Crouzon syndrome

Summary

Crouzon syndrome (MONDO:0007405) is a disease caused by FGFR2 (GenCC Definitive), with 4 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: FGFR2 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 236
• Phenotypes (HPO): 33
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		Europe	Validated
Prevalence at birth	1-9 / 1 000 000	0.9	Europe	Validated
Point prevalence	1-9 / 100 000	1.65	Canada	Validated
Prevalence at birth	1-9 / 100 000	2.6	Australia	Validated

Signs & symptoms

Clinical features (HPO)

33 HPO clinical features (Orphanet curated; top 33 by frequency):

HPO ID	Term	Frequency
HP:0000348	High forehead	Very frequent (80-99%)
HP:0000929	Abnormal skull morphology	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0002007	Frontal bossing	Very frequent (80-99%)
HP:0011324	Multiple suture craniosynostosis	Very frequent (80-99%)
HP:0000248	Brachycephaly	Frequent (30-79%)
HP:0000262	Turricephaly	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000327	Hypoplasia of the maxilla	Frequent (30-79%)
HP:0000405	Conductive hearing impairment	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000508	Ptosis	Frequent (30-79%)
HP:0000509	Conjunctivitis	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0001321	Cerebellar hypoplasia	Frequent (30-79%)
HP:0002308	Chiari malformation	Frequent (30-79%)
HP:0002516	Increased intracranial pressure	Frequent (30-79%)
HP:0011800	Midface retrusion	Frequent (30-79%)
HP:0000189	Narrow palate	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000444	Convex nasal ridge	Occasional (5-29%)
HP:0000453	Choanal atresia	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0000646	Amblyopia	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000956	Acanthosis nigricans	Occasional (5-29%)
HP:0000995	Melanocytic nevus	Occasional (5-29%)
HP:0001053	Hypopigmented skin patches	Occasional (5-29%)
HP:0002093	Respiratory insufficiency	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0005107	Abnormal sacrum morphology	Occasional (5-29%)
HP:0011386	Narrow internal auditory canal	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Crouzon syndrome
Mondo ID	MONDO:0007405
MeSH	D003394
OMIM	123500
Orphanet	207
DOID	DOID:2339
ICD-11	1535725821
NCIT	C84653
SNOMED CT	28861008
UMLS	C0010273
MedGen	1162
GARD	0006206
NORD	1018
Is cancer (heuristic)	no

Also known as: Cfd1 · craniofacial dysostosis · craniofacial dysostosis type 1 · Crouzon craniofacial dysostosis · Crouzon disease · Crouzon syndrome

Data availability: 236 ClinVar variants · 6 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic craniosynostosis › Crouzon syndrome

Related subtypes (39): Beare-Stevenson cutis gyrata syndrome, Shprintzen-Goldberg syndrome, acrocephalopolydactyly, Antley-Bixler syndrome, C syndrome, cranioectodermal dysplasia, cardiocranial syndrome, Pfeiffer type, craniosynostosis-fibular aplasia syndrome, Baller-Gerold syndrome, craniotelencephalic dysplasia, Summitt syndrome, X-linked intellectual disability-plagiocephaly syndrome, Lowry-MacLean syndrome, pseudoaminopterin syndrome, craniosynostosis 4, holoprosencephaly-craniosynostosis syndrome, Hunter-McAlpine craniosynostosis, Curry-Jones syndrome, craniomicromelic syndrome, Muenke syndrome, craniosynostosis-anal anomalies-porokeratosis syndrome, craniosynostosis 2, cloverleaf skull-multiple congenital anomalies syndrome, craniosynostosis-intracranial calcifications syndrome, Crouzon syndrome-acanthosis nigricans syndrome, craniosynostosis and dental anomalies, lethal occipital encephalocele-skeletal dysplasia syndrome, TCF12-related craniosynostosis, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, cloverleaf skull-asphyxiating thoracic dysplasia syndrome, craniosynostosis, Philadelphia type, craniosynostosis-cataract syndrome, familial scaphocephaly syndrome, craniosynostosis-hydrocephalus-Arnold-Chiari malformation type I-radioulnar synostosis syndrome, osteosclerosis-developmental delay-craniosynostosis syndrome, craniosynostosis, Herrmann-Opitz type, trigonocephaly-broad thumbs syndrome, acrocephalosyndactyly, Weiss-Kruszka syndrome

Subtypes (2): cote katsantoni syndrome, Bazopoulou Kyrkanidou 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

236 retrieved; paginated sample, class counts are floors:

102 uncertain significance, 37 conflicting classifications of pathogenicity, 27 benign/likely benign, 21 pathogenic, 17 pathogenic/likely pathogenic, 14 likely benign, 12 benign, 6 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13263	NM_000141.5(FGFR2):c.1025G>A (p.Cys342Tyr)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13264	NM_000141.5(FGFR2):c.1018T>C (p.Tyr340His)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13265	NM_000141.5(FGFR2):c.1061C>G (p.Ser354Cys)	FGFR2	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
13270	NM_000141.5(FGFR2):c.983A>G (p.Tyr328Cys)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13271	NM_000141.5(FGFR2):c.1040C>G (p.Ser347Cys)	FGFR2	Pathogenic/Likely 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
13275	NM_000141.5(FGFR2):c.1026C>G (p.Cys342Trp)	FGFR2	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
13283	NM_000141.5(FGFR2):c.868T>C (p.Trp290Arg)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13284	NM_000141.5(FGFR2):c.868T>G (p.Trp290Gly)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13286	NM_000141.5(FGFR2):c.1052C>G (p.Ser351Cys)	FGFR2	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
13290	NM_000141.5(FGFR2):c.799T>C (p.Ser267Pro)	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
13295	NM_000141.5(FGFR2):c.1576A>G (p.Lys526Glu)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13299	NM_000141.5(FGFR2):c.1084+3A>G	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
1406374	NM_000141.5(FGFR2):c.1070T>C (p.Leu357Ser)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265431	NM_000141.5(FGFR2):c.833G>T (p.Cys278Phe)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
29853	NM_000141.5(FGFR2):c.1009G>C (p.Ala337Pro)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374809	NM_000141.5(FGFR2):c.826T>G (p.Phe276Val)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
374812	NM_000141.5(FGFR2):c.869G>C (p.Trp290Ser)	FGFR2	Pathogenic	criteria provided, single submitter
374813	NM_000141.5(FGFR2):c.923A>G (p.Tyr308Cys)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374815	NM_000141.5(FGFR2):c.1007A>G (p.Asp336Gly)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374816	NM_000141.5(FGFR2):c.1012G>C (p.Gly338Arg)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 58 · Orphanet: 27 · 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	Crouzon syndrome	38
ERF	Supportive	Autosomal dominant	Crouzon syndrome	10
ETF1	Supportive	Autosomal dominant	Crouzon syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
ERF	Orphanet:207	Crouzon syndrome
ERF	Orphanet:647681	Craniosynostosis-facial dysmorphism-Chiari-1 malformation-developmental and language delay syndrome
FGFR3	Orphanet:15	Achondroplasia
FGFR3	Orphanet:1860	Thanatophoric dysplasia type 1
FGFR3	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR3	Orphanet:251576	Gliosarcoma
FGFR3	Orphanet:251579	Giant cell glioblastoma
FGFR3	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
FGFR3	Orphanet:429	Hypochondroplasia
FGFR3	Orphanet:53271	Muenke syndrome
FGFR3	Orphanet:794	Saethre-Chotzen syndrome
FGFR3	Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome
FGFR3	Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome
FGFR3	Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome
FGFR3	Orphanet:93274	Thanatophoric dysplasia type 2

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	gencc,clinvar
ERF	HGNC:3444	ENSG00000105722	P50548	ETS domain-containing transcription factor ERF	gencc
ETF1	HGNC:3477	ENSG00000120705	P62495	Eukaryotic peptide chain release factor subunit 1	gencc
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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…
ERF	ETS domain-containing transcription factor ERF	Potent transcriptional repressor that binds to the H1 element of the Ets2 promoter.
ETF1	Eukaryotic peptide chain release factor subunit 1	Component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons.
FGFR3	Fibroblast growth factor receptor 3	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 and apoptosis.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.5

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	13.9×	0.015
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
ERF	Other/Unknown	no		Ets_dom, WH-like_DNA-bd_sf, WH_DNA-bd_sf
ETF1	Other/Unknown	no		Peptide_chain-rel_eRF1/aRF1, eRF1_Pelota-like_N, eRF1_2
FGFR3	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.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
upper leg skin	2
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1
gall bladder	1
mucosa of stomach	1
right uterine tube	1
islet of Langerhans	1
mucosa of sigmoid colon	1
skin of hip	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
ERF	242	ubiquitous	marker	right uterine tube, mucosa of stomach, gall bladder
ETF1	293	ubiquitous	marker	islet of Langerhans, upper leg skin, mucosa of sigmoid colon
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR3	4,510
ERF	1,115
FGFR2	449
ETF1	313

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR2	P21802	63
ETF1	P62495	33
FGFR3	P22607	15
ERF	P50548	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 35. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by FGFR2 amplification mutants	1	2855.0×	0.002	FGFR2
t(4;14) translocations of FGFR3	1	2855.0×	0.002	FGFR3
Signaling by FGFR2 fusions	1	2855.0×	0.002	FGFR2
Signaling by FGFR3 fusions in cancer	1	2855.0×	0.002	FGFR3
PI3K Cascade	2	135.9×	0.002	FGFR2, FGFR3
Constitutive Signaling by Aberrant PI3K in Cancer	2	63.4×	0.002	FGFR2, FGFR3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	48.4×	0.003	FGFR2, FGFR3
PIP3 activates AKT signaling	2	33.4×	0.006	FGFR2, FGFR3
RAF/MAP kinase cascade	2	30.5×	0.006	FGFR2, FGFR3
FGFR3b ligand binding and activation	1	407.9×	0.009	FGFR3
FGFR2b ligand binding and activation	1	285.5×	0.011	FGFR2
Signaling by activated point mutants of FGFR3	1	237.9×	0.011	FGFR3
FGFR3c ligand binding and activation	1	219.6×	0.011	FGFR3
FGFR2c ligand binding and activation	1	219.6×	0.011	FGFR2
Phospholipase C-mediated cascade; FGFR3	1	219.6×	0.011	FGFR3
Activated point mutants of FGFR2	1	167.9×	0.012	FGFR2
Phospholipase C-mediated cascade; FGFR2	1	158.6×	0.012	FGFR2
PI-3K cascade:FGFR3	1	158.6×	0.012	FGFR3
SHC-mediated cascade:FGFR3	1	150.3×	0.012	FGFR3
Signaling by FGFR2 IIIa TM	1	150.3×	0.012	FGFR2
FRS-mediated FGFR3 signaling	1	135.9×	0.012	FGFR3
Protein hydroxylation	1	135.9×	0.012	ETF1
PI-3K cascade:FGFR2	1	124.1×	0.012	FGFR2
Signaling by FGFR3 in disease	1	124.1×	0.012	FGFR3
SHC-mediated cascade:FGFR2	1	119.0×	0.012	FGFR2
FRS-mediated FGFR2 signaling	1	109.8×	0.012	FGFR2
Negative regulation of FGFR3 signaling	1	109.8×	0.012	FGFR3
FGFR2 alternative splicing	1	105.7×	0.012	FGFR2
Negative regulation of FGFR2 signaling	1	92.1×	0.013	FGFR2
Oncogene Induced Senescence	1	84.0×	0.014	ERF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of phospholipase activity	2	1685.2×	5e-05	FGFR2, FGFR3
endochondral bone growth	2	842.6×	1e-04	FGFR2, FGFR3
bone morphogenesis	2	300.9×	6e-04	FGFR2, FGFR3
fibroblast growth factor receptor signaling pathway	2	142.8×	0.002	FGFR2, FGFR3
bone mineralization	2	135.9×	0.002	FGFR2, FGFR3
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	4213.0×	0.003	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	4213.0×	0.003	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	4213.0×	0.003	FGFR2
negative regulation of developmental growth	1	4213.0×	0.003	FGFR3
lateral sprouting from an epithelium	1	4213.0×	0.003	FGFR2
cytoplasmic translational termination	1	2106.5×	0.003	ETF1
orbitofrontal cortex development	1	2106.5×	0.003	FGFR2
prostate gland morphogenesis	1	2106.5×	0.003	FGFR2
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	1	2106.5×	0.003	FGFR2
mammary gland bud formation	1	2106.5×	0.003	FGFR2
branch elongation involved in salivary gland morphogenesis	1	2106.5×	0.003	FGFR2
mesenchymal cell differentiation involved in lung development	1	2106.5×	0.003	FGFR2
fibroblast growth factor receptor apoptotic signaling pathway	1	2106.5×	0.003	FGFR3
regulation of osteoblast proliferation	1	1404.3×	0.004	FGFR2
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	1404.3×	0.004	FGFR2
prostate epithelial cord elongation	1	1404.3×	0.004	FGFR2
bone maturation	1	1404.3×	0.004	FGFR3
ventricular zone neuroblast division	1	1053.2×	0.004	FGFR2
embryonic organ morphogenesis	1	1053.2×	0.004	FGFR2
reproductive structure development	1	1053.2×	0.004	FGFR2
regulation of morphogenesis of a branching structure	1	1053.2×	0.004	FGFR2
positive regulation of ERK1 and ERK2 cascade	2	42.6×	0.004	FGFR2, FGFR3
positive regulation of MAPK cascade	2	40.3×	0.004	FGFR2, FGFR3
regulation of smooth muscle cell differentiation	1	842.6×	0.004	FGFR2
branching involved in prostate gland morphogenesis	1	842.6×	0.004	FGFR2

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
FGFR2	PONATINIB
FGFR3	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR3	64	4
FGFR2	59	4
ERF	0	0
ETF1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR2, FGFR3
PEMIGATINIB	4	FGFR2, FGFR3
NINTEDANIB	4	FGFR2, FGFR3
FEDRATINIB	4	FGFR2, FGFR3
LENVATINIB	4	FGFR2, FGFR3
AXITINIB	4	FGFR2, FGFR3
SORAFENIB	4	FGFR2, FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR2, FGFR3
INFIGRATINIB	4	FGFR2, FGFR3
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2, FGFR3
VANDETANIB	4	FGFR2, FGFR3
NINTEDANIB ESYLATE	4	FGFR2, FGFR3
BRIGATINIB	4	FGFR2, FGFR3
ERDAFITINIB	4	FGFR2, FGFR3
FUTIBATINIB	4	FGFR2, FGFR3
PAZOPANIB	4	FGFR2, FGFR3
SUNITINIB	4	FGFR2, FGFR3
DASATINIB	4	FGFR2, FGFR3
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2, FGFR3
ENTRECTINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
LINIFANIB	3	FGFR2, FGFR3
SEMAXANIB	3	FGFR2, FGFR3
BRIVANIB	3	FGFR2, FGFR3
CEDIRANIB	3	FGFR2, FGFR3
DOVITINIB	3	FGFR2, FGFR3
LESTAURTINIB	3	FGFR2, FGFR3
ALISERTIB	3	FGFR3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
FGFR3	975	Binding:948, Functional:18, ADMET:9
FGFR2	966	Binding:940, Functional:22, ADMET:4
ETF1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
FGFR3	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
FGFR2	966
FGFR3	975

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	FGFR2, FGFR3
PEMIGATINIB	4	FGFR2, FGFR3
NINTEDANIB	4	FGFR2, FGFR3
FEDRATINIB	4	FGFR2, FGFR3
LENVATINIB	4	FGFR2, FGFR3
AXITINIB	4	FGFR2, FGFR3
SORAFENIB	4	FGFR2, FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR2, FGFR3
INFIGRATINIB	4	FGFR2, FGFR3
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2, FGFR3
VANDETANIB	4	FGFR2, FGFR3
NINTEDANIB ESYLATE	4	FGFR2, FGFR3
BRIGATINIB	4	FGFR2, FGFR3
ERDAFITINIB	4	FGFR2, FGFR3
FUTIBATINIB	4	FGFR2, FGFR3
PAZOPANIB	4	FGFR2, FGFR3
SUNITINIB	4	FGFR2, FGFR3
DASATINIB	4	FGFR2, FGFR3
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2, FGFR3
ENTRECTINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
LINIFANIB	3	FGFR2, FGFR3
SEMAXANIB	3	FGFR2, FGFR3
BRIVANIB	3	FGFR2, FGFR3
CEDIRANIB	3	FGFR2, FGFR3
DOVITINIB	3	FGFR2, FGFR3
LESTAURTINIB	3	FGFR2, FGFR3
ALISERTIB	3	FGFR3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	FGFR2, FGFR3
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	2	ERF, ETF1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ERF	0	—
ETF1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07535372	Not specified	NOT_YET_RECRUITING	ASO Treatment for Syndromic Craniosynostoses