FGFR3

Chr 4ADAR

fibroblast growth factor receptor 3

Also known as: ACH, CD333, CEK2, HSFGFR3EX, JTK4

NCBI Gene: 2261 ENSG00000068078 UniProt: P22607 OMIM: 134934

The protein functions as a fibroblast growth factor receptor with a cytoplasmic tyrosine kinase domain that binds acidic and basic fibroblast growth factors and regulates bone development and maintenance through downstream signaling cascades. Mutations cause multiple skeletal dysplasias including achondroplasia, hypochondroplasia, thanatophoric dysplasia types I and II, and craniosynostosis syndromes such as Muenke syndrome and Crouzon syndrome with acanthosis nigricans, inherited in autosomal dominant or autosomal recessive patterns. The pathogenic mechanism involves gain-of-function mutations that disrupt normal bone and cartilage development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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. [provided by RefSeq, Aug 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

AchondroplasiaMIM #100800

Bladder cancer, somaticMIM #109800

CATSHL syndromeMIM #610474

ADAR

Cervical cancer, somaticMIM #603956

Colorectal cancer, somaticMIM #114500

Crouzon syndrome with acanthosis nigricansMIM #612247

HypochondroplasiaMIM #146000

LADD syndrome 2MIM #620192

Muenke syndromeMIM #602849

Nevus, epidermal, somaticMIM #162900

SADDANMIM #616482

Spermatocytic seminoma, somaticMIM #273300

Thanatophoric dysplasia, type IMIM #187600

Thanatophoric dysplasia, type IIMIM #187601

UniProtCamptodactyly, tall stature, and hearing loss syndrome

UniProtMultiple myeloma

UniProtLacrimo-auriculo-dento-digital syndrome 2

UniProtKeratinocytic non-epidermolytic nevus

Clinical highlights

Gene-disease validity (ClinGen)

Crouzon syndrome-acanthosis nigricans syndrome · ADDefinitivesufficient evidence for diagnostic panels7 gene-disease associations curated in total

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

489

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.60

LOEUF

GOF*

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.60LOEUF

pLI 0.000

Z-score 3.48

OE 0.39 (0.26–0.60)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.26Z-score

OE missense 0.85 (0.78–0.92)

458 obs / 540.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.26–0.60)

0≤0.351.4

Missense OE?0.85 (0.78–0.92)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 15 / 38.2Missense obs/exp: 458 / 540.2Syn Z: -3.39

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FGFR3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Bladder CancerRecurrent Bladder CancerFGFR3 Gene Mutation

A Study of Oral Erdafitinib in People With Recurrent Non-Invasive Bladder Cancer

ACTIVE NOT RECRUITING

NCT04917809Phase PHASE2Memorial Sloan Kettering Cancer CenterStarted 2022-02-17

Erdafitinib

Locally Advanced Bladder Urothelial CarcinomaLocally Advanced Renal Pelvis Urothelial CarcinomaLocally Advanced Ureter Urothelial Carcinoma

Testing Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy

ACTIVE NOT RECRUITING

NCT04963153Phase PHASE1National Cancer Institute (NCI)Started 2022-07-07

Biospecimen CollectionBone ScanComputed Tomography

HER2-Gastric/Gastroesophageal Junction CancerUrothelial CarcinomaNon-Small Cell Lung Cancer

A Phase 2 Clinical Study of ABSK061 and ABSK043

RECRUITING

NCT06632262Phase PHASE2Abbisko Therapeutics Co, LtdStarted 2024-11-13

ABSK061 + ABSK043ABSK061+ABSK043 in combination with CAPOX

Urinary Bladder NeoplasmsNeoplasm MetastasisUreteral Neoplasms

FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3

RECRUITING

NCT05614739Phase PHASE1Eli Lilly and CompanyStarted 2023-01-12

VepugratinibPembrolizumabenfortumab vedotin

Urothelial Carcinoma (UC)Bladder (Urothelial, Transitional Cell) CancerLiquid Biopsy

Using Liquid Biopsy Testing to Identify, Monitor, Predict Recurrence in Urothelial Carcinoma

RECRUITING

NCT07441499Tianjin Medical University Second HospitalStarted 2026-03

Multi-Component Liquid Biopsy for Urothelial Carcinoma

Locally Advanced Urothelial CarcinomaMetastatic Urothelial CarcinomaSolid Tumor

Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations

ACTIVE NOT RECRUITING

NCT05544552Phase PHASE1, PHASE2Tyra Biosciences, IncStarted 2022-11-22

TYRA-300

Bladder CancerBladder Cancer RecurrenceAdjuvant Therapy for Bladder Cancer

Multiplex Mutation Detection Using Mass Spectrometry in Bladder Cancer

RECRUITING

NCT07424560Zhilong DongStarted 2026-02-25

Multiplex Mutation Detection System for Bladder Cancer (Nucleic Acid Mass Spectrometry)

Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)

RECRUITING

NCT03297606Phase PHASE2Canadian Cancer Trials GroupStarted 2018-03-23

OlaparibDasatinibNivolumab plus Ipilimumab

Advanced Malignant Solid NeoplasmAnn Arbor Stage III Non-Hodgkin LymphomaAnn Arbor Stage IV Non-Hodgkin Lymphoma

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)

ACTIVE NOT RECRUITING

NCT03155620Phase PHASE2National Cancer Institute (NCI)Started 2017-07-31

Biopsy ProcedureBiospecimen CollectionBone Marrow Aspiration and Biopsy

Non-Muscle Invasive Bladder Urothelial CarcinomaRecurrent Non-Muscle Invasive Bladder Urothelial Carcinoma

A Randomized Trial of Bicalutamide in Non-Muscle Invasive Bladder Cancer

RECRUITING

NCT05521698Phase PHASE1University of Wisconsin, MadisonStarted 2026-06-25

BicalutamideBiopsy ProcedureBiospecimen Collection

Low Grade Upper Tract Urothelial Carcinoma

Phase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma

RECRUITING

NCT07265947Phase PHASE2Tyra Biosciences, IncStarted 2025-12-22