FGFR2 - dismech genes

Normal function · from ai-gene-review (P21802, commit 79fe13b38970) · AI-generated, not KB evidence

FGFR2 (Fibroblast Growth Factor Receptor 2) encodes a receptor tyrosine kinase that mediates FGF signaling in development, tissue repair, and homeostasis. CRITICAL ISOFORM BIOLOGY: Alternative splicing of exon IIIb vs IIIc in the third Ig-like domain creates isoforms with MUTUALLY EXCLUSIVE ligand specificities: (1) FGFR2IIIb (P21802-3, KGFR) is expressed in EPITHELIAL cells and binds FGF1, FGF3, FGF7 (KGF), and FGF10. FGF7 and FGF10 bind ONLY to IIIb. (2) FGFR2IIIc (P21802-1, BEK) is expressed in MESENCHYMAL cells and binds FGF1, FGF2, FGF4, FGF6, and FGF9. FGF2 binds preferentially to IIIc. This isoform switching enables PARACRINE signaling between epithelium and mesenchyme: mesenchyme produces FGF7/10 to signal to epithelial IIIb, while epithelium produces FGF2/4 to signal to mesenchymal IIIc. Critical for limb development, lung branching morphogenesis, and wound healing. Additional isoforms: Secreted/soluble forms (P21802-14, P21802-19) may act as decoy receptors. Numerous other splice variants exist with various domain combinations. Cancer relevance: IIIb-to-IIIc isoform switching accompanies epithelial-mesenchymal transition (EMT) and correlates with metastatic potential in some cancers.

molecular function: fibroblast growth factor receptor activity · directly involved in: fibroblast growth factor receptor signaling pathway; positive regulation of cell population proliferation; positive regulation of ERK1 and ERK2 cascade; bone development; regulation of morphogenesis of a branching structure; embryonic cranial skeleton morphogenesis; lung development · locations: plasma membrane

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Ameloblastoma	somatic driver somatic	mechanism: Somatic RTK-RAS-MAPK Driver Alterations
Antley-Bixler Syndrome, FGFR2-Related	causative germline	mechanism: Extracellular FGFR2 Pathogenic Variants; Increased FGFR2 Kinase Activity
Beare-Stevenson Cutis Gyrata Syndrome	causative germline	mechanism: FGFR2 Activating Variant
FGFR2-Related Bent Bone Dysplasia	causative germline	mechanism: FGFR2 Transmembrane Polar Substitution
Gastric Adenocarcinoma	somatic driver somatic	mechanism: Receptor Tyrosine Kinase Amplification scoped to subtype: CIN
Pelvic Organ Prolapse	susceptibility
Pfeiffer Syndrome	causative	mechanism: FGFR2 gain-of-function signaling in cranial sutures subtype: FGFR2-related
Apert Syndrome	untyped Causative	mechanism: FGFR2 linker-region activating mutations variant: p.Pro253Arg; p.Ser252Trp animal model: Mouse diagnosis: Molecular genetic testing for FGFR2 hotspot variants
Congenital Pulmonary Airway Malformation	untyped Pathogenic Variants somatic
Crouzon Syndrome	untyped Pathogenic Variants	variant: p.Cys342Trp; p.Trp290Gly
Humeroradial Synostosis	untyped Causative
Jackson-Weiss Syndrome	no genetic record	variant: p.Cys342Arg; p.Cys342Ser

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
Apert syndrome MONDO:0007041	AD	Definitive 2021-12-14	Apert Syndrome untyped
Pfeiffer syndrome MONDO:0007043	AD	Definitive 2022-03-21	Pfeiffer Syndrome causative
Crouzon syndrome MONDO:0007405	AD	Definitive 2021-12-23	Crouzon Syndrome untyped
Beare-Stevenson cutis gyrata syndrome MONDO:0007412	AD	Definitive 2022-03-31	Beare-Stevenson Cutis Gyrata Syndrome causative
LADD syndrome MONDO:0007872	AD	Limited 2022-06-16	no dismech entry
bent bone dysplasia syndrome 1 MONDO:0013815	AD	Definitive 2022-05-19	FGFR2-Related Bent Bone Dysplasia causative

Mechanism modules · computed from kb/

fgfr_gain_of_function_skeletal_dysplasia via Antley-Bixler Syndrome, FGFR2-Related, Apert Syndrome, Beare-Stevenson Cutis Gyrata Syndrome, Pfeiffer Syndrome named in the module itself
sustaining_proliferative_signaling via Ameloblastoma