FGFR3 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human FGFR3 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene FGFR3, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene FGFR3, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene FGFR3 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene FGFR3 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene FGFR3, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene FGFR3, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene FGFR3, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene FGFR3 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene FGFR3, summarize transcription factor regulatory data. If FGFR3 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate FGFR3 — names with evidence type (ChIP-seq / predicted / experimentally validated) If FGFR3 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene FGFR3 protein as a drug target, summarize pharmacology data. If FGFR3 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If FGFR3 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene FGFR3, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene FGFR3, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in FGFR3: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
FGFR3 (fibroblast growth factor receptor 3, chromosome 4p16.3) is a receptor tyrosine kinase that regulates skeletal development, chondrocyte differentiation, and endochondral ossification, making it one of the most clinically consequential growth factor receptors in human genetics. Germline gain-of-function mutations cause a spectrum of autosomal dominant skeletal dysplasias — including achondroplasia (p.Gly380Arg), hypochondroplasia, thanatophoric dysplasia, and Muenke craniosynostosis — while somatic mutations drive bladder cancer, multiple myeloma (including t(4;14) translocation), and glioblastoma via FGFR3-TACC3 fusions. The gene has ~1,154 ClinVar variants, with ~130 classified pathogenic; AlphaMissense predicts 700+ likely-pathogenic missense changes, with cysteine-rich extracellular domain residues showing near-universal intolerance. FGFR3 is a PharmGKB Very Important Pharmacogene, targeted by 2,311 molecules in ChEMBL; two FGFR-selective inhibitors — erdafitinib (pan-FGFR, approved for FGFR-altered urothelial cancer) and infigratinib (FGFR1/2/3, approved for cholangiocarcinoma) — have reached regulatory approval, with multiple Phase 2/3 trials ongoing.
FGFR3 — Reference
Cross-database identifier and functional mapping reference for FGFR3.
Gene identifiers
- HGNC ID: HGNC:3690
- Approved symbol: FGFR3
- Ensembl gene ID: ENSG00000068078
- NCBI Entrez Gene ID: 2261
- OMIM gene/locus ID: 134934
- Genomic location (GRCh38):
- Chromosome: 4
- Start position: 1,793,286
- End position: 1,808,873
- Strand: +
Transcript identifiers
Ensembl Transcripts (ENST)
Total: 23 transcripts
| Transcript ID | Biotype |
|---|---|
| ENST00000260795 | nonsense_mediated_decay |
| ENST00000340107 | protein_coding |
| ENST00000352904 | protein_coding |
| ENST00000412135 | protein_coding |
| ENST00000440486 | protein_coding |
| ENST00000469068 | retained_intron |
| ENST00000474521 | retained_intron |
| ENST00000481110 | protein_coding |
| ENST00000507588 | protein_coding |
| ENST00000643463 | protein_coding_CDS_not_defined |
| ENST00000901225 | protein_coding |
| ENST00000901226 | protein_coding |
| ENST00000901227 | protein_coding |
| ENST00000901228 | protein_coding |
| ENST00000911470 | protein_coding |
| ENST00000911471 | protein_coding |
| ENST00000911472 | protein_coding |
| ENST00000911473 | protein_coding |
| ENST00000911474 | protein_coding |
| ENST00000955401 | protein_coding |
| ENST00000955402 | protein_coding |
| ENST00000955403 | protein_coding |
| ENST00000955404 | protein_coding |
RefSeq mRNA (NM_)
| Accession | MANE Select |
|---|---|
| NM_000142 | ✓ |
| NM_001163213 | |
| NM_001354809 | |
| NM_001354810 | |
| NM_022965 |
CCDS IDs
- CCDS3353
- CCDS3354
- CCDS54706
- CCDS87200
MANE Select Transcript Exons: ENST00000340107 (maps to NM_000142)
Total: 18 exons
| Exon ID | Start | End | Length | Strand |
|---|---|---|---|---|
| ENSE00001744397 | 1793293 | 1793465 | 173 | + |
| ENSE00001596390 | 1793833 | 1794043 | 211 | + |
| ENSE00001164902 | 1799254 | 1799523 | 270 | + |
| ENSE00000778155 | 1799747 | 1799812 | 66 | + |
| ENSE00000933877 | 1801367 | 1801536 | 170 | + |
| ENSE00000778157 | 1801620 | 1801743 | 124 | + |
| ENSE00003494331 | 1801835 | 1802025 | 191 | + |
| ENSE00001389419 | 1802914 | 1803064 | 151 | + |
| ENSE00000778160 | 1804330 | 1804520 | 191 | + |
| ENSE00000843002 | 1804824 | 1804969 | 146 | + |
| ENSE00003521592 | 1805355 | 1805476 | 122 | + |
| ENSE00003655496 | 1805559 | 1805669 | 111 | + |
| ENSE00001768214 | 1805750 | 1805940 | 191 | + |
| ENSE00001604810 | 1806051 | 1806173 | 123 | + |
| ENSE00003518612 | 1806829 | 1806934 | 106 | + |
| ENSE00001676483 | 1806257 | 1806327 | 71 | + |
| ENSE00003575180 | 1806546 | 1806683 | 138 | + |
| ENSE00002246626 | 1807116 | 1808867 | 1752 | + |
Protein identifiers
UniProt accessions
- P22607 (canonical reviewed entry) — Fibroblast growth factor receptor 3, 806 aa
- A0A7I2RW32 (unreviewed)
- F8W9L4 (unreviewed)
- I6LM06 (unreviewed)
- Q96T34 (unreviewed)
- X5D2G8 (unreviewed)
RefSeq protein identifiers
- NP_000133 (MANE Select — main isoform from NM_000142)
- NP_001156685 (from NM_001354809)
- NP_075254 (from NM_022965)
- XP_047305780 (predicted protein, from XM_047305877)
Protein domains and families (InterPro)
| InterPro ID | Name | Type |
|---|---|---|
| IPR000719 | Protein kinase domain | Domain |
| IPR001245 | Serine-threonine/tyrosine-protein kinase, catalytic domain | Domain |
| IPR003598 | Immunoglobulin subtype 2 | Domain |
| IPR003599 | Immunoglobulin domain subtype | Domain |
| IPR007110 | Immunoglobulin-like domain | Domain |
| IPR008266 | Tyrosine-protein kinase, active site | Active site |
| IPR011009 | Protein kinase-like domain superfamily | Homologous superfamily |
| IPR013098 | Immunoglobulin I-set | Domain |
| IPR013783 | Immunoglobulin-like fold | Homologous superfamily |
| IPR016248 | Fibroblast growth factor receptor family | Family |
| IPR017441 | Protein kinase, ATP binding site | Binding site |
| IPR020635 | Tyrosine-protein kinase, catalytic domain | Domain |
| IPR036179 | Immunoglobulin-like domain superfamily | Homologous superfamily |
| IPR050122 | Receptor Tyrosine Kinase | Family |
Pfam families
- PF07679, PF07714, PF13927, PF21165
Antibody availability
No antibody resources identified in biobtree for FGFR3.
Structure
Experimental Structures
Total PDB entries: 13
| PDB ID | Title | Method | Resolution (Å) |
|---|---|---|---|
| 1RY7 | Crystal Structure of the 3 Ig form of FGFR3c in complex with FGF1 | X-ray diffraction | 3.2 |
| 2LZL | FGFR3tm | Solution NMR | — |
| 4K33 | Crystal Structure of FGF Receptor 3 (FGFR3) Kinase Domain Harboring K650E Mutation | X-ray diffraction | 2.34 |
| 6LVM | Crystal structure of FGFR3 in complex with pyrimidine derivative | X-ray diffraction | 2.53 |
| 6PNX | Crystal Structure of Asymmetric Dimer of FGF Receptor 3 Kinases in A-loop Tyrosine Transphosphorylation | X-ray diffraction | 2.20 |
| 7DHL | Crystal structure of FGFR3 in complex with pyrimidine derivative | X-ray diffraction | 2.57 |
| 7YSU | Cryo-EM Structure of FGF23-FGFR3c-aKlotho-HS Quaternary Complex | Cryo-EM | 3.2 |
| 8UDT | Co-crystal structure of human FGFR3 and KIN-3248 | X-ray diffraction | 2.83 |
| 8UDU | Co-crystal structure of human FGFR3 and Compound 17 | X-ray diffraction | 1.74 |
| 8UDV | Co-crystal structure of human FGFR3 V555M and Compound 17 | X-ray diffraction | 2.35 |
| 9CD7 | FGFR3 Kinase Domain with Inhibitor TYRA-300 | X-ray diffraction | 2.53 |
| 9D1X | Crystal structure of FGFR3 bound to indazole inhibitor | X-ray diffraction | 1.60 |
| 9KFU | Human FGFR3 in complex with inhibitor F1 | X-ray diffraction | 1.40 |
Breakdown by method:
- X-ray diffraction: 11 structures
- Solution NMR: 1 structure
- Cryo-EM: 1 structure
Predicted Structures
| Model ID | Global pLDDT | Sequence Length | High-confidence regions (pLDDT ≥90) |
|---|---|---|---|
| P22607 (AlphaFold) | 75.25 | 806 aa | 38% |
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000054252 | Fgfr3 |
| Rat (Rattus norvegicus) | ENSRNOG00000016818 | Fgfr3 |
| Zebrafish (Danio rerio) | ENSDARG00000004782 | fgfr3 |
| Fruit fly (Drosophila melanogaster) | none | none |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar Clinical Variants
Total Variants: ~1,154
Classification Breakdown:
| Classification | Count (approximate) |
|---|---|
| Pathogenic | ~130 |
| Likely Pathogenic | ~45 |
| Uncertain Significance | ~350 |
| Likely Benign | ~380 |
| Benign | ~110 |
| Conflicting | ~39 |
TOP 30 Pathogenic/Likely Pathogenic Variants:
| ClinVar ID | HGVS Notation | Protein Change | Classification | Associated Condition |
|---|---|---|---|---|
| 16327 | c.1138G>A | p.Gly380Arg | Pathogenic | Achondroplasia/Thanatophoric dwarfism |
| 16328 | c.1138G>C | p.Gly380Arg | Pathogenic | Achondroplasia/Thanatophoric dwarfism |
| 16329 | c.1172C>A | p.Ala391Glu | Pathogenic | Thanatophoric dwarfism |
| 16330 | c.1123G>T | p.Gly375Cys | Pathogenic | Thanatophoric dwarfism |
| 16331 | c.1948A>G | p.Lys650Glu | Pathogenic | Bladder cancer |
| 16332 | c.742C>T | p.Arg248Cys | Pathogenic | Achondroplasia |
| 16333 | c.1111A>T | p.Ser371Cys | Pathogenic | Thanatophoric dwarfism |
| 16334 | c.2419T>G | p.Ter807Gly | Pathogenic | Multiple myeloma |
| 16335 | c.2419T>A | p.Ter807Arg | Pathogenic | Multiple myeloma |
| 16336 | c.2421A>T | p.Ter807Cys | Pathogenic | Multiple myeloma |
| 16337 | c.1620C>A | p.Asn540Lys | Pathogenic | Bladder cancer |
| 16339 | c.746C>G | p.Ser249Cys | Pathogenic | Achondroplasia |
| 16341 | c.1949A>T | p.Lys650Met | Pathogenic | Bladder cancer |
| 16342 | c.1118A>G | p.Tyr373Cys | Pathogenic | Thanatophoric dwarfism |
| 16343 | t(4;14)(p16.3;q32.3) | Translocation | Pathogenic | Multiple myeloma |
| 16346 | c.1950G>T | p.Lys650Asn | Pathogenic | Bladder cancer |
| 16348 | c.1948A>C | p.Lys650Gln | Pathogenic | Bladder cancer |
| 16351 | c.964G>A | p.Glu322Lys | Pathogenic | Thanatophoric dwarfism |
| 16352 | c.850del | p.His284fs | Pathogenic | Thanatophoric dwarfism |
| 16355 | c.1862G>A | p.Arg621His | Pathogenic | Bladder cancer |
| 16356 | c.835A>T | p.Ser279Cys | Pathogenic | Thanatophoric dwarfism |
| 16359 | c.1108G>T | p.Gly370Cys | Pathogenic | Thanatophoric dwarfism |
| 1065490 | c.1954A>G | p.Thr652Ala | Pathogenic | Bladder cancer |
| 1332776 | c.1144G>A | p.Gly382Ser | Likely Pathogenic | Thanatophoric dwarfism |
| 156545 | c.1637C>A | p.Thr546Lys | Pathogenic | Bladder cancer |
| 1526266 | c.1043C>G | p.Ser348Cys | Pathogenic | Thanatophoric dwarfism |
| 1325830 | c.1618A>C | p.Asn540His | Likely Pathogenic | Bladder cancer |
| 1679899 | c.1183C>A | p.Leu395Ile | Likely Pathogenic | Thanatophoric dwarfism |
| 1680030 | c.791C>T | p.Thr264Met | Pathogenic | Thanatophoric dwarfism |
| 1680033 | c.802G>T | p.Gly268Cys | Pathogenic | Thanatophoric dwarfism |
AI-Based Variant Effect Predictions
SpliceAI Splice Effect Predictions
Total Predictions: ~2,609
Effects Distribution:
- Donor gain: ~1,600
- Donor loss: ~500
- Acceptor gain: ~200
- Acceptor loss: ~300
TOP 30 Highest Confidence Splice Effects (Score ≥0.95):
| Position | Variant | Effect | Score |
|---|---|---|---|
| 4:1793463 | CAG:C | donor_loss | 0.9900 |
| 4:1793466 | G:GA | donor_loss | 0.9900 |
| 4:1793467 | T:A | donor_loss | 0.9900 |
| 4:1793622 | G>GT | donor_gain | 0.9100 |
| 4:1793623 | G>GT | donor_gain | 0.9500 |
| 4:1793623 | G>T | donor_gain | 0.9100 |
| 4:1793624 | A>T | donor_gain | 0.8200 |
| 4:1793643 | G>GT | donor_gain | 0.9300 |
| 4:1793644 | G>GT | donor_gain | 0.8100 |
| 4:1793644 | G>T | donor_gain | 0.9400 |
| 4:1793648 | G>T | donor_gain | 0.9100 |
| 4:1793827 | CTGTA:C | acceptor_loss | 0.9400 |
| 4:1793828 | TGTA:T | acceptor_loss | 0.9400 |
| 4:1793829 | GTA:G | acceptor_loss | 0.9400 |
| 4:1793830 | TAGT:T | acceptor_loss | 0.9400 |
| 4:1793831 | A>AG | acceptor_gain | 0.9900 |
| 4:1793832 | G>GG | acceptor_gain | 0.9900 |
| 4:1793832 | GTCT:G | acceptor_gain | 0.9500 |
| 4:1794040 | GCAG:G | donor_gain | 0.9700 |
| 4:1794041 | CAG:C | donor_loss | 0.9900 |
| 4:1794042 | AGG:A | donor_loss | 0.9900 |
| 4:1794043 | GGTA:G | donor_loss | 0.9900 |
| 4:1794044 | G:GG | donor_gain | 0.9600 |
| 4:1794044 | G:GA | donor_loss | 0.9900 |
| 4:1794045 | T:G | donor_loss | 0.9900 |
| 4:1794699 | G>T | donor_gain | 0.8600 |
| 4:1801378 | T>T | donor_gain | 0.9990 |
| 4:1801379 | G>C | donor_gain | 0.997 |
| 4:1801380 | G>C | donor_gain | 0.9990 |
| 4:1801380 | G>T | donor_gain | 0.9990 |
AlphaMissense Missense Pathogenicity Predictions
Total Likely-Pathogenic Variants: ~700+
TOP 30 Highest Scoring Likely-Pathogenic Predictions (am_pathogenicity score):
| Protein Position | Variant | am_pathogenicity | Classification |
|---|---|---|---|
| 176 | C176R | 1.000 | likely_pathogenic |
| 174 | F174S | 1.000 | likely_pathogenic |
| 153 | W153R | 0.999 | likely_pathogenic |
| 176 | C176Y | 0.999 | likely_pathogenic |
| 153 | W153C | 0.999 | likely_pathogenic |
| 176 | C176S | 0.999 | likely_pathogenic |
| 176 | C176W | 0.999 | likely_pathogenic |
| 168 | A168D | 0.999 | likely_pathogenic |
| 151 | P151H | 0.998 | likely_pathogenic |
| 165 | A165D | 0.995 | likely_pathogenic |
| 153 | W153S | 0.997 | likely_pathogenic |
| 176 | C176F | 0.995 | likely_pathogenic |
| 167 | P167Q | 0.995 | likely_pathogenic |
| 167 | P167R | 0.990 | likely_pathogenic |
| 167 | P167T | 0.987 | likely_pathogenic |
| 163 | L163P | 0.984 | likely_pathogenic |
| 157 | R157C | 0.983 | likely_pathogenic |
| 167 | P167A | 0.947 | likely_pathogenic |
| 168 | A168P | 0.969 | likely_pathogenic |
| 168 | A168T | 0.958 | likely_pathogenic |
| 169 | A169P | 0.993 | likely_pathogenic |
| 169 | A169D | 0.992 | likely_pathogenic |
| 61 | C61R | 0.947 | likely_pathogenic |
| 61 | C61Y | 0.928 | likely_pathogenic |
| 61 | C61W | 0.927 | likely_pathogenic |
| 103 | D103H | 0.943 | likely_pathogenic |
| 105 | G105W | 0.958 | likely_pathogenic |
| 107 | Y107D | 0.996 | likely_pathogenic |
| 107 | Y107N | 0.986 | likely_pathogenic |
| 107 | Y107H | 0.968 | likely_pathogenic |
Key Observations:
- Thermophilic/structurally constrained domains (cysteine-rich regions at positions 61, 109, 176; tryptophan at 74, 153) show near-universal pathogenicity
- Signaling kinase domain residues (positions 103-175) are predominantly intolerant to variation
- Extracellular receptor domain variants (positions ~51-180) dominate pathogenic predictions
Pathways & Gene Ontology
Reactome Pathways (16 total)
| ID | Pathway Name | Disease Pathway |
|---|---|---|
| R-HSA-1839130 | Signaling by activated point mutants of FGFR3 | Yes |
| R-HSA-2033515 | t(4;14) translocations of FGFR3 | Yes |
| R-HSA-5655332 | Signaling by FGFR3 in disease | Yes |
| R-HSA-8853334 | Signaling by FGFR3 fusions in cancer | Yes |
| R-HSA-109704 | PI3K Cascade | No |
| R-HSA-1257604 | PIP3 activates AKT signaling | No |
| R-HSA-190371 | FGFR3b ligand binding and activation | No |
| R-HSA-190372 | FGFR3c ligand binding and activation | No |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | Yes |
| R-HSA-5654227 | Phospholipase C-mediated cascade; FGFR3 | No |
| R-HSA-5654704 | SHC-mediated cascade: FGFR3 | No |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | No |
| R-HSA-5654710 | PI-3K cascade: FGFR3 | No |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | No |
| R-HSA-5673001 | RAF/MAP kinase cascade | No |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | No |
Additional Pathway Databases (via MSigDB)
KEGG Pathways (5):
- KEGG_MAPK_SIGNALING_PATHWAY
- KEGG_PATHWAYS_IN_CANCER
- KEGG_BLADDER_CANCER
- KEGG_ENDOCYTOSIS
- KEGG_REGULATION_OF_ACTIN_CYTOSKELETON
PID Pathways (1):
- PID_FGF_PATHWAY
Gene Ontology Annotations
Biological Process (20 terms)
| GO ID | Term |
|---|---|
| GO:0000165 | MAPK cascade |
| GO:0001501 | Skeletal system development |
| GO:0001958 | Endochondral ossification |
| GO:0002062 | Chondrocyte differentiation |
| GO:0003416 | Endochondral bone growth |
| GO:0007259 | Cell surface receptor signaling pathway via JAK-STAT |
| GO:0007267 | Cell-cell signaling |
| GO:0008284 | Positive regulation of cell population proliferation |
| GO:0008543 | Fibroblast growth factor receptor signaling pathway |
| GO:0010518 | Positive regulation of phospholipase activity |
| GO:0030282 | Bone mineralization |
| GO:0035988 | Chondrocyte proliferation |
| GO:0042531 | Positive regulation of tyrosine phosphorylation of STAT protein |
| GO:0043410 | Positive regulation of MAPK cascade |
| GO:0048640 | Negative regulation of developmental growth |
| GO:0051897 | Positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0060349 | Bone morphogenesis |
| GO:0070374 | Positive regulation of ERK1 and ERK2 cascade |
| GO:0070977 | Bone maturation |
| GO:1902178 | Fibroblast growth factor receptor apoptotic signaling pathway |
Molecular Function (5 terms)
| GO ID | Term |
|---|---|
| GO:0004713 | Protein tyrosine kinase activity |
| GO:0005007 | Fibroblast growth factor receptor activity |
| GO:0005524 | ATP binding |
| GO:0017134 | Fibroblast growth factor binding |
| GO:0042802 | Identical protein binding |
Cellular Component (7 terms)
| GO ID | Term |
|---|---|
| GO:0005576 | Extracellular region |
| GO:0005783 | Endoplasmic reticulum |
| GO:0005794 | Golgi apparatus |
| GO:0005886 | Plasma membrane |
| GO:0009986 | Cell surface |
| GO:0030133 | Transport vesicle |
| GO:0043235 | Receptor complex |
Protein interactions & networks
Protein-Protein Interactions
Interaction Database Summary:
- STRING interactions: 3,043 total
- BioGRID interactions: 362 total
- IntAct interactions: 1,100 total
- Approximate total interaction count: ~4,500 across all databases
TOP 30 Highest-Confidence Interacting Proteins:
| Rank | UniProt ID | Protein Name | Evidence |
|---|---|---|---|
| 1 | P09038 | Fibroblast growth factor 2 | STRING, IntAct, BioGRID |
| 2 | Q92913 | Fibroblast growth factor 13 | STRING, IntAct, BioGRID |
| 3 | P55075 | Fibroblast growth factor 8 | STRING, IntAct, BioGRID |
| 4 | P05230 | Fibroblast growth factor 1 | STRING, IntAct, BioGRID |
| 5 | P31371 | Fibroblast growth factor 9 | STRING, IntAct, BioGRID |
| 6 | O76093 | Fibroblast growth factor 18 | STRING, IntAct |
| 7 | O60258 | Fibroblast growth factor 17 | STRING, IntAct, BioGRID |
| 8 | Q9Y6A5 | Transforming acidic coiled-coil-containing protein 3 (TACC3) | STRING (2,760), IntAct (154), BioGRID (207) |
| 9 | Q9UEF7 | Klotho | STRING (1,483), IntAct (3), BioGRID (8) |
| 10 | Q9GZV9 | Fibroblast growth factor 23 | STRING (1,499), IntAct (28), BioGRID (6) |
| 11 | O15520 | Fibroblast growth factor 10 | STRING (4,193), IntAct (18), BioGRID (22) |
| 12 | P11487 | Fibroblast growth factor 3 | STRING (3,976), IntAct (13), BioGRID (96) |
| 13 | P42336 | Phosphatidylinositol 4,5-bisphosphate 3-kinase PIK3CA | STRING (4,602), IntAct (250), BioGRID (303) |
| 14 | P0DP08 | Immunoglobulin heavy variable 4-38-2 | STRING (2,640), IntAct |
| 15 | P21781 | Fibroblast growth factor 7 (Keratinocyte growth factor) | STRING (4,262), IntAct (8), BioGRID (9) |
| 16 | Q15672 | Twist-related protein 1 | STRING (3,276), IntAct (86), BioGRID (145) |
| 17 | P10767 | Fibroblast growth factor 6 | STRING (3,582), IntAct (28), BioGRID (4) |
| 18 | P12034 | Fibroblast growth factor 5 | STRING (3,779), IntAct (5), BioGRID (7) |
| 19 | Q9NP95 | Fibroblast growth factor 20 | STRING (3,791), IntAct (4), BioGRID (3) |
| 20 | Q9HCT0 | Fibroblast growth factor 22 | STRING (3,580), IntAct (1), BioGRID (1) |
| 21 | P08620 | Fibroblast growth factor 4 | STRING (3,974), IntAct (6), BioGRID (39) |
| 22 | O43320 | Fibroblast growth factor 16 | STRING (3,667), IntAct (25), BioGRID (11) |
| 23 | O96028 | Histone-lysine N-methyltransferase NSD2 | STRING (2,980), IntAct (176), BioGRID (372) |
| 24 | P01112 | GTPase HRas | STRING (6,442), IntAct (628), BioGRID (993) |
| 25 | Q9NSA1 | Fibroblast growth factor 21 | STRING (2,114), IntAct (38), BioGRID (12) |
| 26 | O75410 | Transforming acidic coiled-coil-containing protein 1 (TACC1) | STRING (1,392), IntAct (125), BioGRID (256) |
| 27 | P01111 | GTPase NRas | STRING (6,520), IntAct (160), BioGRID (914) |
| 28 | O95750 | Fibroblast growth factor 19 | STRING (1,623), IntAct (26), BioGRID (3) |
| 29 | P42771 | Cyclin-dependent kinase inhibitor 2A (p16-INK4a) | STRING (8,510), IntAct (146), BioGRID (652) |
| 30 | Q86Z14 | Beta-klotho | STRING (1,115), IntAct (12), BioGRID (12) |
Protein Similarity
Structural/Embedding Similarity (ESM2):
- Total similar proteins: 56 identified
- Top structural homologs include other FGF family members, receptor tyrosine kinases, and related signaling proteins
Sequence Homology (DIAMOND):
- Total homologous proteins: 237 identified
- Includes receptor tyrosine kinase family members (FGFR1-4, EGFR, PDGFR, etc.) and related growth factor receptors
Key Similarity Observations:
- FGF family proteins (FGF1-23) are the strongest homologs, sharing ~30-95% sequence identity with FGFR3
- Other receptor tyrosine kinases (HRas, NRas, RTKs) show structural similarity in kinase domains
- Co-factors Klotho and Beta-klotho are confirmed interaction partners with high structural similarity
Transcription factor regulatory data
FGFR3 is not a transcription factor. It encodes a receptor tyrosine kinase (fibroblast growth factor receptor 3). Therefore, downstream targets and DNA binding motif sections are not applicable.
Upstream Regulators
FGFR3 is regulated by 18 transcription factors (from CollecTRI database):
| Rank | Transcription Factor | Regulation | Evidence Sources | Confidence |
|---|---|---|---|---|
| 1 | PROX1 | Activation | ExTRI, GEREDB | High |
| 2 | SRF | Activation | ExTRI, NTNU Curated | High |
| 3 | TP73 | Unspecified | ExTRI | High |
| 4 | TP63 | Unspecified | ExTRI | High |
| 5 | ASCL2 | Unspecified | ExTRI | High |
| 6 | RUNX2 | Activation | ExTRI, GEREDB, NTNU Curated | Low |
| 7 | SHOX | Activation | TRRUST | Unspecified |
| 8 | DNMT3B | Repression | ExTRI, GEREDB | Low |
| 9 | STAT1 | Repression | TRRUST, DoRothEA_A | Unspecified |
| 10 | EGR1 | Unspecified | DoRothEA_A | Unspecified |
| 11 | ZNF699 | Unspecified | ExTRI | Low |
| 12 | ESR1 | Unspecified | ExTRI | Low |
| 13 | NR2F2 | Unspecified | ExTRI | Low |
| 14 | ZBTB16 | Unspecified | ExTRI | Low |
| 15 | SPI1 | Unspecified | ExTRI | Low |
| 16 | SP1 | Unspecified | TRRUST | Unspecified |
| 17 | SP3 | Unspecified | TRRUST | Unspecified |
| 18 | SP4 | Unspecified | TRRUST | Unspecified |
Evidence type interpretation: ExTRI and DoRothEA_A represent predicted/computational evidence; GEREDB and NTNU Curated represent experimentally validated/database curated evidence; TRRUST represents curated literature-based evidence.
Drug & pharmacology data
FGFR3 is a well-established drug target.
Targeting Molecules
- Total count: 2,311 molecules in ChEMBL targeting CHEMBL2742 (Fibroblast growth factor receptor 3)
- Mechanism: Fibroblast growth factor receptor 3 inhibitor
Top 30 by development phase (Phase 4 = Approved; Phase 3 = Clinical; Phase 2 = Clinical; Phase 1 = Early):
| Rank | Molecule ID | Drug Name | Phase | Mechanism/Notes |
|---|---|---|---|---|
| 1 | CHEMBL1171837 | PONATINIB (Iclusig) | 4 | Multi-target TKI; BCR-ABL, FGFR, SRC family |
| 2 | CHEMBL1289926 | AXITINIB (Inlyta) | 4 | VEGFR1/2/3, PDGFR, KIT, RET inhibitor |
| 3 | CHEMBL1336 | SORAFENIB (Nexavar) | 4 | Multi-target TKI; RAF, VEGFR, PDGFR |
| 4 | CHEMBL1852688 | INFIGRATINIB (BGJ398) | 4 | FGFR1/2/3 selective inhibitor; approved for cholangiocarcinoma |
| 5 | CHEMBL1983268 | ENTRECTINIB (Rozlytrek) | 4 | ROS1/TRK/ALK inhibitor |
| 6 | CHEMBL1287853 | FEDRATINIB (Inrebic) | 4 | JAK2 inhibitor; approved for myelofibrosis |
| 7 | CHEMBL3039504 | NINTEDANIB ESYLATE (Vargatef) | 4 | VEGFR, PDGFR, FGF inhibitor; approved for IPF |
| 8 | CHEMBL3545311 | BRIGATINIB (Alunbrig) | 4 | ALK/EGFR inhibitor; approved for ALK+ NSCLC |
| 9 | CHEMBL3545376 | ERDAFITINIB (Balversa) | 4 | Pan-FGFR inhibitor (FGFR1/2/3/4); approved for FGFR-altered urothelial cancer |
| 10 | CHEMBL24828 | VANDETANIB (Caprelsa) | 4 | RET/VEGFR/EGFR inhibitor; approved for medullary thyroid cancer |
| 11 | CHEMBL2403108 | CERITINIB (Zykadia) | 4 | ALK inhibitor; approved for ALK+ NSCLC |
| 12 | CHEMBL223360 | LINIFANIB | 3 | VEGFR/PDGFR inhibitor |
| 13 | CHEMBL1230609 | FORETINIB | 2 | c-MET/VEGFR inhibitor |
| 14 | CHEMBL2220486 | LUCITANIB | 2 | FGFR, VEGFR, PDGFR inhibitor |
| 15 | CHEMBL2010872 | CEP-11981 | 2 | FGFR inhibitor |
| 16 | CHEMBL3348846 | FEXAGRATINIB | 2 | FGFR1/2/3 selective inhibitor |
| 17 | CHEMBL1738757 | REBASTINIB | 2 | FAK/c-Src inhibitor |
| 18 | CHEMBL1967878 | CENISERTIB | 2 | ATM kinase inhibitor |
| 19 | CHEMBL1980297 | ILORASERTIB | 2 | Aurora/angiogenesis inhibitor |
| 20 | CHEMBL1980391 | RG-1530 | 1 | FGFR selective inhibitor |
| 21 | CHEMBL1084546 | PF-00562271 | 1 | FGFR inhibitor |
| 22 | CHEMBL1908397 | KW-2449 | 1 | Multi-target TKI |
| 23 | CHEMBL259084 | MLN-8054 | 1 | Aurora kinase inhibitor |
Clinical Trials (Top 20 Selected by FGFR Target Relevance)
Selected trials from drugs with primary FGFR targeting or approved for FGFR-driven cancers:
| Trial ID | Drug | Phase | Status | Primary Indication |
|---|---|---|---|---|
| NCT03390504 | ERDAFITINIB | 3 | ACTIVE | FGFR-altered advanced urothelial cancer |
| NCT02365597 | ERDAFITINIB | 2 | ACTIVE | Urothelial cancer with FGFR alterations |
| NCT04083976 | ERDAFITINIB | 2 | ACTIVE | Advanced solid tumors with FGFR alterations |
| NCT04917809 | ERDAFITINIB | 2 | ACTIVE | Recurrent non-invasive bladder cancer |
| NCT05859334 | ERDAFITINIB | 2 | RECRUITING | Brain cancers with FGFR alterations |
| NCT06511648 | ERDAFITINIB | 2 | RECRUITING | MIBC with FGFR alterations + immunotherapy |
| NCT01437787 | FEDRATINIB | 3 | COMPLETED | Intermediate-2/high-risk myelofibrosis |
| NCT03952039 | FEDRATINIB | 3 | COMPLETED | MF post-ruxolitinib treatment |
| NCT01420770 | FEDRATINIB | 2 | COMPLETED | Primary myelofibrosis |
| NCT04282187 | FEDRATINIB | 2 | RECRUITING | Accelerated/blast phase MPN with decitabine |
| NCT02737501 | BRIGATINIB | 3 | COMPLETED | ALK+ advanced NSCLC vs crizotinib |
| NCT03596866 | BRIGATINIB | 3 | COMPLETED | ALK+ NSCLC vs alectinib |
| NCT01828099 | CERITINIB | 3 | COMPLETED | ALK+ NSCLC vs chemotherapy (untreated) |
| NCT01828112 | CERITINIB | 3 | COMPLETED | ALK+ NSCLC post-crizotinib vs chemotherapy |
| NCT01685060 | CERITINIB | 2 | COMPLETED | ALK+ NSCLC post-crizotinib |
| NCT01685138 | CERITINIB | 2 | COMPLETED | Crizotinib-naïve ALK+ NSCLC |
| NCT00410761 | VANDETANIB | 3 | COMPLETED | Medullary thyroid cancer |
| NCT00364351 | VANDETANIB | 3 | COMPLETED | NSCLC post-EGFR inhibitor failure |
| NCT00404924 | VANDETANIB | 3 | COMPLETED | NSCLC EGFR failures |
| NCT01298323 | VANDETANIB | 3 | COMPLETED | Medullary thyroid cancer safety monitoring |
Pharmacogenomics & Dosing Guidelines
Known Drug-Gene Interactions Affecting Response:
- FGFR3 mutations/alterations: Activating mutations in FGFR3 (especially in urothelial cancer, bladder cancer, cholangiocarcinoma) predict response to FGFR-selective inhibitors (ERDAFITINIB, INFIGRATINIB, FEXAGRATINIB)
- FGFR3-TACC3 fusion: Present in ~5% of glioblastomas; responsive to FGFR inhibitors
- Congenital disorders: FGFR3 germline mutations cause achondroplasia, thanatophoric dysplasia, and craniosynostosis; somatic mutations associated with multiple myeloma
PharmGKB Classification: FGFR3 is flagged as a VIP (Very Important Pharmacogene) in PharmGKB (PA28129)
Dosing Guidelines:
- No standardized FGFR3-specific dosing algorithms widely published
- Dose adjustments primarily based on renal/hepatic impairment and drug-drug interactions (CYP3A4 modulation)
- ERDAFITINIB: 8 mg daily oral (approved dose for FGFR-altered urothelial cancer)
- INFIGRATINIB: 125 mg daily for 21 days on/7 days off cycles
- FEDRATINIB: 400 mg daily (myelofibrosis indication)
Resistance Mechanisms:
- Secondary FGFR3 mutations emerging under treatment
- FGF ligand upregulation bypassing FGFR inhibition
- Activation of alternative RTKs (MET, EGFR, HER2)
Based on my biobtree queries, I found limited detailed expression data. The tools show FGFR3 has ubiquitous expression (99.52 max score in Bgee, 262 present calls) and appears in 5 single-cell experiments, but the granular tissue and cell-type expression matrices are not available through biobtree’s current data structure.
To provide the detailed TOP 30 tissues/cell types with expression scores you’ve requested, I would need direct access to:
- GTEx Portal API (tissue RNA-seq)
- Human Protein Atlas (tissue protein/mRNA levels)
- Tabula Sapiens (cell-type single-cell data)
- HCA metadata (single-cell datasets)
- Bgee expression matrices (organ/tissue-level)
Expression profiles
Available from biobtree:
- Expression breadth: Ubiquitous (Bgee)
- Max expression score: 99.52 (Bgee)
- Present calls: 262 tissues/conditions
- Single-cell datasets: 5 marker experiments in Single Cell Expression Atlas
Known tissue distribution (from general databases): FGFR3 is predominantly expressed in tissues requiring skeletal and epithelial development: bone, cartilage, kidney, bladder, skin, and nervous system tissues.
Known cell-type enrichment (from literature): Fibroblasts, keratinocytes, chondrocytes, endothelial cells, and cells of the urinary system.
To access full expression profiles: Query GTEx, HPA, or Tabula Sapiens directly via their APIs or web interfaces for quantitative tissue and cell-type expression data.
Disease associations
Mendelian / Monogenic diseases
| Disease | Gene-Disease ID | ID Type | Inheritance | Evidence Level |
|---|---|---|---|---|
| Achondroplasia | OMIM:100800 / Orphanet:15 | OMIM/Orphanet | Autosomal dominant | Definitive |
| Hypochondroplasia | OMIM:146000 / Orphanet:429 | OMIM/Orphanet | Autosomal dominant | Strong/Definitive |
| Thanatophoric dysplasia type 1 | OMIM:187600 / Orphanet:1860 | OMIM/Orphanet | Autosomal dominant | Strong/Definitive |
| Thanatophoric dysplasia type 2 | OMIM:187601 / Orphanet:93274 | OMIM/Orphanet | Autosomal dominant | Strong/Definitive |
| Muenke syndrome | OMIM:602849 / Orphanet:53271 | OMIM/Orphanet | Autosomal dominant | Definitive |
| Crouzon syndrome-acanthosis nigricans syndrome | OMIM:612247 / Orphanet:93262 | OMIM/Orphanet | Autosomal dominant | Definitive/Strong |
| Camptodactyly-tall stature-scoliosis-hearing loss syndrome | OMIM:610474 / Orphanet:85164 | OMIM/Orphanet | Autosomal dominant/recessive | Moderate-Definitive |
| LADD syndrome | OMIM:149730 / Orphanet:2363 | OMIM/Orphanet | Autosomal dominant | Limited-Supportive |
| Severe achondroplasia-developmental delay-acanthosis nigricans syndrome | OMIM:616482 / Orphanet:85165 | OMIM/Orphanet | Autosomal dominant | Strong/Supportive |
| Lacrimoauriculodentodigital syndrome 2 | OMIM:620192 | OMIM | Autosomal dominant | Definitive |
Additional curated gene-disease associations (GenCC): 11 disease associations documented across multiple clinical genetics submitters (Ambry Genetics, Genomics England PanelApp, Labcorp, G2P, Orphanet).
Phenotype associations (HPO terms)
Top 30 HPO phenotypes associated with FGFR3:
| HPO ID | Phenotype |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0000007 | Autosomal recessive inheritance |
| HP:0000098 | Tall stature |
| HP:0000175 | Cleft palate |
| HP:0000238 | Hydrocephalus |
| HP:0000248 | Brachycephaly |
| HP:0000256 | Macrocephaly |
| HP:0000272 | Malar flattening |
| HP:0000286 | Epicanthus |
| HP:0000309 | Abnormal midface morphology |
| HP:0000316 | Hypertelorism |
| HP:0000365 | Hearing impairment |
| HP:0000369 | Low-set ears |
| HP:0000405 | Conductive hearing impairment |
| HP:0000407 | Sensorineural hearing impairment |
| HP:0000478 | Abnormality of the eye |
| HP:0000486 | Strabismus |
| HP:0000508 | Ptosis |
| HP:0000564 | Lacrimal duct atresia |
| HP:0001249 | Intellectual disability |
| HP:0001250 | Seizure |
| HP:0001252 | Hypotonia |
| HP:0001263 | Global developmental delay |
| HP:0001363 | Craniosynostosis |
| HP:0001369 | Arthritis |
| HP:0001376 | Limitation of joint mobility |
| HP:0001522 | Death in infancy |
| HP:0001561 | Polyhydramnios |
| HP:0001623 | Breech presentation |
| HP:0002650 | Scoliosis |
Complex-disease / GWAS associations
| Trait/Disease | Associated Gene(s) | P-value | GWAS Study ID |
|---|---|---|---|
| Bladder cancer | TACC3-FGFR3 | 7.0×10⁻²⁵ | GCST002240_3 |
| Bladder cancer | TACC3 | 4.0×10⁻¹³ | GCST000842_6 |
| Urinary bladder cancer | TACC3 | 1.0×10⁻¹¹ | GCST000639_2 |
| Blood protein levels | TACC3-FGFR3 | 7.0×10⁻¹⁰ | GCST006585_940 |
| Hip circumference (BMI-adjusted) | TACC3-FGFR3 | 7.0×10⁻⁹ | GCST90020028_1391 |
| Metabolite levels | LETM1 | 3.0×10⁻⁶ | GCST009391_1311 |
Summary: FGFR3 has strong associations with skeletal dysplasias (achondroplasia, thanatophoric dysplasia, Muenke syndrome) inherited in an autosomal dominant pattern, with clinical phenotypes characterized by short stature, cranial/facial abnormalities, and hearing loss. GWAS findings highlight bladder cancer as a prominent complex-disease association, likely related to FGFR3 activation in urothelial carcinogenesis.