|(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|
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.
|Disease Association||Defects in KL may be a cause of chronic renal failure complications.|
[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.
|qualified_impact||Insufficiently evaluated not reviewed|
[PMID 26843110] Klotho Gene and Selective Serotonin Reuptake Inhibitors: Response to Treatment in Late-Life Major Depressive Disorder.
|CLNDBN||Tumoral calcinosis, familial, hyperphosphatemic|