Multiple endocrine neoplasia

Summary

Multiple endocrine neoplasia (MONDO:0017169) is a disease caused by CDKN1B (GenCC Strong), with 4 cohort genes and 52 clinical trials. Top therapeutic interventions include edotreotide gallium ga-68, fluorodopa f 18, and lansoprazole.

At a glance

• Prevalence: Unknown (Europe) [Orphanet-validated]
• Causal gene: CDKN1B (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 132
• Clinical trials: 52

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.05	Ireland	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple endocrine neoplasia
Mondo ID	MONDO:0017169
MeSH	D009377
OMIM	131100
Orphanet	276161
DOID	DOID:3125
ICD-10-CM	E31.2
NCIT	C6432
SNOMED CT	46724008
UMLS	C0027662
MedGen	45036
GARD	0021044
MedDRA	10061299
Is cancer (heuristic)	no

Also known as: MEN · men syndrome · men syndromes · multiple endocrine adenomatosis · multiple endocrine neoplasia · multiple endocrine neoplasia syndrome · multiple endocrine neoplasia syndrome(s)

Data availability: 132 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › polyendocrinopathy › multiple polyglandular tumor › multiple endocrine neoplasia

Related subtypes (2): Carney triad, Carney-Stratakis syndrome

Subtypes (3): multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 4, multiple endocrine neoplasia type 2

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

132 retrieved; paginated sample, class counts are floors:

66 conflicting classifications of pathogenicity, 32 uncertain significance, 26 benign/likely benign, 6 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
527268	NM_001370259.2(MEN1):c.1049+1G>A	MEN1	Pathogenic	criteria provided, multiple submitters, no conflicts
13946	NM_020975.6(RET):c.2410G>T (p.Val804Leu)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
426555	NM_004936.4(CDKN2B):c.256G>A (p.Asp86Asn)	CDKN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41854	NM_001370259.2(MEN1):c.512G>A (p.Arg171Gln)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135177	NM_020975.6(RET):c.2261C>T (p.Thr754Met)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136095	NM_020975.6(RET):c.1158G>A (p.Ala386=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136103	NM_020975.6(RET):c.1699G>A (p.Asp567Asn)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136105	NM_020975.6(RET):c.1920C>T (p.Ala640=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136115	NM_020975.6(RET):c.3112A>G (p.Thr1038Ala)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136118	NM_020975.6(RET):c.3243T>C (p.Asp1081=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136121	NM_020975.6(RET):c.597C>T (p.Asn199=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
13936	NM_020975.6(RET):c.2372A>T (p.Tyr791Phe)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
13938	NM_020975.6(RET):c.2944C>T (p.Arg982Cys)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
13955	NM_020975.6(RET):c.2332G>A (p.Val778Ile)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161358	NM_020975.6(RET):c.2081G>A (p.Arg694Gln)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
183744	NM_020975.6(RET):c.3253A>G (p.Thr1085Ala)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
184139	NM_020975.6(RET):c.957C>A (p.Leu319=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
184140	NM_020975.6(RET):c.2523G>T (p.Pro841=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
184368	NM_020975.6(RET):c.225G>A (p.Thr75=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188078	NM_020975.6(RET):c.972G>C (p.Trp324Cys)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215909	NM_020975.6(RET):c.1890C>T (p.Cys630=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215914	NM_020975.6(RET):c.2988G>A (p.Pro996=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216726	NM_020975.6(RET):c.334C>T (p.Arg112Cys)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241333	NM_020975.6(RET):c.1063+9G>A	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241336	NM_020975.6(RET):c.1462A>T (p.Thr488Ser)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241343	NM_020975.6(RET):c.2052G>A (p.Pro684=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241348	NM_020975.6(RET):c.2538C>T (p.Leu846=)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
24880	NM_020975.6(RET):c.874G>A (p.Val292Met)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
24887	NM_020975.6(RET):c.1597G>A (p.Gly533Ser)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
24928	NM_020975.6(RET):c.1946C>T (p.Ser649Leu)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 21 · 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
CDKN1B	Definitive	Autosomal dominant	multiple endocrine neoplasia type 4	6
CDKN2B	Limited	Autosomal dominant	multiple endocrine neoplasia	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDKN2B	Orphanet:618	Familial melanoma
CDKN2B	Orphanet:652	Multiple endocrine neoplasia type 1
CDKN1B	Orphanet:276152	Multiple endocrine neoplasia type 4
CDKN1B	Orphanet:652	Multiple endocrine neoplasia type 1
MEN1	Orphanet:2965	Prolactinoma
MEN1	Orphanet:314786	Silent pituitary adenoma
MEN1	Orphanet:314790	Null pituitary adenoma
MEN1	Orphanet:652	Multiple endocrine neoplasia type 1
MEN1	Orphanet:97279	Insulinoma
MEN1	Orphanet:99725	Pituitary gigantism
MEN1	Orphanet:99879	Familial isolated hyperparathyroidism
RET	Orphanet:146	Differentiated thyroid carcinoma
RET	Orphanet:1848	Renal agenesis, bilateral
RET	Orphanet:247698	Multiple endocrine neoplasia type 2A
RET	Orphanet:247709	Multiple endocrine neoplasia type 2B
RET	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
RET	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
RET	Orphanet:388	Hirschsprung disease
RET	Orphanet:93100	Renal agenesis, unilateral
RET	Orphanet:99361	Isolated familial medullary thyroid carcinoma
RET	Orphanet:99803	Haddad syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gencc,clinvar
CDKN1B	HGNC:1785	ENSG00000111276	P46527	Cyclin-dependent kinase inhibitor 1B	gencc
MEN1	HGNC:7010	ENSG00000133895	O00255	Menin	clinvar
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
CDKN1B	Cyclin-dependent kinase inhibitor 1B	Important regulator of cell cycle progression.
MEN1	Menin	Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates ‘Lys-4’ of histone H3 (H3K4).
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	6.9×	0.318
Scaffold/PPI	1	4.3×	0.318
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
CDKN1B	Other/Unknown	no		CDI_dom, CDI_dom_sf
MEN1	Other/Unknown	no		Menin
RET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	2
colonic mucosa	1
jejunal mucosa	1
pigmented layer of retina	1
retina	1
ventricular zone	1
granulocyte	1
right hemisphere of cerebellum	1
dorsal root ganglion	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDKN2B	219	ubiquitous	marker	jejunal mucosa, colonic mucosa, lower esophagus mucosa
CDKN1B	301	ubiquitous	marker	pigmented layer of retina, retina, ventricular zone
MEN1	271	ubiquitous	marker	granulocyte, lower esophagus mucosa, right hemisphere of cerebellum
RET	193	broad	marker	substantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEN1	5,226
CDKN1B	4,635
RET	4,203
CDKN2B	3,431

Intra-cohort edges

A	B	Sources
CDKN1B	CDKN2B	string_interaction
MEN1	RET	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MEN1	O00255	69
RET	P07949	34
CDKN1B	P46527	19

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDKN2B	P42772	90.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 77. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
G1 Phase	2	196.9×	0.002	CDKN2B, CDKN1B
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	2	184.2×	0.002	CDKN2B, MEN1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	2	154.3×	0.002	CDKN2B, MEN1
Cyclin D associated events in G1	2	116.5×	0.002	CDKN2B, CDKN1B
Signaling by TGF-beta Receptor Complex	2	100.2×	0.002	CDKN2B, MEN1
Mitotic G1 phase and G1/S transition	2	92.1×	0.002	CDKN2B, CDKN1B
Cellular Senescence	2	68.8×	0.003	CDKN2B, CDKN1B
RNA Polymerase II Transcription	3	16.9×	0.003	CDKN2B, CDKN1B, MEN1
Signaling by TGFB family members	2	57.7×	0.004	CDKN2B, MEN1
Senescence-Associated Secretory Phenotype (SASP)	2	49.6×	0.005	CDKN2B, CDKN1B
Gene expression (Transcription)	3	13.4×	0.005	CDKN2B, CDKN1B, MEN1
Generic Transcription Pathway	3	11.3×	0.007	CDKN2B, CDKN1B, MEN1
RHO GTPase Effectors	2	34.0×	0.007	CDKN1B, MEN1
PTK6 Regulates Cell Cycle	1	475.8×	0.012	CDKN1B
Cell Cycle, Mitotic	2	24.1×	0.013	CDKN2B, CDKN1B
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1	219.6×	0.016	CDKN1B
AKT phosphorylates targets in the cytosol	1	203.9×	0.016	CDKN1B
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	178.4×	0.016	CDKN1B
p53-Dependent G1 DNA Damage Response	1	178.4×	0.016	CDKN1B
p53-Dependent G1/S DNA damage checkpoint	1	178.4×	0.016	CDKN1B
G1/S DNA Damage Checkpoints	1	167.9×	0.016	CDKN1B
FOXO-mediated transcription of cell cycle genes	1	167.9×	0.016	CDKN1B
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	1	158.6×	0.016	CDKN1B
Formation of the nephric duct	1	158.6×	0.016	RET
Cellular responses to stress	2	18.4×	0.016	CDKN2B, CDKN1B
Cell Cycle	2	18.0×	0.016	CDKN2B, CDKN1B
Signaling by Rho GTPases	2	17.1×	0.016	CDKN1B, MEN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	2	16.7×	0.016	CDKN1B, MEN1
Cellular responses to stimuli	2	15.7×	0.016	CDKN2B, CDKN1B
Signal Transduction	3	7.6×	0.016	CDKN2B, CDKN1B, MEN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 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 transforming growth factor beta receptor signaling pathway	2	263.3×	0.001	CDKN2B, MEN1
regulation of G1/S transition of mitotic cell cycle	2	153.2×	0.001	CDKN2B, CDKN1B
cellular senescence	2	147.8×	0.001	CDKN2B, CDKN1B
negative regulation of epithelial cell proliferation	2	145.3×	0.001	CDKN2B, CDKN1B
negative regulation of cell population proliferation	3	31.6×	0.001	CDKN2B, CDKN1B, MEN1
MAPK cascade	2	76.6×	0.004	MEN1, RET
embryonic epithelial tube formation	1	2106.5×	0.004	RET
posterior midgut development	1	2106.5×	0.004	RET
regulation of lens fiber cell differentiation	1	2106.5×	0.004	CDKN1B
negative regulation of cardiac muscle tissue regeneration	1	2106.5×	0.004	CDKN1B
positive regulation of metanephric glomerulus development	1	1404.3×	0.006	RET
ureter maturation	1	1053.2×	0.006	RET
Peyer’s patch morphogenesis	1	1053.2×	0.006	RET
cellular response to cell-matrix adhesion	1	1053.2×	0.006	CDKN2B
GDF15-GFRAL signaling pathway	1	1053.2×	0.006	RET
autophagic cell death	1	842.6×	0.007	CDKN1B
negative regulation of epithelial cell proliferation involved in prostate gland development	1	702.2×	0.008	CDKN1B
cellular response to antibiotic	1	601.9×	0.008	CDKN1B
cellular response to nutrient	1	526.6×	0.008	CDKN2B
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	526.6×	0.008	MEN1
epithelial cell proliferation involved in prostate gland development	1	526.6×	0.008	CDKN1B
T-helper 2 cell differentiation	1	468.1×	0.008	MEN1
lymphocyte migration into lymphoid organs	1	468.1×	0.008	RET
nuclear export	1	383.0×	0.009	CDKN1B
regulation of cell cycle G1/S phase transition	1	383.0×	0.009	CDKN1B
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	383.0×	0.009	RET
positive regulation of cell size	1	324.1×	0.010	RET
regulation of exit from mitosis	1	300.9×	0.010	CDKN1B
megakaryocyte differentiation	1	300.9×	0.010	CDKN2B
glial cell-derived neurotrophic factor receptor signaling pathway	1	300.9×	0.010	RET

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
MEN1	LOPERAMIDE
RET	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MEN1	475	4
RET	135	4
CDKN2B	0	0
CDKN1B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
BEXAROTENE	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1
NICARDIPINE HYDROCHLORIDE	4	MEN1
PROTRIPTYLINE HYDROCHLORIDE	4	MEN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
RET	1,586	Binding:1573, Functional:10, ADMET:3
MEN1	93	Binding:86, Functional:7
CDKN1B	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RET	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
RET	1,586

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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)
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
BEXAROTENE	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1
NICARDIPINE HYDROCHLORIDE	4	MEN1
PROTRIPTYLINE HYDROCHLORIDE	4	MEN1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	MEN1, RET
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	2	CDKN2B, CDKN1B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDKN2B	0	—
CDKN1B	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 52.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	42
PHASE2	5
PHASE1	2
PHASE4	1
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00204373	PHASE4	COMPLETED	Treatment of Zollinger-Ellison Syndrome With Prevacid
NCT07444723	PHASE2/PHASE3	RECRUITING	Accuracy of 18F-Fluorocholine PET/MR and NeuroEXPLORER PET/CT Imaging for Localization of Parathyroid Tumors
NCT04530916	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Wild Blueberries and Cardiovascular Health in Middle-aged/Older Men and Postmenopausal Women
NCT00001277	PHASE2	COMPLETED	Studies of Elevated Parathyroid Activity
NCT00947167	PHASE2	TERMINATED	A Phase II Study of Pertuzumab and Erlotinib for Metastatic or Unresectable Neuroendocrine Tumors
NCT00990535	PHASE2	COMPLETED	High Dose Somatostatin Analogues in Neuroendocrine Tumors
NCT03452111	PHASE2	COMPLETED	Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception
NCT03455075	PHASE2	COMPLETED	Study of Spermatogenesis Suppression With DMAU Alone or With LNG Versus Placebo Alone in Normal Men
NCT03361384	PHASE1	COMPLETED	Alcohol and Implicit Process in Sexual Risk Behavior in MSM
NCT04470843	PHASE1	COMPLETED	Impact of Acetazolamide in Reducing Referred Postoperative Pain
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03048266	Not specified	RECRUITING	Metabolomics and Genetic Diagnosing Pancreatic Neuroendocrine Tumors in MEN1 Patients
NCT03048279	Not specified	ACTIVE_NOT_RECRUITING	Registry for Multiple Endocrine Neoplasia Syndromes: MEN1/MEN2
NCT03348501	Not specified	RECRUITING	Study and Follow-up of Multiple Endocrine Neoplasia Type 1
NCT04175678	Not specified	ACTIVE_NOT_RECRUITING	Project 1: Diet and Exercise Modulate the Sperm Epigenome in Men
NCT05602376	Not specified	RECRUITING	Improving HIV Testing, Linkage, and Retention in Care for Men Through U=U Messaging
NCT05927519	Not specified	RECRUITING	Comparison of Airtraq in Class 2-3 Obese and Nonobese Men During Intubation: a Prospective Randomized Clinical Study
NCT06573723	Not specified	RECRUITING	Institutional Registry of Rare Diseases
NCT00001345	Not specified	COMPLETED	Studies of Inherited Diseases of Metabolism
NCT00501449	Not specified	COMPLETED	Psychosocial Aspects of Multiple Endocrine Neoplasia (MEN) Syndromes
NCT01481584	Not specified	COMPLETED	Nutritional Evaluation of Canola Protein in Comparison With Soy Protein
NCT01895192	Not specified	COMPLETED	Sperm Morphology by High Magnification in Fertility Men
NCT02555631	Not specified	COMPLETED	PowerUp for Health: A Diabetes Prevention Program for Men
NCT02777112	Not specified	COMPLETED	The Effects of E-mental Health Program and Job Coaching on the Risk of Major Depression in Canadian Working Men
NCT02932384	Not specified	COMPLETED	Reducing HIV Risk With High Risk HIV Negative Black MSM-Passport to Wellness
NCT02938897	Not specified	COMPLETED	Telenutrition Weight Loss Study for Men
NCT03053999	Not specified	UNKNOWN	Variables That Are Correlated to Developing Multiple Endocrine Neoplasia (MEN) and Pancreatic Neuroendocrine Tumors (PNET)
NCT03082794	Not specified	COMPLETED	Dietary Effects on Weight Loss and Lipid Profile in Sedentary Men
NCT03082807	Not specified	COMPLETED	Dietary Guide in Active Older Adult Men
NCT03200652	Not specified	COMPLETED	Metabolic Availability of Lysine From Wheat in Adult Men
NCT03326700	Not specified	COMPLETED	Effects of Hernia Repair on Men’s Sexual Functions
NCT03548077	Not specified	COMPLETED	POWERPLAY: Promoting Men’s Health at Work
NCT03745495	Not specified	COMPLETED	HIV Self-Testing AND Uptake and Retention of PrEP Among Older Adolescent MSM and TGW
NCT03781453	Not specified	COMPLETED	POWERPLAY Phase 2: Development and Evaluation in Male-dominated Workplaces
NCT03812211	Not specified	COMPLETED	Evaluation of a Supplement for Weight Management in Obese and Overweight Individuals
NCT04028479	Not specified	COMPLETED	The Registry of Oncology Outcomes Associated With Testing and Treatment
NCT04267263	Not specified	COMPLETED	A Novel Approach to Reducing Adiposity Among Young Men
NCT04295057	Not specified	UNKNOWN	Register of Therapeutical Patients Over 60 Years
NCT04417946	Not specified	COMPLETED	Peer-led Social Media Intervention to Prevent HIV Among Young Men Who Have Sex With Men (YMSM)
NCT04756635	Not specified	UNKNOWN	Effects of Short- Term Intermittent Fasting Aerobic and Anaerobic Capacity

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EDOTREOTIDE GALLIUM GA-68	4	1
FLUORODOPA F 18	4	1
LANSOPRAZOLE	4	1
LEVONORGESTREL	4	1
PERTUZUMAB	4	1
SEGESTERONE ACETATE	4	1
FLUOROCHOLINE F-18	3	1
SEGESTERONE	2	1
ZENIDOLOL	2	1
CHEMBL1074	0	1