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rs9536314

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(G;G) 1.5 2 copies of KL-VS haplotype; one report links this to lower cognitive function with age
(G;T) 1.5 1 copy of KL-VS haplotype; some reports link having one copy to increased longevity and/or executive function
(T;T) 0 Most common genotype for this SNP
ReferenceGRCh38 38.1/141
Chromosome13
Position33054001
GeneKL
is asnp
is mentioned by
dbSNPrs9536314
ClinGenrs9536314
ebirs9536314
HLIrs9536314
Exacrs9536314
Varsomers9536314
Maprs9536314
PheGenIrs9536314
hapmaprs9536314
1000 genomesrs9536314
hgdprs9536314
ensemblrs9536314
gopubmedrs9536314
geneviewrs9536314
scholarrs9536314
googlers9536314
pharmgkbrs9536314
gwascentralrs9536314
openSNPrs9536314
23andMers9536314
23andMe allrs9536314
SNP Nexus

SNPshotrs9536314
SNPdbers9536314
MSV3drs9536314
GWAS Ctlgrs9536314
GMAF0.1304
Max Magnitude1.5

rs9536314, also known as c.1062T>G, p.Phe352Val and F352V, represents a variant in the KL (Klotho) gene on chromosome 13. Together with rs9527025 (C370S), which it co-segregates with, a haplotype ("KL-VS") has been described that is reported to increase klotho secretion and may alter its functions; the alternative haplotype is named KL-FC (due to the F from F352V and C from C370S).

The klotho protein is a hormone found primarily in the kidney and choroid plexus of the brain. At the genetic level, the Klotho gene is reported to affect longevity in mice [PMID 9363890] and perhaps humans [PMID 11792841OA-icon.png], and KL-VS heterozygosity (but not homozygosity) has been associated with greater brain cortical volume [PMID 25815349OA-icon.png]. At the protein level, older adults with higher plasma klotho concentrations tend to show lower less decline with age on standardized cognitive tests [PMID 26297657], adults with higher stress tend to have lower plasma klotho levels [PMID 26080320OA-icon.png], and transgenic mice bred to have excess human amyloid precursor protein (to simulate Alzheimer's disease) score better on some tests when their klotho levels are increased [PMID 25673831OA-icon.png].

Most of the studies cited above for studies of klotho in humans should be considered preliminary for at least two reasons: they are not based on large sample sizes, and, they haven't been replicated by independent investigators. In addition, there is a report showing no difference in the klotho plasma levels between FC/FC and FC/VS individuals [PMID 28076518OA-icon.png], as well as a report showing KL-VS heterozygotes had poorer cognitive function than noncarriers [PMID 26405063], in contrast to the studies cited above.

? (G;G) (G;T) (T;T) 28
Venter snp
Source plos
Gene KL
allele G
frequency
sift AFFECT FUNCTION
HuRef 1103649192249
Disease Association Defects in KL may be a cause of chronic renal failure complications.



Neighborrs9527025
Distance55
[PMID 20394945] Infantile hypercalcemia and hypercalciuria: new insights into a vitamin D-dependent mechanism and response to ketoconazole treatment


[PMID 21565945OA-icon.png] Lack of association of Klotho gene variants with valvular and vascular calcification in Caucasians: a candidate gene study of the Framingham Offspring Cohort


[PMID 16753056OA-icon.png] The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians.


[PMID 18194558OA-icon.png] A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples.


[PMID 21695423OA-icon.png] Klotho locus, metabolic traits, and serum hemoglobin in hospitalized older patients: a genetic association analysis.

Variation in longevity gene KLOTHO is associated with greater cortical volumes


GET Evidence
KL-F352V
aa_change Phe352Val
aa_change_short F352V
impact not reviewed
qualified_impact Insufficiently evaluated not reviewed
overall_frequency 0.170106
summary



[PMID 26843110] Klotho Gene and Selective Serotonin Reuptake Inhibitors: Response to Treatment in Late-Life Major Depressive Disorder.