FGF2

protein-coding

fibroblast growth factor 2, the group of Receptor ligands|Fibroblast growth factor family

Gene summary

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]

Previous symbols:

FGFB

MANE transcript

NM_001361665.2

Inheritance

—

ClinVar variants

U:15B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr4:122,826,682-122,898,236

External References & Databases

Ensembl (ENSG00000138685)

Transcript & Mutation Effects

hg38 • Region Span ~71.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FGF2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 15

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001361665.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			15 clinvar	1 clinvar		16
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	15	2	0	17

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001361665.2	RefSeq	NP_001348594.1	3	MANE Select
ENST00000644866.2	Ensembl	ENSP00000494222.1	3	MANE Select
NM_002006.6	RefSeq	NP_001997.5	3	Standard
ENST00000264498.10	Ensembl	ENSP00000264498.4	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fgf2	Danio rerio	Structure: whole organism Quality: lethal (sensu genetics) abnormal

Gene / Model

Organism

Observed Phenotype

fgf2

Danio rerio

Structure: whole organism

Quality: lethal (sensu genetics)

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Gastric cancer - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Melanoma - Homo sapiens (human)
Breast cancer - Homo sapiens (human)

Biological Process

MAPK cascade
activation of MAPK activity
branching involved in ureteric bud morphogenesis
positive regulation of endothelial cell proliferation
cell migration involved in sprouting angiogenesis

Molecular Function

protein tyrosine kinase activity
Ras guanyl-nucleotide exchange factor activity
fibroblast growth factor receptor binding
cytokine activity
integrin binding

Cellular Component

extracellular region
extracellular space
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264498
Coding exons: 3
Length: 71529
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.937	95	124	0.764	0.00000615	1763
Missense (PolyPhen)		25	38.556	0.6484		458
Synonymous	-0.0366	52	51.7	1.01	0.00000243	661
Loss of Function	1.49	4	8.78	0.456	5.71e-7	99

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:8663044). Also acts as an integrin ligand which is required for FGF2 signaling (PubMed:28302677). Binds to integrin ITGAV:ITGB3 (PubMed:28302677). Plays an important role in the regulation of cell survival, cell division, cell differentiation and cell migration (PubMed:8663044, PubMed:28302677). Functions as a potent mitogen in vitro (PubMed:3732516, PubMed:3964259). Can induce angiogenesis (PubMed:23469107, PubMed:28302677). {ECO:0000269|PubMed:1721615, ECO:0000269|PubMed:23469107, ECO:0000269|PubMed:28302677, ECO:0000269|PubMed:3732516, ECO:0000269|PubMed:3964259, ECO:0000269|PubMed:8663044}.;

Recessive Scores

pRec: 0.894

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.429

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium