FGF19: Fibroblast Growth Factor 19 – Bile Acid Regulation and Cancer Signaling
A key endocrine fibroblast growth factor involved in bile acid homeostasis, hepatocyte proliferation, and oncogenic signaling in hepatocellular carcinoma and colorectal cancer.
Gene Information Card
| Symbol | FGF19 |
|---|---|
| Full Name | Fibroblast Growth Factor 19 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.3 |
| NCBI Gene ID | 9965 ncbi.nlm.nih.gov/gene/9965 |
| Ensembl ID | ENSG00000162344 |
| UniProt ID | O95750 |
| OMIM ID | 603891 |
| HGNC ID | 3675 |
| Aliases | FGF15 (rodent ortholog) |
Description
FGF19 (Fibroblast Growth Factor 19) is a member of the fibroblast growth factor family. Unlike canonical FGFs, FGF19 functions as an endocrine hormone. It is primarily expressed in the ileum and secreted in response to bile acid absorption. FGF19 binds to the FGFR4/β-Klotho receptor complex to regulate bile acid synthesis, glucose metabolism, and hepatocyte proliferation. Dysregulation of FGF19 is implicated in hepatocellular carcinoma, colorectal cancer, and cholestatic liver diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | FGF19 amplification and overexpression activate FGFR4 signaling, promoting hepatocyte proliferation and tumorigenesis. | COSMIC; NCBI Gene; PMID: 22919067 |
| Colorectal cancer | FGF19 overexpression via β-catenin/TCF signaling contributes to tumor growth and invasion. | NCBI Gene; PMID: 18413744 |
| Cholestatic liver disease | Elevated FGF19 levels suppress CYP7A1, reducing bile acid synthesis and contributing to cholestasis. | OMIM #603891; PMID: 15905404 |
| Bile acid diarrhea | Reduced FGF19 expression leads to impaired feedback inhibition of bile acid synthesis, causing diarrhea. | ClinVar; PMID: 23337448 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Ileum | 58.2 | High |
| Gallbladder | 42.1 | High |
| Liver | 1.3 | Low |
| Colon | 0.8 | Low |
| Kidney | 0.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (hepatocellular carcinoma) | 12.5 | Moderate expression; used in FGF19 signaling studies |
| Caco-2 (colorectal adenocarcinoma) | 8.3 | Low expression; induced by bile acids |
| HEK293 (embryonic kidney) | 0.1 | Not detected; used for recombinant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; likely loss of function |
| c.217C>T (p.Arg73Trp) | Missense | Rare | Unknown significance; reported in ClinVar |
| Amplification (11q13.3) | Copy number gain | ~15% in HCC (COSMIC) | Gain of function; drives FGFR4 signaling |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Met1?) that disrupt protein translation or secretion are classified as loss of function.
Gain of Function (GOF)
Gene amplification and overexpression in hepatocellular carcinoma and colorectal cancer lead to constitutive activation of FGFR4 signaling.
Dominant Negative (DN)
No dominant negative mutations have been reported for FGF19.
View complete mutation data：
Gene Ontology (GO)
Pathways
• FGF19-FGFR4 signaling pathway (Reactome: R-HSA-190374)
• Bile acid and bile salt metabolism (Reactome: R-HSA-194068)
• FGFR4 mutant receptor activation (Reactome: R-HSA-1839122)
• Signaling by FGFR4 in hepatocellular carcinoma (KEGG: hsa05225)
Protein Summary
FGF19 is a 216-amino acid secreted glycoprotein (UniProt O95750) that functions as an endocrine fibroblast growth factor. It contains a core FGF homology domain and a C-terminal tail essential for binding to β-Klotho. The protein is synthesized as a preproprotein and cleaved to release the mature hormone. FGF19 signals through the FGFR4/β-Klotho receptor complex to regulate bile acid synthesis via repression of CYP7A1. It also promotes hepatocyte proliferation and glucose metabolism. Aberrant FGF19 signaling due to amplification or overexpression is oncogenic in liver and colorectal cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FGF19 Knockout HEK293 Cell Line | EDJ-KQ660 | Human | 9965 | Details Get a Quote |
| FGF19 Knockout HCT 116 Cell Line | EDJ-KQ19168 | Human | 9965 | Details Get a Quote |
Displaying Records 1 To 2 Of 2 Records
