Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
| Gene Symbol | FGFR2 | ||||||||||
| Synonyms | BBDS | BEK | BFR-1 | CD332 | CEK3 | CFD1 | ECT1 | JWS | K-SAM | KGFR | TK14 | TK25 | ||||||||||
| Gene Description | FGFR2, fibroblast growth factor receptor 2, is a receptor tyrosine kinase activated upon binding of the FGF ligand, which activates RAS-MAPK and PI3K-AKT pathways (PMID: 22508544). Altered function of FGFR2 through activating mutations, fusions, and amplification increases cell proliferation and tumorigenesis (PMID: 22508544) and is observed in prostate (PMID: 30761180), breast, lung, uterine, and ovarian cancers (PMID: 29104507), while FGFR2 amplification (PMID: 31076567) and overexpression (PMID: 30662521) is commonly observed in gastric cancer. | ||||||||||
|
|||||||||||
| Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
|---|---|---|---|---|
| A264T | missense | unknown | FGFR2 A264T lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A264T has been identified in the scientific literature (PMID: 26645239), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| A314D | missense | unknown | FGFR2 A314D lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A314D has been identified in sequencing studies (PMID: 18552176), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| A315C | missense | unknown | FGFR2 A315C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A315C has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2021). | |
| A315S | missense | unknown | FGFR2 A315S lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A315S has been identified in sequencing studies (PMID: 17525745), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| A315T | missense | unknown | FGFR2 A315T lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A315T has been identified in the scientific literature (PMID: 17525745), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| A344G | missense | unknown | FGFR2 A344G lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A344G has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| A344P | missense | unknown | FGFR2 A344P lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A344P has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| A389T | missense | no effect - predicted | FGFR2 A389T lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). A389T is not transforming in cell culture (PMID: 18552176), and therefore, it is predicted to have no effect on Fgfr2 protein function. | |
| A553D | missense | unknown | FGFR2 A553D lies within the protein kinase domain of the Ffgr2 protein (UniProt.org). A553D has been predicted to affect the protein stability of Fgfr2 by structural modeling (PMID: 32859654), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2021). | |
| A648T | missense | loss of function | FGFR2 A648T lies within the protein kinase domain of the FGFR2 protein (PMID: 19147536). A648T confers a loss of function to the Fgfr2 protein resulting in a loss of protein kinase activity and reduced downstream MAPK signaling pathway activation (PMID: 19147536). | |
| A97T | missense | unknown | FGFR2 A97T lies within the Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). A97T has been identified in sequencing studies (PMID: 28581676, PMID: 18552176), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| act mut | unknown | gain of function | FGFR2 act mut indicates that this variant results in a gain of function in the Fgfr2 protein. However, the specific amino acid change has not been identified. | |
| amp | none | no effect | FGFR2 amp indicates an increased number of copies of the FGFR2 gene. However, the mechanism causing the increase is unspecified. | |
| C278F | missense | unknown | FGFR2 C278F lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C278F results in increased Fgfr2 dimerization and autophosphorylation, however, also leads to rapid Fgfr2 degradation (PMID: 16844695), impaired Erk and Tgf-beta signaling, and decreased cell viability in culture (PMID: 20004243), and therefore, its effect on Fgfr2 protein function is unknown. | |
| C342F | missense | unknown | FGFR2 C342F lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C342F has been identified in sequencing studies (PMID: 11781872), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| C342R | missense | gain of function - predicted | FGFR2 C342R lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C342R demonstrates constitutive activation of the Fgfr2 dimer state in vitro (PMID: 27596331), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| C342S | missense | unknown | FGFR2 C342S lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C342S has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| C342Y | missense | gain of function | FGFR2 C342Y lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C342Y results in activation of Fgfr2 signaling as indicated by decreased differentiation and increased apoptosis in osteoblasts in culture and in transgenic animal models (PMID: 10851026, PMID: 15316116). | |
| C382R | missense | gain of function | FGFR2 C382R (also referred to as C383R) lies within the helical domain of the Fgfr2 protein (UniProt.org). C382R confers a gain of function on the Fgfr2 protein, as demonstrated by constitutive MAPK pathway activation and transformation of cells in culture (PMID: 24993163). | |
| C382Y | missense | no effect - predicted | FGFR2 C382Y lies within the helical domain of the Fgfr2 protein (UniProt.org). C382Y has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| C383R | missense | gain of function - predicted | FGFR2 C383R (corresponds to as C382R in the canonical isoform) lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). C382R results in Fgfr2 autophosphorylation and transformation in culture (PMID: 9136983), and therefore, is predicted to confer a gain of function. | |
| D101Y | missense | gain of function - predicted | FGFR2 D101Y lies within the extracellular Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). D101Y results in the transformation of cells in culture (PMID: 18552176), and therefore, is predicted to result in a gain of FGFR2 protein function. | |
| D138N | missense | unknown | FGFR2 D138N lies within the extracellular domain of the Fgfr2 protein (UniProt.org). D138N has been identified in the scientific literature (PMID: 17360555), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| D247Y | missense | unknown | FGFR2 D247Y lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). D247Y has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| D283N | missense | unknown | FGFR2 D283N lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). D283N has been identified in sequencing studies (PMID: 16140923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| D304N | missense | no effect - predicted | FGFR2 D304N lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). D304N has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| D336N | missense | unknown | FGFR2 D336N lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). D336N has been identified in sequencing studies (PMID: 22810696, PMID: 26373574), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| D479N | missense | unknown | FGFR2 D479N lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). D479N has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| D530N | missense | loss of function | FGFR2 D530N lies within the protein kinase domain of the FGFR2 protein (UniProt.org). D530N confers a loss of function on the FGFR2 protein, as demonstrated by a loss of protein kinase activity and reduced downstream MAPK signaling pathway activation (PMID: 19147536). | |
| D602E | missense | unknown | FGFR2 D602E lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D602E has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| D650A | missense | gain of function - predicted | FGFR2 D650A lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650A demonstrates increased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| D650G | missense | loss of function - predicted | FGFR2 D650G lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650G demonstrates decreased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| D650I | missense | gain of function - predicted | FGFR2 D650I lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650I demonstrates increased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| D650L | missense | gain of function - predicted | FGFR2 D650L lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650L demonstrates increased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| D650V | missense | gain of function - predicted | FGFR2 D650V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650V demonstrates increased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| dec exp | none | no effect | FGFR2 dec exp indicates decreased expression of the Fgfr2 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified. | |
| E116K | missense | unknown | FGFR2 E116K lies within the Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). E116K has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| E160A | missense | unknown | FGFR2 E160A lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). E160A is predicted to disrupt Fgfr2-heparan sulfate interaction and Fgfr dimerization based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| E219K | missense | unknown | FGFR2 E219K lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). E219K is predicted to disrupt Fgf- and heparin-induced Fgfr2 dimerization based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| E470Q | missense | unknown | FGFR2 E470Q lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). E470Q has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| E475K | missense | unknown | FGFR2 E475K lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). E475K demonstrates slightly increased Fgfr2 kinase activity, but also decreases protein stability and cell proliferation in culture (PMID: 19147536), and therefore, its effect on Fgfr2 protein function is unknown. | |
| E565A | missense | gain of function | FGFR2 E565A lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E565A demonstrates resistance to FGFR inhibitors in the context of FGFR2-SHTN1 in culture (PMID: 31911531), and results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937, PMID: 28166054). | Y |
| E565G | missense | gain of function | FGFR2 E565G lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E565G results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| E566A | missense | gain of function | FGFR2 E566A (corresponds to E565A in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E566A results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937, PMID: 28166054) and is also associated with resistance to FGFR inhibitors (PMID: 31109923). | Y |
| E566G | missense | gain of function | FGFR2 E566G (corresponds to E565G in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E566G results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | Y |
| E574K | missense | unknown | FGFR2 E574K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E574K has been identified in the scientific literature (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| E596K | missense | unknown | FGFR2 E596K lies within the protein kinase domain if the Fgfr2 protein (UniProt.org). E596K has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| E636* | nonsense | unknown | FGFR2 E636* results in the premature truncation within the kinase domain of the Fgfr2 at amino acid 636 of 821 (UniProt.org). E636* has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jan 2021). | |
| E636K | missense | unknown | FGFR2 E636K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E636K is predicted to affect the kinase activity of Fgfr2 by structural modeling (PMID: 19147536), but has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jan 2021). | |
| E695K | missense | unknown | FGFR2 E695K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E695K has been identified in sequencing studies (PMID: 24265153, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| E718K | missense | unknown | FGFR2 E718K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E718K has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| E731K | missense | unknown | FGFR2 E731K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E731K results in increased phosphorylation of Fgfr2, Erk signaling, and transcriptional activation of Runx2 in culture (PMID: 21928350), however in another study, results in similar cell proliferation and viability levels as wild-type Fgfr2 in two different cell lines (PMID: 29533785), and therefore, its effect on Fgfr2 protein function is unknown. | |
| E777K | missense | unknown | FGFR2 E777K lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). E777K has been identified in sequencing studies (PMID: 29107334), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| F276C | missense | gain of function | FGFR2 F276C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniPort.org). F276C results in increased Fgfr2 expression, altered cellular localization, and ligand-independent Erk phosphorylation in culture (PMID: 30761385). | |
| F276V | missense | unknown | FGFR2 F276V lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). F276V has been identified in sequencing studies (PMID: 24578066), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| F386_A389del | deletion | no effect - predicted | FGFR2 F386_A389del results in the deletion of four amino acids in the Fgfr2 protein from amino acids 386 to 389 (UniProt.org). F386_A389del has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, it is predicted to have no effect on Fgfr2 protein function. | |
| FGFR2 - AFF3 | fusion | gain of function | FGFR2-AFF3 results from the fusion of FGFR2 and AFF3 (PMID: 23558953), leading to activation of Fgfr downstream signaling and transformation in culture (PMID: 28416604). FGFR2-AFF3 has been identified in breast cancer (PMID: 23558953). | |
| FGFR2 - AHCYL1 | fusion | gain of function | FGFR2-AHCYL1 results from the fusion of FGFR2 and AHCYL1, resulting in the ability to activate MAPK signaling and induce transformation of cells in culture and in animal models (PMID: 24122810). FGFR2-AHCYL1 has been identified in intrahepatic cholangiocarcinoma (PMID: 24122810). | |
| FGFR2 - BFSP2 | fusion | unknown | FGFR2-BFSP2 results in a fusion of FGFR2 and BFSP2 (PMID: 30420614). FGFR2-BFSP2 has been identified in intrahepatic cholangiocarcinoma (PMID: 30420614), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Mar 2021). | |
| FGFR2 - BICC1 | fusion | gain of function | FGFR2-BICC1 results from the fusion of FGFR2 and BICC1, resulting in the ability to induce oligomerization, Fgfr kinase activity, Mapk signaling and transformation of cells in culture and in animal models (PMID: 23558953, PMID: 24122810, PMID: 28416604). FGFR2-BICC1 has been identified in intrahepatic cholangiocarcinoma (PMID: 25608663, PMID: 31899106). | |
| FGFR2 - CASP7 | fusion | gain of function | FGFR2-CASP7 results from the fusion of FGFR2 and CASP7 (PMID: 23558953), leading to activation of Fgfr downstream signaling and transformation in culture (PMID: 28416604). FGFR2-CASP7 has been identified in breast cancer (PMID: 23558953). | |
| FGFR2 - CCAR2 | fusion | unknown | FGFR2-CCAR2 (also referred to as FGFR2-KIAA1967) results from the fusion of FGFR2 and CCAR2 (PMID: 23558953). FGFR2-CCAR2 has been identified in lung cancer (PMID: 27245147, PMID: 23558953), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Nov 2020). | |
| FGFR2 - CCDC186 | fusion | unknown | FGFR2-CCDC186 results from the fusion of FGFR2 and CCDC186 (PMID: 31899106). FGFR2-CCDC186 has been identified in biliary cancer (PMID: 31899106), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Apr 2021). | |
| FGFR2 - CCDC6 | fusion | gain of function | FGFR2-CCDC6 results from the fusion of FGFR2 and CCDC6, resulting in the ability to induce oligomerization, activate Fgfr kinase activity, and induce cell proliferation (PMID: 23558953), and is transforming in culture (PMID: 28416604). FGFR2-CCDC6 has been identified in cholangiocarcinoma (PMID: 27216979). | |
| FGFR2 - CIT | fusion | unknown | FGFR2-CIT results from the fusion of FGFR2 and CIT (PMID: 23558953). FGFR2-CIT has been identified in lung adenocarcinoma (PMID: 23558953), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Nov 2020). | |
| FGFR2 - CLIP1 | fusion | gain of function - predicted | FGFR2-CLIP1 results from the fusion of FGFR2 and CLIP1, and results in increased PI3K, MAPK, and FGFR2 signaling in culture (PMID: 31371345), and therefore, is predicted to lead to a gain of protein function. FGFR2-CLIP1 has been identified in metastatic cholangiocarcinoma (PMID: 31371345). | |
| FGFR2 - COL14A1 | fusion | unknown | FGFR2-COL14A1 results from the fusion of FGFR2 and COL14A1 (PMID: 25485619). FGFR2-COL14A1 has been identified in lung cancer (PMID: 25485619), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Nov 2020). | |
| FGFR2 - CTNNA3 | fusion | unknown | FGFR2-CTNNA3 results from the fusion of FGFR2 and CTNNA3 (PMID: 27812792). FGFR2-CTNNA3 has been identified in polymorphous low-grade neuroepithelial tumor of the young (PMID: 27812792), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Apr 2021). | |
| FGFR2 - DDX21 | fusion | unknown | FGFR2-DDX21 results from the fusion of FGFR2 and DDX21 (PMID: 30745300). FGFR2-DDX21 has been identified in cholangiocarcinoma (PMID: 30745300, PMID: 28642281), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2021). | |
| FGFR2 - DNM3 | fusion | gain of function | FGFR2-DNM3 results from the fusion of FGFR2 and DNM3, resulting in FGFR2 activation, increased PI3K and MAPK pathway signaling, and increased colony formation in culture (PMID: 29203461). FGFR2-DNM3 has been identified in triple-receptor negative breast cancer (PMID: 29203461). | |
| FGFR2 - EIF4A2 | fusion | unknown | FGFR2-EIF4A2 results from the fusion of FGFR2 and EIF4A2 (PMID: 29617662). FGFR2-EIF4A2 has been identified in lung squamous cell carcinoma (PMID: 29617662), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Jan 2021). | |
| FGFR2 - ERC1 | fusion | unknown | FGFR2-ERC1 results from the fusion of FGFR2 and ERC1 (PMID: 30267839). FGFR2-ERC1 has been identified in non-small cell lung cancer (PMID: 30267839), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Apr 2021). | |
| FGFR2 - FAM76A | fusion | gain of function - predicted | FGFR2-FAM76A results from the fusion of FGFR2 and FAM76A, which leads to increased proliferation and transformation in cell culture (PMID: 24563622), and therefore, is predicted to result in a gain of protein function. FGFR2-FAM76A has been identified in ovarian cancer (PMID: 24563622). | |
| FGFR2 - FN1 | fusion | unknown | FGFR2-FN1 results from the fusion of FGFR2 and FN1 (Cancer Res 2019;79(13 Suppl):Abstract nr 2206). FGFR2-FN1 has not been characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2021). | |
| FGFR2 - FRK | fusion | unknown | FGFR2-FRK results from the fusion of FGFR2 and FRK (PMID: 29617662). FGFR2-FRK has been identified in cholangiocarcinoma (PMID: 29617662), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Jan 2021). | |
| FGFR2 - GAB2 | fusion | unknown | FGFR2-GAB2 results from the fusion of FGFR2 and GAB2 (PMID: 28978721). FGFR2-GAB2 has been identified in breast cancer (PMID: 28978721) and esophageal adenocarcinoma (PMID: 28640357), but has not been biochemically characterized and therefore, the effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| FGFR2 - INA | fusion | gain of function | FGFR2-INA results from the fusion of FGFR2 and INA, leading to activation of Mapk and Pi3k signaling pathways and transformation in cell culture (PMID: 29767381). FGFR2-INA has been identified in mixed neuronal-glial tumors (PMID: 29767381) and intrahepatic cholangiocarcinoma (PMID: 31109923). | |
| FGFR2 - KIAA1217 | fusion | unknown | FGFR2-KIAA1217 results from the fusion of FGFR2 and KIAA1217 (PMID: 30745300). FGFR2-KIAA1217 has been identified in cholangiocarcinoma (PMID: 30745300, PMID: 31109923, PMID: 33218975), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2021). | |
| FGFR2 - MBIP | fusion | unknown | FGFR2-MBIP results from the fusion of FGFR2 and NRAP (PMID: 32036070). FGFR2-MBIP has been identified in lung adenocarcinoma (PMID: 32036070), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Jan 2021). | |
| FGFR2 - NRAP | fusion | unknown | FGFR2-NRAP results from the fusion of FGFR2 and NRAP (PMID: 31109923). FGFR2-NRAP has been identified in intrahepatic cholangiocarcinoma (PMID: 31109923), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Nov 2020). | |
| FGFR2 - OFD1 | fusion | gain of function | FGFR2-OFD1 results from the fusion of FGFR2 and OFD1 (PMID: 23558953), leading to activation of Fgfr downstream signaling and transformation in culture (PMID: 28416604). FGFR2-OFD1 has been identified in thyroid carcinoma (PMID: 23558953). | |
| FGFR2 - OGA | fusion | unknown | FGFR2-OGA results from the fusion of FGFR2 and OGA (PMID: 24550739). FGFR2-OGA has been identified in intrahepatic cholangiocarcinoma and is associated with increased Fgfr2 expression and phosphorylation of Frs2 and Erk in patient tissue (PMID: 24550739), but has not been fully biochemically characterized and therefore, the effect on protein function is unknown. | |
| FGFR2 - OPTN | fusion | gain of function - predicted | FGFR2-OPTN results from the fusion of FGFR2 and OPTN (PMID: 28034880), and leads to constitutive FRS2 phosphorylation on Y196 cultured cells (PMID: 31109923), and therefore, is predicted to lead to gain of function. FGFR2-OPTN fusions have been identified in intrahepatic cholangiocarcinoma (PMID: 28034880). | |
| FGFR2 - PPHLN1 | fusion | gain of function | FGFR2-PPHLN1 results from the fusion of FGFR2 and PPHLN1 (PMID: 25608663), resulting in constitutive phosphorylation of the fusion protein and activation of downstream Erk1/2 signaling, and is transforming in culture (PMID: 25608663). FGFR2-PPHLN1 has been identified in intrahepatic cholangiocarcinoma (PMID: 25608663). | |
| FGFR2 - ROCK1 | fusion | unknown | FGFR2-ROCK1 results from the fusion of FGFR2 and ROCK1 (PMID: 30745300). FGFR2-ROCK1 has been identified in cholangiocarcinoma (PMID: 30745300), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2021). | |
| FGFR2 - SH3GLB1 | fusion | unknown | FGFR2-SH3GLB1 results from the fusion of FGFR2 and SH3GLB1 (PMID: 30420614). FGFR2-SH3GLB1 has been identified in intrahepatic cholangiocarcinoma (PMID: 30420614), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Mar 2021). | |
| FGFR2 - SHTN1 | fusion | gain of function - predicted | FGFR2-SHTN1 (also referred to as FGFR2-KIAA1598) results from the fusion of FGFR2 and SHTN1, which has been demonstrated to result in increased phosphorylation of recombinant protein S6, Akt, and mTOR in cultured cells (PMID: 31911531), and therefore, is predicted to lead to a gain of protein function. FGFR2-SHTN1 has been identified in cholangiocarinoma (PMID: 25536104, PMID: 31911531) and non-small cell lung cancer (PMID: 30267839). | |
| FGFR2 - SORBS1 | fusion | unknown | FGFR2-SORBS1 results from the fusion of FGFR2 and SORBS1 (PMID: 31109923). FGFR2-SORBS1 has been identified in intrahepatic cholangiocarcinoma (PMID: 31109923), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2021). | |
| FGFR2 - TACC1 | fusion | unknown | FGFR2-TACC1 results from the fusion of FGFR2 and TACC1 (PMID: 30420614). FGFR2-TACC1 has been identified in intrahepatic cholangiocarcinoma (PMID: 30420614), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Mar 2021). | |
| FGFR2 - TACC2 | fusion | unknown | FGFR2-TACC2 results from the fusion of FGFR2 and TACC2 (PMID: 30420614). FGFR2-TACC2 has been identified in intrahepatic cholangiocarcinoma (PMID: 30420614) and cervical cancer (PMID: 33241100), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Apr 2021). | |
| FGFR2 - TACC3 | fusion | gain of function | FGFR2-TACC3 results from the fusion of FGFR2 and TACC3, resulting in an oncogenic protein as demonstrated by ligand-independent phosphorylation, dimerization, and oncogenic transformation (PMID: 26048680). | |
| FGFR2 - TBC1D1 | fusion | unknown | FGFR2-TBC1D1 results from the fusion of FGFR2 and TBC1D1 (PMID: 28667006). FGFR2-TBC1D1 has been identified in cholangiocarcinoma (PMID: 28667006), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Jan 2021). | |
| FGFR2 - TNS1 | fusion | unknown | FGFR2-TNS1 results from the fusion of FGFR2 and TNS1 (PMID: 29203461). FGFR2-TNS1 has been identified in triple-receptor negative breast cancer (PMID: 29203461), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Nov 2020). | |
| FGFR2 - TP73 | fusion | unknown | FGFR2-TP73 results from the fusion of FGFR2 and TP73 (PMID: 30267839). FGFR2-TP73 has been identified in non-small cell lung cancer (PMID: 30267839), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Apr 2021). | |
| FGFR2 - TTC28 | fusion | unknown | FGFR2-TTC28 results from the fusion of FGFR2 and TTC28 (Cancer Res 2019;79(13 Suppl):Abstract nr 2206). FGFR2-TTC28 has not been characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2021). | |
| FGFR2 - WDR11 | fusion | unknown | FGFR2-WDR11 results from the fusion of FGFR2 and WDR11 (Cancer Res 2019;79(13 Suppl):Abstract nr 2206). FGFR2-WDR11 has not been characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2021). | |
| FGFR2 - ZMYM4 | fusion | unknown | FGFR2-ZMYM4 results from the fusion of FGFR2 and ZMYM4 (PMID: 28034880). FGFR2-ZMYM4 has been identified in intrahepatic cholangiocarcinoma (PMID: 28034880, PMID: 31109923), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2021). | |
| fusion | fusion | unknown | FGFR2 fusion indicates a fusion of the FGFR2 gene, but the fusion partner is unknown. | |
| G183fs | frameshift | loss of function - predicted | FGFR2 G183fs results in a change in the amino acid sequence of the Fgfr2 protein beginning at aa 183 of 821, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), G183fs is predicted to lead to a loss of Fgfr2 function. | |
| G227E | missense | unknown | FGFR2 G227E lies within the Ig-like C2-type 2 domain of the FGFR2 protein (UniProt.org). The functional effect of G227E is conflicting, as it has been reported to impair receptor processing and trafficking to the cell membrane and reduce ligand-dependent cell proliferation in one study (PMID: 19147536), but results in similar cell proliferation and viability levels as wild-type Fgfr2 in two different cell lines in another study (PMID: 29533785), and therefore, its effect on Fgfr2 protein function is unknown. | |
| G227R | missense | unknown | FGFR2 G227R lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniPort.org). G227R has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| G271E | missense | loss of function | FGFR2 G271E lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G271E confers a loss of function to the Fgfr2 protein as indicated by impaired receptor processing and decreased cell proliferation as compared to wild-type Fgfr2 in culture (PMID: 19147536). | |
| G272V | missense | unknown | FGFR2 G272V lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G272V has been identified in the scientific literature (PMID: 20106510), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| G302W | missense | unknown | FGFR2 G302W lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G302W has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| G305R | missense | unknown | FGFR2 G305R lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G305R has been identified in sequencing studies (PMID: 19147536, PMID: 28870692), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| G338R | missense | unknown | FGFR2 G338R lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G338R has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| G384E | missense | unknown | FGFR2 G384E lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). G384E has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| G462E | missense | unknown | FGFR2 G462E lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). G462E has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| G583R | missense | unknown | FGFR2 G583R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G583R has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| G583V | missense | unknown | FGFR2 G583V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G583V has been identified in sequencing studies (PMID: 22980975, PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| G583W | missense | unknown | FGFR2 G583W lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G583W has been identified in sequencing studies (PMID: 22960745, PMID: 24836576), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| G663E | missense | gain of function | FGFR2 G663E lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G663E results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| G690R | missense | unknown | FGFR2 G690R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G690R has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| G701S | missense | unknown | FGFR2 G701S lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G701S is predicted to inhibit Fgfr2 kinase activity indirectly by structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| H167_N173del | deletion | gain of function - predicted | FGFR2 H167_N173del results in the deletion of seven amino acids in the Ig-like C2-type domain 2 of the Fgfr2 protein from amino acids 167 to 173 (UniProt.org). H167_N173del is transforming in cell culture (J Clin Oncol 38, 2020 (suppl 4; abstr 567), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| H213Y | missense | unknown | FGFR2 H213Y lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). H213Y is predicted to disrupt the interaction of Fgfr2 with heparan sulfate based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| H544Q | missense | unknown | FGFR2 H544Q lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). H544Q has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| H683L | missense | unknown | FGFR2 H683L (corresponds to H682L in the canonical isoform) lies within the protein kinase domain of the FGFR2 protein (UniProt.org). H683L has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion in culture (PMID: 31109923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | Y |
| I380V | missense | unknown | FGFR2 I380V lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). I380V has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| I547D | missense | unknown | FGFR2 I547D lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I547D has been identified in sequencing studies (PMID: 22383975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| I547V | missense | gain of function - predicted | FGFR2 I547V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I547V results in elevated kinase activity compared to wild-type Fgfr2 protein in substrate phosphorylation assays (PMID: 28166054), and therefore, is predicted to result in a gain of Fgfr2 protein function. | |
| I548V | missense | gain of function | FGFR2 I548V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I548V confers a gain of function on the Fgfr2 protein, as demonstrated by increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in cell culture (PMID: 23908597). | |
| I590M | missense | unknown | FGFR2 I590M lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I590M has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| I642T | missense | unknown | FGFR2 I642T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I642T has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| I642V | missense | loss of function | FGFR2 I642V lies within the protein kinase domain of the FGFR2 protein (UniProt.org). I642V confers a loss of function on the Fgfr2 protein, as demonstrated by loss of protein kinase activity and reduced downstream MAPK signaling pathway activation (PMID: 19147536). | |
| inact mut | unknown | loss of function | FGFR2 inact mut indicates that this variant results in a loss of function of the Fgfr2 protein. However, the specific amino acid change has not been identified. | |
| K292M | missense | no effect - predicted | FGFR2 K292M lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). K292M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| K310R | missense | no effect - predicted | FGFR2 K310R lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). K310R has not been biochemically characterized, however, is not transforming in cell culture (PMID: 18552176), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| K405E | missense | unknown | FGFR2 K405E lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). K405E has been identified in sequencing studies (PMID: 25669975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| K41E | missense | no effect - predicted | FGFR2 K41E lies within the Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). K41E results in decreased Fgfr2 expression, but demonstrates subcellular localization, basal and ligand-dependent phosphorylation of Erk levels similar to wild-type protein in culture (PMID: 30761385), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| K420I | missense | unknown | FGFR2 K420I lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org).K420I has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| K517R | missense | loss of function | FGFR2 K517R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K517R results in decreased Fgfr2 kinase activity and inhibited cell proliferation in culture (PMID: 19147536). | |
| K525E | missense | gain of function | FGFR2 K525E (corresponds to K641E in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K525E results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| K526E | missense | gain of function - predicted | FGFR2 K526E lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K526E results in increased Fgfr2 autophosphorylation in an in vitro assay (PMID: 17803937), and therefore, is predicted to result in a gain of Fgfr2 protein function. | |
| K641N | missense | gain of function | FGFR2 K641N lies within the protein kinase domain of the Fgfr2b protein (UniProt.org). K641N (reported as K642N) results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| K641R | missense | gain of function | FGFR2 K641R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K641R results in increased Fgfr2 autophosphorylation and activation of Mek1/2, Stat3 signaling in cell culture (PMID: 23527311). | |
| K642R | missense | gain of function | FGFR2 K642R (corresponds to K641R in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K642R confers a gain of function to the Fgfr2 protein, as demonstrated by increased autophosphorylation, increased phosphorylation of FRS2, and increased activation of Mek1/2 and Stat3, upon FGF1 stimulation, and as compared to wild-type Fgfr2 in cell culture (PMID: 23527311). | |
| K659E | missense | gain of function | FGFR2 K659E (also referred to as K660E from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K659E leads to increased phosphorylation of downstream signaling molecules and induces colony formation in culture (PMID: 23786770), and in another study, results in the ability to induce senescence and cooperate with Myc to induce transformation of cell lines in culture (PMID: 19403560). | |
| K659M | missense | gain of function - predicted | FGFR2 K659M (also referred to as K660M from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K659M results in elevated kinase activity compared to wild-type Fgfr2 protein in substrate phosphorylation assays (PMID: 28166054), and therefore, is predicted to result in a gain of Fgfr2 protein function. | |
| K659N | missense | gain of function | FGFR2 K659N (also referred to as K660N from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K659N confers a gain of function to the Fgfr2 protein as demonstrated by increased autophosphorylation and phosphorylation of downstream targets, Mek and Stat3 (PMID: 23527311). | |
| K660E | missense | gain of function | FGFR2 K660E (corresponds to K659E in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K660E results in increased phosphorylation of Fgfr2, activation of downstream signaling, and is transforming in cell culture (PMID: 23786770). | Y |
| K660M | missense | unknown | FGFR2 K660M (corresponds to K659M in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K660M has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion (PMID: 31109923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | Y |
| K660N | missense | gain of function | FGFR2 K660N (corresponds to K559N in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K660N confers a gain of function to the Fgfr2 protein, as demonstrated by increased autophosphorylation, increased phosphorylation of FRS2, and increased activation of Mek1/2 and Stat3, upon FGF1 stimulation, and as compared to wild-type Fgfr2 in cell culture (PMID: 23527311). | |
| K714R | missense | unknown | FGFR2 K714R (also referred to as K715R from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K714R has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion (PMID: 31109923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | Y |
| K715R | missense | unknown | FGFR2 K715R (corresponds to K714R in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K715R has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion (PMID: 31109923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | Y |
| L258F | missense | no effect - predicted | FGFR2 L258F lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). L258F has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| L397M | missense | unknown | FGFR2 L397M lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). L397M has been identified in sequencing studies (PMID: 22383975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| L551I | missense | unknown | FGFR2 L551I lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L551I has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| L617F | missense | unknown | FGFR2 L617F lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). The functional effect of L617F is conflicting, as it results in enhanced Fgfr2 autophosphorylation, activation of Runx2 (PMID: 23913723), and increased substrate phosphorylation (PMID: 28166054), but activation of Mapk/Erk was similar to wild-type Fgfr2 in cell culture (PMID: 23913723) and therefore, its effect on Fgfr2 protein function is unknown. | |
| L617M | missense | unknown | FGFR2 L617M lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L617M has been demonstrated to confer resistance to FGFR inhibitors as a secondary resistance mutation in the context of FGFR2 fusions (PMID: 31911531), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | Y |
| L617V | missense | gain of function - predicted | FGFR2 L617V (also referred to as V618V from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L617V has been shown to confer resistance to Fgfr inhibitors in cell culture (PMID: 28034880), and demonstrates increased Fgfr2 kinase activity compared to wild-type in vitro (PMID: 28166054), and therefore, is predicted to result in a gain of Fgfr2 protein function. | Y |
| L618M | missense | gain of function | FGFR2 L618M (corresponds to L617M in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L618M results in increased Fgfr2 kinase activity, enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597), and elevated kinase activity compared to wild-type Fgfr2 protein in substrate phosphorylation assays (PMID: 28166054). | |
| L618V | missense | gain of function - predicted | FGFR2 L618V (corresponds to L617V in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L618V has been shown to confer resistance to Fgfr inhibitors in cell culture (PMID: 28034880), and demonstrates increased Fgfr2 kinase activity compared to wild-type in vitro (PMID: 28166054), and therefore, is predicted to result in a gain of Fgfr2 protein function. | Y |
| L761Tfs*55 | frameshift | unknown | FGFR2 L761Tfs*55 indicates a shift in the reading frame starting at amino acid 761 and terminating 55 residues downstream causing a premature truncation of the 821 amino acid Fgfr2 protein (UniProt.org). L761Tfs*55 results in increased transformation ability in one of two different cell lines (PMID: 29533785), and therefore, its effect on Fgfr2 protein function is unknown. | |
| L770V | missense | unknown | FGFR2 L770V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L770V is predicted to decrease phospholipase C-gamma activation by Fgfr2 based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| L772F | missense | unknown | FGFR2 L772F lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). L772F has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Apr 2021). | |
| M186T | missense | no effect - predicted | FGFR2 M186T lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). M186T has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| M391R | missense | unknown | FGFR2 M391R lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). The functional effect of M391R is conflicting, as it has been reported to result in increased nucleolar Fgfr2 activity and cell proliferation in one study (PMID: 24908667), but results in similar cell proliferation and viability levels as wild-type Fgfr2 in two different cell lines in another study (PMID: 29533785), and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Feb 2021). | |
| M535T | missense | unknown | FGFR2 M535T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M535T has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| M536I | missense | gain of function | FGFR2 M536I (corresponds to M535I in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M536I results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| M537A | missense | loss of function - predicted | FGFR2 M537A lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M537A demonstrates decreased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| M537I | missense | gain of function - predicted | FGFR2 M537I (also referred to as M538I from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M537I results in elevated kinase activity compared to wild-type Fgfr2 protein in substrate phosphorylation assays (PMID: 28166054), and therefore, is predicted to result in a gain of Fgfr2 protein function. | |
| M538I | missense | gain of function | FGFR2 M538I (corresponds to M537I in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M538I confers a gain of function on the Fgfr2 protein, as demonstrated by increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in cell culture (PMID: 23908597). | Y |
| M538L | missense | unknown | FGFR2 M538L lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M538L has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Feb 2021). | |
| M538R | missense | unknown | FGFR2 M538R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M538R has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| M540A | missense | loss of function - predicted | FGFR2 M540A lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M540A demonstrates decreased kinase activity compared to wild-type Fgfr2 in an vitro assay (PMID: 28166054), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| M584V | missense | unknown | FGFR2 M584V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M584V has been identified in sequencing studies (PMID: 22960745), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| M640I | missense | unknown | FGFR2 M640I lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M640I has been identified in sequencing studies (PMID: 19147536, PMID: 26343386), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| mutant | unknown | unknown | FGFR2 mutant indicates an unspecified mutation in the FGFR2 gene. | |
| N211I | missense | unknown | FGFR2 N211I lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). N211I has been identified in sequencing studies (PMID: 18552176), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| N549D | missense | unknown | FGFR2 N549D lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N549D has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion in culture (PMID: 28034880), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | Y |
| N549H | missense | gain of function | FGFR2 N549H lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N549H demonstrates resistance to FGFR inhibitors in the context of FGFR2-CLIP1 in culture (PMID: 31371345), and confers a gain of function to the Fgfr2 protein as indicated by disengagement of autoinhibitory mechanisms thereby resulting in constitutive activation and downstream pathway activation (PMID: 17525745, PMID: 17803937), and results in elevated kinase activity compared to wild-type Fgfr2 protein in substrate phosphorylation assays (PMID: 28166054). | Y |
| N549K | missense | gain of function | FGFR2 N549K lies within the protein kinase domain of the FGFR2 protein (UniProt.org). N549K confers a gain of function to the Fgfr2 protein, resulting in oncogenic transformation in cell-based studies (PMID: 18552176, PMID: 17803937, PMID: 29533785) and increased MAPK pathway signaling in cultured cells (PMID: 19147536). | Y |
| N549T | missense | gain of function | FGFR2 N549T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N549T results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| N550H | missense | gain of function | FGFR2 N550H (corresponds to N549H in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550H results in increased Fgfr2 kinase activity, as well as increased Fgfr2 phosphorylation and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | Y |
| N550K | missense | gain of function | FGFR2 N550K (corresponds to N549K in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550K results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| N550S | missense | gain of function | FGFR2 N550S lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550S results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| N550T | missense | gain of function | FGFR2 N550T (corresponds to N549T in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550T results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| over exp | none | no effect | FGFR2 over exp indicates an over expression of the Fgfr2 protein and/or mRNA. However, the mechanism causing the over expression is unspecified. | |
| P253L | missense | unknown | FGFR2 P253L lies within the extracellular domain of the Fgfr2 protein (UniProt.org). P253L has been identified in the scientific literature (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Apr 2021). | |
| P253R | missense | gain of function | FGFR2 P253R lies within the extracellular domain of the Fgfr2 protein (UniProt.org). P253R results in loss of ligand specificity, activation of the p38/MAPK pathway in transgenic mouse models, and is transforming in cell culture (PMID: 11121055, PMID: 20175913, PMID: 23786770). | |
| P253S | missense | unknown | FGFR2 P253S lies within the extracellular domain of the Fgfr2 protein (UniProt.org). P253S has been identified in sequencing studies (PMID: 11781872), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| P256S | missense | unknown | FGFR2 P256S lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). P256S has been identified in sequencing studies (PMID: 25669975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| P286S | missense | unknown | FGFR2 P286S lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). P286S has been identified in sequencing studies (PMID: 27103312), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2021). | |
| P303L | missense | unknown | FGFR2 P303L lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniPort.org). P303L has been identified in the scientific literature (PMID: 19812598), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| P582L | missense | unknown | FGFR2 P582L lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). P582L has been identified in sequencing studies (PMID: 27425854, PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| P708S | missense | unknown | FGFR2 P708S lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). P708S has been identified in the scientific literature (PMID: 19147536, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| P775L | missense | unknown | FGFR2 P775L lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). P775L has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| positive | unknown | unknown | FGFR2 positive indicates the presence of the FGFR2 gene, mRNA, and/or protein. | |
| Q212K | missense | unknown | FGFR2 Q212K lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). Q212K has been identified in sequencing studies (PMID: 23917401), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| Q259* | nonsense | no effect - predicted | FGFR2 Q259* results in a premature truncation of the Fgfr2 protein at amino acid 259 of 821 (UniProt.org). Q259* has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2, in two different cell lines (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| Q289P | missense | unknown | FGFR2 Q289P lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). Q289P has been identified in sequencing studies (PMID: 19066959, PMID: 16526917), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| Q620K | missense | unknown | FGFR2 Q620K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). Q620K has been identified in sequencing studies (PMID: 25035393, PMID: 29106415), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| R165W | missense | unknown | FGFR2 R165W lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R165W has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| R178C | missense | unknown | FGFR2 R178C lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R178C has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jan 2021). | |
| R203C | missense | gain of function | FGFR2 R203C lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R203C confers a gain of function to the Fgfr2 protein, as demonstrated by increased autophosphorylation, increased phosphorylation of FRS2, and increased activation of Mek1/2 and Stat3, upon FGF1 stimulation, and as compared to wild-type Fgfr2 in cell culture (PMID: 23527311). | |
| R203H | missense | unknown | FGFR2 R203H lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R203H has been identified in sequencing studies (PMID: 22810696, PMID: 30796031, PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| R210Q | missense | unknown | FGFR2 R210Q lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R210Q has been identified in sequencing studies (PMID: 29937994, PMID: 26343386), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| R251* | nonsense | loss of function - predicted | FGFR2 R251* results in a premature truncation of the Fgfr2 protein at amino acid 251 of 821 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), R251* is predicted to lead to a loss of Fgfr2 function. | |
| R251Q | missense | loss of function | FGFR2 R251Q lies within the region linking Ig-like domains II and III of the Fgfr2 protein (PMID: 11121055). R251Q confers a loss of function on the Fgfr2 protein, as demonstrated by loss of ligand binding and diminished Mapk activation upon Fgf2 stimulation in cell culture (PMID: 19147536). | |
| R255Q | missense | loss of function - predicted | FGFR2 R255Q lies within the extracellular domain of the Fgfr2 protein (UniProt.org). R255Q results in decreased activation of Fgfr2 downstream signaling upon Fgf2 stimulation in culture (PMID: 27323706), and therefore, is predicted to result in a loss of Fgfr2 protein function. | |
| R330W | missense | unknown | FGFR2 R330W lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). R330W has been identified in sequencing studies (PMID: 22197931), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| R625Q | missense | unknown | FGFR2 R625Q lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R625Q has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| R625T | missense | unknown | FGFR2 R625T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R625T has been identified in sequencing studies (PMID: 17344846), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| R664W | missense | loss of function - predicted | FGFR2 R664W lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R664W results in a 60% decrease in autophosphorylation compared to wild-type in an in vitro kinase assay (PMID: 28151998), and therefore, is predicted to result in loss of Fgfr2 protein function. | |
| R678G | missense | gain of function | FGFR2 R678G lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R678G results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| R6P | missense | unknown | FGFR2 R6P does not lie within any known domains of the Fgfr2 protein (UniProt.org). R6P has been identified in sequencing studies (PMID: 30286143), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| R759Q | missense | unknown | FGFR2 R759Q lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R759Q is predicted to disrupt Fgfr2 kinase activity based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein is unknown (PubMed, Dec 2020). | |
| rearrange | unknown | unknown | FGFR2 rearrangement indicates an unspecified rearrangement of the FGFR2 gene. | |
| S24F | missense | unknown | FGFR2 S24F lies within the extracellular domain of the Fgfr2 protein (UniProt.org). S24F has been identified in the scientific literature (PMID: 31453370), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| S252F | missense | unknown | FGFR2 S252F lies within the extracellular domain of the Fgfr2 protein (UniProt.org). S252F has been identified in sequencing studies (PMID: 16418739), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| S252L | missense | unknown | FGFR2 S252L lies within the extracellular domain of the Fgfr2 protein (UniProt.org). S252L has been identified in sequencing studies (PMID: 25669975, PMID: 24952746), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| S252W | missense | gain of function | FGFR2 S252W lies within the extracellular domain of the Fgfr2 protein (UniProt.org). S252W results in loss of ligand specificity, increased Fgfr2 activation, and is transforming in cell culture (PMID: 11121055, PMID: 18552176). | |
| S267P | missense | unknown | FGFR2 S267P lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). S267P has been identified in sequencing studies (PMID: 11325814), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| S267_D273dup | duplication | gain of function | FGFR2 S267_D273dup (also referred to as A266_S267insSTVVGGD) indicates the insertion of seven duplicate amino acids, serine (S)-267 through aspartic acid (D)-273, in the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). S267_D273dup confers a gain of function on Fgfr2 as demonstrated by ligand-independent phosphorylation, dimerization, and oncogenic cell transformation (PMID: 26048680). | |
| S347C | missense | unknown | FGFR2 S347C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). S347C has been identified in sequencing studies (PMID: 12544231), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| S354C | missense | gain of function | FGFR2 S354C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). S354C confers a gain of function to the Fgfr2 protein, as demonstrated by increased transactivation of Runx2, increased autophosphorylation, and increased Erk1/2 phosphorylation, as compared to wild-type in in vitro assays (PMID: 23913723). | |
| S372C | missense | gain of function - predicted | FGFR2 S372C lies within the extracellular domain of the Fgfr2 protein (PMID: 17525745). S372C (also reported as S373C) results in constitutive dimerization of the receptor (PMID: 17525745), and therefore, is predicted to lead to a gain of Fgfr2 protein. | |
| S372F | missense | unknown | FGFR2 S372F lies within the extracellular domain of the Fgfr2 protein (Uniprot.org). S372F has been identified in sequencing studies (PMID: 27892470), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2021). | |
| S436F | missense | no effect - predicted | FGFR2 S436F lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). S436F has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| S57L | missense | unknown | FGFR2 S57L lies within the Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). S57L has been identified in sequencing studies (PMID: 11781872, PMID: 24728327), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| S587C | missense | unknown | FGFR2 S587C lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). S587C has been identified in the scientific literature (PMID: 23000897), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| S688F | missense | unknown | FGFR2 S688F lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). S688F has been identified in the scientific literature (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| S780A | missense | gain of function - predicted | FGFR2 S780A lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). S780A results in sustained Fgfr2 phosphorylation and faster cell migration in response Fgf1 in cell culture (PMID: 31146385), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| S780D | missense | gain of function - predicted | FGFR2 S780D lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). S780D results in sustained Fgfr2 phosphorylation in response Fgf1 in cell culture (PMID: 31146385), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| S780L | missense | gain of function - predicted | FGFR2 S780L lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). S780L results in sustained Fgfr2 phosphorylation and faster cell migration in response Fgf1 in cell culture (PMID: 31146385), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| S799A | missense | no effect - predicted | FGFR2 S799A does not lie within any known functional domains of the Fgfr2 protein (UniProt.org). S799A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| T341P | missense | gain of function | FGFR2 T341P lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). T341P results in increased phosphorylation of Fgfr2 and is transforming in cell culture (PMID: 9539778). | |
| T370R | missense | unknown | FGFR2 T370R lies within the extracellular domain of the Fgfr2 protein (UniProt.org). T370R has been identified in sequencing studies (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| T394A | missense | no effect - predicted | FGFR2 T394A lies within the helical domain of the Fgfr2 protein (UniProt.org). T394A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| T730S | missense | no effect | FGFR2 T730S (corresponds to T729S in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). T730S has activity similar to wild-type Fgfr2 as demonstrated by equivalent substrate phosphorylation and the lack of oncogenic cell transformation (PMID: 26048680). | |
| T764fs | frameshift | unknown | FGFR2 T764fs results in a change in the amino acid sequence of the Fgfr2 protein beginning at aa 764 of 821, likely resulting in premature truncation of the functional protein (UniProt.org). T764fs has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| T786K | missense | unknown | FGFR2 T786K lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). T786K has been identified in sequencing studies (PMID: 22960745), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| V248D | missense | unknown | FGFR2 V248D lies within the extracellular domain of the Fgfr2 protein (UniProt.org). V248D is predicted to destabilize the tertiary fold of the Fgfr2 protein based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2020). | |
| V392A | missense | unknown | FGFR2 V392A lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). V392A has been identified in sequencing studies (PMID: 23619168, PMID: 21798897), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| V392M | missense | no effect - predicted | FGFR2 V392M lies within the helical domain of the Fgfr2 protein (UniProt.org). V392M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| V395D | missense | unknown | FGFR2 V395D lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). V395D has been identified in the scientific literature (PMID: 30914635), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| V514L | missense | unknown | FGFR2 V514L lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V514L has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jan 2021). | |
| V563L | missense | gain of function - predicted | FGFR2 V563L (corresponds to V562L in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V563L is predicted to confer a gain of function to the Fgfr2 protein as indicated by increased Fgfr2 kinase activity in cell culture, and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 25169980, PMID: 31109923). | Y |
| V564F | missense | gain of function - predicted | FGFR2 V564F (also referred to as V565F from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564F is predicted to confer a gain of function as demonstrated by increased Fgfr2 kinase activity in cell culture (PMID: 25169980), and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 28034880). | Y |
| V564I | missense | gain of function - predicted | FGFR2 V564I lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564I is predicted to confer a gain of function to the Fgfr2 protein as indicated by increased Fgfr2 kinase activity in cell culture, and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 25169980). | Y |
| V564L | missense | gain of function - predicted | FGFR2 V564L (also referred to as V565L from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564L has been shown to be associated with secondary resistance to FGFR inhibitors and demonstrates increased Fgfr2 kinase activity in cell culture (PMID: 25169980), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | Y |
| V564M | missense | unknown | FGFR2 V564M lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564M has been demonstrated to confer resistance to Fgfr inhibitors in cell culture (PMID: 28034880, PMID: 25349422), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | Y |
| V564T | missense | no effect - predicted | FGFR2 V564T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564T is predicted to have no effect on Fgfr2 protein function as it demonstrates activation rates similar to wild-type Fgfr2, but has also been demonstrated to confer resistance to Fgfr inhibitors in culture (PMID: 21454610). | Y |
| V565F | missense | gain of function - predicted | FGFR2 V565F (corresponds to V564F in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V565F is predicted to confer a gain of function as demonstrated by increased Fgfr2 kinase activity in cell culture (PMID: 25169980), and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 28034880, PMID: 31109923). | Y |
| V565I | missense | gain of function | FGFR2 V565I (corresponds to V564I in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V565I results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | Y |
| V565L | missense | gain of function - predicted | FGFR2 V565L (corresponds to V564L in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V565L has been shown to be associated with secondary resistance to FGFR inhibitors and demonstrates increased Fgfr2 kinase activity in cell culture (PMID: 25169980), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | Y |
| V755I | missense | no effect | FGFR2 V755I (corresponds to V754I in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V755I has activity similar to wild-type Fgfr2 as demonstrated by equivalent substrate phosphorylation and the lack of oncogenic cell transformation (PMID: 26048680). | |
| V77M | missense | unknown | FGFR2 V77M lies within the Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). V77M has been identified in the scientific literature (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| W290* | nonsense | loss of function - predicted | FGFR2 W290* results in a premature truncation of the Fgfr2 protein at aa 290 of 821 (UniProt.org). Due to a loss of the protein kinase domain (UniProt.org), W290* is predicted to lead to a loss of function. | |
| W290C | missense | gain of function | FGFR2 W290C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). W290C does not result in increased Fgfr2 phosphorylation, but increases both ligand-dependent and ligand-independent dimerization of Fgfr2, is transforming in cell culture, and promotes tumor formation in xenograft models (PMID: 23786770). | |
| W290_I291delinsC | indel | gain of function | FGFR2 W290_I291delinsC results in a deletion of tryptophan (W) at amino acid 290 and isoleucine (I) at amino acid 291 within the Ig3 region of Fgfr2, combined with the insertion of a cysteine (C) at the same site (UniProt.org). W290_I291delinsC confers a gain of function on Fgfr2, as demonstrated by ligand-independent phosphorylation, dimerization, and oncogenic transformation (PMID: 26048680). | |
| wild-type | none | no effect | Wild-type FGFR2 indicates that no mutation has been detected within the FGFR2 gene. | |
| Y281C | missense | unknown | FGFR2 Y281C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). Y281C has been identified in the scientific literature (PMID: 26003532, PMID: 29104507), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| Y340C | missense | unknown | FGFR2 Y340C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). Y340C has been identified in sequencing studies (PMID: 16418739), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| Y340H | missense | unknown | FGFR2 Y340H lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). Y340H has been identified in sequencing studies (PMID: 16418739), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| Y375C | missense | gain of function | FGFR2 Y375C lies within the extracellular juxtamembrane domain of the Fgfr2 protein (PMID: 17525745). Y375C results in constitutive phosphorylation of Fgfr2 in cell culture, activation of Mapk p38 signaling, and abnormal proliferation and differentiation in the skin and skull of transgenic mouse models (PMID: 22585574). | |
| Y376C | missense | gain of function - predicted | FGFR2 Y376C (corresponds to Y375C in the canonical isoform) lies within the extracellular domain of the Fgfr2 protein (PMID: 17525745). Y376C results in constitutive dimerization through inter-molecular disulfide bonds (PMID: 17525745), and therefore, is predicted to lead to a gain of Fgfr2 protein. | |
| Y588D | missense | unknown | FGFR2 Y588D lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). Y588D has been identified in sequencing studies (PMID: 25669975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). | |
| Y769* | nonsense | unknown | FGFR2 Y769* results in a premature truncation of the Fgfr2 protein at amino acid 769 of 821 (UniProt.org). Y769* has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2020). |