Castleman-Kojima disease

Summary

Castleman-Kojima disease (MONDO:0018702) is a disease with 9 cohort genes. The dominant Reactome pathway is Transcriptional regulation by RUNX1 (4 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 9
• ClinVar variants: 7
• Phenotypes (HPO): 25

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		28	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

25 HPO clinical features (Orphanet curated; top 25 by frequency):

HPO ID	Term	Frequency
HP:0001433	Hepatosplenomegaly	Very frequent (80-99%)
HP:0001873	Thrombocytopenia	Very frequent (80-99%)
HP:0002716	Lymphadenopathy	Very frequent (80-99%)
HP:0011227	Elevated circulating C-reactive protein concentration	Very frequent (80-99%)
HP:0012050	Anasarca	Very frequent (80-99%)
HP:0000083	Renal insufficiency	Frequent (30-79%)
HP:0001541	Ascites	Frequent (30-79%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0001974	Leukocytosis	Frequent (30-79%)
HP:0002202	Pleural effusion	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0003155	Elevated circulating alkaline phosphatase concentration	Frequent (30-79%)
HP:0005513	Increased megakaryocyte count	Frequent (30-79%)
HP:0011974	Myelofibrosis	Frequent (30-79%)
HP:0030783	Increased circulating interleukin 6 concentration	Frequent (30-79%)
HP:0031052	Elevated vascular endothelial growth factor level	Frequent (30-79%)
HP:0045041	Reduced circulating lactate dehydrogenase concentration	Occasional (5-29%)
HP:0002664	Neoplasm	Excluded (0%)
HP:0002960	Autoimmunity	Excluded (0%)
HP:0012156	Hemophagocytosis	Excluded (0%)
HP:0031691	Severe viral infection	Excluded (0%)
HP:0032262	Pulmonary tuberculosis	Excluded (0%)
HP:0032288	Polyclonal elevation of circulating IgG	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Castleman-Kojima disease
Mondo ID	MONDO:0018702
Orphanet	457077
ICD-11	1505841618
UMLS	C4552543
MedGen	1672503
GARD	0021902
Is cancer (heuristic)	no

Also known as: TAFRO syndrome · thrombocytopenia-anasarca-fever-renal insufficiency-organomegaly syndrome

Data availability: 7 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › hypersensitivity reaction disease › type IV hypersensitivity disease › autoimmune lymphoproliferative syndrome › Castleman-Kojima disease

Related subtypes (8): autoimmune lymphoproliferative syndrome type 1, autoimmune lymphoproliferative syndrome type 2A, autoimmune lymphoproliferative syndrome type 2B, autoimmune lymphoproliferative syndrome type 4, autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency, FAS-related autoimmune lymphoproliferative immune disorder, type 3 autoimmune lymphoproliferative syndrome, autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

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

7 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
666272	NM_030662.4(MAP2K2):c.383C>T (p.Pro128Leu)	MAP2K2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9861	NM_000044.6(AR):c.1937C>A (p.Ala646Asp)	AR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
666269	NM_152641.4(ARID2):c.3577A>G (p.Thr1193Ala)	ARID2	Uncertain significance	no assertion criteria provided
666270	NM_014727.3(KMT2B):c.1108_1109del (p.Glu370fs)	KMT2B	Uncertain significance	no assertion criteria provided
666271	NM_001039396.2(MPEG1):c.661C>A (p.Leu221Ile)	MPEG1	Uncertain significance	no assertion criteria provided
436618	NM_001754.5(RUNX1):c.259G>T (p.Gly87Cys)	RUNX1	Uncertain significance	reviewed by expert panel
666268	NM_003200.5(TCF3):c.1040A>C (p.Asn347Thr)	TCF3	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 16 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RUNX1	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1	Orphanet:521	Chronic myeloid leukemia
RUNX1	Orphanet:71290	Familial platelet disorder with associated myeloid malignancy
RUNX1	Orphanet:98850	Aggressive systemic mastocytosis
TCF3	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
TCF3	Orphanet:585956	B-lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3)
TCF3	Orphanet:641375	B-lymphoblastic leukemia/lymphoma with t(17;19)
KMT2B	Orphanet:528084	Non-specific syndromic intellectual disability
KMT2B	Orphanet:589618	Dystonia 28
ARID2	Orphanet:1465	Coffin-Siris syndrome
AR	Orphanet:481	Kennedy disease
AR	Orphanet:90797	Partial androgen insensitivity syndrome
AR	Orphanet:95706	Non-syndromic posterior hypospadias
AR	Orphanet:99429	Complete androgen insensitivity syndrome
MAP2K2	Orphanet:1340	Cardiofaciocutaneous syndrome
MAP2K2	Orphanet:638	Neurofibromatosis-Noonan syndrome

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	clinvar
TCF3	HGNC:11633	ENSG00000071564	P15923	Transcription factor E2-alpha	clinvar
TCF7L1	HGNC:11640	ENSG00000152284	Q9HCS4	Transcription factor 7-like 1	clinvar
KMT2B	HGNC:15840	ENSG00000272333	Q9UMN6	Histone-lysine N-methyltransferase 2B	clinvar
ARID2	HGNC:18037	ENSG00000189079	Q68CP9	AT-rich interactive domain-containing protein 2	clinvar
MPEG1	HGNC:29619	ENSG00000197629	Q2M385	Macrophage-expressed gene 1 protein	clinvar
AR	HGNC:644	ENSG00000169083	P10275	Androgen receptor	clinvar
AREG	HGNC:651	ENSG00000109321	P15514	Amphiregulin	clinvar
MAP2K2	HGNC:6842	ENSG00000126934	P36507	Dual specificity mitogen-activated protein kinase kinase 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
TCF3	Transcription factor E2-alpha	Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition.
TCF7L1	Transcription factor 7-like 1	Participates in the Wnt signaling pathway.
KMT2B	Histone-lysine N-methyltransferase 2B	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4) via a non-processive mechanism.
ARID2	AT-rich interactive domain-containing protein 2	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
MPEG1	Macrophage-expressed gene 1 protein	Pore-forming protein involved in both innate and adaptive immunity.
AR	Androgen receptor	Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.
AREG	Amphiregulin	Ligand of the EGF receptor/EGFR.
MAP2K2	Dual specificity mitogen-activated protein kinase kinase 2	Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases.

Protein-family classification

Druggable: 3 · Difficult: 4 · Unknown: 2 · Druggable fraction: 0.33

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
Nuclear receptor	1	42.9×	0.055
Complement	1	29.8×	0.055
Transcription factor	4	3.7×	0.055
Kinase	1	3.1×	0.352
Other/Unknown	2	0.4×	0.992

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
TCF3	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TCF7L1	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
KMT2B	Transcription factor	no		SET_dom, Znf_PHD, Znf_CXXC
ARID2	Transcription factor	no		ARID_dom, DNA-bd_RFX, Znf_C2H2_type
MPEG1	Complement	yes		MACPF, MPEG1
AR	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Andrgn_rcpt, Znf_hrmn_rcpt
AREG	Other/Unknown	no		EGF
MAP2K2	Kinase	yes	2.7.12.2	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

9 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	2
right testis	2
epithelium of bronchus	1
mucosa of paranasal sinus	1
olfactory segment of nasal mucosa	1
embryo	1
ganglionic eminence	1
ventricular zone	1
aorta	1
popliteal artery	1
tibial artery	1
lower esophagus mucosa	1
pancreatic ductal cell	1
secondary oocyte	1
sperm	1
ileal mucosa	1
leukocyte	1
monocyte	1
nipple	1
seminal vesicle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
TCF3	294	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
TCF7L1	230	ubiquitous	marker	popliteal artery, tibial artery, aorta
KMT2B	269	ubiquitous	marker	right testis, left testis, lower esophagus mucosa
ARID2	253	ubiquitous	marker	sperm, pancreatic ductal cell, secondary oocyte
MPEG1	219	broad	marker	monocyte, leukocyte, ileal mucosa
AR	250	ubiquitous	marker	seminal vesicle, urethra, nipple
AREG	216	ubiquitous	marker	mucosa of urinary bladder, endometrium epithelium, right lung
MAP2K2	291	ubiquitous	marker	mucosa of transverse colon, right testis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AR	7,400
RUNX1	4,994
MAP2K2	3,789
AREG	2,745
KMT2B	2,639
ARID2	2,190
TCF7L1	1,635
MPEG1	981
TCF3	457

Structural data

PDB: 8 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AR	P10275	95
RUNX1	Q01196	5
TCF3	P15923	5
MPEG1	Q2M385	5
KMT2B	Q9UMN6	4
MAP2K2	P36507	3
ARID2	Q68CP9	2
AREG	P15514	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TCF7L1	Q9HCS4	52.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 155. Enrichment computed across 9 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transcriptional regulation by RUNX1	4	73.2×	1e-05	RUNX1, TCF3, KMT2B, ARID2
RNA Polymerase II Transcription	6	16.9×	1e-05	RUNX1, TCF3, TCF7L1, KMT2B, ARID2, AR
Gene expression (Transcription)	6	13.4×	4e-05	RUNX1, TCF3, TCF7L1, KMT2B, ARID2, AR
Generic Transcription Pathway	6	11.3×	8e-05	RUNX1, TCF3, TCF7L1, KMT2B, ARID2, AR
Signal Transduction	6	7.6×	7e-04	RUNX1, TCF3, TCF7L1, AR, AREG, MAP2K2
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	2	75.1×	0.008	RUNX1, ARID2
Transcriptional regulation by RUNX3	2	68.0×	0.008	RUNX1, TCF7L1
Transcriptional regulation by RUNX2	2	63.4×	0.008	RUNX1, AR
Deactivation of the beta-catenin transactivating complex	2	58.3×	0.009	TCF7L1, KMT2B
Developmental Biology	4	7.2×	0.020	RUNX1, TCF3, TCF7L1, MAP2K2
MAPK1/MAPK3 signaling	2	32.8×	0.021	AREG, MAP2K2
ESR-mediated signaling	2	32.1×	0.021	RUNX1, AREG
Formation of the beta-catenin:TCF transactivating complex	2	30.1×	0.021	TCF7L1, KMT2B
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	2	30.1×	0.021	RUNX1, KMT2B
RUNX3 regulates RUNX1-mediated transcription	1	475.8×	0.022	RUNX1
Signaling by Overexpressed Wild-Type EGFR in Cancer	1	356.9×	0.023	AREG
Signaling by MAP2K mutants	1	356.9×	0.023	MAP2K2
MAPK family signaling cascades	2	25.7×	0.023	AREG, MAP2K2
Signaling by Nuclear Receptors	2	25.5×	0.023	RUNX1, AREG
RUNX1 regulates transcription of genes involved in differentiation of HSCs	2	23.8×	0.023	RUNX1, TCF3
RUNX1 regulates expression of components of tight junctions	1	285.5×	0.023	RUNX1
RUNX1 regulates transcription of genes involved in interleukin signaling	1	285.5×	0.023	RUNX1
RUNX2 regulates genes involved in differentiation of myeloid cells	1	285.5×	0.023	RUNX1
Negative feedback regulation of MAPK pathway	1	237.9×	0.023	MAP2K2
RUNX1 regulates estrogen receptor mediated transcription	1	237.9×	0.023	RUNX1
RUNX1 regulates transcription of genes involved in BCR signaling	1	237.9×	0.023	RUNX1
RUNX1 regulates transcription of genes involved in WNT signaling	1	237.9×	0.023	RUNX1
Chromatin organization	2	20.4×	0.023	KMT2B, ARID2
Prolonged ERK activation events	1	178.4×	0.026	MAP2K2
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	178.4×	0.026	RUNX1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of DNA-templated transcription	5	15.5×	9e-04	RUNX1, TCF3, KMT2B, AR, MAP2K2
mammary gland alveolus development	2	220.3×	0.002	AR, AREG
insulin-like growth factor receptor signaling pathway	2	110.1×	0.007	AR, MAP2K2
dendritic cell antigen processing and presentation	1	1872.4×	0.008	MPEG1
antigen processing and presentation of exogenous peptide antigen	1	1872.4×	0.008	MPEG1
male somatic sex determination	1	1872.4×	0.008	AR
prostate induction	1	1872.4×	0.008	AR
regulation of connective tissue replacement	1	1872.4×	0.008	RUNX1
regulation of G1/S transition of mitotic cell cycle	2	68.1×	0.008	TCF3, ARID2
positive regulation of cell differentiation	2	59.4×	0.008	ARID2, AR
regulation of developmental growth	1	936.2×	0.012	AR
lateral sprouting involved in mammary gland duct morphogenesis	1	936.2×	0.012	AR
myeloid leukocyte differentiation	1	624.1×	0.012	RUNX1
regulation of plasminogen activation	1	624.1×	0.012	RUNX1
positive regulation of integrin biosynthetic process	1	624.1×	0.012	AR
dichotomous subdivision of terminal units involved in mammary gland duct morphogenesis	1	624.1×	0.012	AREG
tertiary branching involved in mammary gland duct morphogenesis	1	624.1×	0.012	AR
positive regulation of epithelial cell proliferation involved in prostate gland development	1	624.1×	0.012	AR
negative regulation of CD4-positive, alpha-beta T cell differentiation	1	468.1×	0.012	RUNX1
morphogenesis of an epithelial fold	1	468.1×	0.012	AR
cardiac muscle tissue regeneration	1	468.1×	0.012	RUNX1
regulation of Golgi inheritance	1	468.1×	0.012	MAP2K2
positive regulation of extracellular matrix organization	1	468.1×	0.012	RUNX1
B cell lineage commitment	1	374.5×	0.012	TCF3
peptidyl-serine autophosphorylation	1	374.5×	0.012	MAP2K2
positive regulation of CD8-positive, alpha-beta T cell differentiation	1	374.5×	0.012	RUNX1
animal organ formation	1	374.5×	0.012	AR
male genitalia morphogenesis	1	374.5×	0.012	AR
regulation of cardiac muscle cell proliferation	1	374.5×	0.012	RUNX1
epithelial cell proliferation involved in lung morphogenesis	1	374.5×	0.012	MAP2K2

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 6

Druggability breadth: 7 of 9 evidence-associated genes (78%) 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
RUNX1	APOMORPHINE HYDROCHLORIDE
AR	PROGESTERONE
MAP2K2	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AR	116	4
MAP2K2	52	4
RUNX1	2	4
TCF3	0	0
TCF7L1	0	0
KMT2B	0	0
ARID2	0	0
MPEG1	0	0
AREG	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
APOMORPHINE HYDROCHLORIDE	4	RUNX1
PROGESTERONE	4	AR
ENZALUTAMIDE	4	AR
HYDROCORTISONE ACETATE	4	AR
EPLERENONE	4	AR
CHLORMADINONE ACETATE	4	AR
ARIPIPRAZOLE	4	AR
MOMETASONE FUROATE	4	AR
TESTOSTERONE PROPIONATE	4	AR
ESTRADIOL ACETATE	4	AR
OXANDROLONE	4	AR
BECLOMETHASONE DIPROPIONATE	4	AR
DIFLORASONE DIACETATE	4	AR
ETHYNODIOL DIACETATE	4	AR
HALCINONIDE	4	AR
DYDROGESTERONE	4	AR
FLUMETHASONE PIVALATE	4	AR
HALOBETASOL PROPIONATE	4	AR
ESTRADIOL CYPIONATE	4	AR
CLOCORTOLONE PIVALATE	4	AR
FLURANDRENOLIDE	4	AR
MEGESTROL ACETATE	4	AR
NORETHINDRONE ACETATE	4	AR
SERTACONAZOLE	4	AR
PYRVINIUM	4	AR
PRASUGREL	4	AR
OXICONAZOLE	4	AR
NILUTAMIDE	4	AR
MIFEPRISTONE	4	AR
PREDNISOLONE	4	AR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
AR	2,100	Binding:1727, Functional:339, ADMET:33, Unclassified:1
MAP2K2	615	Binding:581, Functional:33, ADMET:1
RUNX1	20	Binding:17, Functional:3
KMT2B	15	Binding:15
ARID2	7	Binding:7
MPEG1	3	Binding:3
AREG	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MAP2K2	2.7.12.2	mitogen-activated protein kinase kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
AR	2,100
MAP2K2	615

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; 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)
APOMORPHINE HYDROCHLORIDE	4	RUNX1
PROGESTERONE	4	AR
ENZALUTAMIDE	4	AR
HYDROCORTISONE ACETATE	4	AR
EPLERENONE	4	AR
CHLORMADINONE ACETATE	4	AR
ARIPIPRAZOLE	4	AR
MOMETASONE FUROATE	4	AR
TESTOSTERONE PROPIONATE	4	AR
ESTRADIOL ACETATE	4	AR
OXANDROLONE	4	AR
BECLOMETHASONE DIPROPIONATE	4	AR
DIFLORASONE DIACETATE	4	AR
ETHYNODIOL DIACETATE	4	AR
HALCINONIDE	4	AR
DYDROGESTERONE	4	AR
FLUMETHASONE PIVALATE	4	AR
HALOBETASOL PROPIONATE	4	AR
ESTRADIOL CYPIONATE	4	AR
CLOCORTOLONE PIVALATE	4	AR
FLURANDRENOLIDE	4	AR
MEGESTROL ACETATE	4	AR
NORETHINDRONE ACETATE	4	AR
SERTACONAZOLE	4	AR
PYRVINIUM	4	AR
PRASUGREL	4	AR
OXICONAZOLE	4	AR
NILUTAMIDE	4	AR
MIFEPRISTONE	4	AR
PREDNISOLONE	4	AR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	RUNX1, AR, MAP2K2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	MPEG1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	TCF3, TCF7L1, KMT2B, ARID2, AREG

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TCF3	0	—
TCF7L1	0	—
KMT2B	15	—
ARID2	7	—
MPEG1	3	—
AREG	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.