FGF19

Chr 11

fibroblast growth factor 19

NCBI Gene: 9965ENSG00000162344UniProt: O95750

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes including embryonic development cell growth, morphogenesis, tissue repair, tumor growth and invasion. This growth factor is a high affinity, heparin dependent ligand for FGFR4. Expression of this gene was detected only in fetal but not adult brain tissue. Synergistic interaction of the chick homolog and Wnt-8c has been shown to be required for initiation of inner ear development. [provided by RefSeq, Jul 2008]

36
ClinVar variants
8
Pathogenic / LP
0.57
pLI score
4
Active trials
Clinical Summary— FGF19
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.57) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 27 VUS of 36 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.12LOEUF
pLI 0.570
Z-score 1.49
OE 0.00 (0.00–1.12)
Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.93Z-score
OE missense 0.72 (0.59–0.89)
63 obs / 87.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–1.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.59–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 0 / 2.6Missense obs/exp: 63 / 87.4Syn Z: 0.57

ClinVar Variant Classifications

36 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS27
Likely Benign1
6
Pathogenic
2
Likely Pathogenic
27
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
26
1
0
27
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total0279036

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FGF19 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH.
Tacke F et al.·J Hepatol
2023Review
FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2.
Xie M et al.·J Hepatol
2023
FGF-based drug discovery: advances and challenges.
Chen G et al.·Nat Rev Drug Discov
2025Review
Genetic Landscape and Biomarkers of Hepatocellular Carcinoma.
Zucman-Rossi J et al.·Gastroenterology
2015Review
Bile acid receptor FXR promotes intestinal epithelial ferroptosis and subsequent ILC3 dysfunction in neonatal necrotizing enterocolitis.
Zhang Y et al.·Immunity
2025
Suppressing the intestinal farnesoid X receptor/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis.
Wu Q et al.·J Clin Invest
2021
FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC.
Chen X et al.·Theranostics
2023
FGF19-Activated Hepatic Stellate Cells Release ANGPTL4 that Promotes Colorectal Cancer Liver Metastasis.
Fan X et al.·Adv Sci (Weinh)
2025
Role of signaling pathways in age-related orthopedic diseases: focus on the fibroblast growth factor family.
Li HZ et al.·Mil Med Res
2024Review
Circulating mediators linking cardiometabolic diseases to HFpEF: a mediation Mendelian randomization analysis.
Lin M et al.·Cardiovasc Diabetol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Crohns Disease

Oral N-acetylglucosamine in Crohn's Disease

NOT YET RECRUITING
NCT07225998Phase PHASE2Johns Hopkins UniversityStarted 2026-04-01
N-Acetylglucosamine (GlcNAc)
Advanced Oesophageal Squamous Cell Carcinoma

A Study of Simmitinib Versus Chemotherapy for Participants With Advanced Oesophageal Squamous Cell Carcinoma

NOT YET RECRUITING
NCT06656091Phase PHASE3Shanghai Runshi Pharmaceutical Technology Co., LtdStarted 2024-10-31
simmitinibinvestigator's choice of chemotherapy,include docetaxel or irinotecan.
Solid TumorPrecision Medicine

Precision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion

RECRUITING
NCT06739395Phase PHASE2Tianjin Medical University Second HospitalStarted 2024-11-01
Olaparib tabletTemozolomide capsuleAnlotinib
Metastatic Hepatocellular CarcinomaSolid TumorsSolid Tumor, Adult

Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations

RECRUITING
NCT06915753Phase PHASE1Tyra Biosciences, IncStarted 2025-04-24
TYRA-430

External Resources

Links to major genomics databases and tools