rs9536314

plus

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

Reference

GRCh38 38.1/141

Chromosome

13

Position

33054001

Gene

KL

is a	snp
is	mentioned by
dbSNP	rs9536314
dbSNP (classic)	rs9536314
ClinGen	rs9536314
ebi	rs9536314
HLI	rs9536314
Exac	rs9536314
Gnomad	rs9536314
Varsome	rs9536314
LitVar	rs9536314
Map	rs9536314
PheGenI	rs9536314
Biobank	rs9536314
1000 genomes	rs9536314
hgdp	rs9536314
ensembl	rs9536314
geneview	rs9536314
scholar	rs9536314
google	rs9536314
pharmgkb	rs9536314
gwascentral	rs9536314
openSNP	rs9536314
23andMe	rs9536314
SNPshot	rs9536314
SNPdbe	rs9536314
MSV3d	rs9536314
GWAS Ctlg	rs9536314

GMAF

0.1304

Max Magnitude

1.5

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 11792841 ], and KL-VS heterozygosity (but not homozygosity) has been associated with greater brain cortical volume [PMID 25815349 ]. 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 26080320 ], 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 25673831 ].

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 28076518 ], 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

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

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

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

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

[PMID 21695423 ] 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

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

ClinVar
Risk	rs9536314(A;A) Rs9536314(G;G)
Alt	rs9536314(A;A) Rs9536314(G;G)
Reference	Rs9536314(T;T)
Significance	Probable-non-pathogenic
Disease	Tumoral calcinosis
Variation	info
Gene	KL
CLNDBN	Tumoral calcinosis, familial, hyperphosphatemic
Reversed	0
HGVS	NC_000013.10:g.33628138T>G
CLNSRC
CLNACC	RCV000323675.1,