Multiple epiphyseal dysplasia

Summary

Multiple epiphyseal dysplasia (MONDO:0016648) is a disease (an umbrella term covering 10 Mondo subtypes) with 7 cohort genes. The dominant Reactome pathway is ECM proteoglycans (3 cohort genes).

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Umbrella term: 10 Mondo subtypes
• Cohort genes: 7
• ClinVar variants: 35

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	5	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple epiphyseal dysplasia
Mondo ID	MONDO:0016648
OMIM	132400
Orphanet	251
DOID	DOID:12721
ICD-11	2009123831
SNOMED CT	59708000
UMLS	C0026760
MedGen	6461
GARD	0010756
MedDRA	10028197
NORD	1468
Is cancer (heuristic)	no

Also known as: Dominant Multiple Epiphyseal Dysplasia · EDM · epiphyseal dysplasia, multiple · MED · multiple epiphyseal dysplasia · multiple epiphyseal dysplasia (disease) · Polyepiphyseal dysplasia · polyepiphyseal dysplasia

Data availability: 35 ClinVar variants · 1 HPO phenotype · 1 cell line.

Disease family

An umbrella term covering 10 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › multiple epiphyseal dysplasia

Related subtypes (49): atelosteogenesis, midface dysplasia, Kashin-Beck disease, achondroplasia, Boomerang dysplasia, campomelic dysplasia, cleidocranial dysplasia 1, Leri-Weill dyschondrosteosis, hypochondroplasia, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, Kniest dysplasia, pseudoachondroplasia, ulna metaphyseal dysplasia syndrome, acheiropody, microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism type II, bone dysplasia, lethal Holmgren type, cleidocranial dysplasia, recessive form, diastrophic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, lethal Kniest-like dysplasia, metaphyseal chondrodysplasia, Kaitila type, metaphyseal chondrodysplasia, Spahr type, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, pycnodysostosis, pyknoachondrogenesis, Pyle disease, schneckenbecken dysplasia, mesomelia-synostoses syndrome, lethal chondrodysplasia, Seller type, acrocapitofemoral dysplasia, brachyolmia, Desbuquois dysplasia, fibrochondrogenesis, spondyloepiphyseal dysplasia, thanatophoric dysplasia, Blount disease, osteogenesis imperfecta, achondrogenesis, acromesomelic dysplasia, neonatal osteosclerotic dysplasia, Akaba Hayasaka syndrome, Fairbank disease, mesomelic dysplasia, spondyloepimetaphyseal dysplasia, cleidocranial dysplasia 2, arterial tortuosity-bone fragility syndrome, linkeropathy

Subtypes (10): multiple epiphyseal dysplasia type 1, multiple epiphyseal dysplasia, Beighton type, multiple epiphyseal dysplasia type 4, multiple epiphyseal dysplasia, Lowry type, multiple epiphyseal dysplasia type 5, multiple epiphyseal dysplasia, Al-Gazali type, multiple epiphyseal dysplasia, with severe proximal femoral dysplasia, multiple epiphyseal dysplasia, with miniepiphyses, multiple epiphyseal dysplasia due to collagen 9 anomaly, epiphyseal dysplasia, multiple, 7

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

35 retrieved; paginated sample, class counts are floors:

9 not provided, 7 uncertain significance, 7 pathogenic/likely pathogenic, 6 likely pathogenic, 5 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
40994	NM_000095.3(COMP):c.1754C>G (p.Thr585Arg)	COMP	Pathogenic	criteria provided, single submitter
40995	NM_000095.3(COMP):c.1754C>T (p.Thr585Met)	COMP	Pathogenic	criteria provided, multiple submitters, no conflicts
65557	NM_000095.3(COMP):c.2153G>C (p.Arg718Pro)	COMP	Pathogenic	criteria provided, single submitter
9189	NM_000095.3(COMP):c.1569C>G (p.Asn523Lys)	COMP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9193	NM_000095.3(COMP):c.1405GAC[6] (p.Asp473dup)	COMP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9198	NM_000095.3(COMP):c.2152C>T (p.Arg718Trp)	COMP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988351	NM_000095.3(COMP):c.1153G>A (p.Asp385Asn)	COMP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
65664	NM_002381.5(MATN3):c.359C>T (p.Thr120Met)	MATN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7540	NM_002381.5(MATN3):c.581T>A (p.Val194Asp)	MATN3	Pathogenic	no assertion criteria provided
7541	NM_002381.5(MATN3):c.361C>T (p.Arg121Trp)	MATN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7543	NM_002381.5(MATN3):c.656C>A (p.Ala219Asp)	MATN3	Pathogenic	criteria provided, single submitter
4994	NM_021625.5(TRPV4):c.1781G>A (p.Arg594His)	TRPV4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
441248	NM_001159773.2(CANT1):c.511A>T (p.Ile171Phe)	CANT1	Likely pathogenic	criteria provided, single submitter
374114	NM_001844.5(COL2A1):c.1916G>A (p.Gly639Asp)	COL2A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1327423	NM_000095.3(COMP):c.1501G>A (p.Gly501Ser)	COMP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4526458	NM_023110.3(FGFR1):c.2424_2425del (p.Arg809fs)	FGFR1	Likely pathogenic	criteria provided, single submitter
4526459	NM_023110.3(FGFR1):c.2436_2440del (p.Gln813fs)	FGFR1	Likely pathogenic	criteria provided, single submitter
1675209	NM_002381.5(MATN3):c.400G>A (p.Glu134Lys)	MATN3	Likely pathogenic	criteria provided, single submitter
13669	NM_000478.6(ALPL):c.892G>A (p.Glu298Lys)	ALPL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
65555	NM_000095.3(COMP):c.1813G>A (p.Asp605Asn)	COMP	Uncertain significance	criteria provided, single submitter
1011244	NM_002381.5(MATN3):c.626G>C (p.Arg209Pro)	MATN3	Uncertain significance	criteria provided, single submitter
1675212	NM_002381.5(MATN3):c.575T>A (p.Ile192Asn)	MATN3	Uncertain significance	criteria provided, single submitter
1675216	NM_002381.5(MATN3):c.693G>C (p.Lys231Asn)	MATN3	Uncertain significance	criteria provided, multiple submitters, no conflicts
195171	NM_002381.5(MATN3):c.518C>A (p.Ala173Asp)	MATN3	Uncertain significance	criteria provided, multiple submitters, no conflicts
7545	NM_002381.5(MATN3):c.209G>A (p.Arg70His)	MATN3	Uncertain significance	criteria provided, multiple submitters, no conflicts
801652	NM_002381.5(MATN3):c.659T>C (p.Val220Ala)	MATN3	Uncertain significance	criteria provided, single submitter
1675208	NM_000095.3(COMP):c.500G>A (p.Gly167Glu)	COMP	not provided	no classification provided
1675213	NM_000095.3(COMP):c.1099_1104del (p.Arg367_Gly368del)	COMP	not provided	no classification provided
65553	NM_000095.3(COMP):c.1156_1158del (p.Asn386del)	COMP	not provided	no classification provided
65554	NM_000095.3(COMP):c.1665C>A (p.Asn555Lys)	COMP	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 56 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPV4	Orphanet:1216	Autosomal dominant congenital benign spinal muscular atrophy
TRPV4	Orphanet:263482	Spondyloepimetaphyseal dysplasia, Maroteaux type
TRPV4	Orphanet:2635	Metatropic dysplasia
TRPV4	Orphanet:431255	Scapuloperoneal spinal muscular atrophy
TRPV4	Orphanet:85169	Familial digital arthropathy-brachydactyly
TRPV4	Orphanet:86820	Familial avascular necrosis of femoral head
TRPV4	Orphanet:93304	Autosomal dominant brachyolmia
TRPV4	Orphanet:93314	Spondylometaphyseal dysplasia, Kozlowski type
TRPV4	Orphanet:99937	Autosomal dominant Charcot-Marie-Tooth disease type 2C
CANT1	Orphanet:1425	Desbuquois syndrome
CANT1	Orphanet:647676	Multiple epiphyseal dysplasia type 7
COL2A1	Orphanet:137678	Spondyloepiphyseal dysplasia with metatarsal shortening
COL2A1	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL2A1	Orphanet:1856	Spondyloperipheral dysplasia-short ulna syndrome
COL2A1	Orphanet:209867	Autosomal dominant rhegmatogenous retinal detachment
COL2A1	Orphanet:2380	Legg-Calvé-Perthes disease
COL2A1	Orphanet:459051	Spondyloepiphyseal dysplasia, Stanescu type
COL2A1	Orphanet:485	Kniest dysplasia
COL2A1	Orphanet:85166	Platyspondylic dysplasia, Torrance type
COL2A1	Orphanet:85198	Dysspondyloenchondromatosis
COL2A1	Orphanet:86820	Familial avascular necrosis of femoral head
COL2A1	Orphanet:90653	Stickler syndrome type 1
COL2A1	Orphanet:93279	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
COL2A1	Orphanet:93296	Achondrogenesis type 2
COL2A1	Orphanet:93297	Hypochondrogenesis
COL2A1	Orphanet:93315	Spondylometaphyseal dysplasia, ‘corner fracture’ type
COL2A1	Orphanet:93316	Spondylometaphyseal dysplasia, Schmidt type
COL2A1	Orphanet:93346	Spondyloepimetaphyseal dysplasia congenita, Strudwick type
COL2A1	Orphanet:94068	Spondyloepiphyseal dysplasia congenita
COMP	Orphanet:750	Pseudoachondroplasia
COMP	Orphanet:93308	Multiple epiphyseal dysplasia type 1
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
ALPL	Orphanet:247623	Perinatal lethal hypophosphatasia
ALPL	Orphanet:247638	Prenatal benign hypophosphatasia

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRPV4	HGNC:18083	ENSG00000111199	Q9HBA0	Transient receptor potential cation channel subfamily V member 4	clinvar
CANT1	HGNC:19721	ENSG00000171302	Q8WVQ1	Soluble calcium-activated nucleotidase 1	clinvar
COL2A1	HGNC:2200	ENSG00000139219	P02458	Collagen alpha-1(II) chain	clinvar
COMP	HGNC:2227	ENSG00000105664	P49747	Cartilage oligomeric matrix protein	clinvar
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	clinvar
ALPL	HGNC:438	ENSG00000162551	P05186	Alkaline phosphatase, tissue-nonspecific isozyme	clinvar
MATN3	HGNC:6909	ENSG00000132031	O15232	Matrilin-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPV4	Transient receptor potential cation channel subfamily V member 4	Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity.
CANT1	Soluble calcium-activated nucleotidase 1	Calcium-dependent nucleotidase with a preference for UDP.
COL2A1	Collagen alpha-1(II) chain	Type II collagen is specific for cartilaginous tissues.
COMP	Cartilage oligomeric matrix protein	Plays a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin.
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.
ALPL	Alkaline phosphatase, tissue-nonspecific isozyme	Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis.
MATN3	Matrilin-3	Major component of the extracellular matrix of cartilage and may play a role in the formation of extracellular filamentous networks.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.57

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
Ion channel	1	15.9×	0.201
Phosphatase	1	12.0×	0.201
Kinase	1	4.0×	0.378
Enzyme (other)	1	1.7×	0.571
Other/Unknown	3	0.8×	0.858

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPV4	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TrpV1-4
CANT1	Enzyme (other)	yes	3.6.1.5	Apyrase, Apyrase_sf
COL2A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
COMP	Other/Unknown	no		EGF, EGF-like_Ca-bd_dom, Thrombospondin_3-like_rpt
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
ALPL	Phosphatase	yes	3.1.3.1	Alkaline_phosphatase, Alkaline_phosphatase_core_sf, Alkaline_phosphatase_AS
MATN3	Other/Unknown	no		EGF, EGF-like_Ca-bd_dom, VWF_A

Expression context

Cohort genes with no expression data: 0.

6 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	4
tibia	3
calcaneal tendon	2
lower esophagus mucosa	1
olfactory segment of nasal mucosa	1
colonic mucosa	1
mucosa of transverse colon	1
pancreatic ductal cell	1
corpus epididymis	1
buccal mucosa cell	1
stromal cell of endometrium	1
left adrenal gland cortex	1
right adrenal gland	1
right adrenal gland cortex	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPV4	171	ubiquitous	marker	cartilage tissue, lower esophagus mucosa, olfactory segment of nasal mucosa
CANT1	280	ubiquitous	marker	pancreatic ductal cell, mucosa of transverse colon, colonic mucosa
COL2A1	145	broad	marker	tibia, cartilage tissue, corpus epididymis
COMP	195	broad	marker	tibia, cartilage tissue, calcaneal tendon
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
ALPL	200	broad	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland cortex
MATN3	167	broad	yes	tibia, cartilage tissue, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
COL2A1	2,491
COMP	2,205
ALPL	2,146
TRPV4	1,948
MATN3	1,918
CANT1	1,231

Intra-cohort edges

A	B	Sources
COL2A1	COMP	string_interaction
COL2A1	MATN3	intact
COMP	MATN3	intact, string_interaction

Structural data

PDB: 6 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR1	P11362	83
TRPV4	Q9HBA0	19
COL2A1	P02458	11
ALPL	P05186	5
CANT1	Q8WVQ1	4
COMP	P49747	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MATN3	O15232	79.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 46. Enrichment computed across 7 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
ECM proteoglycans	3	64.4×	4e-04	COL2A1, COMP, MATN3
Signaling by FGFR1 amplification mutants	1	815.7×	0.019	FGFR1
Integrin cell surface interactions	2	38.4×	0.019	COL2A1, COMP
FGFR1c and Klotho ligand binding and activation	1	407.9×	0.023	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	407.9×	0.023	FGFR1
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	203.9×	0.036	FGFR1
FGFR1b ligand binding and activation	1	181.3×	0.036	FGFR1
Signaling by activated point mutants of FGFR1	1	135.9×	0.042	FGFR1
FGFR1c ligand binding and activation	1	108.8×	0.043	FGFR1
Phospholipase C-mediated cascade: FGFR1	1	96.0×	0.043	FGFR1
Fibronectin matrix formation	1	81.6×	0.043	COL2A1
Downstream signaling of activated FGFR1	1	77.7×	0.043	FGFR1
Signal transduction by L1	1	74.2×	0.043	FGFR1
PI-3K cascade:FGFR1	1	74.2×	0.043	FGFR1
SHC-mediated cascade:FGFR1	1	70.9×	0.043	FGFR1
FRS-mediated FGFR1 signaling	1	65.3×	0.043	FGFR1
TRP channels	1	58.3×	0.043	TRPV4
Formation of paraxial mesoderm	1	58.3×	0.043	FGFR1
MET activates PTK2 signaling	1	54.4×	0.043	COL2A1
Negative regulation of FGFR1 signaling	1	52.6×	0.043	FGFR1
Signaling by FGFR1 in disease	1	41.8×	0.049	FGFR1
PI3K Cascade	1	38.8×	0.049	FGFR1
NCAM signaling for neurite out-growth	1	38.8×	0.049	FGFR1
Collagen chain trimerization	1	37.1×	0.049	COL2A1
Signaling by PDGF	1	36.2×	0.049	COL2A1
NCAM1 interactions	1	35.5×	0.049	COL2A1
Developmental Lineage of Pancreatic Ductal Cells	1	32.6×	0.052	COL2A1
Assembly of collagen fibrils and other multimeric structures	1	28.6×	0.057	COL2A1
Collagen degradation	1	25.1×	0.061	COL2A1
Collagen biosynthesis and modifying enzymes	1	24.4×	0.061	COL2A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
skeletal system development	5	89.8×	1e-07	COL2A1, COMP, FGFR1, ALPL, MATN3
cartilage development involved in endochondral bone morphogenesis	2	687.8×	2e-04	TRPV4, COL2A1
cementum mineralization	2	687.8×	2e-04	FGFR1, ALPL
response to sodium phosphate	2	481.5×	3e-04	FGFR1, ALPL
endochondral ossification	2	155.3×	0.002	COL2A1, ALPL
calcium ion homeostasis	2	126.7×	0.003	FGFR1, ALPL
hyperosmotic salinity response	1	2407.4×	0.005	TRPV4
pyridoxal 5’-phosphate metabolic process	1	2407.4×	0.005	ALPL
blood vessel endothelial cell delamination	1	2407.4×	0.005	TRPV4
negative regulation of hemostasis	1	2407.4×	0.005	COMP
chondrocyte differentiation	2	86.0×	0.005	COL2A1, FGFR1
inner ear morphogenesis	2	86.0×	0.005	COL2A1, FGFR1
bone mineralization	2	77.7×	0.005	COMP, ALPL
cartilage development	2	71.9×	0.005	COL2A1, MATN3
response to insulin	2	66.0×	0.005	TRPV4, ALPL
collagen fibril organization	2	64.2×	0.005	COL2A1, COMP
vasopressin secretion	1	1203.7×	0.006	TRPV4
response to vitamin B6	1	1203.7×	0.006	ALPL
positive regulation of striated muscle contraction	1	1203.7×	0.006	TRPV4
regulation of response to osmotic stress	1	1203.7×	0.006	TRPV4
vitamin D3 metabolic process	1	1203.7×	0.006	FGFR1
futile creatine cycle	1	1203.7×	0.006	ALPL
calcium ion import into cytosol	1	1203.7×	0.006	TRPV4
positive regulation of mitotic cell cycle DNA replication	1	1203.7×	0.006	FGFR1
positive regulation of parathyroid hormone secretion	1	1203.7×	0.006	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	1203.7×	0.006	FGFR1
regulation of phosphate transport	1	802.5×	0.007	FGFR1
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	802.5×	0.007	FGFR1
regulation of lateral mesodermal cell fate specification	1	802.5×	0.007	FGFR1
cellular hypotonic salinity response	1	802.5×	0.007	TRPV4

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 7 evidence-associated genes (57%) 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
ALPL	SULCONAZOLE NITRATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
ALPL	7	4
TRPV4	6	3
CANT1	0	0
COL2A1	0	0
COMP	0	0
MATN3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	FGFR1
DASATINIB	4	FGFR1
MIDOSTAURIN	4	FGFR1
SULCONAZOLE NITRATE	4	ALPL
THEOPHYLLINE	4	ALPL
LEVAMISOLE	4	ALPL
MICONAZOLE NITRATE	4	ALPL
LEVAMISOLE HYDROCHLORIDE	4	ALPL

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
TRPV4	99	Binding:94, Functional:5
ALPL	58	Binding:50, Functional:4, ADMET:3, Toxicity:1
COL2A1	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CANT1	3.6.1.5	apyrase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
ALPL	3.1.3.1	alkaline phosphatase

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; 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
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	FGFR1
DASATINIB	4	FGFR1
MIDOSTAURIN	4	FGFR1
SULCONAZOLE NITRATE	4	ALPL
THEOPHYLLINE	4	ALPL
LEVAMISOLE	4	ALPL
MICONAZOLE NITRATE	4	ALPL
LEVAMISOLE HYDROCHLORIDE	4	ALPL

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	FGFR1, ALPL
B	Phased (≥1) drug, not yet approved	1	TRPV4
C	Druggable family + PDB, no drug	1	CANT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	COL2A1, COMP, MATN3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CANT1	0	—
COL2A1	2	—
COMP	0	—
MATN3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.