FGF1

protein-coding

fibroblast growth factor 1, 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 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 protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]

Previous symbols:

FGFA

MANE transcript

NM_000800.5

Inheritance

—

ClinVar variants

U:16B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr5:142,592,178-142,698,070

External References & Databases

Ensembl (ENSG00000113578)

Transcript & Mutation Effects

hg38 • Region Span ~105.9 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 FGF1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 15

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000800.5. 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						0
missense			15 clinvar		1 clinvar	16
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	16	0	1	17

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 125 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000800.5	RefSeq	NP_000791.1	3	MANE Select
ENST00000337706.7	Ensembl	ENSP00000338548.2	3	MANE Select
NM_001144892.3	RefSeq	NP_001138364.1	3	Standard
NM_001144934.2	RefSeq	NP_001138406.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fgf1a	Danio rerio	Structure: post-vent region Quality: kinked abnormal

Gene / Model

Organism

Observed Phenotype

fgf1a

Danio rerio

Structure: post-vent region

Quality: kinked

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)
Melanoma - Homo sapiens (human)
Breast cancer - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)

Biological Process

MAPK cascade
activation of MAPK activity
angiogenesis
organ induction
signal transduction

Molecular Function

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

Cellular Component

extracellular region
extracellular space
nucleolus
cytosol
cell cortex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359370
Coding exons: 3
Length: 105875
Individuals with no LoFs: 125740
Homozygous LoFs: 1
Heterozygous LoFs: 3
Defined: 125744
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.464	77	89.4	0.862	0.00000484	1022
Missense (PolyPhen)		32	38.952	0.82153		433
Synonymous	-0.682	45	39.5	1.14	0.00000249	295
Loss of Function	1.78	1	5.49	0.182	2.29e-7	75

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000089	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:18441324, PubMed:20422052). Can induce angiogenesis (PubMed:23469107). {ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:20145243, ECO:0000269|PubMed:20422052, ECO:0000269|PubMed:23469107, ECO:0000269|PubMed:8663044}.;

Recessive Scores

pRec: 0.952

Intolerance Scores

LoFtool: 0.258
RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.903

Gene Damage Prediction

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