Gene Name
FGFR2
essential gene (from dbNSFP)
UniProt accession
P21802
Ensembl protein identifier
ENSP00000263451 Not principal
Long Name
fibroblast growth factor receptor 2
Summary
The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene.
Kinase Group
Tyr: tyrosine protein kinase. (Log odds ratio: 0.628591)
FDA approved inhibitors
None found

GO terms

Gene Ontology - Biological Process Log-odds ratio
GO:0009880 embryonic pattern specification 5.2187
GO:0061031 endodermal digestive tract morphogenesis 5.1671
GO:0060916 mesenchymal cell proliferation involved in lung development 5.1671
GO:0060915 mesenchymal cell differentiation involved in lung development 5.1671
GO:0060687 regulation of branching involved in prostate gland morphogenesis 5.1671
GO:0060670 branching involved in labyrinthine layer morphogenesis 5.1671
GO:0060667 branch elongation involved in salivary gland morphogenesis 5.1671
GO:0060664 epithelial cell proliferation involved in salivary gland morphogenesis 5.1671
GO:0060615 mammary gland bud formation 5.1671
GO:0060601 lateral sprouting from an epithelium 5.1671
GO:0060595 fibroblast growth factor receptor signaling pathway involved in mammary gland specification 5.1671
GO:0060529 squamous basal epithelial stem cell differentiation involved in prostate gland acinus development 5.1671
GO:0060527 prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis 5.1671
GO:0060523 prostate epithelial cord elongation 5.1671
GO:0060512 prostate gland morphogenesis 5.1671
GO:0060501 positive regulation of epithelial cell proliferation involved in lung morphogenesis 5.1671
GO:0060449 bud elongation involved in lung branching 5.1671
GO:0060442 branching involved in prostate gland morphogenesis 5.1671
GO:0060365 coronal suture morphogenesis 5.1671
GO:0060174 limb bud formation 5.1671
GO:0055010 ventricular cardiac muscle tissue morphogenesis 5.1671
GO:0051150 regulation of smooth muscle cell differentiation 5.1671
GO:0048730 epidermis morphogenesis 5.1671
GO:0048333 mesodermal cell differentiation 5.1671
GO:0035604 fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow 5.1671
GO:0035603 fibroblast growth factor receptor signaling pathway involved in hemopoiesis 5.1671
GO:0035602 fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow 5.1671
GO:0032808 lacrimal gland development 5.1671
GO:0031069 hair follicle morphogenesis 5.1671
GO:0030916 otic vesicle formation 5.1671
GO:0021860 pyramidal neuron development 5.1671
GO:0021769 orbitofrontal cortex development 5.1671
GO:0016331 morphogenesis of embryonic epithelium 5.1671
GO:0003149 membranous septum morphogenesis 5.1671
GO:0003148 outflow tract septum morphogenesis 5.1671
GO:0060045 positive regulation of cardiac muscle cell proliferation 5.0296
GO:0001657 ureteric bud development 5.0205
GO:0060445 branching involved in salivary gland morphogenesis 5.0064
GO:0035607 fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development 5.0064
GO:0030901 midbrain development 5.0064
GO:0021847 ventricular zone neuroblast division 5.0064
GO:0048489 synaptic vesicle transport 4.8452
GO:0010453 regulation of cell fate commitment 4.8342
GO:0048762 mesenchymal cell differentiation 4.7939
GO:0040014 regulation of multicellular organism growth 4.7682
GO:0001837 epithelial to mesenchymal transition 4.7077
GO:0035265 organ growth 4.6337
GO:0060348 bone development 4.6228
GO:0060463 lung lobe morphogenesis 4.6146
GO:0048755 branching morphogenesis of a nerve 4.5822
GO:0035264 multicellular organism growth 4.5822
GO:0033688 regulation of osteoblast proliferation 4.5822
GO:0050680 negative regulation of epithelial cell proliferation 4.5302
GO:0048557 embryonic digestive tract morphogenesis 4.1931
GO:0060484 lung-associated mesenchyme development 4.1584
GO:0048565 digestive tract development 4.1448
GO:0070307 lens fiber cell development 4.1162
GO:0060349 bone morphogenesis 4.1162
GO:0030282 bone mineralization 4.0232
GO:0040036 regulation of fibroblast growth factor receptor signaling pathway 3.9972
GO:0048701 embryonic cranial skeleton morphogenesis 3.9867
GO:0002053 positive regulation of mesenchymal cell proliferation 3.8788
GO:0048705 skeletal system morphogenesis 3.7979
GO:0042472 inner ear morphogenesis 3.6445
GO:0050673 epithelial cell proliferation 3.5508
GO:0042476 odontogenesis 3.5233
GO:0048286 lung alveolus development 3.4682
GO:0060688 regulation of morphogenesis of a branching structure 3.3333
GO:0022612 gland morphogenesis 3.2223
GO:0045667 regulation of osteoblast differentiation 2.9707
GO:0000122 negative regulation of transcription from RNA polymerase II promoter 2.9404
GO:0009887 organ morphogenesis 2.9034
GO:0048562 embryonic organ morphogenesis 2.8833
GO:0090263 positive regulation of canonical Wnt signaling pathway 2.8497
GO:0030177 positive regulation of Wnt signaling pathway 2.8497
GO:0030324 lung development 2.7863
GO:0030855 epithelial cell differentiation 2.7695
GO:0007267 cell-cell signaling 2.7107
GO:0009791 post-embryonic development 2.6977
GO:0008286 insulin receptor signaling pathway 2.6753
GO:0051781 positive regulation of cell division 2.6588
GO:0038095 Fc-epsilon receptor signaling pathway 2.6516
GO:0045787 positive regulation of cell cycle 2.6488
GO:0050678 regulation of epithelial cell proliferation 2.5853
GO:0008589 regulation of smoothened signaling pathway 2.5312
GO:0048568 embryonic organ development 2.5086
GO:0050679 positive regulation of epithelial cell proliferation 2.4585
GO:0001525 angiogenesis 2.3743
GO:0008543 fibroblast growth factor receptor signaling pathway 2.304
GO:0010518 positive regulation of phospholipase activity 2.2223
GO:0048661 positive regulation of smooth muscle cell proliferation 2.1977
GO:0007409 axonogenesis 2.1415
GO:0007528 neuromuscular junction development 2.0638
GO:0045165 cell fate commitment 2.0379
GO:0007173 epidermal growth factor receptor signaling pathway 1.9814
GO:0045839 negative regulation of mitotic nuclear division 1.8543
GO:0008285 negative regulation of cell proliferation 1.8411
GO:0048015 phosphatidylinositol-mediated signaling 1.8351
GO:0070374 positive regulation of ERK1 and ERK2 cascade 1.7915
GO:0048608 reproductive structure development 1.7268
GO:0008284 positive regulation of cell proliferation 1.7256
GO:0048011 neurotrophin TRK receptor signaling pathway 1.5523
GO:0045944 positive regulation of transcription from RNA polymerase II promoter 1.4738
GO:0045087 innate immune response 1.3607
GO:0042127 regulation of cell proliferation 1.3369
GO:0001701 in utero embryonic development 1.2833
GO:0043410 positive regulation of MAPK cascade 1.2383
GO:0018108 peptidyl-tyrosine phosphorylation 1.2044
GO:0070372 regulation of ERK1 and ERK2 cascade 1.1504
GO:0046777 protein autophosphorylation 0.6626
GO:0006915 apoptotic process 0.5959
GO:0006468 protein phosphorylation 0.4403
GO:0060441 epithelial tube branching involved in lung morphogenesis 0.0
Gene Ontology - Molecular Function Log-odds ratio
GO:0008201 heparin binding 4.2408
GO:0017134 fibroblast growth factor binding 3.9404
GO:0005007 fibroblast growth factor-activated receptor activity 3.9404
GO:0042803 protein homodimerization activity 1.406
GO:0004713 protein tyrosine kinase activity 0.592
GO:0005515 protein binding 0.2913
GO:0004672 protein kinase activity 0.0196
GO:0005524 ATP binding 0.0021
GO:0016772 transferase activity, transferring phosphorus-containing groups 0.0
Gene Ontology - Cellular Component Log-odds ratio
GO:0060076 excitatory synapse 4.3858
GO:0009986 cell surface 2.5127
GO:0005938 cell cortex 1.9595
GO:0005887 integral component of plasma membrane 1.7364
GO:0016023 cytoplasmic membrane-bounded vesicle 1.6292
GO:0016021 integral component of membrane 1.4044
GO:0005886 plasma membrane 1.403
GO:0016020 membrane 1.2128
GO:0005794 Golgi apparatus 1.1841
GO:0005576 extracellular region 0.6549
GO:0005634 nucleus 0.4352
GO:0043231 intracellular membrane-bounded organelle 0.2935
GO:0031012 extracellular matrix 0.0
GO:0005654 nucleoplasm -0.1796
GO:0005737 cytoplasm -0.355

The JMOL viwer can load structure PDB files associated to that UniProt protein, as well as models provided by Interactome3D. The SVG image and the sequence scroller bellow correspond to the Ensembl protein associated with that UniProt: ENSP00000263451

In order to adress all inconsistencies between the sequences in UniProt, Ensembl, and UniProt, coordinate maps are built using Smith-Waterman pairwise alignment.

Mark
Clear
Align
ENSP00000263451 Transmembrane ... Low complexity (... Cleavage site (Si... SSF48726 Kinase-like_dom Superfamily dom... Ig_sub Tyr_kinase_cat_dom Ser/Thr_dual-sp_kinase_dom Ig_sub2 SMART domains Ser-Thr/Tyr_kinase_cat_dom Prints domain Immunoglobulin Ser-Thr/Tyr_kinase_cat_dom Ig_I-set Prot_kinase_dom Pfam domain Ig-like_dom Prot_kinase_dom PROSITE profiles FGF_rcpt_fam PIRSF domain Sequence variant... COSMIC somatic ... 0 80 160 240 320 400 480 560 640 720 0 819 Scale bar Stop gained Frameshift variant Missense variant Splice region variant Synonymous variant Coding sequence variant Insert Delete Variation Legend
MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGESLEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVDSETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFHSAWLTVLPAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTKRIPLRRQVSAESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT* _________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________| ________10________20________30________40________50________60________70________80________90_______100_______110_______120_______130_______140_______150_______160_______170_______180_______190_______200_______210_______220_______230_______240_______250_______260_______270_______280_______290_______300_______310_______320_______330_______340_______350_______360_______370_______380_______390_______400_______410_______420_______430_______440_______450_______460_______470_______480_______490_______500_______510_______520_______530_______540_______550_______560_______570_______580_______590_______600_______610_______620_______630_______640_______650_______660_______670_______680_______690_______700_______710_______720_______730_______740_______750_______760_______770_______780_______790_______800_______810_______820

Scroll horizontaly across the sequence

The following information is extracted from Structure-PPi, a workflow for the annotation of protein residues. It finds features overlapping the variant or overlapping any residue that is in close physical proximity to the variant: 5 angstroms spatial distance or adjacent in the sequence if no PDB covers that area.

It may also report protein protein interfaces that might be affected by the variant, i.e. when they are at a distance of 8 angstroms from residues from a partner protein.

The structure PDB files used for these calculations are all those associated with the UniProt protein in UniProt and Interactome3D, which extends this set with models of single proteins and protein-protein interaction complexes. Pairwise alignment is used to resolve any sequence discrepancies.

The databases examined are UniProt, InterPro, COSMIC and Appris. The COSMIC database reports variants affecting that residue, not necessarily the same amino-acid change. Appris agglutinates features from FireDB, which are catalytic sites, and ligand-binding sites, and others such as trans-membrane domains, signal peptides, and ligand binding sites.

Structure-PPi A module for the annotation of cancer-related single-nucleotide variants at protein-protein interfaces. Miguel Vazquez, Alfonso Valencia, Tirso Pons. 2015. Bioinformatics. DOI: 10.1093/bioinformatics/btv142

KinMut Random Forest is a method specific for prediction of the pathogenicity of variants affecting the protein kinase superfamily. It characterizes the variants at the gene, domain and residue level with a combination of general and kinase-specific features. The pathogenicity of variants is evaluated by a random forest algorithm. Predictions are accompanied with a reliability score. Our approach outperforms available methods in a cross-validation experiment on the 3689 kinase variants in Uniprot. (Accuracy: 88.45%, Precision: 81.62%, recall: 75.22%, f-score: 78.29% and MCC: 0.68)

KinMut Random Forest
disease if score >0, neutral if score <0
Score
0.962
Prediction
disease

Group log-odds ratio
0.629
Kyte-Doolittle Hydrophobicity
1
GO log-odds ratio
510
Volume
101
C-beta branching
0
Formal charge
0
FireDB residue
No
PhosphoELM residue
No
Uniprot residue
No
Active site
No
Binding
No
Carbohydrate
No
Disulfide
No
Metal
No
Modified residue
No
NP Binding
No
Repeat
No
Signal
No
Site
No
Trans-membrane
No
Zinc finger
No
Other predictors (dbNSFP)
SIFT
disease if score <0.05
Score
0.0
Prediction
disease
Polyphen2_HDIV
possible if >0.453, disease if >0.957
Score
1.0
Prediction
disease
Polyphen2_HVAR
possible if >0.447, disease if >0.909
Score
0.967
Prediction
disease
MutationTaster
disease if score >0.5
Score
1.0
Prediction
disease
MutationAssessor
possible if >1.9, disease if >3.5
Score
3.195
Prediction
possible
FATHMM
disease if score <-1.5
Score
-1.43
Prediction
neutral
VEST3
disease if score >0.8
Score
0.942
Prediction
disease
CADD
disease if score >3.5
Score
6.089583
Prediction
disease
CADD Kircher (2014) Nature Genetics 46(3):310-5
FATHMM Shihab (2013) Human Mutation 34(1):57-65
VEST3 Carter (2013) BMC Genomics 14(3):1-16
Mutation Assessor Reva (2011) Nucleic Acids Research 1-14
Mutation Taster Schwarz (2014) Nature Methods 11, 361-362
Polyphen2 Adzhubei (2010) Nature Methods 7(4), 248-249
SIFT Ng (2001) Genome Research 11(45), 863-874
These literature co-mentions have been extracted automatically from the literature with iHop. Although it has proved to be a powerful guide to gather contextual information, manual inspection of these results might be required. Refer to Hoffmann and Valencia, 2004 for further details.

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