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Aliases for KL Gene

Aliases for KL Gene

  • Klotho 2 3
  • EC 3.2.1.31 4 63
  • EC 3.2.1 63
  • KLOTHO 6

External Ids for KL Gene

Previous GeneCards Identifiers for KL Gene

  • GC13P031576
  • GC13P027577
  • GC13P032526
  • GC13P031388
  • GC13P032488
  • GC13P033590
  • GC13P014401

Summaries for KL Gene

Entrez Gene Summary for KL Gene

  • This gene encodes a type-I membrane protein that is related to beta-glucosidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. [provided by RefSeq, Jul 2008]

GeneCards Summary for KL Gene

KL (Klotho) is a Protein Coding gene. Diseases associated with KL include hyperphosphatemic familial tumoral calcinosis, kl-related and skin atrophy. Among its related pathways are PI-3K cascade and PI-3K cascade. GO annotations related to this gene include signal transducer activity and fibroblast growth factor receptor binding. An important paralog of this gene is GBA3.

UniProtKB/Swiss-Prot for KL Gene

  • May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).

  • The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.

Gene Wiki entry for KL Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for KL Gene

Genomics for KL Gene

Regulatory Elements for KL Gene

Genomic Location for KL Gene

Start:
33,016,063 bp from pter
End:
33,066,145 bp from pter
Size:
50,083 bases
Orientation:
Plus strand

Genomic View for KL Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for KL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KL Gene

Proteins for KL Gene

  • Protein details for KL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UEF7-KLOT_HUMAN
    Recommended name:
    Klotho
    Protein Accession:
    Q9UEF7
    Secondary Accessions:
    • Q5VZ95
    • Q96KV5
    • Q96KW5
    • Q9UEI9
    • Q9Y4F0

    Protein attributes for KL Gene

    Size:
    1012 amino acids
    Molecular mass:
    116181 Da
    Quaternary structure:
    • Homodimer. Interacts with FGF23 and FGFR1.
    Miscellaneous:
    • Defects in KL may be a cause of chronic renal failure complications

    Alternative splice isoforms for KL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KL Gene

Proteomics data for KL Gene at MOPED

Selected DME Specific Peptides for KL Gene

Post-translational modifications for KL Gene

  • N-glycosylated.
  • Glycosylation at Asn106, Asn159, Asn283, Asn344, Asn607, Asn612, and Asn694
  • Modification sites at PhosphoSitePlus

Other Protein References for KL Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for KL Gene

Suggested Antigen Peptide Sequences for KL Gene

Graphical View of Domain Structure for InterPro Entry

Q9UEF7

UniProtKB/Swiss-Prot:

KLOT_HUMAN :
  • Q9UEF7
Domain:
  • Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 239, and the second one lacks the essential Glu active site residue at position 872
Family:
  • Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.
genes like me logo Genes that share domains with KL: view

No data available for Gene Families for KL Gene

Function for KL Gene

Molecular function for KL Gene

GENATLAS Biochemistry: murine klotho gene homolog,with two spliced variants one secreted predominantly over the membrane form
UniProtKB/Swiss-Prot CatalyticActivity: A beta-D-glucuronoside + H(2)O = D-glucuronate + an alcohol
UniProtKB/Swiss-Prot Function: May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).
UniProtKB/Swiss-Prot Function: The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.

Enzyme Numbers (IUBMB) for KL Gene

Gene Ontology (GO) - Molecular Function for KL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds --
GO:0004566 beta-glucuronidase activity IEA --
GO:0004871 signal transducer activity IEA --
GO:0005104 fibroblast growth factor receptor binding IEA --
GO:0005179 hormone activity IEA --
genes like me logo Genes that share ontologies with KL: view
genes like me logo Genes that share phenotypes with KL: view

Animal Models for KL Gene

MGI Knock Outs for KL:
  • Kl tm1Lex
  • Kl tm1Yin
  • Kl tm1.2Tel

miRNA for KL Gene

miRTarBase miRNAs that target KL

No data available for Transcription Factor Targeting and HOMER Transcription for KL Gene

Localization for KL Gene

Subcellular locations from UniProtKB/Swiss-Prot for KL Gene

Isoform 1: Cell membrane; Single-pass type I membrane protein. Note=Isoform 1 shedding leads to a soluble peptide.
Isoform 2: Secreted.
Klotho peptide: Secreted.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for KL Gene COMPARTMENTS Subcellular localization image for KL gene
Compartment Confidence
extracellular 5
plasma membrane 5
endoplasmic reticulum 2
golgi apparatus 2
cytoskeleton 1
cytosol 1
nucleus 1

Gene Ontology (GO) - Cellular Components for KL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space TAS 11792841
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 9464267
GO:0016021 integral component of membrane TAS 11792841
genes like me logo Genes that share ontologies with KL: view

Pathways for KL Gene

SuperPathways for KL Gene

Superpath Contained pathways
1 PI-3K cascade
2 Signaling by FGFR
3 Insulin receptor signalling cascade
4 FGFR ligand binding and activation
5 Downstream Signaling Events Of B Cell Receptor (BCR)
genes like me logo Genes that share pathways with KL: view

Gene Ontology (GO) - Biological Process for KL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002526 acute inflammatory response IEA --
GO:0005975 carbohydrate metabolic process IEA --
GO:0006112 energy reserve metabolic process IEA --
GO:0007173 epidermal growth factor receptor signaling pathway TAS --
GO:0007568 aging IMP 11792841
genes like me logo Genes that share ontologies with KL: view

Compounds for KL Gene

(8) HMDB Compounds for KL Gene

Compound Synonyms Cas Number PubMed IDs
1-Butanol
  • 1-Butanol
71-36-3
1-Hexanol
  • 1-Hexyl alcohol
111-27-3
1-Pentanol
  • 1-Pentol
71-41-0
Calcium
  • Ca
7440-70-2
Ethanol
  • 1-Hydroxyethane
64-17-5

(2) Novoseek inferred chemical compound relationships for KL Gene

Compound -log(P) Hits PubMed IDs
vegf 21.4 3
tyrosine 2.42 1
genes like me logo Genes that share compounds with KL: view

Transcripts for KL Gene

mRNA/cDNA for KL Gene

Unigene Clusters for KL Gene

Klotho:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for KL Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4a · 4b · 4c ^ 5a · 5b ^ 6
SP1: - -
SP2:
SP3:

Relevant External Links for KL Gene

GeneLoc Exon Structure for
KL
ECgene alternative splicing isoforms for
KL

Expression for KL Gene

mRNA expression in normal human tissues for KL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KL Gene

This gene is overexpressed in Kidney - Cortex (10.0).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for KL Gene

SOURCE GeneReport for Unigene cluster for KL Gene Hs.524953

mRNA Expression by UniProt/SwissProt for KL Gene

Q9UEF7-KLOT_HUMAN
Tissue specificity: Present in cortical renal tubules (at protein level). Soluble peptide is present in serum and cerebrospinal fluid. Expressed in kidney, placenta, small intestine and prostate. Down-regulated in renal cell carcinomas, hepatocellular carcinomas, and in chronic renal failure kidney.
genes like me logo Genes that share expressions with KL: view

Orthologs for KL Gene

This gene was present in the common ancestor of animals.

Orthologs for KL Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia KL 35
  • 99.41 (n)
  • 99.21 (a)
KL 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia KL 35
  • 88.65 (n)
  • 90.01 (a)
KL 36
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia KL 35
  • 85.96 (n)
  • 87.83 (a)
KL 36
  • 88 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Kl 35
  • 84.51 (n)
  • 86.93 (a)
Kl 16
Kl 36
  • 86 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia KL 36
  • 80 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia KL 36
  • 77 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Kl 35
  • 83.83 (n)
  • 85.6 (a)
chicken
(Gallus gallus)
Aves KL 35
  • 72.91 (n)
  • 72.26 (a)
KL 36
  • 71 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia KL 36
  • 65 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia kl 35
  • 67.26 (n)
  • 67.43 (a)
zebrafish
(Danio rerio)
Actinopterygii kl 35
  • 58.2 (n)
  • 53.52 (a)
kl 36
  • 52 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG9701 36
  • 33 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea klo-1 36
  • 31 (a)
ManyToMany
klo-2 36
  • 31 (a)
ManyToMany
C50F7.10 37
  • 31 (a)
E02H9.5 37
  • 31 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 36 (a)
OneToMany
Species with no ortholog for KL:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for KL Gene

ENSEMBL:
Gene Tree for KL (if available)
TreeFam:
Gene Tree for KL (if available)

Paralogs for KL Gene

Paralogs for KL Gene

Selected SIMAP similar genes for KL Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with KL: view

Variants for KL Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for KL Gene

Q9UEF7-KLOT_HUMAN
Homozygosity for KL-VS allele is associated with decreased longevity and increased cardiovascular disease risk

Sequence variations from dbSNP and Humsavar for KL Gene

SNP ID Clin Chr 13 pos Sequence Context AA Info Type MAF
rs118050 -- 33,022,374(+) ATGTT(A/G)TCTTT intron-variant
rs118051 -- 33,022,382(+) TTTTT(A/G)AGGCA intron-variant
rs211234 -- 33,020,990(+) ACTTC(A/G)CTTTG intron-variant
rs211235 -- 33,021,062(-) CCCAG(A/C)TAGCG intron-variant
rs211236 -- 33,021,595(+) AATGT(A/G)TTTGG intron-variant

Relevant External Links for KL Gene

HapMap Linkage Disequilibrium report
KL
Human Gene Mutation Database (HGMD)
KL
Locus Specific Mutation Databases (LSDB)
KL

No data available for Structural Variations from Database of Genomic Variants (DGV) for KL Gene

Disorders for KL Gene

(1) OMIM Diseases for KL Gene (604824)

UniProtKB/Swiss-Prot

KLOT_HUMAN
  • Tumoral calcinosis, hyperphosphatemic, familial (HFTC) [MIM:211900]: A severe metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients manifest recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement. {ECO:0000269 PubMed:17710231}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(1) Novoseek inferred disease relationships for KL Gene

Disease -log(P) Hits PubMed IDs
tumors 0 1

Relevant External Links for KL

Genetic Association Database (GAD)
KL
Human Genome Epidemiology (HuGE) Navigator
KL
genes like me logo Genes that share disorders with KL: view

Publications for KL Gene

  1. Klotho gene polymorphisms are associated with osteocalcin levels but not bone density of aged postmenopausal women. (PMID: 16151675) Mullin B.H. … Prince R.L. (Calcif. Tissue Int. 2005) 3 23 48
  2. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. (PMID: 17710231) Ichikawa S. … Econs M.J. (J. Clin. Invest. 2007) 3 4 23
  3. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. (PMID: 9464267) Matsumura Y. … Nabeshima Y. (Biochem. Biophys. Res. Commun. 1998) 2 3 4
  4. Association of human aging with a functional variant of klotho. (PMID: 11792841) Arking D.E. … Dietz H.C. (Proc. Natl. Acad. Sci. U.S.A. 2002) 3 4 48
  5. Association between a functional variant of the KLOTHO gene and high- density lipoprotein cholesterol, blood pressure, stroke, and longevity. (PMID: 15677572) Arking D.E. … Dietz H.C. (Circ. Res. 2005) 3 4 48

Products for KL Gene

Sources for KL Gene

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