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Aliases for KL Gene

Aliases for KL Gene

  • Klotho 2 3 5
  • EC 3.2.1.31 4 63
  • EC 3.2.1 63

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 tumoral calcinosis, hyperphosphatemic, familial and hyperphosphatemic familial tumoral calcinosis, kl-related. Among its related pathways are Signaling by GPCR and Metabolism. GO annotations related to this gene include signal transducer activity and hydrolase activity, hydrolyzing O-glycosyl compounds. An important paralog of this gene is LCT.

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

Promoters for KL Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around KL on UCSC Golden Path with GeneCards custom track

Genomic Location for KL Gene

Chromosome:
13
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

Genes around KL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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 Asn 106, Asn 159, Asn 283, Asn 344, Asn 607, Asn 612, and Asn 694
  • Modification sites at PhosphoSitePlus

Other Protein References for KL Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for KL Gene

Suggested Antigen Peptide Sequences for KL Gene

Graphical View of Domain Structure for InterPro Entry

Q9UEF7

UniProtKB/Swiss-Prot:

KLOT_HUMAN :
  • 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.
  • Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.
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:0005104 fibroblast growth factor receptor binding IEA,IBA --
GO:0017134 fibroblast growth factor binding IEA,IPI 18829467
GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity TAS --
genes like me logo Genes that share ontologies with KL: view
genes like me logo Genes that share phenotypes with KL: view

Human Phenotype Ontology for KL Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for KL Gene

MGI Knock Outs for KL:
  • Kl tm2Yin
  • Kl tm1Yin
  • Kl tm1Lex
  • Kl tm1.2Tel

Animal Model Products

miRNA for KL Gene

No data available for Transcription Factor Targets 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. Apical cell membrane; Single-pass type I membrane protein. Note=Isoform 1 shedding leads to a soluble peptide. {ECO:0000250 UniProtKB:O35082}.
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
mitochondrion 1
nucleus 1

Gene Ontology (GO) - Cellular Components for KL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0070062 extracellular exosome IDA 19056867
genes like me logo Genes that share ontologies with KL: view

Pathways & Interactions for KL Gene

SuperPathways for KL Gene

Superpath Contained pathways
1 Interleukin-3, 5 and GM-CSF signaling
2 PI3K events in ERBB4 signaling
3 Immune System
4 Downstream signaling events of B Cell Receptor (BCR)
5 Negative regulation of FGFR1 signaling
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:0000186 activation of MAPKK activity TAS --
GO:0006112 energy reserve metabolic process IEA --
GO:0007173 epidermal growth factor receptor signaling pathway TAS --
GO:0007264 small GTPase mediated signal transduction TAS --
GO:0008286 insulin receptor signaling pathway IEA,TAS --
genes like me logo Genes that share ontologies with KL: view

No data available for SIGNOR curated interactions for KL Gene

Drugs & Compounds for KL Gene

(5) Drugs for KL Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
1-Butanol Experimental Pharma 0
1-Proponol Experimental Pharma 0
D-Glucuronic acid Experimental Pharma 0
calcium Nutra 0

(6) Additional Compounds for KL Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
1-Hexanol
  • 1-Hexanol
  • 1-Hexyl alcohol
  • 1-Hydroxyhexane
  • Alcohol C-6
  • Alcohol(C6)
111-27-3
1-Pentanol
  • 1-Pentanol
  • 1-Pentol
  • 1-Pentyl alcohol
  • Alcool amylique
  • Alcool amylique (french)
71-41-0
Isobutanol
  • 1-Hydroxymethylpropane
  • 2-Methyl propanol
  • 2-Methyl-1-propanol
  • 2-Methyl-1-propanyl alcohol
  • 2-Methylpropan-1-ol
78-83-1
Isopropyl alcohol
  • 2-Propanol
  • 2-Propyl alcohol
  • Alcojel
  • Alkolave
  • Avantin
67-63-0
Water
  • Dihydrogen oxide
  • Steam
7732-18-5
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 (x10.0).

Protein differential expression in normal tissues from HIPED for KL Gene

This gene is overexpressed in Pancreatic juice (62.9).

Integrated Proteomics: protein expression in normal tissues and cell lines 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 expression patterns with KL: view

Protein tissue co-expression partners for KL Gene

Primer Products

In Situ Assay Products

Orthologs for KL Gene

This gene was present in the common ancestor of animals.

Orthologs for KL Gene

Organism Taxonomy Gene Similarity Type Details
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
chimpanzee
(Pan troglodytes)
Mammalia KL 35
  • 99.41 (n)
  • 99.21 (a)
KL 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Kl 35
  • 83.83 (n)
  • 85.6 (a)
oppossum
(Monodelphis domestica)
Mammalia KL 36
  • 80 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia KL 36
  • 77 (a)
OneToOne
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 C50F7.10 37
  • 31 (a)
E02H9.5 37
  • 31 (a)
klo-1 36
  • 31 (a)
ManyToMany
klo-2 36
  • 31 (a)
ManyToMany
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

(2) 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
VAR_023582 -
VAR_023583 -
rs9536314 - 33,054,001(+) CTGAT(A/G/T)TTACT reference, missense
rs9527025 - 33,054,056(+) TCTTT(C/G)CTTTG reference, missense
VAR_036449 A colorectal cancer sample

Variation tolerance for KL Gene

Residual Variation Intolerance Score: 57% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.72; 89.34% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for KL Gene

HapMap Linkage Disequilibrium report
KL
Human Gene Mutation Database (HGMD)
KL

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

Disorders for KL Gene

MalaCards: The human disease database

(17) MalaCards diseases for KL Gene - From: OMIM, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
tumoral calcinosis, hyperphosphatemic, familial
  • tumoral calcinosis, hyperphosphatemic
hyperphosphatemic familial tumoral calcinosis, kl-related
  • kl-related hftc
familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome
  • hypercalcemic tumoral calcinosis
calcinosis
  • pathologic calcification
skin atrophy
  • atrophic condition of skin
- elite association - COSMIC cancer census association via MalaCards
Search KL in MalaCards View complete list of genes associated with diseases

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.

Relevant External Links for KL

Genetic Association Database (GAD)
KL
Human Genome Epidemiology (HuGE) Navigator
KL
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
KL
genes like me logo Genes that share disorders with KL: view

No data available for Genatlas for KL Gene

Publications for KL Gene

  1. 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 67
  2. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. (PMID: 17710231) Ichikawa S. … Econs M.J. (J. Clin. Invest. 2007) 3 23
  3. 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
  4. 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
  5. The demonstration of I+Klotho deficiency in human chronic kidney disease with a novel synthetic antibody. (PMID: 25324355) Barker S.L. … Sidhu S.S. (Nephrol. Dial. Transplant. 2015) 3

Products for KL Gene

Sources for KL Gene

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