Jackson-Weiss syndrome

Summary

Jackson-Weiss syndrome (MONDO:0007400) is a disease caused by variants in FGFR2 and FGFR1, with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal genes: FGFR2 (GenCC Definitive), FGFR1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 263
• Phenotypes (HPO): 21

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Cases/families		200	Worldwide	Not yet validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0000262	Turricephaly	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0001770	Toe syndactyly	Very frequent (80-99%)
HP:0001783	Broad metatarsal	Very frequent (80-99%)
HP:0010059	Broad hallux phalanx	Very frequent (80-99%)
HP:0010743	Short metatarsal	Very frequent (80-99%)
HP:0011800	Midface retrusion	Very frequent (80-99%)
HP:0000174	Abnormal palate morphology	Frequent (30-79%)
HP:0000303	Mandibular prognathia	Frequent (30-79%)
HP:0000327	Hypoplasia of the maxilla	Frequent (30-79%)
HP:0000444	Convex nasal ridge	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000508	Ptosis	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0009891	Underdeveloped supraorbital ridges	Frequent (30-79%)
HP:0001839	Split foot	Occasional (5-29%)
HP:0001841	Preaxial foot polydactyly	Occasional (5-29%)
HP:0002991	Abnormal fibula morphology	Occasional (5-29%)
HP:0004691	2-3 toe syndactyly	Occasional (5-29%)
HP:0009773	Symphalangism affecting the phalanges of the hand	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Jackson-Weiss syndrome
Mondo ID	MONDO:0007400
MeSH	C537559
OMIM	123150
Orphanet	1540
DOID	DOID:0111337
NCIT	C123814
SNOMED CT	709105005
UMLS	C0795998
MedGen	208653
GARD	0006796
NORD	1306
Is cancer (heuristic)	no

Also known as: craniosynostosis-midfacial hypoplasia-foot abnormalities syndrome · Jackson-Weiss syndrome · JWS

Data availability: 263 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic craniosynostosis › acrocephalosyndactyly › Jackson-Weiss syndrome

Related subtypes (3): acrocephalopolysyndactyly, Apert syndrome, Saethre-Chotzen syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

263 retrieved; paginated sample, class counts are floors:

144 uncertain significance, 44 conflicting classifications of pathogenicity, 33 likely benign, 14 benign/likely benign, 12 pathogenic, 9 pathogenic/likely pathogenic, 5 likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
16279	NM_023110.3(FGFR1):c.755C>G (p.Pro252Arg)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
235087	NM_023110.3(FGFR1):c.1977+1G>A	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2505415	NM_023110.3(FGFR1):c.710G>A (p.Gly237Asp)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
502125	NM_023110.3(FGFR1):c.214C>T (p.Gln72Ter)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13263	NM_000141.5(FGFR2):c.1025G>A (p.Cys342Tyr)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13266	NM_000141.5(FGFR2):c.1024T>C (p.Cys342Arg)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13267	NM_000141.5(FGFR2):c.1024T>A (p.Cys342Ser)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13268	NM_000141.5(FGFR2):c.1032G>A (p.Ala344=)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13269	NM_000141.5(FGFR2):c.1031C>G (p.Ala344Gly)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13272	NM_000141.5(FGFR2):c.755C>G (p.Ser252Trp)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13273	NM_000141.5(FGFR2):c.758C>G (p.Pro253Arg)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13276	NM_000141.5(FGFR2):c.866A>C (p.Gln289Pro)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13277	NM_000141.5(FGFR2):c.1124A>G (p.Tyr375Cys)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13289	NM_000141.5(FGFR2):c.943G>T (p.Ala315Ser)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13293	NM_000141.5(FGFR2):c.870G>T (p.Trp290Cys)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
374817	NM_000141.5(FGFR2):c.1013G>A (p.Gly338Glu)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374819	NM_000141.5(FGFR2):c.1025G>T (p.Cys342Phe)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
374820	NM_000141.5(FGFR2):c.1025G>C (p.Cys342Ser)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
374823	NM_000141.5(FGFR2):c.1694A>G (p.Glu565Gly)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449024	NM_000141.5(FGFR2):c.314A>G (p.Tyr105Cys)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
478046	NM_000141.5(FGFR2):c.1150G>A (p.Gly384Arg)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
1338542	NM_023110.3(FGFR1):c.809G>A (p.Gly270Asp)	FGFR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3595591	NM_023110.3(FGFR1):c.1854+2T>C	FGFR1	Likely pathogenic	criteria provided, single submitter
4294512	NM_023110.3(FGFR1):c.104dup (p.Ala36fs)	FGFR1	Likely pathogenic	criteria provided, single submitter
4796553	NM_023110.3(FGFR1):c.2156T>C (p.Met719Thr)	FGFR1	Likely pathogenic	criteria provided, single submitter
654366	NM_023110.3(FGFR1):c.448+1G>A	FGFR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1156684	NM_023110.3(FGFR1):c.789C>T (p.Ala263=)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1186398	NM_023110.3(FGFR1):c.266A>G (p.Gln89Arg)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1197448	NM_023110.3(FGFR1):c.448+1G>C	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1302903	NM_023110.3(FGFR1):c.2428C>T (p.His810Tyr)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 74 · Orphanet: 29 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FGFR2	Definitive	Autosomal dominant	Jackson-Weiss syndrome	38
FGFR1	Strong	Autosomal dominant	Jackson-Weiss syndrome	36

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis
FGFR1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
FGFR1	Orphanet:478	Kallmann syndrome
FGFR1	Orphanet:93258	Pfeiffer syndrome type 1
FGFR1	Orphanet:93924	Lobar holoprosencephaly
FGFR1	Orphanet:99798	Oligodontia
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	gencc,clinvar
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	2	27.7×	0.001

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
calcaneal tendon	1
stromal cell of endometrium	1
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
FGFR2	449

Intra-cohort edges

A	B	Sources
FGFR1	FGFR2	intact

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR1	P11362	83
FGFR2	P21802	63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 35. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PI3K Cascade	2	271.9×	5e-04	FGFR1, FGFR2
Constitutive Signaling by Aberrant PI3K in Cancer	2	126.9×	0.001	FGFR1, FGFR2
Signaling by FGFR2 amplification mutants	1	5710.0×	0.001	FGFR2
Signaling by FGFR2 fusions	1	5710.0×	0.001	FGFR2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	96.8×	0.001	FGFR1, FGFR2
PIP3 activates AKT signaling	2	66.8×	0.001	FGFR1, FGFR2
RAF/MAP kinase cascade	2	61.1×	0.001	FGFR1, FGFR2
Signaling by FGFR1 amplification mutants	1	2855.0×	0.002	FGFR1
FGFR1c and Klotho ligand binding and activation	1	1427.5×	0.002	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	1427.5×	0.002	FGFR1
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	713.8×	0.004	FGFR1
FGFR1b ligand binding and activation	1	634.4×	0.005	FGFR1
FGFR2b ligand binding and activation	1	571.0×	0.005	FGFR2
Signaling by activated point mutants of FGFR1	1	475.8×	0.005	FGFR1
FGFR2c ligand binding and activation	1	439.2×	0.005	FGFR2
FGFR1c ligand binding and activation	1	380.7×	0.006	FGFR1
Activated point mutants of FGFR2	1	335.9×	0.006	FGFR2
Phospholipase C-mediated cascade: FGFR1	1	335.9×	0.006	FGFR1
Phospholipase C-mediated cascade; FGFR2	1	317.2×	0.006	FGFR2
Signaling by FGFR2 IIIa TM	1	300.5×	0.006	FGFR2
Downstream signaling of activated FGFR1	1	271.9×	0.006	FGFR1
Signal transduction by L1	1	259.6×	0.006	FGFR1
PI-3K cascade:FGFR1	1	259.6×	0.006	FGFR1
SHC-mediated cascade:FGFR1	1	248.3×	0.006	FGFR1
PI-3K cascade:FGFR2	1	248.3×	0.006	FGFR2
SHC-mediated cascade:FGFR2	1	237.9×	0.006	FGFR2
FRS-mediated FGFR1 signaling	1	228.4×	0.006	FGFR1
FRS-mediated FGFR2 signaling	1	219.6×	0.006	FGFR2
FGFR2 alternative splicing	1	211.5×	0.006	FGFR2
Formation of paraxial mesoderm	1	203.9×	0.006	FGFR1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	2	5617.3×	3e-06	FGFR1, FGFR2
ventricular zone neuroblast division	2	4213.0×	3e-06	FGFR1, FGFR2
positive regulation of phospholipase activity	2	3370.4×	3e-06	FGFR1, FGFR2
lung-associated mesenchyme development	2	1685.2×	1e-05	FGFR1, FGFR2
branching involved in salivary gland morphogenesis	2	1404.3×	1e-05	FGFR1, FGFR2
positive regulation of cardiac muscle cell proliferation	2	624.1×	5e-05	FGFR1, FGFR2
positive regulation of mesenchymal cell proliferation	2	601.9×	5e-05	FGFR1, FGFR2
midbrain development	2	601.9×	5e-05	FGFR1, FGFR2
skeletal system morphogenesis	2	495.6×	6e-05	FGFR1, FGFR2
ureteric bud development	2	455.5×	7e-05	FGFR1, FGFR2
peptidyl-tyrosine phosphorylation	2	421.3×	7e-05	FGFR1, FGFR2
epithelial to mesenchymal transition	2	312.1×	1e-04	FGFR1, FGFR2
inner ear morphogenesis	2	300.9×	1e-04	FGFR1, FGFR2
fibroblast growth factor receptor signaling pathway	2	285.6×	1e-04	FGFR1, FGFR2
protein autophosphorylation	2	145.3×	4e-04	FGFR1, FGFR2
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	8426.0×	9e-04	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	8426.0×	9e-04	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	8426.0×	9e-04	FGFR2
lateral sprouting from an epithelium	1	8426.0×	9e-04	FGFR2
positive regulation of MAPK cascade	2	80.6×	0.001	FGFR1, FGFR2
orbitofrontal cortex development	1	4213.0×	0.001	FGFR2
prostate gland morphogenesis	1	4213.0×	0.001	FGFR2
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	1	4213.0×	0.001	FGFR2
mammary gland bud formation	1	4213.0×	0.001	FGFR2
branch elongation involved in salivary gland morphogenesis	1	4213.0×	0.001	FGFR2
mesenchymal cell differentiation involved in lung development	1	4213.0×	0.001	FGFR2
vitamin D3 metabolic process	1	4213.0×	0.001	FGFR1
positive regulation of mitotic cell cycle DNA replication	1	4213.0×	0.001	FGFR1
positive regulation of parathyroid hormone secretion	1	4213.0×	0.001	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	4213.0×	0.001	FGFR1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
FGFR1	PONATINIB
FGFR2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
FGFR2	59	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR1, FGFR2
PEMIGATINIB	4	FGFR1, FGFR2
NINTEDANIB	4	FGFR1, FGFR2
FEDRATINIB	4	FGFR1, FGFR2
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1, FGFR2
AXITINIB	4	FGFR1, FGFR2
SORAFENIB	4	FGFR1, FGFR2
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1, FGFR2
INFIGRATINIB	4	FGFR1, FGFR2
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1, FGFR2
NINTEDANIB ESYLATE	4	FGFR1, FGFR2
BRIGATINIB	4	FGFR1, FGFR2
ERDAFITINIB	4	FGFR1, FGFR2
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1, FGFR2
PAZOPANIB	4	FGFR1, FGFR2
SUNITINIB	4	FGFR1, FGFR2
DASATINIB	4	FGFR1, FGFR2
MIDOSTAURIN	4	FGFR1, FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
ERLOTINIB	4	FGFR2
LINIFANIB	3	FGFR1, FGFR2
SEMAXANIB	3	FGFR1, FGFR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
FGFR2	966	Binding:940, Functional:22, ADMET:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
FGFR1	1,465
FGFR2	966

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	FGFR1, FGFR2
PEMIGATINIB	4	FGFR1, FGFR2
NINTEDANIB	4	FGFR1, FGFR2
FEDRATINIB	4	FGFR1, FGFR2
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1, FGFR2
AXITINIB	4	FGFR1, FGFR2
SORAFENIB	4	FGFR1, FGFR2
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1, FGFR2
INFIGRATINIB	4	FGFR1, FGFR2
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1, FGFR2
NINTEDANIB ESYLATE	4	FGFR1, FGFR2
BRIGATINIB	4	FGFR1, FGFR2
ERDAFITINIB	4	FGFR1, FGFR2
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1, FGFR2
PAZOPANIB	4	FGFR1, FGFR2
SUNITINIB	4	FGFR1, FGFR2
DASATINIB	4	FGFR1, FGFR2
MIDOSTAURIN	4	FGFR1, FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
ERLOTINIB	4	FGFR2
LINIFANIB	3	FGFR1, FGFR2
SEMAXANIB	3	FGFR1, FGFR2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	FGFR1, FGFR2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.