FGF19

Chr 11

fibroblast growth factor 19

NCBI Gene: 9965 ENSG00000162344 UniProt: O95750 OMIM: 603891

This protein is a fibroblast growth factor that suppresses bile acid biosynthesis by down-regulating CYP7A1 expression and stimulates glucose uptake in adipocytes, functioning through FGFR4 and requiring KLB as a co-receptor. Mutations in FGF19 cause bile acid synthesis defect, congenital, 4, which follows autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants and is expressed in fetal brain tissue during development.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

183

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.12

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.93Z-score

OE missense 0.72 (0.59–0.89)

63 obs / 87.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.12)

0≤0.351.4

Missense OE?0.72 (0.59–0.89)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 0 / 2.6Missense obs/exp: 63 / 87.4Syn Z: 0.57

Background carrier burden — how many people carry a rare variant somewhere in FGF19?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

270 rare PASS variants

Rare truncating (LoF)

1 in 20,000

19 rare PASS variants

Rare synonymous (reference)

1 in 700

136 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FGF19. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 26,000
South Asian	~43k	1 in 240	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 200	1 in 5,600
European (Finnish)	~27k	1 in 490	≈ 1 in 27,000
Admixed American	~22k	1 in 170	none seen
African / African American	~21k	1 in 200	≈ 1 in 4,300
East Asian	~20k	1 in 220	≈ 1 in 9,800
Ashkenazi Jewish	~13k	≈ 1 in 2,600	none seen
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 3.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

FGF19 is a biomarker associated with prognosis and immunity in colorectal cancer

Wang P et al.·Int J Immunopathol Pharmacol

2025