Ollier disease

Summary

Ollier disease (MONDO:0008145) is a disease with 6 cohort genes and 5 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 6
• ClinVar variants: 16
• Phenotypes (HPO): 26
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

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

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0001028	Hemangioma	Very frequent (80-99%)
HP:0002763	Abnormal cartilage morphology	Very frequent (80-99%)
HP:0002797	Osteolysis	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0005701	Multiple enchondromatosis	Very frequent (80-99%)
HP:0100761	Visceral angiomatosis	Very frequent (80-99%)
HP:0001387	Joint stiffness	Frequent (30-79%)
HP:0001482	Subcutaneous nodule	Frequent (30-79%)
HP:0002653	Bone pain	Frequent (30-79%)
HP:0000324	Facial asymmetry	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002664	Neoplasm	Occasional (5-29%)
HP:0002756	Pathologic fracture	Occasional (5-29%)
HP:0002857	Genu valgum	Occasional (5-29%)
HP:0002967	Cubitus valgus	Occasional (5-29%)
HP:0002970	Genu varum	Occasional (5-29%)
HP:0003067	Madelung deformity	Occasional (5-29%)
HP:0004936	Venous thrombosis	Occasional (5-29%)
HP:0006765	Chondrosarcoma	Occasional (5-29%)
HP:0006824	Cranial nerve paralysis	Occasional (5-29%)
HP:0100242	Sarcoma	Occasional (5-29%)
HP:0100559	Lower limb asymmetry	Occasional (5-29%)
HP:0100560	Upper limb asymmetry	Occasional (5-29%)
HP:0100764	Lymphangioma	Occasional (5-29%)
HP:0200042	Skin ulcer	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Ollier disease
Mondo ID	MONDO:0008145
OMIM	166000
Orphanet	296
DOID	DOID:4624
ICD-10-CM	Q78.4
ICD-11	1648299787
NCIT	C3008
SNOMED CT	268274005
UMLS	C0014084
MedGen	41775
GARD	0007251
MedDRA	10014642
NORD	1526
Is cancer (heuristic)	no

Also known as: dyschondroplasia · enchondromatosis · multiple cartilaginous enchondroses · multiple enchondromatosis · Ollier disease · Ollier type enchondromatosis · Ollier’s disease · osteochondromatosis

Data availability: 16 ClinVar variants · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › Ollier disease

Related subtypes (118): osteochondrodysplasia, diaphyseal medullary stenosis-bone malignancy syndrome, fibular aplasia-ectrodactyly syndrome, cerebrocostomandibular syndrome, cleidorhizomelic syndrome, dyschondrosteosis-nephritis syndrome, dysplasia epiphysealis hemimelica, carpotarsal osteochondromatosis, Camurati-Engelmann disease, genochondromatosis, autosomal dominant osteosclerosis, Worth type, coxopodopatellar syndrome, Lenz-Majewski hyperostotic dwarfism, delayed membranous cranial ossification, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, oculodentodigital dysplasia, osteoglophonic dysplasia, parietal foramina with cleidocranial dysplasia, chondromalacia patellae, Currarino triad, Proteus syndrome, brachydactyly-elbow wrist dysplasia syndrome, tricho-dento-osseous syndrome, bird headed-dwarfism, Montreal type, Yunis-Varon syndrome, split hand-foot malformation 1 with sensorineural hearing loss, ghosal hematodiaphyseal dysplasia, hyperostosis corticalis generalisata, Larsen-like syndrome, B3GAT3 type, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal acroscyphodysplasia, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, familial osteodysplasia, Anderson type, pseudodiastrophic dysplasia, rhizomelic syndrome, Urbach type, Richieri Costa-Pereira syndrome, craniometadiaphyseal dysplasia, wormian bone type, Weaver syndrome, SHOX-related short stature, craniofrontonasal syndrome, Eiken syndrome, 2q37 microdeletion syndrome, skeletal dysplasia-epilepsy-short stature syndrome, rhizomelic dysplasia, Patterson-Lowry type, pelvic dysplasia-arthrogryposis of lower limbs syndrome, Marshall-Smith syndrome, baby rattle pelvis dysplasia, metaphyseal dysplasia, Braun-Tinschert type, genitopatellar syndrome, osteofibrous dysplasia, Larsen-like osseous dysplasia-short stature syndrome, pancreatic insufficiency-anemia-hyperostosis syndrome, microcephalic primordial dwarfism due to ZNF335 deficiency, Hartsfield-Bixler-Demyer syndrome, colobomatous microphthalmia-rhizomelic dysplasia syndrome, Tatton-Brown-Rahman overgrowth syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, Catel-Manzke syndrome, cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome, complex lethal osteochondrodysplasia, amniotic band syndrome, metaphyseal anadysplasia, syndromic craniosynostosis, thin ribs-tubular bones-dysmorphism syndrome, dysplasia of head of femur, Meyer type, epimetaphyseal skeletal dysplasia, melorheostosis with osteopoikilosis, Cole-Carpenter syndrome, spondylometaphyseal dysplasia, omodysplasia, Bruck syndrome, osteopetrosis, congenital absence of upper arm and forearm with hand present, congenital absence of thigh and lower leg with foot present, congenital absence of both forearm and hand, congenital absence of both lower leg and foot, acheiria, apodia, chondroectodermal dysplasia with night blindness, TRPV4-related bone disorder, adactyly of foot, short stature-advanced bone age-early-onset osteoarthritis syndrome, McCune-Albright syndrome, parietal foramina, Sotos syndrome, dysspondyloenchondromatosis, autosomal recessive cutis laxa type 2, FGFR3-related chondrodysplasia, filamin-related bone disorder, short rib dysplasia, spondylodysplastic dysplasia, acromelic dysplasia, bent bone dysplasia, chondrodysplasia punctata, primary osteolysis, non-syndromic limb reduction defect, Robinow syndrome, synpolydactyly, acrocoxomesomelic dysplasia, bone dysplasia Moore type, bone dysplasia corpus callosum agenesis, type 2 collagenopathy, LRP5-related primary osteoporosis, SLC26A2-related skeletal dysplasia, COMP-related skeletal dysplasia, primordial dwarfism and slender bone disorder, polydactyly-syndactyly-triphalangism, lysosomal storage disease with skeletal involvement, abnormal mineralization disorder, calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia, de la Chapelle dysplasia, mesomelic dysplasia-digital anomalies-intellectual disability syndrome, proximal femoral focal deficiency, rhizomelic dysplasia, Ain-Naz type, craniotubular dysplasia, Ikegawa type, TRIP11-related skeletal dysplasia, FAM111A-related skeletal dysplasia

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

16 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
156444	NM_005896.4(IDH1):c.395G>A (p.Arg132His)	IDH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375891	NM_005896.4(IDH1):c.394C>T (p.Arg132Cys)	IDH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1803802	NM_001530.4(HIF1A):c.1892G>A (p.Arg631His)	HIF1A	Likely pathogenic	criteria provided, single submitter
1803804	NM_001530.4(HIF1A):c.2075C>G (p.Ser692Cys)	HIF1A	Likely pathogenic	criteria provided, single submitter
1803800	NM_001530.4(HIF1A):c.644C>T (p.Pro215Leu)	HIF1A-AS3	Likely pathogenic	criteria provided, single submitter
134518	NM_005896.4(IDH1):c.565A>G (p.Ile189Val)	IDH1	Likely pathogenic	criteria provided, single submitter
782785	NM_001530.4(HIF1A):c.1264G>T (p.Asp422Tyr)	HIF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158664	NM_002168.4(IDH2):c.1304C>T (p.Thr435Met)	IDH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211176	NM_002168.4(IDH2):c.673G>A (p.Asp225Asn)	IDH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4279963	NM_005896.4(IDH1):c.580C>T (p.His194Tyr)	IDH1	Uncertain significance	criteria provided, single submitter
4279964	NM_005896.4(IDH1):c.297A>G (p.Ile99Met)	IDH1	Uncertain significance	criteria provided, single submitter
1803797	NM_001146696.2(KDM4C):c.11A>G (p.Tyr4Cys)	KDM4C	Uncertain significance	criteria provided, single submitter
1803798	NM_015061.6(KDM4C):c.2320G>A (p.Ala774Thr)	KDM4C	Uncertain significance	criteria provided, single submitter
161401	NM_000551.4(VHL):c.538A>G (p.Ile180Val)	LOC107303340	Uncertain significance	criteria provided, multiple submitters, no conflicts
161402	NM_000551.4(VHL):c.154G>A (p.Glu52Lys)	VHL	Benign	reviewed by expert panel
2233	NM_000551.4(VHL):c.241C>T (p.Pro81Ser)	VHL	Benign	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 22 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VHL	Orphanet:238557	Chuvash erythrocytosis
VHL	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
VHL	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
VHL	Orphanet:892	Von Hippel-Lindau disease
IDH1	Orphanet:163634	Maffucci syndrome
IDH1	Orphanet:251576	Gliosarcoma
IDH1	Orphanet:251579	Giant cell glioblastoma
IDH1	Orphanet:296	Ollier disease
IDH1	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
IDH1	Orphanet:99646	Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria
IDH2	Orphanet:163634	Maffucci syndrome
IDH2	Orphanet:251589	Anaplastic astrocytoma
IDH2	Orphanet:251598	Protoplasmic astrocytoma
IDH2	Orphanet:251601	Fibrillary astrocytoma
IDH2	Orphanet:251604	Gemistocytic astrocytoma
IDH2	Orphanet:251627	Oligodendroglioma
IDH2	Orphanet:251630	Anaplastic oligodendroglioma
IDH2	Orphanet:251656	Oligoastrocytoma
IDH2	Orphanet:251663	Anaplastic oligoastrocytoma
IDH2	Orphanet:296	Ollier disease
IDH2	Orphanet:79315	D-2-hydroxyglutaric aciduria
IDH2	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features

Cohort genes → proteins

6 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
VHL	HGNC:12687	ENSG00000134086	P40337	von Hippel-Lindau disease tumor suppressor	clinvar
KDM4C	HGNC:17071	ENSG00000107077	Q9H3R0	Lysine-specific demethylase 4C	clinvar
HIF1A-AS1	HGNC:43014	ENSG00000258777		HIF1A antisense RNA 1	clinvar
HIF1A	HGNC:4910	ENSG00000100644	Q16665	Hypoxia-inducible factor 1-alpha	clinvar
IDH1	HGNC:5382	ENSG00000138413	O75874	Isocitrate dehydrogenase [NADP] cytoplasmic	clinvar
IDH2	HGNC:5383	ENSG00000182054	P48735	Isocitrate dehydrogenase [NADP], mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VHL	von Hippel-Lindau disease tumor suppressor	Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
KDM4C	Lysine-specific demethylase 4C	Histone demethylase that specifically demethylates ‘Lys-9’ and ‘Lys-36’ residues of histone H3, thereby playing a central role in histone code.
HIF1A	Hypoxia-inducible factor 1-alpha	Functions as a master transcriptional regulator of the adaptive response to hypoxia.
IDH1	Isocitrate dehydrogenase [NADP] cytoplasmic	Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase.
IDH2	Isocitrate dehydrogenase [NADP], mitochondrial	Plays a role in intermediary metabolism and energy production.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	3	6.0×	0.029
Transcription factor	2	2.8×	0.237
Other/Unknown	1	0.3×	0.993

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VHL	Enzyme (other)	yes	2.3.2.B13	VHL_tumour_suppress_b/a_dom, VHL_alpha_dom, VHL_beta_dom
KDM4C	Transcription factor	no	1.14.11.27	Znf_PHD, Tudor, JmjC_dom
HIF1A-AS1	Other/Unknown	no
HIF1A	Transcription factor	no		PAS, HIF-1_alpha, PAC
IDH1	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
IDH2	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom

Expression context

Cohort genes with no expression data: 0.

5 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	2
cortical plate	1
monocyte	1
mononuclear cell	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
ganglionic eminence	1
male germ line stem cell (sensu Vertebrata) in testis	1
ventricular zone	1
epithelial cell of pancreas	1
pancreatic ductal cell	1
adrenal tissue	1
jejunal mucosa	1
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VHL	186	ubiquitous	marker	cortical plate, monocyte, mononuclear cell
KDM4C	250	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
HIF1A-AS1	117	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, ganglionic eminence, ventricular zone
HIF1A	295	ubiquitous	marker	pancreatic ductal cell, epithelial cell of pancreas, corpus epididymis
IDH1	294	ubiquitous	marker	corpus epididymis, jejunal mucosa, adrenal tissue
IDH2	292	ubiquitous	marker	apex of heart, gastrocnemius, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HIF1A	9,734
IDH1	5,464
IDH2	4,912
VHL	3,522
KDM4C	1,380
HIF1A-AS1	0

Intra-cohort edges

A	B	Sources
HIF1A	KDM4C	biogrid_interaction, string_interaction
HIF1A	VHL	biogrid_interaction, intact, string_interaction
IDH1	IDH2	biogrid_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VHL	P40337	142
IDH1	O75874	61
HIF1A	Q16665	25
IDH2	P48735	11
KDM4C	Q9H3R0	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 6 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate	1	2284.0×	0.007	IDH1
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	2	78.8×	0.007	VHL, HIF1A
NADPH regeneration	1	1142.0×	0.010	IDH1
NFE2L2 regulating TCA cycle genes	1	761.3×	0.010	IDH1
Replication of the SARS-CoV-1 genome	1	571.0×	0.010	VHL
Replication of the SARS-CoV-2 genome	1	571.0×	0.010	VHL
PTK6 Expression	1	380.7×	0.013	HIF1A
PTK6 promotes HIF1A stabilization	1	326.3×	0.013	HIF1A
RHOBTB3 ATPase cycle	1	228.4×	0.015	VHL
STAT3 nuclear events downstream of ALK signaling	1	207.6×	0.015	HIF1A
Regulation of gene expression by Hypoxia-inducible Factor	1	190.3×	0.015	HIF1A
Cellular response to hypoxia	1	175.7×	0.015	HIF1A
Neddylation	2	18.9×	0.015	VHL, HIF1A
Maturation of TCA enzymes and regulation of TCA cycle	1	114.2×	0.021	IDH2
Citric acid cycle (TCA cycle)	1	84.6×	0.027	IDH2
RHO GTPases activate PKNs	1	63.4×	0.033	KDM4C
SUMOylation of ubiquitinylation proteins	1	58.6×	0.034	VHL
NOTCH1 Intracellular Domain Regulates Transcription	1	47.6×	0.039	HIF1A
HDMs demethylate histones	1	45.7×	0.039	KDM4C
Transcriptional activation of mitochondrial biogenesis	1	40.8×	0.041	IDH2
Peroxisomal protein import	1	34.6×	0.045	IDH1
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	1	33.6×	0.045	KDM4C
Mitochondrial protein degradation	1	22.8×	0.064	IDH2
Regulation of PD-L1(CD274) transcription	1	21.8×	0.064	HIF1A
Interleukin-4 and Interleukin-13 signaling	1	20.6×	0.065	HIF1A
Chromatin organization	1	16.3×	0.078	KDM4C
Chromatin modifying enzymes	1	14.5×	0.085	KDM4C
RHO GTPase Effectors	1	13.6×	0.087	KDM4C
Ub-specific processing proteases	1	10.6×	0.106	HIF1A
Antigen processing: Ubiquitination & Proteasome degradation	1	7.4×	0.144	VHL

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glyoxylate cycle	2	3370.4×	9e-06	IDH1, IDH2
isocitrate metabolic process	2	1348.2×	4e-05	IDH1, IDH2
NADP+ metabolic process	2	612.8×	2e-04	IDH1, IDH2
2-oxoglutarate metabolic process	2	374.5×	3e-04	IDH1, IDH2
regulation of gene expression	3	50.1×	4e-04	VHL, KDM4C, HIF1A
tricarboxylic acid cycle	2	204.3×	8e-04	IDH1, IDH2
regulation of phospholipid catabolic process	1	3370.4×	0.005	IDH1
elastin metabolic process	1	1685.2×	0.006	HIF1A
positive regulation of chemokine-mediated signaling pathway	1	1685.2×	0.006	HIF1A
regulation of phospholipid biosynthetic process	1	1685.2×	0.006	IDH1
negative regulation of glial cell migration	1	1685.2×	0.006	IDH2
negative regulation of matrix metallopeptidase secretion	1	1685.2×	0.006	IDH2
cellular response to hypoxia	2	48.5×	0.006	VHL, HIF1A
neural fold elevation formation	1	1123.5×	0.007	HIF1A
positive regulation of hormone biosynthetic process	1	1123.5×	0.007	HIF1A
obsolete positive regulation of nitric oxide metabolic process	1	1123.5×	0.007	HIF1A
B-1 B cell homeostasis	1	842.6×	0.007	HIF1A
regulation of transforming growth factor beta2 production	1	842.6×	0.007	HIF1A
intestinal epithelial cell maturation	1	842.6×	0.007	HIF1A
epithelial cell differentiation involved in mammary gland alveolus development	1	842.6×	0.007	HIF1A
hypoxia-inducible factor-1alpha signaling pathway	1	842.6×	0.007	HIF1A
NADPH regeneration	1	674.1×	0.008	IDH1
connective tissue replacement involved in inflammatory response wound healing	1	561.7×	0.009	HIF1A
hemoglobin biosynthetic process	1	561.7×	0.009	HIF1A
regulation of cellular response to hypoxia	1	561.7×	0.009	VHL
glandular epithelial cell maturation	1	481.5×	0.009	HIF1A
NADP+ biosynthetic process	1	481.5×	0.009	IDH2
vascular endothelial growth factor production	1	481.5×	0.009	HIF1A
negative regulation of mesenchymal cell apoptotic process	1	481.5×	0.009	HIF1A
negative regulation of gene expression	2	27.6×	0.009	VHL, HIF1A

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 1

Druggability breadth: 5 of 6 evidence-associated genes (83%) 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
VHL	OSIMERTINIB
HIF1A	EMETINE
IDH1	ENASIDENIB
IDH2	ENASIDENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HIF1A	255	4
IDH1	10	4
VHL	7	4
IDH2	7	4
KDM4C	4	3
HIF1A-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OSIMERTINIB	4	VHL
BRIGATINIB	4	VHL
CRIZOTINIB	4	VHL
ADAGRASIB	4	VHL
EMETINE	4	HIF1A
DOXORUBICIN	4	HIF1A
TOPOTECAN	4	HIF1A
LEVOSALBUTAMOL	4	HIF1A
LEVODOPA	4	HIF1A
DIENESTROL	4	HIF1A
PROGESTERONE	4	HIF1A
DICLOFENAC SODIUM	4	HIF1A
CLOTRIMAZOLE	4	HIF1A
BUMETANIDE	4	HIF1A
MORICIZINE	4	HIF1A
HYDROCORTISONE ACETATE	4	HIF1A
CHLORMADINONE ACETATE	4	HIF1A
DROPERIDOL	4	HIF1A
AMOXAPINE	4	HIF1A
TORSEMIDE	4	HIF1A
PREDNISOLONE ACETATE	4	HIF1A
BENOXINATE	4	HIF1A
NICARDIPINE HYDROCHLORIDE	4	HIF1A
PHENYLEPHRINE HYDROCHLORIDE	4	HIF1A
SULCONAZOLE NITRATE	4	HIF1A
HYDROXYZINE PAMOATE	4	HIF1A
PYRITHIONE ZINC	4	HIF1A
HYDROCORTISONE SODIUM SUCCINATE	4	HIF1A
DIFLORASONE DIACETATE	4	HIF1A
GUANABENZ ACETATE	4	HIF1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
VHL	3,575	Binding:3482, Functional:54, ADMET:39
IDH1	488	Binding:475, Functional:12, ADMET:1
HIF1A	427	Binding:411, Functional:16
KDM4C	122	Binding:120, Functional:2
IDH2	84	Binding:84

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
VHL	2.3.2.B13
KDM4C	1.14.11.27, 1.14.11.66, 1.14.11.69	[histone H3]-dimethyl-L-lysine36 demethylase, [histone H3]-trimethyl-L-lysine9 demethylase, [histone H3]-trimethyl-L-lysine36 demethylase
IDH1	1.1.1.42	isocitrate dehydrogenase (NADP+)
IDH2	1.1.1.42	isocitrate dehydrogenase (NADP+)

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
VHL	3,575
KDM4C	122
HIF1A	427
IDH1	488

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
OSIMERTINIB	4	VHL
BRIGATINIB	4	VHL
CRIZOTINIB	4	VHL
ADAGRASIB	4	VHL
EMETINE	4	HIF1A
DOXORUBICIN	4	HIF1A
TOPOTECAN	4	HIF1A
LEVOSALBUTAMOL	4	HIF1A
LEVODOPA	4	HIF1A
DIENESTROL	4	HIF1A
PROGESTERONE	4	HIF1A
DICLOFENAC SODIUM	4	HIF1A
CLOTRIMAZOLE	4	HIF1A
BUMETANIDE	4	HIF1A
MORICIZINE	4	HIF1A
HYDROCORTISONE ACETATE	4	HIF1A
CHLORMADINONE ACETATE	4	HIF1A
DROPERIDOL	4	HIF1A
AMOXAPINE	4	HIF1A
TORSEMIDE	4	HIF1A
PREDNISOLONE ACETATE	4	HIF1A
BENOXINATE	4	HIF1A
NICARDIPINE HYDROCHLORIDE	4	HIF1A
PHENYLEPHRINE HYDROCHLORIDE	4	HIF1A
SULCONAZOLE NITRATE	4	HIF1A
HYDROXYZINE PAMOATE	4	HIF1A
PYRITHIONE ZINC	4	HIF1A
HYDROCORTISONE SODIUM SUCCINATE	4	HIF1A
DIFLORASONE DIACETATE	4	HIF1A
GUANABENZ ACETATE	4	HIF1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	VHL, HIF1A, IDH1, IDH2
B	Phased (≥1) drug, not yet approved	1	KDM4C
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	HIF1A-AS1

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)
HIF1A-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04134572	Not specified	RECRUITING	Registry of Ollier Disease and Maffucci Syndrome
NCT06749366	Not specified	RECRUITING	Uncovering Genes Behind Cartilage Tumors and Vascular Anomalies Using Genomic Sequencing
NCT04844697	Not specified	COMPLETED	Resilience and Coping in a Rare Skeletal Disease Population to Face Coronavirus (COVID-19) Outbreak Distress: a Longitudinal Study
NCT06397443	Not specified	COMPLETED	Ready to Sail: Evaluating Sailing’s Feasibility as Ergotherapy
NCT07379008	Not specified	COMPLETED	Safety and Efficacy of Non-Setting Paste in Bone Defect Reconstruction