FRS3: Fibroblast Growth Factor Receptor Substrate 3
A key adaptor protein in FGF and neurotrophin signaling pathways
Gene Information Card
| Symbol | FRS3 |
|---|---|
| Full Name | Fibroblast Growth Factor Receptor Substrate 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.1 |
| NCBI Gene ID | 10817 ncbi.nlm.nih.gov/gene/10817 |
| Ensembl ID | ENSG00000111837 |
| UniProt ID | O43559 |
| OMIM ID | 607744 |
| HGNC ID | 3968 |
| Aliases | SNT-2, SNT2, FRS2B |
Description
FRS3 (Fibroblast Growth Factor Receptor Substrate 3) encodes a member of the fibroblast growth factor receptor substrate family. This adaptor protein links activated FGF receptors and neurotrophin receptors to downstream signaling pathways, including the RAS/MAPK cascade. FRS3 is involved in cell proliferation, differentiation, and survival. It is structurally similar to FRS2 but has distinct tissue expression and binding partners.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | FRS3 overexpression may enhance FGF signaling, promoting tumor growth and metastasis. | COSMIC; PMID: 25691885 |
| Lung cancer | Somatic mutations in FRS3 have been identified, potentially altering MAPK pathway activation. | COSMIC; PMID: 22980975 |
| Gastric cancer | FRS3 amplification and overexpression linked to poor prognosis. | COSMIC; PMID: 23542377 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 7.8 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.1 | Embryonic kidney cells |
| A549 | 8.5 | Lung carcinoma |
| MCF7 | 12.3 | Breast adenocarcinoma |
| HepG2 | 5.6 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gly116Arg | Missense | 0.02% | Alters SH2 domain binding |
| p.Pro204Leu | Missense | 0.01% | Unknown functional impact |
| p.Arg248* | Nonsense | <0.01% | Truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg248*) lead to truncated protein lacking C-terminal binding sites.
Gain of Function (GOF)
Missense mutations in the PTB domain may enhance FRS3 recruitment to receptors.
Dominant Negative (DN)
Not well characterized; potential interference with FRS2 signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• FGF signaling pathway (KEGG: hsa04010)
• MAPK signaling pathway (KEGG: hsa04010)
• RAS signaling pathway (Reactome: R-HSA-5673001)
• Signaling by NTRK1 (TRKA) (Reactome: R-HSA-187037)
Protein Summary
FRS3 is a 492-amino acid adaptor protein containing an N-terminal myristoylation site, a phosphotyrosine-binding (PTB) domain, and multiple C-terminal tyrosine phosphorylation sites. It localizes to the plasma membrane and is phosphorylated upon FGF or NGF stimulation, recruiting GRB2 and SOS to activate RAS/MAPK signaling. FRS3 is expressed in neural and epithelial tissues and is implicated in cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FRS3 Knockout HEK293 Cell Line | EDJ-KQ7181 | Human | 10817 | Details Get a Quote |
| FRS3 Knockout A-549 Cell Line | EDJ-KQ32112 | Human | 10817 | Details Get a Quote |
| FRS3 Knockout HCT 116 Cell Line | EDJ-KQ32113 | Human | 10817 | Details Get a Quote |
| FRS3 Knockout HeLa Cell Line | EDJ-KQ32114 | Human | 10817 | Details Get a Quote |
