Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

KL

contributors: mct - updated : 14-09-2018

HGNC name	klotho
HGNC id	6344

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   down-regulated in renal cell carcinomas, hepatocellular carcinomas constitutional     --low   down-regulated in chronic renal failure kidney, and decrease in circulating Klotho may contribute to vascular lesions in the patients with chronic renal failure ( constitutional       loss of function downregulates SIRT1 activity in arterial endothelial and smooth muscle cells constitutional     --over   in patients with diabetes and s-KL levels, but decreased with increasing albumin excretion

Susceptibility

to early-onset coronary artery disease and atherosclerosis to osteoporosis in postmenopausal women to decreased longevity to variation of BMD in male adults to breast and ovarian cancers

Variant & Polymorphism SNP , other	associated with decreased longevity
	G395A or C1818T increasing the risk of osteoporosis in postmenopausal women
	allelic variants of Klotho constitute one of the genetic factors influencing BMD in male adults
	KL-VS allele defined by the presence of 6 SNPs in exon 2 and flanking sequence impairs the trafficking and catalytic activity of KL
	some SNPs are associated with sickle cell osteonecrosis
	G395A is associated with blood pressure and C1818T is associated with glucose metabolism in Korean women
	KLOTHO-V allele was associated with increased breast and ovarian cancers risk

Candidate gene	DNA methylation markers of Gastric cancer (GC), which may serve as useful markers that may identify a distinct subset of GC
Marker	reduced serum KL concentrations and decreased vascular KL gene expression were associated with the presence and severity of coronary artery disease (CAD) independently of established cardiovascular risk factors
Therapy target
	System Type Disorder Pubmed cardiovascular aquired   might be a therapeutic target for preventing cardiovascular disease that complicates various diseases such as chronic kidney disease

ANIMAL & CELL MODELS

	transgenic mice
	in klotho-null mice, the activity of calpain is elevated and the activity of its endogenous inhibitor is significantly decreased
	klotho mice have a barely detectable amount of white adipose tissue, increased glucose tolerance and insulin sensitivity
	overexpression of klotho in mice extends life span
	mice heterozygously deficient for klotho gene showed blood flow recovery and impaired angiogenesis after ischemic hindlimb injury
	Klotho-hypomorphic (Klotho(hm)) mice suffer from renal salt wasting and hypovolemia despite hyperaldosteronism
	disruption of the Klotho gene in mice results in hypervitaminosis D and a syndrome resembling accelerated aging that includes osteopenia and vascular calcifications
	in the mdx mouse model of DMD epigenetic silencing of Klotho during muscular dystrophy contributes substantially to lost regenerative capacity and increased fibrosis of dystrophic muscle during late progressive stages of the disease