GenAge entry for KL (Homo sapiens)
Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism
Gene name (HAGRID: 17)
- HGNC symbol
- KL
- Aliases
- Common name
- klotho
Potential relevance to the human ageing process
- Main reason for selection
- Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism
- Description
The KL gene encodes two proteins: one membrane protein and one secreted transcript that acts as a circulating hormone. KL regulates INS, Wnt, and FGF23 signalling.
Mice mutant for KL show multiple signs of accelerated ageing [20]. The accelerated ageing phenotype of KL deficient mice is similar to that observed in FGF23 deficient mice. KL binds FGF receptors and is a co-factor essential for the activation of the receptor [1851]. In this process KL acts as a scaffold protein and tethers the FGF receptor to FGF23 by its C-terminal tail, conferring stability to the complex [4511].
In contrast, overexpression of KL in mice increases lifespan by 20-30% (perhaps through repression of intracellular INS/IGF1 signals [1485]), dramatically improves renal function [3630], and protects against neurodegenerative diseases such as Alzheimer’s and Parkinson’s [3629][4512]. KL enhances neuroprotection and normal cognition, in part, by optimising synaptic functions. Peripheral expression of a KL fragment enhanced brain function in young and ageing mice, in addition to an alpha-synuclein transgenic mouse model of Parkinson’s disease. The KL fragment induced cleavage of an NMDAR subunit and increased synaptic plasticity [4512]. Injection of KL into the central nervous system resulted in enhanced learning and memory 6 months after injection [4513].
KL alleles have also been implicated in human longevity and age-related diseases [146]. Even though its other functions remain a mystery, KL may also be involved in calcium metabolism and in a vitamin D endocrine system. Premature ageing phenotypes in mice mutant for KL are largely rescued by keeping the animals on a vitamin-D-deficient diet [245]. It is plausible that KL plays some role in human ageing but more work is necessary to confirm this notion and elucidate the mechanisms involved.
Cytogenetic information
- Cytogenetic band
- 13q12
- Location
- 33,016,433 bp to 33,066,145 bp
- Orientation
- Plus strand
Protein information
- Gene Ontology
-
Process: GO:0000165; MAPK cascade
GO:0005975; carbohydrate metabolic process
GO:0006112; energy reserve metabolic process
GO:0007568; aging
GO:0008286; insulin receptor signaling pathway
GO:0008543; fibroblast growth factor receptor signaling pathway
GO:0014066; regulation of phosphatidylinositol 3-kinase signaling
GO:0030501; positive regulation of bone mineralization
GO:0036092; phosphatidylinositol-3-phosphate biosynthetic process
GO:0043547; positive regulation of GTPase activity
GO:0046854; phosphatidylinositol phosphorylation
GO:0048015; phosphatidylinositol-mediated signaling
GO:0055074; calcium ion homeostasis
GO:0090080; positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway
GO:1901657; glycosyl compound metabolic process
Cellular component: GO:0005576; extracellular region
GO:0005615; extracellular space
GO:0005622; intracellular
GO:0005886; plasma membrane
GO:0005887; integral component of plasma membrane
GO:0016324; apical plasma membrane
GO:0070062; extracellular exosome
Hide GO termsFunction: GO:0004566; beta-glucuronidase activity
GO:0004871; signal transducer activity
GO:0005088; Ras guanyl-nucleotide exchange factor activity
GO:0005104; fibroblast growth factor receptor binding
GO:0005179; hormone activity
GO:0005499; vitamin D binding
GO:0008422; beta-glucosidase activity
GO:0016303; 1-phosphatidylinositol-3-kinase activity
GO:0017134; fibroblast growth factor binding
GO:0046934; phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Protein interactions and network
No interactions in records.
Retrieve sequences for KL
Homologs in model organisms
In other databases
- GenAge model organism genes
- A homolog of this gene for Mus musculus is present as Kl
- LongevityMap
- This gene is present as KL
- CellAge
- This gene is present as KL