Atypical endometrial hyperplasia

disease

On this page

Also known as atypical hyperplasia of endometriumatypical hyperplasia of the endometriumendometrial hyperplasia with atypia

Summary

Atypical endometrial hyperplasia (MONDO:0006096) is a disease with 6 cohort genes and 27 clinical trials. The dominant Reactome pathway is Ovarian tumor domain proteases (3 cohort genes). Top therapeutic interventions include megestrol acetate, gonadorelin acetate, and progesterone.

At a glance

Cohort genes: 6
ClinVar variants: 7
Clinical trials: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atypical endometrial hyperplasia
Mondo ID	MONDO:0006096
EFO	EFO:1000098
NCIT	C4654
SNOMED CT	277158007
UMLS	C0349579
MedGen	138105
Is cancer (heuristic)	no

Also known as: atypical hyperplasia of endometrium · atypical hyperplasia of the endometrium · endometrial hyperplasia with atypia

Data availability: 7 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › female reproductive system disorder › uterine disorder › endometrial disorder › atypical endometrial hyperplasia

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:

2 uncertain significance, 2 pathogenic, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
217986	NM_000038.6(APC):c.4645C>T (p.Gln1549Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
12582	NM_004985.5(KRAS):c.35G>A (p.Gly12Asp)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2447221	NM_000314.8(PTEN):c.332G>A (p.Trp111Ter)	PTEN	Pathogenic	criteria provided, multiple submitters, no conflicts
17580	NM_001904.4(CTNNB1):c.121A>G (p.Thr41Ala)	CTNNB1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
428889	NM_000546.6(TP53):c.785G>T (p.Gly262Val)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1007891	NM_000077.5(CDKN2A):c.175G>A (p.Val59Met)	CDKN2A	Uncertain significance	criteria provided, multiple submitters, no conflicts
827117	NM_000314.8(PTEN):c.754G>A (p.Asp252Asn)	PTEN	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 70 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
CTNNB1	Orphanet:1501	Adrenocortical carcinoma
CTNNB1	Orphanet:210159	Adult hepatocellular carcinoma
CTNNB1	Orphanet:2780	Osteopathia striata-cranial sclerosis syndrome
CTNNB1	Orphanet:33402	Pediatric hepatocellular carcinoma
CTNNB1	Orphanet:404473	Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome
CTNNB1	Orphanet:54595	Craniopharyngioma
CTNNB1	Orphanet:569248	Microcystic stromal tumor
CTNNB1	Orphanet:689430	Adenoid ameloblastoma
CTNNB1	Orphanet:873	Desmoid tumor
CTNNB1	Orphanet:891	Familial exudative vitreoretinopathy
CTNNB1	Orphanet:91414	Pilomatrixoma
CTNNB1	Orphanet:952	Acrofacial dysostosis, Weyers type
APC	Orphanet:220460	Attenuated familial adenomatous polyposis
APC	Orphanet:261584	5q22 microdeletion syndrome
APC	Orphanet:314022	Gastric adenocarcinoma and proximal polyposis of the stomach
APC	Orphanet:3258	Cenani-Lenz syndrome
APC	Orphanet:873	Desmoid tumor
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	clinvar
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	clinvar
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.
APC	Adenomatous polyposis coli protein	Tumor suppressor.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

Protein-family classification

Druggable: 2 · Difficult: 2 · 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
Phosphatase	1	14.0×	0.347
Scaffold/PPI	1	2.9×	0.674
Enzyme (other)	1	2.0×	0.674
Transcription factor	1	1.4×	0.674
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom

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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
ganglionic eminence	1
tendon of biceps brachii	1
cervix squamous epithelium	1
parotid gland	1
pituitary gland	1
adrenal tissue	1
periodontal ligament	1
medial globus pallidus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
nipple	1
pylorus	1
trigeminal ganglion	1
calcaneal tendon	1
endothelial cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
CTNNB1	15,668
KRAS	14,509
PTEN	11,626
CDKN2A	9,311
APC	2,903

Intra-cohort edges

A	B	Sources
APC	CTNNB1	intact, string_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	TP53	string_interaction
CTNNB1	PTEN	biogrid_interaction
KRAS	PTEN	string_interaction
KRAS	TP53	string_interaction
PTEN	TP53	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
CTNNB1	P35222	50
APC	P25054	31
PTEN	P60484	12
CDKN2A	P42771	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 235. Enrichment computed across 6 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Ovarian tumor domain proteases	3	139.3×	1e-04	TP53, APC, PTEN
Transcriptional Regulation by VENTX	3	132.8×	1e-04	TP53, CDKN2A, CTNNB1
RUNX3 regulates p14-ARF	2	380.7×	6e-04	CDKN2A, KRAS
Signaling by GSK3beta mutants	2	253.8×	6e-04	CTNNB1, APC
CTNNB1 S33 mutants aren’t phosphorylated	2	253.8×	6e-04	CTNNB1, APC
CTNNB1 S37 mutants aren’t phosphorylated	2	253.8×	6e-04	CTNNB1, APC
CTNNB1 S45 mutants aren’t phosphorylated	2	253.8×	6e-04	CTNNB1, APC
CTNNB1 T41 mutants aren’t phosphorylated	2	253.8×	6e-04	CTNNB1, APC
Stabilization of p53	2	253.8×	6e-04	TP53, CDKN2A
Beta-catenin phosphorylation cascade	2	223.9×	7e-04	CTNNB1, APC
SUMOylation of transcription factors	2	190.3×	9e-04	TP53, CDKN2A
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	2	190.3×	9e-04	CDKN2A, CTNNB1
Disassembly of the destruction complex and recruitment of AXIN to the membrane	2	119.0×	0.002	CTNNB1, APC
Oncogene Induced Senescence	2	112.0×	0.002	TP53, CDKN2A
Regulation of TP53 Degradation	2	97.6×	0.003	TP53, CDKN2A
Deactivation of the beta-catenin transactivating complex	2	77.7×	0.004	CTNNB1, APC
APC truncation mutants are not K63 polyubiquitinated	1	1903.3×	0.005	APC
Evasion of Oncogene Induced Senescence Due to p14ARF Defects	1	1903.3×	0.005	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects	1	1903.3×	0.005	CDKN2A
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	1903.3×	0.005	TP53
Ca2+ pathway	2	59.5×	0.005	CTNNB1, KRAS
Regulation of PTEN gene transcription	2	59.5×	0.005	TP53, PTEN
Degradation of beta-catenin by the destruction complex	2	57.7×	0.005	CTNNB1, APC
Apoptosis	2	56.0×	0.005	CDKN2A, APC
Programmed Cell Death	2	48.8×	0.006	CDKN2A, APC
PTEN Loss of Function in Cancer	1	951.7×	0.008	PTEN
Regulation of TP53 Expression	1	951.7×	0.008	TP53
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	1	951.7×	0.008	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	1	951.7×	0.008	CDKN2A
Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function	1	951.7×	0.008	CDKN2A

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of cell population proliferation	5	35.1×	2e-05	TP53, CDKN2A, CTNNB1, APC, PTEN
negative regulation of cell cycle G1/S phase transition	2	802.5×	2e-04	APC, PTEN
Ras protein signal transduction	3	102.8×	2e-04	TP53, CDKN2A, KRAS
positive regulation of apoptotic process	4	37.8×	2e-04	TP53, CDKN2A, CTNNB1, APC
negative regulation of cyclin-dependent protein serine/threonine kinase activity	2	702.2×	2e-04	CDKN2A, APC
myoblast proliferation	2	468.1×	5e-04	CTNNB1, KRAS
positive regulation of cellular senescence	2	432.1×	5e-04	TP53, KRAS
rRNA transcription	2	330.4×	6e-04	TP53, CDKN2A
replicative senescence	2	330.4×	6e-04	TP53, CDKN2A
glial cell proliferation	2	295.6×	7e-04	TP53, KRAS
epithelial tube branching involved in lung morphogenesis	2	280.9×	7e-04	CTNNB1, KRAS
cell fate specification	2	175.5×	0.002	CTNNB1, APC
protein stabilization	3	33.4×	0.002	TP53, CDKN2A, PTEN
T cell differentiation in thymus	2	137.0×	0.002	TP53, CTNNB1
neuroblast proliferation	2	122.1×	0.003	TP53, CTNNB1
negative regulation of G1/S transition of mitotic cell cycle	2	119.5×	0.003	APC, PTEN
stem cell proliferation	2	104.0×	0.004	TP53, CTNNB1
cellular senescence	2	98.5×	0.004	TP53, CDKN2A
positive regulation of neuron apoptotic process	2	90.6×	0.004	TP53, CTNNB1
glial cell fate determination	1	2808.7×	0.005	CTNNB1
canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation	1	2808.7×	0.005	CTNNB1
negative regulation of helicase activity	1	2808.7×	0.005	TP53
response to mineralocorticoid	1	2808.7×	0.005	KRAS
cranial ganglion development	1	2808.7×	0.005	CTNNB1
cellular response to actinomycin D	1	2808.7×	0.005	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	2808.7×	0.005	TP53
negative regulation of G1 to G0 transition	1	2808.7×	0.005	TP53
apoptotic signaling pathway	2	74.9×	0.005	CDKN2A, CTNNB1
positive regulation of gene expression	3	19.4×	0.005	TP53, CTNNB1, KRAS
positive regulation of transcription by RNA polymerase II	4	9.9×	0.005	TP53, CDKN2A, CTNNB1, PTEN

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Progesterone	Approved (phase 4)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Exemestane.

Drug target analysis

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

Druggability breadth: 6 of 6 evidence-associated genes (100%) 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
TP53	NITROFURANTOIN
CTNNB1	DITHIAZANINE IODIDE
KRAS	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
KRAS	11	4
CTNNB1	4	4
CDKN2A	0	0
APC	0	0
PTEN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
CTNNB1	361	Binding:358, Functional:3
APC	24	Binding:24
PTEN	8	Binding:8
CDKN2A	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KRAS	3.6.5.2	small monomeric GTPase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869
CTNNB1	361
KRAS	861

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	TP53, CTNNB1, KRAS
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PTEN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CDKN2A, APC

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
APC	24	CTNNB1
PTEN	8	TP53
CDKN2A	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 27.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2/PHASE3	11
PHASE2	7
Not specified	7
PHASE4	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07462663	PHASE4	NOT_YET_RECRUITING	SHAPE-ENDO: Multimodal Pre-Surgical Optimization in Patients With Obesity and Early-Stage Endometrial Cancer (Phase 1)
NCT03463252	PHASE2/PHASE3	RECRUITING	Value of LNG-IUS as Fertility-preserving Treatment of EAH and EC
NCT05316493	PHASE2/PHASE3	RECRUITING	Weight Management Plus LNG-IUS/Megestrol Acetate in Endometrial Atypical Hyperplasia
NCT05316935	PHASE2/PHASE3	RECRUITING	GnRHa + Letrozole in Non-obese Progestin-insensitive Endometrial Cancer and Atypical Hyperplasia Patients
NCT06379113	PHASE2/PHASE3	RECRUITING	GnRHa + Letrozole in Obese Progestin-insensitive Endometrial Cancer Patients
NCT06390904	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	GnRHa + Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients
NCT00490087	PHASE3	COMPLETED	Resectoscopic Treatment of Atypical Endometrial Polyps in Fertile Women
NCT03241888	PHASE2/PHASE3	COMPLETED	Megestrol Acetate Plus LNG-IUS in Young Women With Endometrial Atypical Hyperplasia
NCT04385667	PHASE2/PHASE3	COMPLETED	LVN- IUS Versus Oral Megesterol Acetate in Treatment of Atypical Endometrial Hyperplasia
NCT04491682	PHASE2/PHASE3	COMPLETED	Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia
NCT04607252	PHASE2/PHASE3	TERMINATED	Metformin Plus Megestrol Acetate As a Fertility-sparing Treatment in Patients with Atypical Endometrial Hyperplasia
NCT04683237	PHASE2/PHASE3	WITHDRAWN	Liraglutide Plus Megestrol Acetate in Endometrial Atypical Hyperplasia
NCT05172999	PHASE2/PHASE3	COMPLETED	Loxenatide Plus LNG-IUS in Endometrial Atypical Hyperplasia
NCT00788671	PHASE2	ACTIVE_NOT_RECRUITING	Levonorgestrel-Releasing Intrauterine System in Treating Patients With Complex Atypical Hyperplasia or Grade I Endometrial Cancer
NCT02397083	PHASE2	ACTIVE_NOT_RECRUITING	Levonorgestrel-Releasing Intrauterine System With or Without Everolimus in Treating Patients With Atypical Hyperplasia or Stage IA Grade 1 Endometrial Cancer
NCT03671811	PHASE2	ACTIVE_NOT_RECRUITING	Megestrol Acetate With or Without Pterostilbene in Treating Patients With Endometrial Cancer Undergoing Hysterectomy
NCT05675787	PHASE2	RECRUITING	Medroxyprogesterone Acetate Plus Atorvastatin in Young Women With Early Endometrial Carcinoma and Atypical Endometrial Hyperplasia
NCT07377734	PHASE2	RECRUITING	Intrauterine Injection of Type III Collage in FST of EC/AEH
NCT00483327	PHASE2	COMPLETED	Management of Atypical Endometrial Hyperplasia and Endometrial Carcinoma Using Megestrol Acetate
NCT01943058	PHASE2	WITHDRAWN	Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer
NCT00892866	Not specified	ACTIVE_NOT_RECRUITING	CA-IX, p16, Proliferative Markers, and HPV in Diagnosing Cervical Lesions in Patients With Abnormal Cervical Cells
NCT05051722	Not specified	RECRUITING	Leveraging Methylated DNA Markers (MDMs) in the Detection of Endometrial Cancer, Ovarian Cancer, and Cervical Cancer
NCT05647109	Not specified	RECRUITING	Patient-derived Tumor-like Cell Clusters Predict Progesterone Sensitivity in Patients With Early Endometrial Cancer
NCT07028242	Not specified	NOT_YET_RECRUITING	Ultrasound and Histology in AEH and Early EEC Treated Conservatively
NCT07544680	Not specified	RECRUITING	Endometrial Cancer Vaginal Fluid Specimen Collection Study
NCT05717634	Not specified	UNKNOWN	Endometrial Changes in Breast Cancer Women.
NCT06115577	Not specified	COMPLETED	Endometrial Tissues and Mononuclear Cells Receptivity in Pathogenesis of Endometrial Proliferative Processes

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MEGESTROL ACETATE	4	7
GONADORELIN ACETATE	4	3
PROGESTERONE	4	2
MEDROXYPROGESTERONE ACETATE	4	1
PTEROSTILBENE	2	1
CHEMBL4567541	0	6
CHEMBL2370644	0	3
CHEMBL4071215	0	1
CHEMBL4303505	0	1
CHEMBL465542	0	1
CHEMBL1390	0	1
CHEMBL4559687	0	1
CHEMBL4792931	0	1

Cohort genes: TP53, CDKN2A, CTNNB1, APC, KRAS, PTEN
Drugs: Megestrol Acetate, Gonadorelin Acetate, Progesterone, Medroxyprogesterone Acetate