Crouzon syndrome-acanthosis nigricans syndrome

Summary

Crouzon syndrome-acanthosis nigricans syndrome (MONDO:0012833) is a disease caused by FGFR3 (GenCC Definitive), with 1 cohort gene and 14 clinical trials. Top therapeutic interventions include cinacalcet, cyclosporine, and calcitriol.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: FGFR3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 37
• Phenotypes (HPO): 28
• Clinical trials: 14

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.1	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000348	High forehead	Very frequent (80-99%)
HP:0000956	Acanthosis nigricans	Very frequent (80-99%)
HP:0002007	Frontal bossing	Very frequent (80-99%)
HP:0000238	Hydrocephalus	Frequent (30-79%)
HP:0000248	Brachycephaly	Frequent (30-79%)
HP:0000262	Turricephaly	Frequent (30-79%)
HP:0000272	Malar flattening	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:0000453	Choanal atresia	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000508	Ptosis	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0002308	Chiari malformation	Frequent (30-79%)
HP:0002516	Increased intracranial pressure	Frequent (30-79%)
HP:0003312	Abnormal form of the vertebral bodies	Frequent (30-79%)
HP:0005916	Abnormal metacarpal morphology	Frequent (30-79%)
HP:0007360	Aplasia/Hypoplasia of the cerebellum	Frequent (30-79%)
HP:0100533	Inflammatory abnormality of the eye	Frequent (30-79%)
HP:0000174	Abnormal palate morphology	Occasional (5-29%)
HP:0000444	Convex nasal ridge	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0002076	Migraine	Occasional (5-29%)
HP:0002093	Respiratory insufficiency	Occasional (5-29%)
HP:0005107	Abnormal sacrum morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Crouzon syndrome-acanthosis nigricans syndrome
Mondo ID	MONDO:0012833
MeSH	C567382
OMIM	612247
Orphanet	93262
DOID	DOID:0111161
NCIT	C38145
SNOMED CT	702361006
UMLS	C2677099
MedGen	394201
GARD	0016810
Is cancer (heuristic)	no

Also known as: CAN · chronic allograft nephropathy · Chronic kidney allograft nephropathy · Crouzon syndrome with acanthosis nigricans · Crouzon-dermoskeletal syndrome · Crouzonodermoskeletal syndrome

Data availability: 37 ClinVar variants · 7 GenCC gene-disease records.

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 › Crouzon syndrome-acanthosis nigricans 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, Beare-Stevenson cutis gyrata 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, 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

37 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 10 pathogenic, 5 benign/likely benign, 5 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16327	NM_000142.5(FGFR3):c.1138G>A (p.Gly380Arg)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16329	NM_000142.5(FGFR3):c.1172C>A (p.Ala391Glu)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16331	NM_000142.5(FGFR3):c.1948A>G (p.Lys650Glu)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16332	NM_000142.5(FGFR3):c.742C>T (p.Arg248Cys)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16335	NM_000142.5(FGFR3):c.2419T>A (p.Ter807Arg)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16338	NM_000142.5(FGFR3):c.1620C>G (p.Asn540Lys)	FGFR3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16339	NM_000142.5(FGFR3):c.746C>G (p.Ser249Cys)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16340	NM_000142.5(FGFR3):c.749C>G (p.Pro250Arg)	FGFR3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16341	NM_000142.5(FGFR3):c.1949A>T (p.Lys650Met)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16347	NM_000142.5(FGFR3):c.1950G>C (p.Lys650Asn)	FGFR3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16358	NM_000142.5(FGFR3):c.251C>T (p.Ser84Leu)	FGFR3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16359	NM_000142.5(FGFR3):c.1108G>T (p.Gly370Cys)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
65562	NM_000142.5(FGFR3):c.2420G>T (p.Ter807Leu)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
65855	NM_000142.5(FGFR3):c.1949A>C (p.Lys650Thr)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
1680106	NM_000142.5(FGFR3):c.1827C>G (p.Ala609=)	FGFR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287276	NM_000142.5(FGFR3):c.598C>T (p.Arg200Cys)	FGFR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
521225	NM_000142.5(FGFR3):c.2153A>G (p.Asn718Ser)	FGFR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
546226	NM_000142.5(FGFR3):c.200G>A (p.Gly67Asp)	FGFR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
579912	NM_000142.5(FGFR3):c.2005C>G (p.Arg669Gly)	FGFR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1309951	NM_000142.5(FGFR3):c.1255C>T (p.Leu419Phe)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1310646	NM_000142.5(FGFR3):c.1547A>G (p.Asp516Gly)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1680065	NM_000142.5(FGFR3):c.1267G>C (p.Val423Leu)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1680111	NM_000142.5(FGFR3):c.1946A>G (p.Lys649Arg)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1684285	NM_000142.5(FGFR3):c.184C>T (p.Pro62Ser)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1691355	NM_000142.5(FGFR3):c.1718C>T (p.Pro573Leu)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2874249	NM_000142.5(FGFR3):c.2105A>T (p.Glu702Val)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
374825	NM_000142.5(FGFR3):c.739G>A (p.Glu247Lys)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892110	NM_000142.5(FGFR3):c.166G>A (p.Ala56Thr)	FGFR3	Uncertain significance	criteria provided, single submitter
465350	NM_000142.5(FGFR3):c.1993G>T (p.Ala665Ser)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
533891	NM_000142.5(FGFR3):c.2294C>T (p.Ala765Val)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 52 · Orphanet: 13 · 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
FGFR3	Definitive	Autosomal dominant	Crouzon syndrome-acanthosis nigricans syndrome	52

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 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)
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.

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
skin of hip	1
upper arm skin	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR3	P22607	15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
t(4;14) translocations of FGFR3	1	11420.0×	7e-04	FGFR3
Signaling by FGFR3 fusions in cancer	1	11420.0×	7e-04	FGFR3
FGFR3b ligand binding and activation	1	1631.4×	0.003	FGFR3
Signaling by activated point mutants of FGFR3	1	951.7×	0.003	FGFR3
FGFR3c ligand binding and activation	1	878.5×	0.003	FGFR3
Phospholipase C-mediated cascade; FGFR3	1	878.5×	0.003	FGFR3
PI-3K cascade:FGFR3	1	634.4×	0.003	FGFR3
SHC-mediated cascade:FGFR3	1	601.0×	0.003	FGFR3
FRS-mediated FGFR3 signaling	1	543.8×	0.003	FGFR3
Signaling by FGFR3 in disease	1	496.5×	0.003	FGFR3
Negative regulation of FGFR3 signaling	1	439.2×	0.003	FGFR3
PI3K Cascade	1	271.9×	0.005	FGFR3
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.010	FGFR3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.012	FGFR3
PIP3 activates AKT signaling	1	66.8×	0.016	FGFR3
RAF/MAP kinase cascade	1	61.1×	0.016	FGFR3

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
negative regulation of developmental growth	1	16852.0×	0.001	FGFR3
fibroblast growth factor receptor apoptotic signaling pathway	1	8426.0×	0.001	FGFR3
bone maturation	1	5617.3×	0.001	FGFR3
positive regulation of phospholipase activity	1	3370.4×	0.001	FGFR3
endochondral bone growth	1	1685.2×	0.002	FGFR3
chondrocyte proliferation	1	1053.2×	0.003	FGFR3
positive regulation of tyrosine phosphorylation of STAT protein	1	732.7×	0.004	FGFR3
bone morphogenesis	1	601.9×	0.004	FGFR3
endochondral ossification	1	543.6×	0.004	FGFR3
chondrocyte differentiation	1	300.9×	0.006	FGFR3
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.006	FGFR3
fibroblast growth factor receptor signaling pathway	1	285.6×	0.006	FGFR3
bone mineralization	1	271.8×	0.006	FGFR3
MAPK cascade	1	153.2×	0.009	FGFR3
skeletal system development	1	125.8×	0.011	FGFR3
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.014	FGFR3
positive regulation of MAPK cascade	1	80.6×	0.014	FGFR3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.014	FGFR3
cell-cell signaling	1	69.6×	0.015	FGFR3
positive regulation of cell population proliferation	1	33.6×	0.030	FGFR3

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
FGFR3	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR3	64	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR3
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3
FEDRATINIB	4	FGFR3
LENVATINIB	4	FGFR3
AXITINIB	4	FGFR3
SORAFENIB	4	FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR3
INFIGRATINIB	4	FGFR3
ENTRECTINIB	4	FGFR3
CERITINIB	4	FGFR3
VANDETANIB	4	FGFR3
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3
SUNITINIB	4	FGFR3
DASATINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
MIDOSTAURIN	4	FGFR3
LINIFANIB	3	FGFR3
SEMAXANIB	3	FGFR3
BRIVANIB	3	FGFR3
ALISERTIB	3	FGFR3
CEDIRANIB	3	FGFR3
DOVITINIB	3	FGFR3
LESTAURTINIB	3	FGFR3
TANDUTINIB	2	FGFR3
FORETINIB	2	FGFR3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FGFR3	975	Binding:948, Functional:18, ADMET:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
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
FGFR3	975

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	FGFR3
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3
FEDRATINIB	4	FGFR3
LENVATINIB	4	FGFR3
AXITINIB	4	FGFR3
SORAFENIB	4	FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR3
INFIGRATINIB	4	FGFR3
ENTRECTINIB	4	FGFR3
CERITINIB	4	FGFR3
VANDETANIB	4	FGFR3
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3
SUNITINIB	4	FGFR3
DASATINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
MIDOSTAURIN	4	FGFR3
LINIFANIB	3	FGFR3
SEMAXANIB	3	FGFR3
BRIVANIB	3	FGFR3
ALISERTIB	3	FGFR3
CEDIRANIB	3	FGFR3
DOVITINIB	3	FGFR3
LESTAURTINIB	3	FGFR3
TANDUTINIB	2	FGFR3
FORETINIB	2	FGFR3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	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	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: 14.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE4	4
PHASE3	3
PHASE2	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00541814	PHASE4	UNKNOWN	Calcineurin Inhibitor Minimisation in Renal Transplant Recipients With Stable Allograft Function
NCT00999258	PHASE4	UNKNOWN	Impact of Conversion From Tacrolimus to Sirolimus in African American Renal Transplant Recipients
NCT01265615	PHASE4	COMPLETED	Paricalcitol Versus Calcitriol for the Management of Renocardiac Syndrome in Renal Transplant Patients
NCT04769778	PHASE4	UNKNOWN	Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
NCT00005010	PHASE3	COMPLETED	Prevention of Kidney Transplant Rejection
NCT00975000	PHASE3	COMPLETED	Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients
NCT01056835	PHASE3	COMPLETED	Effects of PGI2 Analogue Use on the Development of Chronic Allograft Nephropathy
NCT00568477	PHASE2	TERMINATED	Value of Rituximab in Humoral Chronic Rejection After Renal Transplantation
NCT00659620	PHASE1/PHASE2	UNKNOWN	Mesenchymal Stem Cell Transplantation in the Treatment of Chronic Allograft Nephropathy
NCT01531257	Not specified	RECRUITING	Proteogenomic Monitoring and Assessment of Kidney Transplant Recipients
NCT00007787	Not specified	COMPLETED	Antibody and Delayed Cyclosporine Versus Initial Cyclosporine Alone in Patients Receiving Kidney Transplants
NCT01346397	Not specified	COMPLETED	Study Cyclosporine (CsA) Versus Tacrolimus (Tacro) After Campath Induction in Kidney Transplantation
NCT05043636	Not specified	UNKNOWN	Diabetic Neuropathy Screening Study 1.1 + Substudy 1.2-1.3-1.4
NCT05682313	Not specified	COMPLETED	Validity of Strain Elastography for the Evaluation of Chronic Allograft Nephropathy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CINACALCET	4	3
CYCLOSPORINE	4	2
CALCITRIOL	4	1
CHOLECALCIFEROL	4	1
IRBESARTAN	4	1
PARICALCITOL	4	1
PRAVASTATIN	4	1
SIROLIMUS	4	1
CHEMBL406352	0	1