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
Display region using the UCSC Genome Browser (GRCh38/hg38)

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
Function: 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
Hide GO terms

Protein interactions and network

No interactions in records.

Retrieve sequences for KL

ORF
ORF
CDS
CDS

Homologs in model organisms

Danio rerio
kl
Mus musculus
Kl
Rattus norvegicus
Kl

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

Selected references

External links

EPD
ORF Accession
NM_004795
CDS Accession
NP_004786
OMIM
604824
HPRD
05316
Ensembl
KL
UniProt/Swiss-Prot
KLOT_HUMAN
GeneCards
KL
Entrez Gene
9365
UniGene
524953
GenAtlas
KL
Internet
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