LongevityMap Gene

Gene details

HGNC symbol: KL
Aliases
Common name: klotho
Description: This gene encodes a type-I membrane protein that is related to beta-glucosidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. [provided by RefSeq, Jul 2008]
Cytogenetic Location: 13q13.1
UCSC Genome Browser: View 13q13.1 on the UCSC genome browser
OMIM: 604824
Ensembl: ENSG00000133116
UniProt/Swiss-Prot: KLOT_HUMAN
Entrez Gene: 9365
UniGene: 524953
1000 Genomes: 1000 Genomes

Homologs in model organisms

Caenorhabditis elegans: klo-2
Caenorhabditis elegans: klo-1
Danio rerio: kl
Mus musculus: Kl
Rattus norvegicus: Kl

In other databases

GenAge model organism genes

A homolog of this gene for Mus musculus is present as Kl
A homolog of this gene for Caenorhabditis elegans is present as klo-1
A homolog of this gene for Caenorhabditis elegans is present as klo-2

GenAge human genes

This gene is present as KL

CellAge

This gene is present as KL

Studies (5)

Significant/Non-significant: 4/1

Study 1

Longevity Association

Population

Study Design

A total of 1,089 (669 women and 420 men) unrelated individuals from 19 to 109 years, born and residing in northern and central Italy, were subdivided into three age classes, and genotyped for the KL-VS allele

Conclusions

Significant increase of the heterozygous Klotho genotype was found in the class of elderly people compared to young controls. However, no difference was present between centenarians and young controls.

Indentifier

Reference

Study 2

Longevity Association: Significant
Population: Danish
Study Design: Alleles in candidate pathways (GH/IGF1 signaling, DNA damage signaling and repair and pro/antioxidants) were investigated for association with longevity in 1089 oldest-old (age 92-93) and 736 middle-aged Danes
Conclusions: Eleven SNPs (in GSR, KL, GHRHR, INS, GHSR, IGF2R, RAD52, WRN, RAD23B, POLB and NTLH1) were associated with longevity after correction for multiple hypothesis testing. No replications were observed in German and Dutch populations.
Indentifier

Study 3

Longevity Association

Population

Ashkenazi Jewish, Czechs (Bohemian)

Study Design

525 Ashkenazi Jews composed of 216 probands (age ≥95 years) and 309 unrelated individuals (ages 51 to 94) were genotyped for the functional variant of KLOTHO, termed KL-VS. 435 elderly individuals (≥75 years) were genotyped.

Conclusions

A common variant of KLOTHO, the KL-VS allele, was associated with human longevity. A heterozygous advantage for longevity was observed for individuals ≥79 years of age (P<0.004).

Indentifier

Reference

Study 4

Longevity Association

Population

Czechs (Bohemian), Americans (Baltimore Caucasians and African-Americans)

Study Design

Amino acid substitutions F352V and C370S SNPs were examined in 435 elderly individuals (>75 years) and 611 contemporary newborns (Bohemian Czech), 965 elderly individuals (>65 years) and 646 control infants (Baltimore Caucasians and Baltimore African-Americans)

Conclusions

Homozygous elderly individuals were underrepresented in all populations

Indentifier

Reference

Study 5

Longevity Association: Non-significant
Population: American (Caucasian)
Study Design: Genome-wide association study for longevity-related traits in up to 1345 Framingham Study participants from 330 families; 713 participants achieved age 65 years or greater. A total of 79 potential candidate genes and regions associated with longevity were also studied.
Conclusions: Although no genome-wide associations were significant, several SNPs in some previously associated genes with longevity had suggestive associations with age at death or morbidity-free survival at age 65 years. Noteworthy results included two SNPs within FOXO1A (rs10507486 and rs4943794) associated with age at death.
Indentifier