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KL klotho [ Homo sapiens (human) ]

Gene ID: 9365, updated on 2-Nov-2024

Summary

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Official Symbol
KLprovided by HGNC
Official Full Name
klothoprovided by HGNC
Primary source
HGNC:HGNC:6344
See related
Ensembl:ENSG00000133116 MIM:604824; AllianceGenome:HGNC:6344
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
KLA; HFTC3
Summary
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]
Expression
Biased expression in kidney (RPKM 80.6), placenta (RPKM 14.7) and 1 other tissue See more
Orthologs
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Genomic context

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Location:
13q13.1
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (33016243..33066143)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (32233557..32283464)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (33590561..33640280)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr13:33395368-33395536 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7565 Neighboring gene long intergenic non-protein coding RNA 423 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7566 Neighboring gene TOMM22 pseudogene 3 Neighboring gene translation initiation factor IF-2-like Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:33590165-33590740 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:33590741-33591318 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5254 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7567 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr13:33666443-33666999 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7568 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7569 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7570 Neighboring gene StAR related lipid transfer domain containing 13 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7571 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7572 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr13:33760051-33761250 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7573 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:33770183-33770373 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7574 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7575 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5255 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7576 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:33834523-33835023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7577 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7578 Neighboring gene STARD13 antisense RNA Neighboring gene long intergenic non-protein coding RNA 2344

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Soluble klotho as a marker of renal fibrosis and podocyte injuries in human kidneys. Cho NJ, et al. PLoS One, 2018. PMID 29590173, Free PMC Article
  2. Association Between Klotho Gene Polymorphism and Markers of Bone Metabolism in Patients Receiving Maintenance Hemodialysis in Iran. Nazarian A, et al. Iran J Kidney Dis, 2017 Nov. PMID 29190606
  3. Relationship of low-circulating "anti-aging" klotho hormone with disability in activities of daily living among older community-dwelling adults. Crasto CL, et al. Rejuvenation Res, 2012 Jun. PMID 22530731, Free PMC Article
  4. The KL-VS polymorphism of KLOTHO gene is protective against retinopathy incidence in patients with type 1 diabetes. Słomiński B, et al. Biochim Biophys Acta Mol Basis Dis, 2018 Mar. PMID 29247834
  5. The role of klotho in systemic sclerosis. Talotta R, et al. Reumatismo, 2017 Dec 21. PMID 29320841

See all (529) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Abnormal Histopathological Expression of Klotho, Ferroptosis, and Circadian Clock Regulators in Pancreatic Ductal Adenocarcinoma: Prognostic Implications and Correlation Analyses.
    Title: Abnormal Histopathological Expression of Klotho, Ferroptosis, and Circadian Clock Regulators in Pancreatic Ductal Adenocarcinoma: Prognostic Implications and Correlation Analyses.
  2. Gender-specific association between circulating serum Klotho and metabolic components in adults.
    Title: Gender-specific association between circulating serum Klotho and metabolic components in adults.
  3. Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging.
    Title: Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging.
  4. Apolipoproteine and KLOTHO Gene Variants Do Not Affect the Penetrance of Fragile X-Associated Tremor/Ataxia Syndrome.
    Title: Apolipoproteine and KLOTHO Gene Variants Do Not Affect the Penetrance of Fragile X-Associated Tremor/Ataxia Syndrome.
  5. The association between serum soluble alpha-Klotho and thyroid profile among adults from NHANES 2007-2012.
    Title: The association between serum soluble α-Klotho and thyroid profile among adults from NHANES 2007-2012.
  6. Association of Alpha-Klotho with regulation of Keap1/Nrf2/Interleukin-1 pathway and AMPA receptor trafficking in the brain of suicide victims.
    Title: Association of Α-Klotho with regulation of Keap1/Nrf2/Interleukin-1 pathway and AMPA receptor trafficking in the brain of suicide victims.
  7. Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation.
    Title: Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation.
  8. ADAM10 as a major activator of reactive oxygen species production and klotho shedding in podocytes under diabetic conditions.
    Title: ADAM10 as a major activator of reactive oxygen species production and klotho shedding in podocytes under diabetic conditions.
  9. alpha-Klotho levels in girls with central precocious puberty: potential as a diagnostic and monitoring marker.
    Title: α-Klotho levels in girls with central precocious puberty: potential as a diagnostic and monitoring marker.
  10. Relationships of serum FGF23 and alpha-klotho with atherosclerosis in patients with type 2 diabetes mellitus.
    Title: Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus.
Submit: New GeneRIF Correction See all GeneRIFs (489)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Tumoral calcinosis, hyperphosphatemic, familial, 3
MedGen: C4693864 OMIM: 617994 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables beta-glucosidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables beta-glucuronidase activity IEA
Inferred from Electronic Annotation
more info
  
enables fibroblast growth factor binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables fibroblast growth factor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables fibroblast growth factor receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables hormone activity IEA
Inferred from Electronic Annotation
more info
  
enables vitamin D binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in calcium ion homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in carbohydrate metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in determination of adult lifespan IEA
Inferred from Electronic Annotation
more info
  
involved_in energy reserve metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in fibroblast growth factor receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of systemic arterial blood pressure IEA
Inferred from Electronic Annotation
more info
  
involved_in norepinephrine biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of bone mineralization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in response to activity IEA
Inferred from Electronic Annotation
more info
  
involved_in response to angiotensin IEA
Inferred from Electronic Annotation
more info
  
involved_in response to vitamin D IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in apical plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in extracellular space TAS
Traceable Author Statement
more info
 PubMed 
located_in membrane TAS
Traceable Author Statement
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
klotho
Names
alpha-klotho
NP_004786.2
XP_006719958.1
XP_047286731.1
XP_047286732.1
XP_054231165.1
XP_054231166.1
XP_054231167.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011485.2 RefSeqGene

    Range
    5182..54902
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_004795.4 → NP_004786.2  klotho precursor

    See identical proteins and their annotated locations for NP_004786.2

    Status: REVIEWED

    Source sequence(s)
    AA890465, AB005142, AL161898
    Consensus CDS
    CCDS9347.1
    UniProtKB/Swiss-Prot
    Q5VZ95, Q96KV5, Q96KW5, Q9UEF7, Q9UEI9, Q9Y4F0
    Related
    ENSP00000369442.3, ENST00000380099.4
    Conserved Domains (1) summary
    cl23725
    Location:58 → 506
    Glyco_hydro_1; Glycosyl hydrolase family 1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

    Range
    33016243..33066143
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006719895.3 → XP_006719958.1  klotho isoform X1

    Conserved Domains (1) summary
    cl23725
    Location:210 → 646
    Glyco_hydro_1; Glycosyl hydrolase family 1

  2. XM_047430776.1 → XP_047286732.1  klotho isoform X3

  3. XM_047430775.1 → XP_047286731.1  klotho isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060937.1 Alternate T2T-CHM13v2.0

    Range
    32233557..32283464
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054375190.1 → XP_054231165.1  klotho isoform X1

  2. XM_054375192.1 → XP_054231167.1  klotho isoform X3

  3. XM_054375191.1 → XP_054231166.1  klotho isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_153683.2: Suppressed sequence

    Description
    NM_153683.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UEF7.2 GenPept UniProtKB/Swiss-Prot:Q9UEF7

Gene LinkOut

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