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FLASH GENE
Symbol KLB contributors: mct - updated : 19-03-2020
HGNC name klotho beta
HGNC id 15527
Location 4p14      Physical location : 39.408.472 - 39.453.151
Synonym name
  • klotho beta like protein
  • BetaKlotho
  • Synonym symbol(s) MGC142213, BKL
    DNA
    TYPE functioning gene
    STRUCTURE 44.68 kb     5 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 6079 119.6 1044 - 2007 17627937
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   moderately Homo sapiens
     pancreas exocrine     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificadipocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an extracellular domains with two internal repeats, each repeat sharing 20-40 p100 sequence identity to mammalian lactase glycosylceramidase, beta-glucosidase-like domain
  • C-terminal region is critical for Klotho specificity determination and interaction
  • HOMOLOGY
    Homologene
    FAMILY
  • glycosyl hydrolase 1 family
  • klotho subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    text integral to membrane
    basic FUNCTION
  • acting as a glucosidase
  • plays a critical role in the regulation of calcium and phosphorus homeostasis by negatively regulating active vitamin D synthesis
  • plays a protective role against lipotoxicity and inflammation in hepatocytes
  • required for FGF19 binding to FGFR4, intracellular signaling, and downstream modulation of gene expression
  • required for FGF21 to activate two specific FGFR subtypes: FGFR1c and FGFR3c
  • regulating FGF21 (its expression is a crucial determinant of the FGF21 specificity of the target cells upon which it acts in an endocrine fashion)
  • may play a central role by binding to and recruiting FGF21 to FGFR to induce activation
  • key regulator of bile acid/cholesterol metabolism
  • indispensible role in FGF21-induced ERK1/2 activation, GLUT1 gene transactivation, and glucose uptake in adipocytes
  • suppresses tumor growth in hepatocellular carcinom
  • link of ER stress with up-regulation of hepatic KLB expression and the molecular mechanism underlying ER stress-regulated FGF21 signaling
  • pro-adipogenic role for KLB in skeletal muscle fibro/adipogenesis
  • inhibits epithelial&
  • 8209;mesenchymal transition (EMT) and plays a tumor&
    8209;suppressive role in PCa, linking FGF/FGFR/KLB signaling to the regulation of Prostate cancer (PCa) progression
  • is a gatekeeper of hepatic integrity through direct action (mediating FGF21 anti-inflammatory signaling) and indirect mechanisms (mediating FGF19 signaling that maintains bile acid (BA) level and composition)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
  • FGF21/KLB/FGFR1 signaling plays an essential role in GnRH biology, potentially linking metabolism with reproduction
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • functions as a cofactor essential for FGF21 activity
  • essential cofactor for FGF23 to activate FGF23 signaling
  • interacts directly with FGF19 and FGF21 but not with FGF23
  • novel FGFR4 coreceptor required for FGF19 liver specific functions
  • interacting with FGF19
  • not only interacts with heparan sulfate-FGFR4 to form a complex with high affinity for endocrine FGF19 but also impacts the quality of downstream signaling and biological end points activated by either FGF19 or canonical FGF1
  • both FGF19 and FGF21 but not FGF1 exhibit binding affinity to KLB
  • is essential for FGF21 activity and KLB in adipose tissue contributes to the beneficial metabolic actions of FGF21
  • KLB is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans
  • KLB serves as a primary 'zip code'-like receptor that acts as a targeting signal for FGF21, and FGFR functions as a catalytic subunit that mediates intracellular signalling
  • is an obligate coreceptor, mediating both fibroblast growth factor FGF19 and FGF21 signaling
  • cell & other
    REGULATION
    induced by during differentiation from preadipocytes to adipocytes
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    could increase renal damage induced by angiotensin II
    tumoral     --over  
    inhibited prostate tumor growth and epithelial&8209;mesenchymal transition (EMT)
    constitutional germinal mutation     loss of function
    in Congenital hypogonadotropic hypogonadism (CHH)
    tumoral       loss of function
    in human hepatocellular carcinoma tissues compared with that in paired adjacent non-tumourous liver tissues
    Susceptibility
  • to severity of Non-alcoholic fatty liver disease (NAFLD) in pediatric patients
  • Variant & Polymorphism other
  • association between the rs17618244 KLB variant, which leads to reduced KLB expression, and the severity of NAFLD in pediatric patients
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Klb-/- mice are refractory to metabolic Fgf19 and Fgf21 action and exhibit derepressed (increased) bile acid (BA) synthesis
  • in mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to Fgf21