Beare-Stevenson cutis gyrata syndrome

Summary

Beare-Stevenson cutis gyrata syndrome (MONDO:0007412) is a disease caused by FGFR2 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FGFR2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 203
• Phenotypes (HPO): 44

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		12	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

44 HPO clinical features (Orphanet curated; top 44 by frequency):

HPO ID	Term	Frequency
HP:0000262	Turricephaly	Very frequent (80-99%)
HP:0000268	Dolichocephaly	Very frequent (80-99%)
HP:0000271	Abnormality of the face	Very frequent (80-99%)
HP:0000272	Malar flattening	Very frequent (80-99%)
HP:0000364	Hearing abnormality	Very frequent (80-99%)
HP:0000400	Macrotia	Very frequent (80-99%)
HP:0000453	Choanal atresia	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000508	Ptosis	Very frequent (80-99%)
HP:0000520	Proptosis	Very frequent (80-99%)
HP:0000929	Abnormal skull morphology	Very frequent (80-99%)
HP:0000956	Acanthosis nigricans	Very frequent (80-99%)
HP:0000982	Palmoplantar keratoderma	Very frequent (80-99%)
HP:0000995	Melanocytic nevus	Very frequent (80-99%)
HP:0001482	Subcutaneous nodule	Very frequent (80-99%)
HP:0001732	Abnormality of the pancreas	Very frequent (80-99%)
HP:0002098	Respiratory distress	Very frequent (80-99%)
HP:0002676	Cloverleaf skull	Very frequent (80-99%)
HP:0004450	Preauricular skin furrow	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0007469	Palmoplantar cutis gyrata	Very frequent (80-99%)
HP:0009804	Tooth agenesis	Very frequent (80-99%)
HP:0009906	Aplasia/Hypoplasia of the earlobes	Very frequent (80-99%)
HP:0010669	Hypoplasia of the zygomatic bone	Very frequent (80-99%)
HP:0011800	Midface retrusion	Very frequent (80-99%)
HP:0100761	Visceral angiomatosis	Very frequent (80-99%)
HP:0000048	Bifid scrotum	Frequent (30-79%)
HP:0000189	Narrow palate	Frequent (30-79%)
HP:0001363	Craniosynostosis	Frequent (30-79%)
HP:0003246	Prominent scrotal raphe	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000391	Thickened helices	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000478	Abnormality of the eye	Occasional (5-29%)
HP:0000504	Abnormality of vision	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001537	Umbilical hernia	Occasional (5-29%)
HP:0001545	Anteriorly placed anus	Occasional (5-29%)
HP:0001597	Abnormality of the nail	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Beare-Stevenson cutis gyrata syndrome
Mondo ID	MONDO:0007412
MeSH	C565129
OMIM	123790
Orphanet	1555
DOID	DOID:0050660
ICD-11	947865461
NCIT	C123813
SNOMED CT	703528008
UMLS	C1852406
MedGen	377668
GARD	0000332
Is cancer (heuristic)	no

Also known as: Beare Stevenson syndrome · Beare-Stevenson cutis gyrata syndrome · BSTVS · cutis gyrata - acanthosis nigricans - craniosynostosis · cutis gyrata-acanthosis nigricans-craniosynostosis syndrome

Data availability: 203 ClinVar variants · 3 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Beare-Stevenson cutis gyrata syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid 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

203 retrieved; paginated sample, class counts are floors:

102 uncertain significance, 34 conflicting classifications of pathogenicity, 27 benign/likely benign, 14 likely benign, 12 benign, 7 pathogenic/likely pathogenic, 7 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
13268	NM_000141.5(FGFR2):c.1032G>A (p.Ala344=)	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
13277	NM_000141.5(FGFR2):c.1124A>G (p.Tyr375Cys)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13278	NM_000141.5(FGFR2):c.1115C>G (p.Ser372Cys)	FGFR2	Pathogenic	criteria provided, single submitter
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
29852	NM_000141.5(FGFR2):c.859_921del (p.His287_Pro307del)	FGFR2	Pathogenic	no assertion criteria provided
374817	NM_000141.5(FGFR2):c.1013G>A (p.Gly338Glu)	FGFR2	Pathogenic/Likely 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
376431	NM_000141.5(FGFR2):c.1144T>C (p.Cys382Arg)	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
1000813	NM_000141.5(FGFR2):c.16C>T (p.Arg6Cys)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1052478	NM_000141.5(FGFR2):c.1348C>T (p.Arg450Cys)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134387	NM_000141.5(FGFR2):c.34G>A (p.Val12Met)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134388	NM_000141.5(FGFR2):c.23T>G (p.Ile8Ser)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1415015	NM_000141.5(FGFR2):c.2426T>C (p.Leu809Pro)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1503438	NM_000141.5(FGFR2):c.287G>T (p.Gly96Val)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2891853	NM_000141.5(FGFR2):c.1029G>A (p.Leu343=)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2977031	NM_000141.5(FGFR2):c.963C>A (p.Asp321Glu)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
298985	NM_000141.5(FGFR2):c.*674G>T	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
298994	NM_000141.5(FGFR2):c.*111G>A	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
298995	NM_000141.5(FGFR2):c.2416G>A (p.Glu806Lys)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
298998	NM_000141.5(FGFR2):c.1774C>T (p.Arg592Cys)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
299000	NM_000141.5(FGFR2):c.1562-11A>G	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
299002	NM_000141.5(FGFR2):c.1539C>A (p.Thr513=)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
299003	NM_000141.5(FGFR2):c.1239G>A (p.Pro413=)	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
299007	NM_000141.5(FGFR2):c.625-10A>G	FGFR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 38 · Orphanet: 12 · 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	Strong	Autosomal dominant	Beare-Stevenson cutis gyrata syndrome	38

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
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)
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: 1 · 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	1	27.7×	0.036

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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
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
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR2	449

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR2	P21802	63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 1 evidence-associated genes (1 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 1 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	11420.0×	8e-04	FGFR2
Signaling by FGFR2 fusions	1	11420.0×	8e-04	FGFR2
FGFR2b ligand binding and activation	1	1142.0×	0.004	FGFR2
FGFR2c ligand binding and activation	1	878.5×	0.004	FGFR2
Activated point mutants of FGFR2	1	671.8×	0.004	FGFR2
Phospholipase C-mediated cascade; FGFR2	1	634.4×	0.004	FGFR2
Signaling by FGFR2 IIIa TM	1	601.0×	0.004	FGFR2
PI-3K cascade:FGFR2	1	496.5×	0.004	FGFR2
SHC-mediated cascade:FGFR2	1	475.8×	0.004	FGFR2
FRS-mediated FGFR2 signaling	1	439.2×	0.004	FGFR2
FGFR2 alternative splicing	1	423.0×	0.004	FGFR2
Negative regulation of FGFR2 signaling	1	368.4×	0.004	FGFR2
PI3K Cascade	1	271.9×	0.005	FGFR2
Signaling by FGFR2 in disease	1	265.6×	0.005	FGFR2
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.009	FGFR2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.012	FGFR2
PIP3 activates AKT signaling	1	66.8×	0.016	FGFR2
RAF/MAP kinase cascade	1	61.1×	0.016	FGFR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 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 negative regulation of apoptotic process in bone marrow cell	1	16852.0×	0.001	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	16852.0×	0.001	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	16852.0×	0.001	FGFR2
lateral sprouting from an epithelium	1	16852.0×	0.001	FGFR2
orbitofrontal cortex development	1	8426.0×	0.001	FGFR2
prostate gland morphogenesis	1	8426.0×	0.001	FGFR2
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	1	8426.0×	0.001	FGFR2
mammary gland bud formation	1	8426.0×	0.001	FGFR2
branch elongation involved in salivary gland morphogenesis	1	8426.0×	0.001	FGFR2
mesenchymal cell differentiation involved in lung development	1	8426.0×	0.001	FGFR2
regulation of osteoblast proliferation	1	5617.3×	0.001	FGFR2
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	5617.3×	0.001	FGFR2
prostate epithelial cord elongation	1	5617.3×	0.001	FGFR2
ventricular zone neuroblast division	1	4213.0×	0.001	FGFR2
embryonic organ morphogenesis	1	4213.0×	0.001	FGFR2
reproductive structure development	1	4213.0×	0.001	FGFR2
regulation of morphogenesis of a branching structure	1	4213.0×	0.001	FGFR2
positive regulation of phospholipase activity	1	3370.4×	0.001	FGFR2
regulation of smooth muscle cell differentiation	1	3370.4×	0.001	FGFR2
branching involved in prostate gland morphogenesis	1	3370.4×	0.001	FGFR2
epithelial cell proliferation involved in salivary gland morphogenesis	1	3370.4×	0.001	FGFR2
mesenchymal cell proliferation involved in lung development	1	3370.4×	0.001	FGFR2
epidermis morphogenesis	1	2808.7×	0.001	FGFR2
gland morphogenesis	1	2407.4×	0.001	FGFR2
branching morphogenesis of a nerve	1	2407.4×	0.001	FGFR2
bud elongation involved in lung branching	1	2407.4×	0.001	FGFR2
positive regulation of epithelial cell proliferation involved in lung morphogenesis	1	2407.4×	0.001	FGFR2
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	1	2407.4×	0.001	FGFR2
pyramidal neuron development	1	2106.5×	0.001	FGFR2
otic vesicle formation	1	2106.5×	0.001	FGFR2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
FGFR2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR2	59	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR2
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2
FEDRATINIB	4	FGFR2
LENVATINIB	4	FGFR2
AXITINIB	4	FGFR2
SORAFENIB	4	FGFR2
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2
NINTEDANIB ESYLATE	4	FGFR2
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2
SUNITINIB	4	FGFR2
DASATINIB	4	FGFR2
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2
LINIFANIB	3	FGFR2
SEMAXANIB	3	FGFR2
BRIVANIB	3	FGFR2
CEDIRANIB	3	FGFR2
DOVITINIB	3	FGFR2
LESTAURTINIB	3	FGFR2
TANDUTINIB	2	FGFR2
DORAMAPIMOD	2	FGFR2
FORETINIB	2	FGFR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FGFR2	966	Binding:940, Functional:22, ADMET:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
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
FGFR2	966

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2
FEDRATINIB	4	FGFR2
LENVATINIB	4	FGFR2
AXITINIB	4	FGFR2
SORAFENIB	4	FGFR2
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2
NINTEDANIB ESYLATE	4	FGFR2
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2
SUNITINIB	4	FGFR2
DASATINIB	4	FGFR2
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2
LINIFANIB	3	FGFR2
SEMAXANIB	3	FGFR2
BRIVANIB	3	FGFR2
CEDIRANIB	3	FGFR2
DOVITINIB	3	FGFR2
LESTAURTINIB	3	FGFR2
TANDUTINIB	2	FGFR2
DORAMAPIMOD	2	FGFR2
FORETINIB	2	FGFR2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	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.