FGF2

Chr 4

fibroblast growth factor 2

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

NCBI Gene: 2247 ENSG00000138685 UniProt: P09038 OMIM: 134920

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.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from non-AUG (CUG) and AUG initiation codons, resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

481

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.04

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — FGF2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.018

Z-score 1.49

OE 0.46 (0.22–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.94Z-score

OE missense 0.76 (0.65–0.91)

95 obs / 124.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.22–1.04)

0≤0.351.4

Missense OE?0.76 (0.65–0.91)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 4 / 8.8Missense obs/exp: 95 / 124.4Syn Z: -0.04

Background carrier burden — how many people carry a rare variant somewhere in FGF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

421 rare PASS variants

Rare truncating (LoF)

1 in 2,100

53 rare PASS variants

Rare synonymous (reference)

1 in 250

216 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FGF2. 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 200	1 in 2,000
South Asian	~43k	1 in 150	1 in 1,900
Remaining (unassigned)	~30k	1 in 130	1 in 2,300
European (Finnish)	~27k	1 in 490	1 in 3,600
Admixed American	~22k	1 in 130	1 in 990
African / African American	~21k	1 in 230	1 in 2,800
East Asian	~20k	1 in 120	1 in 1,600
Ashkenazi Jewish	~13k	1 in 760	≈ 1 in 9,500
Middle Eastern	~2,884	1 in 210	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): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓