Gene Name
FGFR3
essential gene (from dbNSFP)
UniProt accession
P22607
Ensembl protein identifier
ENSP00000231803 Not principal
Long Name
fibroblast growth factor receptor 3
Summary
This gene encodes a member of the fibroblast growth factor receptor (FGFR) family, with its amino acid sequence being highly conserved between members and among divergent species. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist 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 binds acidic and basic fibroblast growth hormone and plays a role in bone development and maintenance. Mutations in this gene lead to craniosynostosis and multiple types of skeletal dysplasia. Three alternatively spliced transcript variants that encode different protein isoforms have been described.
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:0070307 lens fiber cell development 4.1162
GO:0060349 bone morphogenesis 4.1162
GO:0090080 positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway 4.1116
GO:0030282 bone mineralization 4.0232
GO:0002062 chondrocyte differentiation 3.6136
GO:0001501 skeletal system development 3.2602
GO:0051216 cartilage development 3.0232
GO:0000122 negative regulation of transcription from RNA polymerase II promoter 2.9404
GO:0090263 positive regulation of canonical Wnt signaling pathway 2.8497
GO:0048546 digestive tract morphogenesis 2.8207
GO:0045597 positive regulation of cell differentiation 2.7947
GO:0072148 epithelial cell fate commitment 2.7643
GO:0042511 positive regulation of tyrosine phosphorylation of Stat1 protein 2.755
GO:0035019 somatic stem cell maintenance 2.755
GO:1902178 fibroblast growth factor receptor apoptotic signaling pathway 2.7483
GO:0070977 bone maturation 2.7483
GO:0060113 inner ear receptor cell differentiation 2.7483
GO:0022010 central nervous system myelination 2.7483
GO:0002089 lens morphogenesis in camera-type eye 2.7483
GO:0008286 insulin receptor signaling pathway 2.6753
GO:0038095 Fc-epsilon receptor signaling pathway 2.6516
GO:0035988 chondrocyte proliferation 2.5233
GO:0003416 endochondral bone growth 2.5233
GO:0002009 morphogenesis of an epithelium 2.4327
GO:0001938 positive regulation of endothelial cell proliferation 2.41
GO:0045879 negative regulation of smoothened signaling pathway 2.3858
GO:0008543 fibroblast growth factor receptor signaling pathway 2.304
GO:0010518 positive regulation of phospholipase activity 2.2223
GO:0090102 cochlea development 2.0963
GO:0048712 negative regulation of astrocyte differentiation 2.0963
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein 2.0196
GO:0007173 epidermal growth factor receptor signaling pathway 1.9814
GO:0001958 endochondral ossification 1.9163
GO:0060385 axonogenesis involved in innervation 1.9003
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:0061144 alveolar secondary septum development 1.7483
GO:0021762 substantia nigra development 1.7483
GO:0008284 positive regulation of cell proliferation 1.7256
GO:0000165 MAPK cascade 1.6588
GO:0048678 response to axon injury 1.6015
GO:0048011 neurotrophin TRK receptor signaling pathway 1.5523
GO:0007259 JAK-STAT cascade 1.3858
GO:0045087 innate immune response 1.3607
GO:0043410 positive regulation of MAPK cascade 1.2383
GO:0018108 peptidyl-tyrosine phosphorylation 1.2044
GO:0030154 cell differentiation 1.085
GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity 1.0024
GO:0031398 positive regulation of protein ubiquitination 0.9163
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation 0.8369
GO:0043525 positive regulation of neuron apoptotic process 0.8008
GO:0046777 protein autophosphorylation 0.6626
GO:0048640 negative regulation of developmental growth 0.6015
GO:0006468 protein phosphorylation 0.4403
GO:0014003 oligodendrocyte development 0.0
GO:0048839 inner ear development -1.1992
GO:0030900 forebrain development -1.7841
Gene Ontology - Molecular Function Log-odds ratio
GO:0017134 fibroblast growth factor binding 3.9404
GO:0005007 fibroblast growth factor-activated receptor activity 3.9404
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:0005764 lysosome 4.0659
GO:0009898 cytoplasmic side of plasma membrane 2.1227
GO:0005887 integral component of plasma membrane 1.7364
GO:0048471 perinuclear region of cytoplasm 1.4149
GO:0016021 integral component of membrane 1.4044
GO:0005886 plasma membrane 1.403
GO:0005794 Golgi apparatus 1.1841
GO:0005576 extracellular region 0.6549
GO:0005783 endoplasmic reticulum 0.0024
GO:0005925 focal adhesion -0.2257
GO:0030133 transport vesicle -56.642

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: ENSP00000231803

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
ENSP00000231803 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 60 120 180 240 300 360 420 480 540 600 0 694 Scale bar Stop gained Frameshift variant Stop lost Missense variant Splice region variant Synonymous variant Coding sequence variant Insert Delete Variation Legend
MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLTQRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAGNPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVGPDGTPYVTVLKVSLESNASMSSNTPLVRIARLSSGEGPTLANVSELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPPAPPSSGGSRT* _________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________| ________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

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
-0.1
GO log-odds ratio
1e+03
Volume
139
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
0.029
Prediction
disease
Polyphen2_HDIV
possible if >0.453, disease if >0.957
Score
0.99
Prediction
disease
Polyphen2_HVAR
possible if >0.447, disease if >0.909
Score
0.907
Prediction
possible
MutationTaster
disease if score >0.5
Score
0.0282314
Prediction
neutral
MutationAssessor
possible if >1.9, disease if >3.5
Score
2.59
Prediction
possible
FATHMM
disease if score <-1.5
Score
-3.19
Prediction
disease
VEST3
disease if score >0.8
Score
0.708
Prediction
neutral
CADD
disease if score >3.5
Score
3.080295
Prediction
neutral
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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