FGF4

protein-coding

fibroblast growth factor 4, 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 gene was identified by its oncogenic transforming activity. This gene and FGF3, another oncogenic growth factor, are located closely on chromosome 11. Co-amplification of both genes was found in various kinds of human tumors. Studies on the mouse homolog suggested a function in bone morphogenesis and limb development through the sonic hedgehog (SHH) signaling pathway. [provided by RefSeq, Jul 2008]

Previous symbols:

HSTF1

MANE transcript

NM_002007.4

Inheritance

ClinVar variants

P:1U:28B:3

Top phenotype

Short-rib thoracic dysplasia 22 without polydactyly

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr11:69,771,022-69,775,341

External References & Databases

Ensembl (ENSG00000075388)

Transcript & Mutation Effects

hg38 • Region Span ~4.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

thoracic malformationLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0015929

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FGF4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 29

not providedTotal: 3

Short-rib thoracic dysplasia 22 without polydactylyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002007.4. 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	1 clinvar		28 clinvar	2 clinvar		31
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	28	3	0	32

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002007.4	RefSeq	NP_001998.1	3	MANE Select
ENST00000168712.3	Ensembl	ENSP00000168712.1	3	MANE Select
ENST00001137774.1	Ensembl	ENSP00000801327.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fgf4	Danio rerio	Structure: trunk Quality: bent abnormal

Gene / Model

Organism

Observed Phenotype

fgf4

Danio rerio

Structure: trunk

Quality: bent

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
cartilage condensation
signal transduction
cell-cell signaling
positive regulation of cell population proliferation

Molecular Function

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

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000168712
Coding exons: 3
Length: 2375
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125718
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.00	69	96.8	0.713	0.00000522	1267
Missense (PolyPhen)		30	42.826	0.70051		506
Synonymous	0.0914	45	45.8	0.983	0.00000283	440
Loss of Function	1.45	2	5.77	0.347	3.32e-7	74

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	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal limb and cardiac valve development during embryogenesis. {ECO:0000269|PubMed:8663044}.;

Recessive Scores

pRec: 0.609

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.146

Gene Damage Prediction

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