LADD syndrome

Summary

LADD syndrome (MONDO:0007872) is a disease with 3 cohort genes. The dominant Reactome pathway is PI3K Cascade (3 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 97
• Phenotypes (HPO): 63

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

63 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000164	Abnormality of the dentition	Very frequent (80-99%)
HP:0000217	Xerostomia	Frequent (30-79%)
HP:0000377	Abnormal pinna morphology	Frequent (30-79%)
HP:0000478	Abnormality of the eye	Frequent (30-79%)
HP:0000670	Carious teeth	Frequent (30-79%)
HP:0000682	Abnormality of dental enamel	Frequent (30-79%)
HP:0001097	Keratoconjunctivitis sicca	Frequent (30-79%)
HP:0009926	Epiphora	Frequent (30-79%)
HP:0010286	Abnormal salivary gland morphology	Frequent (30-79%)
HP:0011297	Abnormal digit morphology	Frequent (30-79%)
HP:0011481	Abnormal lacrimal duct morphology	Frequent (30-79%)
HP:0011482	Abnormal lacrimal gland morphology	Frequent (30-79%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000378	Cupped ear	Occasional (5-29%)
HP:0000405	Conductive hearing impairment	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000410	Mixed hearing impairment	Occasional (5-29%)
HP:0000495	Recurrent corneal erosions	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000668	Hypodontia	Occasional (5-29%)
HP:0000691	Microdontia	Occasional (5-29%)
HP:0001092	Absent lacrimal punctum	Occasional (5-29%)
HP:0001096	Keratoconjunctivitis	Occasional (5-29%)
HP:0001159	Syndactyly	Occasional (5-29%)
HP:0001172	Abnormal thumb morphology	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0001999	Abnormal facial shape	Occasional (5-29%)
HP:0002984	Hypoplasia of the radius	Occasional (5-29%)
HP:0006101	Finger syndactyly	Occasional (5-29%)
HP:0006297	Enamel hypoplasia	Occasional (5-29%)
HP:0007656	Lacrimal gland aplasia	Occasional (5-29%)
HP:0007892	Hypoplasia of the lacrimal punctum	Occasional (5-29%)
HP:0007925	Lacrimal duct aplasia	Occasional (5-29%)
HP:0009777	Absent thumb	Occasional (5-29%)
HP:0009778	Short thumb	Occasional (5-29%)
HP:0009942	Duplication of thumb phalanx	Occasional (5-29%)
HP:0011496	Corneal neovascularization	Occasional (5-29%)
HP:0012155	Decreased corneal sensation	Occasional (5-29%)
HP:0012804	Corneal ulceration	Occasional (5-29%)
HP:0030084	Clinodactyly	Occasional (5-29%)
HP:0032107	Limbal stem cell deficiency	Occasional (5-29%)
HP:0000028	Cryptorchidism	Very rare (<1-4%)
HP:0000076	Vesicoureteral reflux	Very rare (<1-4%)
HP:0000089	Renal hypoplasia	Very rare (<1-4%)
HP:0000126	Hydronephrosis	Very rare (<1-4%)
HP:0000193	Bifid uvula	Very rare (<1-4%)
HP:0000202	Orofacial cleft	Very rare (<1-4%)
HP:0000347	Micrognathia	Very rare (<1-4%)
HP:0000453	Choanal atresia	Very rare (<1-4%)
HP:0000458	Anosmia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	LADD syndrome
Mondo ID	MONDO:0007872
MeSH	C538132
OMIM	149730
Orphanet	2363
DOID	DOID:0050331, DOID:0081370
SNOMED CT	23817003
UMLS	C0265269
MedGen	78545
GARD	0006848
NORD	1345
Is cancer (heuristic)	no

Also known as: Lacrimo-auriculo-dento-digital syndrome · Lacrimoauriculodento-digital syndrome · LACRIMOAURICULODENTODIGITAL syndrome · lacrimoauriculodentodigital syndrome · Lacrimoauriculoradiodental syndrome · LADD · LADD syndrome · lard syndrome · Levy Hollister syndrome · Levy-Hollister syndrome

Data availability: 97 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › LADD 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, 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

Subtypes (3): LADD syndrome 1, lacrimoauriculodentodigital syndrome 2, lacrimoauriculodentodigital syndrome 3

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

97 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 16 pathogenic, 12 likely benign, 10 conflicting classifications of pathogenicity, 10 benign/likely benign, 10 likely pathogenic, 9 pathogenic/likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1064421	NC_000005.9:g.44300489_44312646del	FGF10	Pathogenic	criteria provided, single submitter
1322898	NM_004465.2(FGF10):c.190G>T (p.Gly64Ter)	FGF10	Pathogenic	criteria provided, multiple submitters, no conflicts
13263	NM_000141.5(FGFR2):c.1025G>A (p.Cys342Tyr)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
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
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
13296	NM_000141.5(FGFR2):c.1942G>A (p.Ala648Thr)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
374817	NM_000141.5(FGFR2):c.1013G>A (p.Gly338Glu)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374823	NM_000141.5(FGFR2):c.1694A>G (p.Glu565Gly)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449024	NM_000141.5(FGFR2):c.314A>G (p.Tyr105Cys)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
478046	NM_000141.5(FGFR2):c.1150G>A (p.Gly384Arg)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
810729	NM_000141.5(FGFR2):c.1544C>T (p.Ala515Val)	FGFR2	Pathogenic	no assertion criteria provided
16327	NM_000142.5(FGFR3):c.1138G>A (p.Gly380Arg)	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
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
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
1801340	NM_004465.2(FGF10):c.374C>A (p.Ala125Asp)	FGF10	Likely pathogenic	criteria provided, single submitter
547371	NM_004465.2(FGF10):c.1A>G (p.Met1Val)	FGF10	Likely pathogenic	criteria provided, single submitter
547372	NM_004465.2(FGF10):c.232del (p.Arg78fs)	FGF10	Likely pathogenic	criteria provided, single submitter
547373	NM_004465.2(FGF10):c.256del (p.Thr86fs)	FGF10	Likely pathogenic	criteria provided, single submitter
547374	NM_004465.2(FGF10):c.356del (p.Gly119fs)	FGF10	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 98 · 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	LADD syndrome 1	38
FGF10	Supportive	Autosomal dominant	LADD syndrome	8
FGFR3	Supportive	Autosomal dominant	LADD syndrome	52

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGF10	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGF10	Orphanet:86815	Aplasia of lacrimal and salivary glands
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
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

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGF10	HGNC:3666	ENSG00000070193	O15520	Fibroblast growth factor 10	gencc,clinvar
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	gencc,clinvar
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)
FGF10	Fibroblast growth factor 10	Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation.
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…
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: 1 · Druggable fraction: 0.67

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	18.5×	0.008
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGF10	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
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.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
endocervix	1
synovial joint	1
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1
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
FGF10	169	broad	marker	buccal mucosa cell, synovial joint, endocervix
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR3	4,510
FGF10	4,233
FGFR2	449

Intra-cohort edges

A	B	Sources
FGF10	FGFR2	biogrid_interaction, intact
FGF10	FGFR3	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR2	P21802	63
FGFR3	P22607	15
FGF10	O15520	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PI3K Cascade	3	271.9×	2e-06	FGF10, FGFR2, FGFR3
Constitutive Signaling by Aberrant PI3K in Cancer	3	126.9×	9e-06	FGF10, FGFR2, FGFR3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	3	96.8×	1e-05	FGF10, FGFR2, FGFR3
FGFR2b ligand binding and activation	2	761.3×	2e-05	FGF10, FGFR2
PIP3 activates AKT signaling	3	66.8×	3e-05	FGF10, FGFR2, FGFR3
RAF/MAP kinase cascade	3	61.1×	3e-05	FGF10, FGFR2, FGFR3
Activated point mutants of FGFR2	2	447.8×	4e-05	FGF10, FGFR2
Phospholipase C-mediated cascade; FGFR2	2	423.0×	4e-05	FGF10, FGFR2
PI-3K cascade:FGFR2	2	331.0×	5e-05	FGF10, FGFR2
SHC-mediated cascade:FGFR2	2	317.2×	5e-05	FGF10, FGFR2
FRS-mediated FGFR2 signaling	2	292.8×	5e-05	FGF10, FGFR2
Negative regulation of FGFR2 signaling	2	245.6×	7e-05	FGF10, FGFR2
Signaling by FGFR2 in disease	2	177.1×	1e-04	FGF10, FGFR2
Signaling by FGFR2 amplification mutants	1	3806.7×	6e-04	FGFR2
t(4;14) translocations of FGFR3	1	3806.7×	6e-04	FGFR3
Signaling by FGFR2 fusions	1	3806.7×	6e-04	FGFR2
Signaling by FGFR3 fusions in cancer	1	3806.7×	6e-04	FGFR3
FGFR3b ligand binding and activation	1	543.8×	0.004	FGFR3
Regulation of gene expression in early pancreatic precursor cells	1	475.8×	0.004	FGF10
FGFR1b ligand binding and activation	1	423.0×	0.005	FGF10
Signaling by activated point mutants of FGFR3	1	317.2×	0.005	FGFR3
FGFR3c ligand binding and activation	1	292.8×	0.005	FGFR3
FGFR2c ligand binding and activation	1	292.8×	0.005	FGFR2
Phospholipase C-mediated cascade; FGFR3	1	292.8×	0.005	FGFR3
FGFRL1 modulation of FGFR1 signaling	1	292.8×	0.005	FGF10
Developmental Lineage of Mammary Stem Cells	1	253.8×	0.006	FGF10
Phospholipase C-mediated cascade: FGFR1	1	223.9×	0.006	FGF10
PI-3K cascade:FGFR3	1	211.5×	0.006	FGFR3
SHC-mediated cascade:FGFR3	1	200.3×	0.006	FGFR3
Signaling by FGFR2 IIIa TM	1	200.3×	0.006	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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mammary gland bud formation	2	5617.3×	1e-06	FGF10, FGFR2
branch elongation involved in salivary gland morphogenesis	2	5617.3×	1e-06	FGF10, FGFR2
mesenchymal cell differentiation involved in lung development	2	5617.3×	1e-06	FGF10, FGFR2
fibroblast growth factor receptor apoptotic signaling pathway	2	5617.3×	1e-06	FGF10, FGFR3
fibroblast growth factor receptor signaling pathway	3	285.6×	2e-06	FGF10, FGFR2, FGFR3
positive regulation of phospholipase activity	2	2246.9×	6e-06	FGFR2, FGFR3
epithelial cell proliferation involved in salivary gland morphogenesis	2	2246.9×	6e-06	FGF10, FGFR2
bud elongation involved in lung branching	2	1605.0×	1e-05	FGF10, FGFR2
otic vesicle formation	2	1404.3×	1e-05	FGF10, FGFR2
lacrimal gland development	2	1404.3×	1e-05	FGF10, FGFR2
endochondral bone growth	2	1123.5×	2e-05	FGFR2, FGFR3
limb bud formation	2	1021.3×	2e-05	FGF10, FGFR2
positive regulation of ERK1 and ERK2 cascade	3	85.1×	2e-05	FGF10, FGFR2, FGFR3
positive regulation of MAPK cascade	3	80.6×	3e-05	FGF10, FGFR2, FGFR3
embryonic digestive tract morphogenesis	2	624.1×	4e-05	FGF10, FGFR2
regulation of smoothened signaling pathway	2	416.1×	9e-05	FGF10, FGFR2
bone morphogenesis	2	401.2×	9e-05	FGFR2, FGFR3
embryonic pattern specification	2	362.4×	1e-04	FGF10, FGFR2
hair follicle morphogenesis	2	330.4×	1e-04	FGF10, FGFR2
positive regulation of cell population proliferation	3	33.6×	2e-04	FGF10, FGFR2, FGFR3
bone mineralization	2	181.2×	4e-04	FGFR2, FGFR3
positive regulation of epithelial cell proliferation	2	162.8×	4e-04	FGF10, FGFR2
embryonic genitalia morphogenesis	1	5617.3×	9e-04	FGF10
regulation of activin receptor signaling pathway	1	5617.3×	9e-04	FGF10
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	5617.3×	9e-04	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	5617.3×	9e-04	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	5617.3×	9e-04	FGFR2
negative regulation of developmental growth	1	5617.3×	9e-04	FGFR3
urothelial cell proliferation	1	5617.3×	9e-04	FGF10
positive regulation of urothelial cell proliferation	1	5617.3×	9e-04	FGF10

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
FGF10	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

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: 3; 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	1	FGF10

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FGF10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.