FGFR2

Chr 10AD

fibroblast growth factor receptor 2

Also known as: BBDS, BEK, BFR-1, CD332, CEK3, CFD1, ECT1, JWS

NCBI Gene: 2263 ENSG00000066468 UniProt: P21802 OMIM: 176943

This gene encodes a transmembrane tyrosine kinase receptor that binds fibroblast growth factors and activates downstream signaling cascades that regulate cell proliferation and differentiation. Mutations cause multiple autosomal dominant craniosynostosis syndromes including Apert, Crouzon, Pfeiffer, Jackson-Weiss, Beare-Stevenson, and Saethre-Chotzen syndromes, as well as other skeletal dysplasias like Antley-Bixler syndrome and bent bone dysplasia. The pathogenic mutations typically result in gain-of-function effects that lead to premature fusion of cranial sutures and associated craniofacial abnormalities.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Jan 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Scaphocephaly, maxillary retrusion, and impaired intellectual developmentMIM #609579

Antley-Bixler syndrome without genital anomalies or disordered steroidogenesisMIM #207410

Apert syndromeMIM #101200

Beare-Stevenson cutis gyrata syndromeMIM #123790

Bent bone dysplasia syndromeMIM #614592

Craniofacial-skeletal-dermatologic dysplasiaMIM #101600

Craniosynostosis, nonspecific

Crouzon syndromeMIM #123500

Gastric cancer, somaticMIM #613659

Jackson-Weiss syndromeMIM #123150

LADD syndrome 1MIM #149730

Pfeiffer syndromeMIM #101600

Saethre-Chotzen syndromeMIM #101400

Scaphocephaly and Axenfeld-Rieger anomaly

UniProtFamilial scaphocephaly syndrome

UniProtLacrimo-auriculo-dento-digital syndrome 1

Clinical highlights

Gene–disease validity (ClinGen)

+1 more curated pair

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

603

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

GOF*

Mechanism· G2P

📖

GeneReview available — FGFR2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in FGFR2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

876 rare PASS variants

Rare truncating (LoF)

1 in 1,300

77 rare PASS variants

Rare synonymous (reference)

1 in 86

455 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FGFR2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 1,400
South Asian	~43k	1 in 68	1 in 550
Remaining (unassigned)	~30k	1 in 88	1 in 1,400
European (Finnish)	~27k	1 in 300	1 in 3,300
Admixed American	~22k	1 in 82	1 in 1,000
African / African American	~21k	1 in 54	1 in 3,600
East Asian	~20k	1 in 90	1 in 560
Ashkenazi Jewish	~13k	1 in 800	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 110	1 in 390

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 17 coding exons well covered in gnomAD exomes and genomes.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FGFR2 · 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

📖

GeneReview available — FGFR2

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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

Rare Malignant Neoplasm

Marker Assisted Selective ThErapy in Rare Cancers: Knowledge Database Establishing registrY Asia

RECRUITING

NCT05217407National Cancer Center, JapanStarted 2021-11-30

Genomic sequence

Advanced CholangiocarcinomaFGFR2 FusionsGene Rearrangement

Study of Futibatinib in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusion or Rearrangement

RECRUITING

NCT05727176Phase PHASE2Taiho Oncology, Inc.Started 2023-07-05

TAS-120

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

FGFR2 Gene Fusion/RearrangementOther Solid Tumors, Adult

A Study of Lirafugratinib in Non-CCA Solid Tumors With FGFR2 Fusion or Rearrangement

RECRUITING

NCT07359820Phase PHASE2Elevar TherapeuticsStarted 2026-06-04

Lirafugratinib

CraniosynostosesCrouzon SyndromeSaethre Chotzen Syndrome

ASO Treatment for Syndromic Craniosynostoses

RECRUITING

NCT07535372Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2026-04-20

Design of patient specific ASO

Intrahepatic CholangiocarcinomaFGFR2 Gene RearrangementFGFR2 Gene Mutation

A Phase II Study of Pemigatinib Plus Durvalumab in Previously Treated Advanced Intrahepatic Cholangiocarcinoma Patients With FGFR-2 Fusion or Rearrangement

RECRUITING

NCT06728410Phase PHASE2Mehmet AkceStarted 2026-01-27

PemigatinibDurvalumab

Intrahepatic Cholangiocarcinoma (Icc)CholangiocarcinomaOther Solid Tumors, Adult

A Study of an FGFR2/3 Inhibitor (CGT4859) in Patients With Cholangiocarcinoma and Other Advanced Solid Tumors

ACTIVE NOT RECRUITING

NCT06777316Phase PHASE1, PHASE2Cogent Biosciences, Inc.Started 2025-01-22

CGT4859

Advanced Pancreatic CarcinomaMetastatic Pancreatic CarcinomaStage II Pancreatic Cancer AJCC v8

A Phase II Nationwide, Fully Decentralized, Telemedicine Study of Pemigatinib in Adult Patients With Advanced or Metastatic Pancreatic Cancer With FGFR Genetic Alterations

RECRUITING

NCT06906562Phase PHASE2Sameek RoychowdhuryStarted 2025-08-26

PemigatinibComputed Tomography (CT)Magnetic Resonance Imaging

Biliary Tract Cancer

A Post-marketing Observational Study of Tasfygo in Participants With Unresectable Biliary Tract Cancer With Fibroblast Growth Factor Receptor 2 (FGFR2) Fusion Gene Positivity Who Progressed After Chemotherapy

RECRUITING

NCT06793709Eisai Co., Ltd.Started 2025-07-10

No Intervention

Gastric and Cardia Adenocarcinomas

Biomoleculars Markers of Sensitivity to Pre- and Post-operative Chemotherapy of Gastric and Cardia Adenocarcinomas: a Pilot Study

RECRUITING

NCT02491840Phase NAUniversity Hospital, Strasbourg, FranceStarted 2016-05

Biopsy

Intrahepatic Cholangiocarcinoma (Icc)Advanced Cholangiocarcinoma

Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations

NOT YET RECRUITING

NCT07328919Phase PHASE3TransThera Sciences (Nanjing), Inc.Started 2026-01

TT-00420 (tinengotinib)Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Key Publications

Landmark & review papers · by relevance

PubMed

Cholangiocarcinoma - novel biological insights and therapeutic strategies.

Ilyas SI et al.·Nat Rev Clin Oncol

2023Review