KLB Gene (Klotho Beta)
A key regulator of FGF19 and FGF21 signaling, involved in bile acid, glucose, and energy metabolism.
Gene Information Card
| Symbol | KLB |
|---|---|
| Full Name | Klotho Beta |
| Gene Type | Protein coding |
| Chromosomal Location | 4p14 |
| NCBI Gene ID | 152831 ncbi.nlm.nih.gov/gene/152831 |
| Ensembl ID | ENSG00000163435 |
| UniProt ID | Q86Z14 |
| OMIM ID | 611135 |
| HGNC ID | 15511 |
| Aliases | BKL, betaKlotho |
Description
KLB encodes a transmembrane protein that functions as a co-receptor for fibroblast growth factors FGF19 and FGF21. It forms a complex with FGFR4 (for FGF19) or FGFR1c (for FGF21) to mediate signaling. KLB is essential for bile acid homeostasis (via FGF19) and for glucose and lipid metabolism (via FGF21).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity and Type 2 Diabetes | KLB is required for FGF21 signaling; reduced KLB expression leads to FGF21 resistance, impairing glucose uptake and energy expenditure. | ClinVar, OMIM |
| Cholestasis and Bile Acid Disorders | KLB mediates FGF19 signaling via FGFR4; loss of function disrupts bile acid synthesis regulation, contributing to cholestatic liver disease. | OMIM, NCBI |
| Hepatocellular Carcinoma | KLB expression is altered in liver cancer; FGF19-KLB-FGFR4 signaling can promote tumor growth. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 5.2 | Medium |
| Adipose Tissue | 3.8 | Low |
| Pancreas | 2.1 | Low |
| Kidney | 1.5 | Low |
| Small Intestine | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 4.5 | Hepatocellular carcinoma cell line |
| Huh-7 | 3.9 | Hepatoma cell line |
| 3T3-L1 (adipocyte) | 2.8 | Differentiated adipocytes |
| HEK293 | 0.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.943G>A (p.Gly315Arg) | Missense | <0.01% | Unknown; predicted to affect protein stability |
| c.1124C>T (p.Thr375Met) | Missense | <0.01% | Unknown; reported in ClinVar |
| c.1465C>T (p.Arg489*) | Nonsense | <0.01% | Loss of function; predicted to truncate protein |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the FGF-binding domain lead to loss of co-receptor function, impairing FGF19/FGF21 signaling.
Gain of Function (GOF)
Not well documented; some missense variants may enhance receptor binding but are not clinically validated.
Dominant Negative (DN)
No known dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • signaling receptor binding (GO:0005102) | • protein binding (GO:0005515) |
| • integral component of membrane (GO:0016021) | • protein homodimerization activity (GO:0042803) |
| • FGF receptor signaling pathway (GO:0060197) |
Pathways
• FGF19 signaling pathway (via FGFR4)
• FGF21 signaling pathway (via FGFR1c)
• Bile acid metabolism
• Glucose and lipid metabolism
Protein Summary
Klotho Beta (KLB) is a 1044-amino acid single-pass transmembrane protein with a large extracellular domain containing two glycosyl hydrolase-like repeats. It acts as a co-receptor for FGF19 and FGF21, forming a ternary complex with specific FGFRs. KLB is predominantly expressed in liver, adipose tissue, and pancreas, and is critical for metabolic homeostasis. Its dysfunction is linked to metabolic diseases and certain cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLB Knockout HEK293 Cell Line | EDJ-KQ3794 | Human | 152831 | Details Get a Quote |
| KLB Knockout A-549 Cell Line | EDJ-KQ25903 | Human | 152831 | Details Get a Quote |
| KLB Knockout HeLa Cell Line | EDJ-KQ58717 | Human | 152831 | Details Get a Quote |
| KLB Knockout HCT 116 Cell Line | EDJ-KQ75604 | Human | 152831 | Details Get a Quote |
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