Gene
Klotho KL-VS Variant
Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
The interesting genotype-phenotype pattern
KL-VS is unusual in showing heterozygote advantage: people with ONE copy do better; people with TWO copies do worse. Heterozygotes have:
- ~20% reduction in coronary artery disease incidence.
- Better cognitive performance, especially in older adults.
- Slower cognitive decline.
- ~20% increase in life expectancy estimates.
Homozygotes (rare) lose the benefits and show shorter survival.
Mechanism (probable)
KL-VS heterozygosity produces higher serum Klotho concentration than either reference homozygotes or KL-VS homozygotes — consistent with a non-linear dose-response. Klotho protein supports cognitive function, suppresses insulin/IGF-1 signalling, and maintains cardiovascular health.
Therapeutic implications
The KL-VS effect motivates Klotho-based therapeutics: recombinant Klotho, AAV-Klotho gene therapy, small-molecule Klotho inducers. Pre- clinical work is active; nothing approved.
Testing
KL-VS genotyping is available in some research panels (e.g. 23andMe raw data can be checked for rs9536314 G/T, rs9527025 G/C). Not clinically actionable, just informative.
Related entries
References
- Dubal, D. B. et al. Life extension factor klotho enhances cognition. Cell Rep. 7, 1065–1076 (2014).