in model organisms

Danio rerio
LOC100334726
Mus musculus
Pik3ca
Rattus norvegicus
Pik3ca

In other databases

GenAge human genes
  • This gene is present as PIK3CA
CellAge
  • This gene is present as PIK3CA

POT1

1.
Identifier
POT1
Cytogenetic Location
7q31.33
UCSC Genome Browser
View 7q31.33 on the UCSC genome browser

Gene details

HGNC symbol
POT1
Aliases
GLM9; CMM10; HPOT1 
Common name
protection of telomeres 1 
Description
This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein functions as a member of a multi-protein complex that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. Increased transcriptional expression of this gene is associated with stomach carcinogenesis and its progression. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]
Other longevity studies of this gene
5
OMIM
606478
Ensembl
ENSG00000128513
UniProt/Swiss-Prot
A0A024R739_HUMAN
Entrez Gene
25913
UniGene
31968
HapMap
View on HapMap

Homologs in model organisms

Danio rerio
pot1
Mus musculus
Pot1
Rattus norvegicus
Pot1b
Schizosaccharomyces pombe
pot1

In other databases

CellAge
  • This gene is present as POT1

SGK1

1.
Identifier
SGK1
In Other Studies (IDs)
1057
Cytogenetic Location
6q23.2
UCSC Genome Browser
View 6q23.2 on the UCSC genome browser

Gene details

HGNC symbol
SGK1
Aliases
SGK 
Common name
serum/glucocorticoid regulated kinase 1 
Description
This gene encodes a serine/threonine protein kinase that plays an important role in cellular stress response. This kinase activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. High levels of expression of this gene may contribute to conditions such as hypertension and diabetic nephropathy. Several alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]
Other longevity studies of this gene
1
OMIM
602958
Ensembl
ENSG00000118515
UniProt/Swiss-Prot
B7Z325_HUMAN
Entrez Gene
6446
UniGene
510078
HapMap
View on HapMap

Homologs in model organisms

Danio rerio
sgk1
Mus musculus
Sgk1
Rattus norvegicus
Sgk1

In other databases

GenAge microarray genes
  • This gene is present as SGK1
CellAge
  • This gene is present as SGK1

SGK3

1.
Identifier
SGK3
Cytogenetic Location
8q13.1
UCSC Genome Browser
View 8q13.1 on the UCSC genome browser

Gene details

HGNC symbol
SGK3
Aliases
CISK; SGK2; SGKL 
Common name
serum/glucocorticoid regulated kinase family member 3 
Description
This gene is a member of the Ser/Thr protein kinase family and encodes a phosphoprotein with a PX (phox homology) domain. The protein phosphorylates several target proteins and has a role in neutral amino acid transport and activation of potassium and chloride channels. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
OMIM
607591
Ensembl
ENSG00000104205
UniProt/Swiss-Prot
A0A024R807_HUMAN
Entrez Gene
23678
UniGene
613417
HapMap
View on HapMap

Homologs in model organisms

Danio rerio
sgk3
Mus musculus
Sgk3
Rattus norvegicus
Sgk3
Saccharomyces cerevisiae
YPK1

In other databases

GenAge model organism genes
  • A homolog of this gene for Saccharomyces cerevisiae is present as YPK1

YWHAG

1.
Identifier
YWHAG
Cytogenetic Location
7q11.23
UCSC Genome Browser
View 7q11.23 on the UCSC genome browser

Gene details

HGNC symbol
YWHAG
Aliases
PPP1R170; 14-3-3GAMMA 
Common name
tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma 
Description
This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the rat ortholog. It is induced by growth factors in human vascular smooth muscle cells, and is also highly expressed in skeletal and heart muscles, suggesting an important role for this protein in muscle tissue. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways. [provided by RefSeq, Jul 2008]
OMIM
605356
Ensembl
ENSG00000170027
UniProt/Swiss-Prot
1433G_HUMAN
Entrez Gene
7532
UniGene
744840
HapMap
View on HapMap

Homologs in model organisms

Danio rerio
ywhag1
Mus musculus
Ywhag
Rattus norvegicus
Ywhag

References

Deelen et al. (2013)

Other variants which are also part of this study