Pfeiffer syndrome

Summary

Pfeiffer syndrome (MONDO:0007043) is a disease (an umbrella term covering 5 Mondo subtypes) caused by variants in FGFR1 and FGFR2, with 5 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal genes: FGFR1 (GenCC Definitive), FGFR2 (GenCC Definitive)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 858
• Phenotypes (HPO): 22
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1	Europe	Validated
Prevalence at birth	1-9 / 1 000 000	0.3	Australia	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0000508	Ptosis	Very frequent (80-99%)
HP:0010669	Hypoplasia of the zygomatic bone	Very frequent (80-99%)
HP:0011304	Broad thumb	Very frequent (80-99%)
HP:0000262	Turricephaly	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000348	High forehead	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0006101	Finger syndactyly	Frequent (30-79%)
HP:0009773	Symphalangism affecting the phalanges of the hand	Frequent (30-79%)
HP:0000194	Open mouth	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000303	Mandibular prognathia	Occasional (5-29%)
HP:0000322	Short philtrum	Occasional (5-29%)
HP:0000324	Facial asymmetry	Occasional (5-29%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0001385	Hip dysplasia	Occasional (5-29%)
HP:0003307	Hyperlordosis	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0005048	Synostosis of carpal bones	Occasional (5-29%)
HP:0012368	Flat face	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Pfeiffer syndrome
Mondo ID	MONDO:0007043
OMIM	101600
Orphanet	710
DOID	DOID:14705
ICD-11	1075159878
NCIT	C99100
SNOMED CT	70410008
UMLS	C0220658
MedGen	67390
GARD	0007380
NORD	1572
Is cancer (heuristic)	no

Also known as: acrocephalosyndactyly type 5 · acrocephalosyndactyly type V · ACS5 · Noack syndrome · Pfeiffer syndrome · Pfeiffer type acrocephalosyndactyly · type V Acrocephalosyndactyly

Data availability: 858 ClinVar variants · 8 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic craniosynostosis › acrocephalosyndactyly › acrocephalopolysyndactyly › Pfeiffer syndrome

Related subtypes (3): Sakati-Nyhan syndrome, Goodman syndrome, Carpenter syndrome

Subtypes (5): Pfeiffer syndrome type 1, Pfeiffer syndrome type 2, Pfeiffer syndrome type 3, FGFR1-related Pfeiffer syndrome, FGFR2-related Pfeiffer 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

600 retrieved; paginated sample, class counts are floors:

248 uncertain significance, 200 likely benign, 58 conflicting classifications of pathogenicity, 44 pathogenic, 17 pathogenic/likely pathogenic, 15 likely pathogenic, 11 benign/likely benign, 7 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1455925	NC_000008.10:g.(?37595441)(38961219_?)del	EIF4EBP1	Pathogenic	criteria provided, single submitter
1074220	NM_023110.3(FGFR1):c.979_983del (p.His327fs)	FGFR1	Pathogenic	criteria provided, single submitter
1335817	NM_023110.3(FGFR1):c.1981C>T (p.Arg661Ter)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1418780	NM_023110.3(FGFR1):c.1265dup (p.Leu423fs)	FGFR1	Pathogenic	criteria provided, single submitter
16279	NM_023110.3(FGFR1):c.755C>G (p.Pro252Arg)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
16282	NM_023110.3(FGFR1):c.1864C>T (p.Arg622Ter)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16290	NM_023110.3(FGFR1):c.1141T>C (p.Cys381Arg)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16296	NM_023110.3(FGFR1):c.1825C>T (p.Arg609Ter)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
16303	NM_023110.3(FGFR1):c.749G>A (p.Arg250Gln)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
1801171	NM_023110.3(FGFR1):c.246_247del (p.Glu84fs)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
180154	NM_023110.3(FGFR1):c.1037_1038del (p.Ser346fs)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
180160	NM_023110.3(FGFR1):c.2059G>A (p.Gly687Arg)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1997422	NM_023110.3(FGFR1):c.111del (p.Val38fs)	FGFR1	Pathogenic	criteria provided, single submitter
2011123	NM_023110.3(FGFR1):c.625del (p.Arg209fs)	FGFR1	Pathogenic	criteria provided, single submitter
2029325	NM_023110.3(FGFR1):c.780del (p.Leu261fs)	FGFR1	Pathogenic	criteria provided, single submitter
2097346	NM_023110.3(FGFR1):c.1568_1569dup (p.Asp524fs)	FGFR1	Pathogenic	criteria provided, single submitter
2105298	NM_023110.3(FGFR1):c.2048T>G (p.Val683Gly)	FGFR1	Pathogenic	criteria provided, single submitter
2136660	NM_023110.3(FGFR1):c.1883A>G (p.Asn628Ser)	FGFR1	Pathogenic	criteria provided, single submitter
2136661	NM_023110.3(FGFR1):c.302G>T (p.Cys101Phe)	FGFR1	Pathogenic	criteria provided, single submitter
235087	NM_023110.3(FGFR1):c.1977+1G>A	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2426796	NC_000008.10:g.(?38314854)(38314964_?)del	FGFR1	Pathogenic	criteria provided, single submitter
2505392	NM_023110.3(FGFR1):c.1589C>G (p.Ser530Ter)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
2505401	NM_023110.3(FGFR1):c.1977+1G>T	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
2505417	NM_023110.3(FGFR1):c.760C>T (p.Arg254Trp)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2505445	NM_023110.3(FGFR1):c.289G>A (p.Gly97Ser)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2505462	NM_023110.3(FGFR1):c.154C>T (p.Gln52Ter)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
2921666	NM_023110.3(FGFR1):c.1631_1632dup (p.Ile545fs)	FGFR1	Pathogenic	criteria provided, single submitter
2948865	NM_023110.3(FGFR1):c.1864dup (p.Arg622fs)	FGFR1	Pathogenic	criteria provided, single submitter
2949496	NM_023110.3(FGFR1):c.1946del (p.His649fs)	FGFR1	Pathogenic	criteria provided, single submitter

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
FGFR1	Definitive	Autosomal dominant	Pfeiffer syndrome	36
FGFR2	Definitive	Autosomal dominant	Pfeiffer syndrome	38

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

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

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
ADGRA2	HGNC:17849	ENSG00000020181	Q96PE1	Adhesion G protein-coupled receptor A2	clinvar
EIF4EBP1	HGNC:3288	ENSG00000187840	Q13541	Eukaryotic translation initiation factor 4E-binding protein 1	clinvar
MDM4	HGNC:6974	ENSG00000198625	O15151	Protein Mdm4	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…
ADGRA2	Adhesion G protein-coupled receptor A2	Endothelial receptor which functions together with RECK to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B).
EIF4EBP1	Eukaryotic translation initiation factor 4E-binding protein 1	Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation.
MDM4	Protein Mdm4	Contributes to p53/TP53 regulation.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.6

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	11.1×	0.048
GPCR	1	4.8×	0.384
Transcription factor	1	1.6×	0.634
Other/Unknown	1	0.4×	0.983

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
ADGRA2	GPCR	yes		GPS, Cys-rich_flank_reg_C, GPCR_2_secretin-like
EIF4EBP1	Other/Unknown	no		EIF4EBP
MDM4	Transcription factor	no		Znf_RING, Znf_RanBP2, SWIB_MDM2_domain

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	2
buccal mucosa cell	1
calcaneal tendon	1
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1
endocervix	1
seminal vesicle	1
body of pancreas	1
lower esophagus mucosa	1
parotid gland	1
colonic epithelium	1
nipple	1
oocyte	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
ADGRA2	226	ubiquitous	marker	stromal cell of endometrium, seminal vesicle, endocervix
EIF4EBP1	251	ubiquitous	marker	body of pancreas, parotid gland, lower esophagus mucosa
MDM4	270	ubiquitous	marker	nipple, oocyte, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
MDM4	3,431
EIF4EBP1	2,189
ADGRA2	1,345
FGFR2	449

Intra-cohort edges

A	B	Sources
FGFR1	FGFR2	intact

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR1	P11362	83
FGFR2	P21802	63
MDM4	O15151	39
EIF4EBP1	Q13541	24

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADGRA2	Q96PE1	70.47

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 66. Enrichment computed across 5 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
PI3K Cascade	2	135.9×	0.005	FGFR1, FGFR2
Signaling by FGFR2 amplification mutants	1	2855.0×	0.006	FGFR2
Signaling by FGFR2 fusions	1	2855.0×	0.006	FGFR2
Constitutive Signaling by Aberrant PI3K in Cancer	2	63.4×	0.006	FGFR1, FGFR2
Signaling by FGFR1 amplification mutants	1	1427.5×	0.008	FGFR1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	48.4×	0.008	FGFR1, FGFR2
FGFR1c and Klotho ligand binding and activation	1	713.8×	0.010	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	713.8×	0.010	FGFR1
PIP3 activates AKT signaling	2	33.4×	0.010	FGFR1, FGFR2
RAF/MAP kinase cascade	2	30.5×	0.010	FGFR1, FGFR2
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	356.9×	0.017	FGFR1
FGFR1b ligand binding and activation	1	317.2×	0.017	FGFR1
FGFR2b ligand binding and activation	1	285.5×	0.017	FGFR2
Signaling by activated point mutants of FGFR1	1	237.9×	0.017	FGFR1
FGFR2c ligand binding and activation	1	219.6×	0.017	FGFR2
FGFR1c ligand binding and activation	1	190.3×	0.017	FGFR1
Stabilization of p53	1	190.3×	0.017	MDM4
p53-Dependent G1 DNA Damage Response	1	178.4×	0.017	MDM4
p53-Dependent G1/S DNA damage checkpoint	1	178.4×	0.017	MDM4
Activated point mutants of FGFR2	1	167.9×	0.017	FGFR2
Phospholipase C-mediated cascade: FGFR1	1	167.9×	0.017	FGFR1
G1/S DNA Damage Checkpoints	1	167.9×	0.017	MDM4
Phospholipase C-mediated cascade; FGFR2	1	158.6×	0.017	FGFR2
Signaling by FGFR2 IIIa TM	1	150.3×	0.017	FGFR2
Downstream signaling of activated FGFR1	1	135.9×	0.017	FGFR1
Regulation of TP53 Activity through Methylation	1	135.9×	0.017	MDM4
Signal transduction by L1	1	129.8×	0.017	FGFR1
PI-3K cascade:FGFR1	1	129.8×	0.017	FGFR1
Regulation of TP53 Expression and Degradation	1	129.8×	0.017	MDM4
SHC-mediated cascade:FGFR1	1	124.1×	0.017	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 5 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	2246.9×	4e-05	FGFR1, FGFR2
ventricular zone neuroblast division	2	1685.2×	4e-05	FGFR1, FGFR2
positive regulation of phospholipase activity	2	1348.2×	4e-05	FGFR1, FGFR2
lung-associated mesenchyme development	2	674.1×	1e-04	FGFR1, FGFR2
branching involved in salivary gland morphogenesis	2	561.7×	2e-04	FGFR1, FGFR2
positive regulation of cardiac muscle cell proliferation	2	249.7×	6e-04	FGFR1, FGFR2
positive regulation of mesenchymal cell proliferation	2	240.7×	6e-04	FGFR1, FGFR2
midbrain development	2	240.7×	6e-04	FGFR1, FGFR2
skeletal system morphogenesis	2	198.3×	8e-04	FGFR1, FGFR2
ureteric bud development	2	182.2×	8e-04	FGFR1, FGFR2
peptidyl-tyrosine phosphorylation	2	168.5×	9e-04	FGFR1, FGFR2
epithelial to mesenchymal transition	2	124.8×	0.001	FGFR1, FGFR2
inner ear morphogenesis	2	120.4×	0.001	FGFR1, FGFR2
fibroblast growth factor receptor signaling pathway	2	114.2×	0.001	FGFR1, FGFR2
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	3370.4×	0.003	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	3370.4×	0.003	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	3370.4×	0.003	FGFR2
lateral sprouting from an epithelium	1	3370.4×	0.003	FGFR2
orbitofrontal cortex development	1	1685.2×	0.003	FGFR2
prostate gland morphogenesis	1	1685.2×	0.003	FGFR2
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	1	1685.2×	0.003	FGFR2
mammary gland bud formation	1	1685.2×	0.003	FGFR2
branch elongation involved in salivary gland morphogenesis	1	1685.2×	0.003	FGFR2
mesenchymal cell differentiation involved in lung development	1	1685.2×	0.003	FGFR2
vitamin D3 metabolic process	1	1685.2×	0.003	FGFR1
regulation of establishment of blood-brain barrier	1	1685.2×	0.003	ADGRA2
positive regulation of mitotic cell cycle DNA replication	1	1685.2×	0.003	FGFR1
positive regulation of parathyroid hormone secretion	1	1685.2×	0.003	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	1685.2×	0.003	FGFR1
positive regulation of canonical Wnt signaling pathway	2	61.8×	0.003	FGFR2, ADGRA2

Therapeutics

Drug target analysis

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

Druggability breadth: 5 of 5 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
MDM4	DIOSMIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
FGFR2	59	4
MDM4	7	4
ADGRA2	0	0
EIF4EBP1	0	0

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
DIOSMIN	4	MDM4
VERTEPORFIN	4	MDM4

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
MDM4	149	Binding:148, Functional:1
EIF4EBP1	33	Binding:33
ADGRA2	2	Binding:2

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
MDM4	149

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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
DIOSMIN	4	MDM4
VERTEPORFIN	4	MDM4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	FGFR1, FGFR2, MDM4
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ADGRA2
E	Difficult family or no structure, no drug	1	EIF4EBP1

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)
ADGRA2	2	—
EIF4EBP1	33	—

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