FGFR1

Chr 8AD

fibroblast growth factor receptor 1

Also known as: BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1, FLG, FLT-2

The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) 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 binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Encephalocraniocutaneous lipomatosis, somatic mosaicMIM #613001
Hartsfield syndromeMIM #615465
AD
Hypogonadotropic hypogonadism 2 with or without anosmiaMIM #147950
AD
Jackson-Weiss syndromeMIM #123150
AD
Osteoglophonic dysplasiaMIM #166250
AD
Pfeiffer syndromeMIM #101600
AD
Trigonocephaly 1MIM #190440
AD

Clinical highlights

Gene-disease validity (ClinGen)
Pfeiffer syndrome type 1 · ADDefinitivesufficient evidence for diagnostic panels3 gene-disease associations curated in total
Interpreting a novel variant
Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.
7
Active trials
665
Pubs (1 yr)
P/LP submissions
P/LP missense
0.21
LOEUF· LoF intol.
Multiple*
Mechanism· G2P
📖
GeneReview available — FGFR1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.21LOEUF
pLI 1.000
Z-score 5.48
OE 0.09 (0.040.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.49Z-score
OE missense 0.69 (0.630.75)
348 obs / 505.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.09 (0.040.21)
00.351.4
Missense OE?0.69 (0.630.75)
00.61.4
Synonymous OE?1.12
01.21.6
LoF obs/exp: 4 / 42.5Missense obs/exp: 348 / 505.2Syn Z: -1.40

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FGFR1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Lung CancerTKI ResistanceEGFR Sensitive Mutation

A Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations and Failed EGFR TKIs With the Combination of Enrotinib and Paclitaxel Monoclonal Antibody

NOT YET RECRUITING
NCT06048315Phase PHASE3Degan LuStarted 2023-09
AnlotinibPenpulimab
GliomaGlioblastoma (GBM)MGMT-Methylated Glioblastoma

STUPP Regimen With or Without Lenvatinib for Newly Diagnosed Glioblastoma With MGMT Promoter Methylation

NOT YET RECRUITING
NCT07754734Phase PHASE2Dongguan People's HospitalStarted 2026-08-10
LenvatinibTMZ (Temozolomide)radiotherapy
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
Locally Advanced CholangiocarcinomaIntrahepatic CholangiocarcinomaSolid Tumor

Safety and Anti-Tumor Activity of TYRA-200 in Advanced Cholangiocarcinoma With Activating FGFR2 Gene Alterations

ACTIVE NOT RECRUITING
NCT06160752Phase PHASE1Tyra Biosciences, IncStarted 2023-11-22
Phase 1 Part A - dose escalation TYRA-200 taken once daily by mouth in 28-day cyclesPhase 1 Part B - dose expansion TYRA-200 taken once daily by mouth in 28-day cycles
Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

RECRUITING
NCT02693535Phase PHASE2American Society of Clinical OncologyStarted 2016-03-14
SunitinibTemsirolimusTrastuzumab and Pertuzumab
CraniosynostosesCrouzon SyndromeSaethre Chotzen Syndrome

ASO Treatment for Syndromic Craniosynostoses

RECRUITING
NCT07535372Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2026-04-20
Design of patient specific ASO
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