FGF2

Chr 4

fibroblast growth factor 2

Also known as: BFGF, FGF-2, FGFB, HBGF-2

This protein functions as a fibroblast growth factor that binds to multiple FGF receptors and integrins to regulate cell survival, division, differentiation, migration, and angiogenesis, with particular importance in limb and nervous system development. Mutations in FGF2 cause craniosynostosis, and the gene shows tolerance to loss-of-function variants based on population genetics data. Inheritance pattern has not been definitively established for FGF2-related craniosynostosis.

Summary from RefSeq, UniProt
Research Assistant →
5
Active trials
314
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
1.04
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryFGF2
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 55 VUS of 99 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — FGF2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.018
Z-score 1.49
OE 0.46 (0.221.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.94Z-score
OE missense 0.76 (0.650.91)
95 obs / 124.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.46 (0.221.04)
00.351.4
Missense OE0.76 (0.650.91)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 4 / 8.8Missense obs/exp: 95 / 124.4Syn Z: -0.04
DN
0.6356th %ile
GOF
0.73top 25%
LOF
0.4726th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

99 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic1
VUS55
Likely Benign7
Benign2
24
Pathogenic
1
Likely Pathogenic
55
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
1
0
1
VUS
0
48
7
0
55
Likely Benign
0
4
0
3
7
Benign
0
1
1
0
2
Total05333389

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

View in ClinVar →

Protein Context — Lollipop Plot

FGF2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Clinical Literature
Open Research Assistant →