Aliases for KLB Gene

Aliases for KLB Gene

  • Klotho Beta 2 3 5
  • Klotho Beta-Like Protein 3 4
  • Beta-Klotho 3 4
  • BetaKlotho 3 4
  • B-Klotho 2 3
  • BKL 3 4
  • Klotho Beta Like 3
  • EC 3.2.1 50
  • KLB 5

External Ids for KLB Gene

Previous GeneCards Identifiers for KLB Gene

  • GC04P039232
  • GC04P039084
  • GC04P038733

Summaries for KLB Gene

GeneCards Summary for KLB Gene

KLB (Klotho Beta) is a Protein Coding gene. Diseases associated with KLB include Outlet Dysfunction Constipation and Functional Diarrhea. Among its related pathways are RET signaling and Downstream signaling of activated FGFR2. Gene Ontology (GO) annotations related to this gene include hydrolase activity, hydrolyzing O-glycosyl compounds and fibroblast growth factor binding. An important paralog of this gene is KL.

UniProtKB/Swiss-Prot Summary for KLB Gene

  • Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of FGFR1 and FGFR4 to bind FGF21 (By similarity).

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KLB Gene

Genomics for KLB Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KLB Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J039407 Promoter 1 Ensembl 250.7 +0.2 171 0.2 CEBPA ATF3 YY1 HOMEZ KMT2B THAP11 SMAD4 RXRA ZNF511 SAP130 KLB MIR5591 RPL9
GH04J039406 Promoter 1 EPDnew 250.7 0.0 -19 0.1 CEBPA ATF3 YY1 HOMEZ KMT2B THAP11 SMAD4 RXRA ZNF511 SAP130 KLB RNU6-887P RFC1
GH04J039408 Enhancer 0.3 Ensembl 250.7 +0.6 571 0.2 KAT7 ZGPAT KLB MIR5591 RPL9
GH04J039468 Promoter/Enhancer 1.5 Ensembl ENCODE CraniofacialAtlas dbSUPER 10.3 +62.6 62606 1.5 ZNF654 IKZF1 ZNF592 KLF9 CEBPA YY1 CTCF REST TRIM22 HOMEZ RPL9 PDS5A ENSG00000255458 SMIM14 KLB RNU6-887P HSALNG0033952 LIAS NONHSAG037782.2 UGDH
GH04J039352 Enhancer 1.4 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 11 -53.1 -53092 3.2 BCLAF1 YY1 BCL11A ZNF592 TRIM22 ZNF639 IRF2 RXRA IRF4 CBFB RNU6-887P KLB RNU6-32P WDR19 RFC1 ENSG00000249685 lnc-RPL9-2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KLB on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KLB

Top Transcription factor binding sites by QIAGEN in the KLB gene promoter:
  • ARP-1
  • CUTL1
  • HOXA9
  • HOXA9B
  • Meis-1
  • Meis-1b
  • Pax-3
  • RSRFC4
  • Sox9
  • TGIF

Genomic Locations for KLB Gene

Latest Assembly
chr4:39,406,930-39,451,533
(GRCh38/hg38)
Size:
44,604 bases
Orientation:
Plus strand

Previous Assembly
chr4:39,408,550-39,453,153
(GRCh37/hg19 by Entrez Gene)
Size:
44,604 bases
Orientation:
Plus strand

chr4:39,408,473-39,453,156
(GRCh37/hg19 by Ensembl)
Size:
44,684 bases
Orientation:
Plus strand

Genomic View for KLB Gene

Genes around KLB on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLB Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLB Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KLB Gene

Proteins for KLB Gene

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

    Protein Symbol:
    Q86Z14-KLOTB_HUMAN
    Recommended name:
    Beta-klotho
    Protein Accession:
    Q86Z14
    Secondary Accessions:
    • Q2M3K8

    Protein attributes for KLB Gene

    Size:
    1044 amino acids
    Molecular mass:
    119808 Da
    Quaternary structure:
    • Interacts with FGFR1 and FGFR4 (By similarity). Interacts with FGF19; this interaction is direct. Interacts (via C-terminus) with FGF21; this interaction is direct.

    Three dimensional structures from OCA and Proteopedia for KLB Gene

neXtProt entry for KLB Gene

Selected DME Specific Peptides for KLB Gene

Q86Z14:
  • VKYWITI
  • GLFYVDF

Post-translational modifications for KLB Gene

  • Glycosylation at Asn71, Asn120, Asn125, Asn211, Asn308, Asn391, Asn554, Asn611, Asn702, Asn706, and Asn971
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • KLOTB_HUMAN (1040)

Other Protein References for KLB Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for KLB Gene

Gene Families for KLB Gene

Protein Domains for KLB Gene

Suggested Antigen Peptide Sequences for KLB Gene

GenScript: Design optimal peptide antigens:
  • KLB protein (B7ZL50_HUMAN)
  • Klotho beta-like protein (KLOTB_HUMAN)
  • KLB protein (Q49AQ7_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q86Z14

UniProtKB/Swiss-Prot:

KLOTB_HUMAN :
  • Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 241, and the second one lacks the essential Glu active site residue at position 889. These domains are therefore predicted to be inactive.
  • 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 241, and the second one lacks the essential Glu active site residue at position 889. These domains are therefore predicted to be inactive.
Family:
  • Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.
genes like me logo Genes that share domains with KLB: view

Function for KLB Gene

Molecular function for KLB Gene

UniProtKB/Swiss-Prot Function:
Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of FGFR1 and FGFR4 to bind FGF21 (By similarity).

Enzyme Numbers (IUBMB) for KLB Gene

Phenotypes From GWAS Catalog for KLB Gene

Gene Ontology (GO) - Molecular Function for KLB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds IEA --
GO:0005104 fibroblast growth factor receptor binding IBA,IPI 17627937
GO:0005515 protein binding IPI 19059246
GO:0017134 fibroblast growth factor binding IPI 18829467
genes like me logo Genes that share ontologies with KLB: view
genes like me logo Genes that share phenotypes with KLB: view

Animal Models for KLB Gene

MGI Knock Outs for KLB:
  • Klb Klb<tm1.1Akha>
  • Klb Klb<tm1.2Sakl>
  • Klb Klb<tm1Yin>

Animal Models for research

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLB

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for KLB Gene

Localization for KLB Gene

Subcellular locations from UniProtKB/Swiss-Prot for KLB Gene

Cell membrane. Single-pass type III membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KLB gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 4
extracellular 2
mitochondrion 2
peroxisome 2
nucleus 2
cytosol 2
cytoskeleton 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for KLB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IBA 21873635
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with KLB: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for KLB Gene

Pathways & Interactions for KLB Gene

PathCards logo

SuperPathways for KLB Gene

SuperPathway Contained pathways
1 RET signaling
2 PI3K/AKT activation
3 Downstream signaling of activated FGFR2
4 Developmental Biology
5 Cytokine Signaling in Immune system
genes like me logo Genes that share pathways with KLB: view

Pathways by source for KLB Gene

Gene Ontology (GO) - Biological Process for KLB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0005975 carbohydrate metabolic process IEA --
GO:0008284 positive regulation of cell proliferation IEA --
GO:0008543 fibroblast growth factor receptor signaling pathway IEA,TAS --
GO:0051897 positive regulation of protein kinase B signaling TAS --
genes like me logo Genes that share ontologies with KLB: view

No data available for SIGNOR curated interactions for KLB Gene

Drugs & Compounds for KLB Gene

(1) Drugs for KLB Gene - From: PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Ethanol Approved Pharma 3544
genes like me logo Genes that share compounds with KLB: view

Transcripts for KLB Gene

mRNA/cDNA for KLB Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLB

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

No ASD Table

Relevant External Links for KLB Gene

GeneLoc Exon Structure for
KLB

Expression for KLB Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KLB Gene

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

This gene is overexpressed in Liver (x17.2), Adipose - Subcutaneous (x7.6), and Adipose - Visceral (Omentum) (x7.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for KLB Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KLB

SOURCE GeneReport for Unigene cluster for KLB Gene:

Hs.90756

Evidence on tissue expression from TISSUES for KLB Gene

  • Liver(4.6)
  • Gall bladder(2.7)
  • Nervous system(2.5)
  • Intestine(2.3)
  • Pancreas(2.3)
  • Blood(2.2)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with KLB: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for KLB Gene

Orthologs for KLB Gene

This gene was present in the common ancestor of animals.

Orthologs for KLB Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KLB 29 30
  • 99.27 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia KLB 29 30
  • 88.69 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia KLB 29 30
  • 87.72 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Klb 29
  • 83.24 (n)
Mouse
(Mus musculus)
Mammalia Klb 29 16 30
  • 81.16 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia KLB 30
  • 77 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia KLB 30
  • 69 (a)
OneToOne
Chicken
(Gallus gallus)
Aves KLB 29 30
  • 71.86 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia KLB 30
  • 62 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia klb 29
  • 60.23 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.13366 29
Zebrafish
(Danio rerio)
Actinopterygii KLB 30
  • 45 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG9701 30
  • 34 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea klo-2 30
  • 31 (a)
ManyToMany
klo-1 30
  • 31 (a)
ManyToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 35 (a)
OneToMany
Species where no ortholog for KLB was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 Vase (Ciona intestinalis)
  • 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 KLB Gene

ENSEMBL:
Gene Tree for KLB (if available)
TreeFam:
Gene Tree for KLB (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KLB: view image
Alliance of Genome Resources:
Additional Orthologs for KLB

Paralogs for KLB Gene

Paralogs for KLB Gene

(4) SIMAP similar genes for KLB Gene using alignment to 3 proteins:

  • KLOTB_HUMAN
  • B7ZL50_HUMAN
  • Q49AQ7_HUMAN
genes like me logo Genes that share paralogs with KLB: view

Variants for KLB Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KLB Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
rs116274139 Benign: not provided 39,434,581(+) G/A
NM_175737.4(KLB):c.1197G>A (p.Ala399=)
SYNONYMOUS
rs138789592 Likely Benign: not provided 39,407,079(+) C/T
NM_175737.4(KLB):c.130C>T (p.Leu44Phe)
MISSENSE
rs140150766 Benign: not provided 39,448,584(+) C/G
NM_175737.4(KLB):c.3033C>G (p.Leu1011=)
SYNONYMOUS
rs143809363 Likely Benign: not provided 39,448,675(+) G/A
NM_175737.4(KLB):c.3124G>A (p.Val1042Ile)
MISSENSE
rs144494424 Benign: not provided 39,434,314(+) G/A
NM_175737.4(KLB):c.930G>A (p.Ser310=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for KLB Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for KLB Gene

Variant ID Type Subtype PubMed ID
esv2665681 CNV deletion 23128226
esv2673187 CNV deletion 23128226
esv3365745 CNV duplication 20981092
esv3600279 CNV gain 21293372
esv3600281 CNV loss 21293372
esv3600282 CNV loss 21293372
esv3600283 CNV gain 21293372
nsv1010189 CNV gain 25217958
nsv1010784 CNV gain 25217958
nsv1109593 CNV deletion 24896259
nsv1114514 CNV deletion 24896259

Variation tolerance for KLB Gene

Residual Variation Intolerance Score: 79.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.67; 78.49% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KLB Gene

Human Gene Mutation Database (HGMD)
KLB
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLB
Leiden Open Variation Database (LOVD)
KLB

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KLB Gene

Disorders for KLB Gene

MalaCards: The human disease database

(4) MalaCards diseases for KLB Gene - From: COP

Disorder Aliases PubMed IDs
outlet dysfunction constipation
functional diarrhea
  • functional diarrhoea
hepatocellular clear cell carcinoma
  • clear cell carcinoma of the liver cells
leber plus disease
  • lhon plus disease
- elite association - COSMIC cancer census association via MalaCards
Search KLB in MalaCards View complete list of genes associated with diseases

Additional Disease Information for KLB

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with KLB: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KLB Gene

Publications for KLB Gene

  1. Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. (PMID: 20800603) Flachsbart F … Nebel A (Mutation research 2010) 3 40
  2. FGF21 signalling pathway and metabolic traits - genetic association analysis. (PMID: 20717167) Kaess BM … Tomaszewski M (European journal of human genetics : EJHG 2010) 3 40
  3. Different roles of N- and C- termini in the functional activity of FGF21. (PMID: 19117008) Micanovic R … Kharitonenkov A (Journal of cellular physiology 2009) 3 4
  4. C-terminal tail of FGF19 determines its specificity toward Klotho co-receptors. (PMID: 18829467) Wu X … Li Y (The Journal of biological chemistry 2008) 3 4
  5. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. (PMID: 17623664) Kurosu H … Kuro-O M (The Journal of biological chemistry 2007) 3 22

Products for KLB Gene

  • Boster Bio Antibodies for KLB
  • Boster Bio ELISA Kits for KLB

Sources for KLB Gene