Endometriosis

Summary

Endometriosis (MONDO:0005133) is a disease (an umbrella term covering 7 Mondo subtypes) with 56 cohort genes (1,029 GWAS associations across 67 studies) and 705 clinical trials. Top therapeutic interventions include elagolix, leuprolide, and dienogest.

At a glance

• Umbrella term: 7 Mondo subtypes
• Cohort genes: 56
• GWAS associations: 1,029
• ClinVar variants: 5
• Clinical trials: 705

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	endometriosis
Mondo ID	MONDO:0005133
EFO	EFO:0001065
MeSH	D004715
DOID	DOID:289
ICD-10-CM	N80
ICD-11	1838213761
NCIT	C3014
SNOMED CT	129103003
UMLS	C0014175
MedGen	8620
Is cancer (heuristic)	no

Also known as: endometriosis · endometriosis (disease)

Data availability: 5 ClinVar variants · 1,029 GWAS associations (67 studies) · 1 HPO phenotype · 37 cell lines.

Disease family

An umbrella term covering 7 Mondo subtypes.

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

Related subtypes (6): endometritis, tamoxifen-related endometrial lesion, atypical endometrial hyperplasia, endometrial polyp, adenomyosis, endometrium neoplasm

Subtypes (7): fallopian tube endometriosis, endometriosis of intestine, endometriosis of pelvic peritoneum, endometriosis in cutaneous scar, endometriosis of rectovaginal septum and vagina, cervix endometriosis, ovarian endometriosis

Genetics & variants

GWAS landscape

1,029 GWAS associations across 67 studies. Top hits map to 22 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs58415480	1e-61	SYNE1	C	0.03
rs11031005	1e-61	ARL14EP-DT	T	0.03
rs55938609	5e-51	WNT4	C	0.05
rs10517343	2e-45	KDR - RN7SL822P	A	0.03
rs10917151	5e-44	CDC42	A	1.14
rs1865573	2e-42	GREB1	A	0.03
rs56319427	4e-41	CDC42	T	0.05
rs74485684	1e-34	ARL14EP-DT	?
rs72665317	5e-34	CDC42-AS1	?	0.04
rs1537377	9e-33	CDKN2B-AS1	T	0.03
rs3858429	6e-32	ARL14EP-DT	?	0.04
rs71575922	1e-31	SYNE1	G	1.12
rs4762308	5e-31	VEZT	A	0.02
chr6:152562271	2e-30		C	0.18
rs13211170	6e-30	SYNE1	A	0.86
chr11:30226356	3e-27		T	0.19
rs1903068	7e-27	KDR - RN7SL822P	A	0.03
rs17215781	9e-27	SYNE1	A	0.06
rs11674184	3e-26	GREB1	T	1.08
rs73236109	1e-24	KDR - RN7SL822P	?	0.03
rs10090060	3e-24	GDAP1	A	0.02
rs12111427	1e-22	SYNE1	?	0.03
rs2235529	1e-22	WNT4	?
chr1:22462111	3e-22		A	0.16
chr6:151816011	3e-22		T	0.15
rs56062135	7e-22	SMAD3	T	0.09
rs6456259	1e-21	LNC-LBCS	A	0.02
rs57439315	2e-21	GREB1	G	1.12
rs74713348	5e-21	ESR1	?
rs2917868	9e-21	CD109 - TXNP7	T	0.02

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90310260	McGrath IM	2023	204,641	77,257	Genomic characterisation of the overlap of endometriosis with 76 comorbidities identifies pleiotropic and causal mechanisms underlying disease risk.
GCST90258638	Rahmioglu N	2023	58,961	700,345	The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.
GCST90205183	Rahmioglu N	2023	21,779	449,087	The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.
GCST90269970	Rahmioglu N	2023	21,779	449,087	The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.
GCST90454213	Pujol Gualdo N	2025	19,588	213,669	Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.
GCST010178	Adewuyi EO	2020	17,054	191,858	Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity.
GCST010859	Adewuyi EO	2020	17,054	191,858	Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality.
GCST004549	Sapkota Y	2017	14,926	189,715	Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism.
GCST90018839	Sakaue S	2021	4,511	227,260	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90080652	Backman JD	2021	4,475	205,856	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	2
Tier 4: intronic/intergenic	47

MAF distribution

Bucket	Variants
common (>=0.05)	43
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	6

Functional consequences

Consequence	Count
intron_variant	33
intergenic_variant	8
unknown	6
regulatory_region_variant	2
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs58415480	6	152241136	C>G,T	0.409	intron_variant	SYNE1	1e-61	Tier 4: intronic/intergenic
rs11031005	11	30204809	T>C	0.401	intron_variant	ARL14EP-DT	1e-61	Tier 4: intronic/intergenic
rs55938609	1	22143958	G>C	0.116	intron_variant	WNT4	5e-51	Tier 4: intronic/intergenic
rs10517343	4	55136100	T>A	0.185	intergenic_variant	KDR - RN7SL822P	2e-45	Tier 4: intronic/intergenic
rs10917151	1	22096228	G>A,C,T	0.05	3_prime_UTR_variant	CDC42	5e-44	Tier 2: splice/UTR
rs1865573	2	11583732	G>A,T	0.251	intron_variant	GREB1	2e-42	Tier 4: intronic/intergenic
rs56319427	1	22070505	T>C	0.168	intron_variant	CDC42	4e-41	Tier 4: intronic/intergenic
rs74485684	11	30220740	T>C	0.05	intron_variant	ARL14EP-DT	1e-34	Tier 4: intronic/intergenic
rs72665317	1	22040580	T>A,G	0.05	intron_variant	CDC42-AS1	5e-34	Tier 4: intronic/intergenic
rs1537377	9	22169701	T>C	0.42	regulatory_region_variant	CDKN2B-AS1	9e-33	Tier 3: regulatory
rs3858429	11	30322210	C>T	0.05	intron_variant	ARL14EP-DT	6e-32	Tier 4: intronic/intergenic
rs71575922	6	152232879	C>G,T	0.05	intron_variant	SYNE1	1e-31	Tier 4: intronic/intergenic
rs4762308	12	95255237	G>A,C,T	0.313	intron_variant	VEZT	5e-31	Tier 4: intronic/intergenic
chr6:152562271							2e-30	Tier 4: intronic/intergenic
rs13211170	6	152289837	A>C,G	0.05	intron_variant	SYNE1	6e-30	Tier 4: intronic/intergenic
chr11:30226356							3e-27	Tier 4: intronic/intergenic
rs1903068	4	55142310	A>G	0.323	intergenic_variant	KDR - RN7SL822P	7e-27	Tier 4: intronic/intergenic
rs17215781	6	152249139	A>G	0.075	intron_variant	SYNE1	9e-27	Tier 4: intronic/intergenic
rs11674184	2	11581409	T>A,G	0.05	intron_variant	GREB1	3e-26	Tier 4: intronic/intergenic
rs73236109	4	55141258	C>G,T	0.05	intergenic_variant	KDR - RN7SL822P	1e-24	Tier 4: intronic/intergenic
rs10090060	8	74345373	A>G	0.408	intron_variant	GDAP1	3e-24	Tier 4: intronic/intergenic
rs12111427	6	152235391	C>T	0.05	intron_variant	SYNE1	1e-22	Tier 4: intronic/intergenic
rs2235529	1	22123994	C>A,G,T	0.05	intron_variant	WNT4	1e-22	Tier 4: intronic/intergenic
chr1:22462111							3e-22	Tier 4: intronic/intergenic
chr6:151816011							3e-22	Tier 4: intronic/intergenic
rs56062135	15	67163292	C>T	0.05	intron_variant	SMAD3	7e-22	Tier 4: intronic/intergenic
rs6456259	6	19761487	A>G	0.378	intron_variant	LNC-LBCS	1e-21	Tier 4: intronic/intergenic
rs57439315	2	11593362	G>C,T	0.05	intron_variant	GREB1	2e-21	Tier 4: intronic/intergenic
rs74713348	6	151758904	C>T	0.05	intron_variant	ESR1	5e-21	Tier 4: intronic/intergenic
rs2917868	6	73900357	T>A,G	0.453	intergenic_variant	CD109 - TXNP7	9e-21	Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 drug response, 1 benign; affects; association; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
225964	NC_000006.12:g.31575254G>A	TNF	drug response	reviewed by expert panel
810665	t(3;10)(q22;q25.3)		Uncertain significance	criteria provided, single submitter
810664	t(1;5)(q25;q12)	FAM163A	Uncertain significance	criteria provided, single submitter
1339474	NC_000002.12:g.(?112924872)(113105404_?)del	LOC129934601	Uncertain significance	no assertion criteria provided
869137	NM_000576.3(IL1B):c.315C>T (p.Phe105=)	IL1B	Benign; Affects; association; other	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 30 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
C2	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency
WNT4	Orphanet:139466	SERKAL syndrome
WNT4	Orphanet:247768	Müllerian aplasia and hyperandrogenism
WNT4	Orphanet:2578	Mayer-Rokitansky-Küster-Hauser syndrome type 2
FOXP2	Orphanet:209908	Isolated childhood apraxia of speech
FOXP2	Orphanet:251061	7q31 microdeletion syndrome
CDC73	Orphanet:143	Parathyroid carcinoma
CDC73	Orphanet:99879	Familial isolated hyperparathyroidism
CDC73	Orphanet:99880	Hyperparathyroidism-jaw tumor syndrome
SYNE1	Orphanet:319332	Autosomal recessive myogenic arthrogryposis multiplex congenita
SYNE1	Orphanet:88644	Autosomal recessive ataxia, Beauce type
SYNE1	Orphanet:98853	Autosomal dominant Emery-Dreifuss muscular dystrophy
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
CDKN2B	Orphanet:618	Familial melanoma
CDKN2B	Orphanet:652	Multiple endocrine neoplasia type 1
EMX2	Orphanet:485275	Acquired schizencephaly
ESR1	Orphanet:785	Estrogen resistance syndrome
FSHB	Orphanet:52901	Isolated follicle stimulating hormone deficiency
HLA-DRA	Orphanet:505	Graham Little-Piccardi-Lassueur syndrome
IGF1R	Orphanet:73273	Growth delay due to insulin-like growth factor I resistance
KDR	Orphanet:3303	Tetralogy of Fallot
LAMC3	Orphanet:280640	Occipital pachygyria and polymicrogyria
PDE1C	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

56 cohort genes, 52 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	53
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNF	HGNC:11892	ENSG00000232810	P01375	Tumor necrosis factor	clinvar
C2	HGNC:1248	ENSG00000166278	P06681	Complement C2	gwas
WNT4	HGNC:12783	ENSG00000162552	P56705	Protein Wnt-4	gwas
HNRNPA3P1	HGNC:13729	ENSG00000226790		heterogeneous nuclear ribonucleoprotein A3 pseudogene 1	gwas
FOXP2	HGNC:13875	ENSG00000128573	O15409	Forkhead box protein P2	gwas
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas
TFAP2D	HGNC:15581	ENSG00000008197	Q7Z6R9	Transcription factor AP-2-delta	gwas
TLR10	HGNC:15634	ENSG00000174123	Q9BXR5	Toll-like receptor 10	gwas
IL33	HGNC:16028	ENSG00000137033	O95760	Interleukin-33	gwas
KLF3	HGNC:16516	ENSG00000109787	P57682	Krueppel-like factor 3	gwas
MOAP1	HGNC:16658	ENSG00000165943	Q96BY2	Modulator of apoptosis 1	gwas
CAPN14	HGNC:16664	ENSG00000214711	A8MX76	Calpain-14	gwas
SORCS1	HGNC:16697	ENSG00000108018	Q8WY21	VPS10 domain-containing receptor SorCS1	gwas
CDC73	HGNC:16783	ENSG00000134371	Q6P1J9	Parafibromin	gwas
SYNE1	HGNC:17089	ENSG00000131018	Q8NF91	Nesprin-1	gwas
CDH20	HGNC:1760	ENSG00000101542	Q9HBT6	Cadherin-20	gwas
RHOU	HGNC:17794	ENSG00000116574	Q7L0Q8	Rho-related GTP-binding protein RhoU	gwas
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	gwas
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gwas
VEZT	HGNC:18258	ENSG00000028203	Q9HBM0	Vezatin	gwas
KSR2	HGNC:18610	ENSG00000171435	Q6VAB6	Kinase suppressor of Ras 2	gwas
C14orf132	HGNC:20346	ENSG00000227051	Q9NPU4	Uncharacterized protein C14orf132	gwas
CCDC170	HGNC:21177	ENSG00000120262	Q8IYT3	Coiled-coil domain-containing protein 170	gwas
RNF144B	HGNC:21578	ENSG00000137393	Q7Z419	E3 ubiquitin-protein ligase RNF144B	gwas
CHLSN	HGNC:22421	ENSG00000146540	Q9BRJ6	Protein cholesin	gwas
NAALADL2	HGNC:23219	ENSG00000177694	Q58DX5	Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2	gwas
ETAA1	HGNC:24648	ENSG00000143971	Q9NY74	Ewing’s tumor-associated antigen 1	gwas
RBM43	HGNC:24790	ENSG00000184898	Q6ZSC3	RNA-binding protein 43	gwas
GREB1	HGNC:24885	ENSG00000196208	Q4ZG55	Protein GREB1	gwas
PARP1P2	HGNC:276	ENSG00000258995		poly(ADP-ribose) polymerase 1 pseudogene 2	gwas
DEFA1	HGNC:2761	ENSG00000206047	P59665	Neutrophil defensin 1	gwas
FAM163A	HGNC:28274	ENSG00000143340	Q96GL9	Protein FAM163A	clinvar
ZBTB40	HGNC:29045	ENSG00000184677	Q9NUA8	Zinc finger and BTB domain-containing protein 40	gwas
EMX2	HGNC:3341	ENSG00000170370	Q04743	Homeobox protein EMX2	gwas
CDKN2B-AS1	HGNC:34341	ENSG00000240498		CDKN2B and CDKN2A antisense cis and trans regulatory RNA 1	gwas
ESR1	HGNC:3467	ENSG00000091831	P03372	Estrogen receptor	gwas
FSHB	HGNC:3964	ENSG00000131808	P01225	Follitropin subunit beta	gwas
ALCAM	HGNC:400	ENSG00000170017	Q13740	CD166 antigen	gwas
HLA-DRA	HGNC:4947	ENSG00000204287	P01903	HLA class II histocompatibility antigen, DR alpha chain	gwas
ID4	HGNC:5363	ENSG00000172201	P47928	DNA-binding protein inhibitor ID-4	gwas
IGF1R	HGNC:5465	ENSG00000140443	P08069	Insulin-like growth factor 1 receptor	gwas
RMP24P1	HGNC:57042	ENSG00000251647		RMP24 pseudogene 1	gwas
IL1A	HGNC:5991	ENSG00000115008	P01583	Interleukin-1 alpha	gwas
IL1B	HGNC:5992	ENSG00000125538	P01584	Interleukin-1 beta	clinvar
ITPK1	HGNC:6177	ENSG00000100605	Q13572	Inositol-tetrakisphosphate 1-kinase	gwas
KDR	HGNC:6307	ENSG00000128052	P35968	Vascular endothelial growth factor receptor 2	gwas
LAMC3	HGNC:6494	ENSG00000050555	Q9Y6N6	Laminin subunit gamma-3	gwas
RND3	HGNC:671	ENSG00000115963	P61587	Rho-related GTP-binding protein RhoE	gwas
MAP3K4	HGNC:6856	ENSG00000085511	Q9Y6R4	Mitogen-activated protein kinase kinase kinase 4	gwas
RHOJ	HGNC:688	ENSG00000126785	Q9H4E5	Rho-related GTP-binding protein RhoJ	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNF	Tumor necrosis factor	Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
C2	Complement C2	Precursor of the catalytic component of the C3 and C5 convertase complexes, which are part of the complement pathway, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive i…
WNT4	Protein Wnt-4	Ligand for members of the frizzled family of seven transmembrane receptors.
FOXP2	Forkhead box protein P2	Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
TFAP2D	Transcription factor AP-2-delta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
TLR10	Toll-like receptor 10	Participates in the innate immune response to microbial agents.
IL33	Interleukin-33	Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells.
KLF3	Krueppel-like factor 3	Binds to the CACCC box of erythroid cell-expressed genes.
MOAP1	Modulator of apoptosis 1	Retrotransposon-derived protein that forms virion-like capsids.
CAPN14	Calpain-14	Calcium-regulated non-lysosomal thiol-protease.
CDC73	Parafibromin	Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways.
SYNE1	Nesprin-1	Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization.
CDH20	Cadherin-20	Cadherins are calcium-dependent cell adhesion proteins.
RHOU	Rho-related GTP-binding protein RhoU	Binds to and activates protein kinase PAK1.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
VEZT	Vezatin	Plays a pivotal role in the establishment of adherens junctions and their maintenance in adult life.
KSR2	Kinase suppressor of Ras 2	Location-regulated scaffold connecting MEK to RAF.
CCDC170	Coiled-coil domain-containing protein 170	Plays a role in Golgi-associated microtubules organization and stabilization.
RNF144B	E3 ubiquitin-protein ligase RNF144B	E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates such as LCMT2, thereby promoting their…
CHLSN	Protein cholesin	Hormone secreted from the intestine in response to cholesterol, where it acts to inhibit cholesterol synthesis in the liver and VLDL secretion,leading to a reduction in circulating cholesterol levels.
NAALADL2	Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2	May be catalytically inactive.
ETAA1	Ewing’s tumor-associated antigen 1	Replication stress response protein that accumulates at DNA damage sites and promotes replication fork progression and integrity.
GREB1	Protein GREB1	May play a role in estrogen-stimulated cell proliferation.
DEFA1	Neutrophil defensin 1	Effector molecule of the innate immune system that acts via antibiotic-like properties against a broad array of infectious agents including bacteria, fungi, and viruses or by promoting the activation and maturation of some APCs.
ZBTB40	Zinc finger and BTB domain-containing protein 40	May be involved in transcriptional regulation.
EMX2	Homeobox protein EMX2	Transcription factor, which in cooperation with EMX1, acts to generate the boundary between the roof and archipallium in the developing brain.
ESR1	Estrogen receptor	Nuclear hormone receptor.
FSHB	Follitropin subunit beta	Together with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer.
ALCAM	CD166 antigen	Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts.
HLA-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
ID4	DNA-binding protein inhibitor ID-4	Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity.
IGF1R	Insulin-like growth factor 1 receptor	Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1).
IL1A	Interleukin-1 alpha	Cytokine constitutively present intracellularly in nearly all resting non-hematopoietic cells that plays an important role in inflammation and bridges the innate and adaptive immune systems.
IL1B	Interleukin-1 beta	Potent pro-inflammatory cytokine.
ITPK1	Inositol-tetrakisphosphate 1-kinase	Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3.
KDR	Vascular endothelial growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.
LAMC3	Laminin subunit gamma-3	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
RND3	Rho-related GTP-binding protein RhoE	Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins.
MAP3K4	Mitogen-activated protein kinase kinase kinase 4	Component of a protein kinase signal transduction cascade.
RHOJ	Rho-related GTP-binding protein RhoJ	Plasma membrane-associated small GTPase specifically involved in angiogenesis.
MEIS1	Homeobox protein Meis1	Acts as a transcriptional regulator of PAX6.
NFE2L3	Nuclear factor erythroid 2-related factor 3	Activates erythroid-specific, globin gene expression.
OR1D2	Olfactory receptor 1D2	Odorant receptor which may be involved in sperm chemotaxis.
OR1G1	Olfactory receptor 1G1	Odorant receptor.
PDE1C	Dual specificity calcium/calmodulin-dependent 3’,5’-cyclic nucleotide phosphodiesterase 1C	Calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
PTPRD	Receptor-type tyrosine-protein phosphatase delta	Can bidirectionally induce pre- and post-synaptic differentiation of neurons by mediating interaction with IL1RAP and IL1RAPL1 trans-synaptically.

Protein-family classification

Druggable: 16 · Difficult: 12 · Unknown: 28 · Druggable fraction: 0.29

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	6.9×	0.393
Complement	1	4.8×	0.393
Kinase	5	2.5×	0.393
Protease	3	2.0×	0.393
Transcription factor	10	1.5×	0.393
Antibody/Immunoglobulin	3	1.6×	0.501
Phosphatase	1	1.5×	0.699
Other/Unknown	28	0.9×	0.844
GPCR	2	0.8×	0.844
Scaffold/PPI	2	0.6×	0.844

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNF	Other/Unknown	no		TNF_alpha, TNF_dom, TNF
C2	Protease	yes		Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
WNT4	Other/Unknown	no		Wnt, Wnt4, Wnt_CS
HNRNPA3P1	Other/Unknown	no
FOXP2	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
TFAP2D	Transcription factor	no		TF_AP2, TF_AP2_C
TLR10	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
IL33	Other/Unknown	no		IL-33, IL33_C
KLF3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
MOAP1	Other/Unknown	no		PNMA, PNMA_C, PNMA_N
CAPN14	Protease	yes		Pept_cys_AS, Peptidase_C2_calpain_cat, EF_hand_dom
SORCS1	Antibody/Immunoglobulin	yes		PKD_dom, VPS10, Ig-like_fold
CDC73	Other/Unknown	no		Cdc73/Parafibromin, CDC73_C, Cdc73_N
SYNE1	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
CDH20	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
RHOU	Other/Unknown	no		Small_GTPase, Small_GTPase_Rho, Small_GTP-bd
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
VEZT	Other/Unknown	no		Vezatin, Myosin-bd
KSR2	Kinase	yes	2.7.11.25	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
C14orf132	Other/Unknown	no
CCDC170	Other/Unknown	no		CCDC170-like
RNF144B	Transcription factor	no		Znf_RING, IBR_dom, Znf_RING/FYVE/PHD
CHLSN	Other/Unknown	no		WKF
NAALADL2	Protease	yes		Peptidase_M28, TFR-like_dimer_dom_sf, Peptidase_M28B
ETAA1	Other/Unknown	no		ETAA1
RBM43	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
GREB1	Other/Unknown	no		GREB1, GREB1_N, GREB1-like_C
PARP1P2	Other/Unknown	no
DEFA1	Other/Unknown	no		Alpha-defensin_N, Beta/alpha-defensin_C, Alpha-defensin_C
FAM163A	Other/Unknown	no		FAM163, FAM163A
ZBTB40	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
EMX2	Transcription factor	no		HTH_motif, HD, Homeodomain-like_sf
CDKN2B-AS1	Other/Unknown	no
ESR1	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Estr_rcpt, Znf_hrmn_rcpt
FSHB	Other/Unknown	no		Gonadotropin_bsu, Glyco_hormone_CN, Gonadotropin_bsu_CS
ALCAM	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
HLA-DRA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
ID4	Transcription factor	no		bHLH_dom, DNA-bd_prot-inh, HLH_DNA-bd_sf
IGF1R	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
RMP24P1	Other/Unknown	no
IL1A	Other/Unknown	no		IL-1_fam, IL-1_alpha, IL-1_propep
IL1B	Other/Unknown	no		IL-1_fam, IL-1_propep, IL1/FGF
ITPK1	Kinase	yes	2.7.1.134	Inositol_tetrakis-P_1-kinase, ATP-grasp, InsP(3)kin_ATP-grasp
KDR	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
LAMC3	Other/Unknown	no		Laminin_IV, EGF, LE_dom
RND3	Other/Unknown	no		Small_GTPase, Small_GTPase_Rho, Small_GTP-bd
MAP3K4	Kinase	yes	2.7.12.2	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
RHOJ	Other/Unknown	no		Small_GTPase, Small_GTPase_Rho, Small_GTP-bd

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	2
moderate (6-20)	1
broad (>20)	53
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	7
cortical plate	4
middle temporal gyrus	4
colonic epithelium	4
pituitary gland	4
primordial germ cell in gonad	4
granulocyte	3
male germ line stem cell (sensu Vertebrata) in testis	3
buccal mucosa cell	3
Brodmann (1909) area 23	3
secondary oocyte	3
sural nerve	3
C1 segment of cervical spinal cord	3
monocyte	3
placenta	2
decidua	2
ganglionic eminence	2
stromal cell of endometrium	2
mucosa of paranasal sinus	2
right coronary artery	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNF	119	broad	marker	granulocyte, male germ line stem cell (sensu Vertebrata) in testis, bone marrow
C2	138	ubiquitous	marker	liver, right lobe of liver, placenta
WNT4	177	broad	marker	islet of Langerhans, decidua, type B pancreatic cell
HNRNPA3P1	25		yes	stromal cell of endometrium, ganglionic eminence, cortical plate
FOXP2	237	broad	marker	buccal mucosa cell, tibialis anterior, mucosa of paranasal sinus
CSMD1	179	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, primary visual cortex
TFAP2D	25		marker	oocyte, buccal mucosa cell, secondary oocyte
TLR10	166	tissue_specific	marker	lymph node, ileal mucosa, ileum
IL33	239	broad	marker	calcaneal tendon, right coronary artery, olfactory segment of nasal mucosa
KLF3	271	ubiquitous	marker	upper leg skin, penis, esophagus squamous epithelium
MOAP1	142	ubiquitous	marker	superior frontal gyrus, prefrontal cortex, frontal cortex
CAPN14	116	tissue_specific	yes	lower esophagus mucosa, pharyngeal mucosa, esophagus mucosa
SORCS1	188	broad	marker	cortical plate, sural nerve, trigeminal ganglion
CDC73	271	ubiquitous	marker	calcaneal tendon, sural nerve, colonic epithelium
SYNE1	275	ubiquitous	marker	cerebellar hemisphere, right hemisphere of cerebellum, calcaneal tendon
CDH20	148	broad	marker	ventricular zone, C1 segment of cervical spinal cord, amygdala
RHOU	134	ubiquitous	marker	corpus callosum, C1 segment of cervical spinal cord, duodenum
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
CDKN2B	219	ubiquitous	marker	jejunal mucosa, colonic mucosa, lower esophagus mucosa
VEZT	274	ubiquitous	marker	adrenal tissue, cortical plate, calcaneal tendon
KSR2	114	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, postcentral gyrus
C14orf132	263	ubiquitous	marker	middle temporal gyrus, endothelial cell, Brodmann (1909) area 23
CCDC170	182	broad	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
RNF144B	255	ubiquitous	marker	deltoid, skeletal muscle tissue of rectus abdominis, quadriceps femoris
CHLSN	243	ubiquitous	marker	adenohypophysis, right coronary artery, pituitary gland
NAALADL2	183	ubiquitous	marker	calcaneal tendon, colonic epithelium, primordial germ cell in gonad
ETAA1	224	ubiquitous	marker	secondary oocyte, calcaneal tendon, primordial germ cell in gonad
RBM43	218	ubiquitous	yes	oviduct epithelium, calcaneal tendon, fallopian tube
GREB1	219	broad	marker	left ovary, right ovary, ovary
PARP1P2	70		yes	male germ line stem cell (sensu Vertebrata) in testis, ganglionic eminence, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 18.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ESR1	12,382
TNF	11,116
CDKN2A	9,311
IL1B	8,564
IGF1R	6,823
IL1A	5,171
KDR	4,960
CDC73	4,592
VEZT	4,323
RHOJ	3,990

Intra-cohort edges

A	B	Sources
CCDC170	ESR1	string_interaction
CCDC170	SYNE1	string_interaction
CCDC170	ZBTB40	string_interaction
CDKN2A	CDKN2B	biogrid_interaction
CSMD1	NAALADL2	string_interaction
CSMD1	PTPRD	string_interaction
EMX2	MEIS1	intact
ESR1	GREB1	biogrid_interaction, string_interaction
ESR1	IGF1R	string_interaction
GREB1	VEZT	string_interaction
GREB1	WNT4	string_interaction
IGF1R	VEZT	intact
IL1A	IL1B	string_interaction
IL1A	TNF	string_interaction
IL1B	IL33	string_interaction
IL1B	TNF	string_interaction
RBM43	RNF144B	string_interaction
RBM43	VEZT	string_interaction

Structural data

PDB: 26 · AlphaFold-only: 26 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ESR1	P03372	478
HLA-DRA	P01903	140
IL1B	P01584	64
KDR	P35968	54
TNF	P01375	52
IGF1R	P08069	46
CDC73	Q6P1J9	20
DEFA1	P59665	19
C2	P06681	14
KSR2	Q6VAB6	9
PTPRD	P23468	8
RND3	P61587	7
FSHB	P01225	6
IL33	O95760	5
CDKN2A	P42771	5
IL1A	P01583	4
ITPK1	Q13572	4
SYNE1	Q8NF91	3
FOXP2	O15409	2
MEIS1	O00470	2
CSMD1	Q96PZ7	1
TLR10	Q9BXR5	1
MOAP1	Q96BY2	1
RHOU	Q7L0Q8	1
ETAA1	Q9NY74	1
ALCAM	Q13740	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT4	P56705	91.41
CDKN2B	P42772	90.12
RHOJ	Q9H4E5	88.63
OR1D2	P34982	86.41
CAPN14	A8MX76	86.02
OR1G1	P47890	84.11
RNF144B	Q7Z419	82.64
CCDC170	Q8IYT3	82.06
NAALADL2	Q58DX5	78.78
SORCS1	Q8WY21	77.77
CDH20	Q9HBT6	77.33
RBM43	Q6ZSC3	77.12
CHLSN	Q9BRJ6	75.36
LAMC3	Q9Y6N6	75.23
PDE1C	Q14123	71.53
GREB1	Q4ZG55	71.10
ID4	P47928	68.34
EMX2	Q04743	67.26
C14orf132	Q9NPU4	66.98
MAP3K4	Q9Y6R4	66.66
ZBTB40	Q9NUA8	66.33
VEZT	Q9HBM0	66.08
TFAP2D	Q7Z6R9	62.75
FAM163A	Q96GL9	58.54
NFE2L3	Q9Y4A8	54.20
KLF3	P57682	54.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 203. Enrichment computed across 56 evidence-associated genes (36 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 36 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-1 processing	2	70.5×	0.032	IL1A, IL1B
Interleukin-10 signaling	3	19.4×	0.032	TNF, IL1A, IL1B
Interleukin-4 and Interleukin-13 signaling	4	11.4×	0.032	TNF, RHOU, IL1A, IL1B
Formation of the nephric duct	2	35.2×	0.073	EMX2, ID4
Evasion of Oncogene Induced Senescence Due to p14ARF Defects	1	317.2×	0.082	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects	1	317.2×	0.082	CDKN2A
Pyroptosis	2	23.5×	0.082	IL1A, IL1B
Purinergic signaling in leishmaniasis infection	2	23.5×	0.082	IL1A, IL1B
G1 Phase	2	21.9×	0.084	CDKN2A, CDKN2B
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	1	158.6×	0.091	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	1	158.6×	0.091	CDKN2A
Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function	1	158.6×	0.091	CDKN2A
Interleukin-33 signaling	1	105.7×	0.091	IL33
Diseases of Cellular Senescence	1	105.7×	0.091	CDKN2A
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	1	105.7×	0.091	CDKN2A
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	105.7×	0.091	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	1	105.7×	0.091	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	105.7×	0.091	CDKN2A
Diseases of cellular response to stress	1	105.7×	0.091	CDKN2A
Oncogene Induced Senescence	2	18.7×	0.091	CDKN2A, CDKN2B
Senescence-Associated Secretory Phenotype (SASP)	3	8.3×	0.091	CDKN2A, CDKN2B, IL1A
Cyclin D associated events in G1	2	12.9×	0.096	CDKN2A, CDKN2B
Cam-PDE 1 activation	1	79.3×	0.102	PDE1C
Neuropilin interactions with VEGF and VEGFR	1	79.3×	0.102	KDR
IRAK4 deficiency (TLR5)	1	79.3×	0.102	TLR10
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB	1	63.4×	0.112	KDR
CASP4-mediated substrate cleavage	1	63.4×	0.112	IL1B
CASP5-mediated substrate cleavage	1	63.4×	0.112	IL1B
TNFR1-mediated ceramide production	1	52.9×	0.112	TNF
CLEC7A/inflammasome pathway	1	52.9×	0.112	IL1B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 49 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fever generation	2	229.3×	0.005	IL1A, IL1B
positive regulation of fever generation	2	172.0×	0.005	TNF, IL1B
positive regulation of protein-containing complex disassembly	2	172.0×	0.005	TNF, IGF1R
mammary gland branching involved in pregnancy	2	172.0×	0.005	CSMD1, ESR1
positive regulation of neuroinflammatory response	3	73.7×	0.005	TNF, IL33, IL1B
positive regulation of MAPK cascade	6	9.9×	0.005	TNF, WNT4, KSR2, IGF1R, IL1B, KDR
signal transduction	12	3.9×	0.005	RHOU, ESR1, ALCAM, IGF1R, IL1B, ITPK1, RND3, RHOJ (+4 more)
immune response	7	6.7×	0.006	TNF, TLR10, DEFA1, HLA-DRA, IGF1R, IL1A, IL1B
positive regulation of mitotic nuclear division	3	33.3×	0.007	TNF, IL1A, IL1B
positive regulation of immature T cell proliferation in thymus	2	114.6×	0.008	IL1A, IL1B
vascular endothelial growth factor production	2	98.3×	0.009	TNF, IL1B
extrinsic apoptotic signaling pathway in absence of ligand	3	28.7×	0.009	MOAP1, IL1A, IL1B
positive regulation of nitric oxide biosynthetic process	3	27.9×	0.009	TNF, ESR1, IL1B
positive regulation of interleukin-6 production	4	13.6×	0.010	TNF, IL33, IL1A, IL1B
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	3	25.2×	0.010	TNF, IL1A, IL1B
regulation of establishment of endothelial barrier	2	76.4×	0.012	TNF, IL1B
positive regulation of transcription by RNA polymerase II	11	3.3×	0.013	TNF, TFAP2D, IL33, CDC73, CDKN2A, ESR1, FSHB, ID4 (+3 more)
positive regulation of heterotypic cell-cell adhesion	2	52.9×	0.022	TNF, IL1B
positive regulation of JUN kinase activity	2	52.9×	0.022	TNF, MAP3K4
positive regulation of cytokine production	3	16.6×	0.026	TNF, IL33, IL1A
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1	343.9×	0.033	HLA-DRA
positive regulation of cellular defense response	1	343.9×	0.033	IL33
caudate nucleus development	1	343.9×	0.033	FOXP2
putamen development	1	343.9×	0.033	FOXP2
female sex determination	1	343.9×	0.033	WNT4
positive regulation of translational initiation by iron	1	343.9×	0.033	TNF
positive regulation of cell adhesion molecule production	1	343.9×	0.033	IL1B
negative regulation of branching involved in lung morphogenesis	1	343.9×	0.033	TNF
negative regulation of testicular blood vessel morphogenesis	1	343.9×	0.033	WNT4
seminal vesicle morphogenesis	1	343.9×	0.033	ID4

Therapeutics

Drugs indicated or in trials for this disease

3 approved drugs — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Danazol	Approved (phase 4)
Medroxyprogesterone Acetate	Approved (phase 4)
Norethindrone Acetate	Approved (phase 4)

31 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Cyproterone Acetate	Phase 3
Degarelix	Phase 3
Dienogest	Phase 3
Elagolix	Phase 3
Estradiol	Phase 3
Ethinyl Estradiol	Phase 3
Leuprolide	Phase 3
Levonorgestrel	Phase 3
Linzagolix	Phase 3
Naltrexone	Phase 3
Norethindrone	Phase 3
Pentoxifylline	Phase 3
Relugolix	Phase 3
Triptorelin	Phase 3
Anastrozole	Phase 2
Asoprisnil	Phase 2
Atosiban	Phase 2
Cabergoline	Phase 2
Cannabidiol	Phase 2
Cetrorelix	Phase 2
Epigalocatechin Gallate	Phase 2
Filgrastim	Phase 2
Infliximab	Phase 2
Letrozole	Phase 2
Mifepristone	Phase 2
Rosiglitazone	Phase 2
Sodium Ascorbate	Phase 2
Tanezumab	Phase 2
Telapristone Acetate	Phase 2
Vilaprisan	Phase 2
Vitamin E	Phase 2

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 8 · Undrugged: 48

Druggability breadth: 21 of 56 evidence-associated genes (38%) 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
TNF	PREDNISOLONE
ESR1	CANDESARTAN CILEXETIL
IGF1R	FEDRATINIB
IL1B	POMALIDOMIDE
KDR	VANDETANIB
MAP3K4	FEDRATINIB
PDE1C	VARDENAFIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KDR	172	4
ESR1	162	4
IGF1R	27	4
MAP3K4	21	4
PDE1C	15	4
TNF	12	4
IL1B	4	4
CDC73	1	2
C2	0	0
WNT4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	IL1B, TNF
PENTOXIFYLLINE	4	TNF
MESALAMINE	4	KDR, TNF
LENALIDOMIDE	4	IL1B, TNF
CANDESARTAN CILEXETIL	4	ESR1
DIENESTROL	4	ESR1
BEXAROTENE	4	ESR1
VARENICLINE	4	ESR1
ACETOPHENAZINE	4	ESR1
ARIPIPRAZOLE	4	ESR1
RALOXIFENE HYDROCHLORIDE	4	ESR1
NORETHINDRONE	4	ESR1
TRIMETREXATE	4	ESR1
ESTRADIOL ACETATE	4	ESR1
ETHYLESTRENOL	4	ESR1
ETHYNODIOL DIACETATE	4	ESR1
CHLOROTRIANISENE	4	ESR1
ESTRADIOL CYPIONATE	4	ESR1
MESTRANOL	4	ESR1
QUINESTROL	4	ESR1
RIBOFLAVIN 5’-PHOSPHATE	4	ESR1
ESTETROL ANHYDROUS	4	ESR1
OXYBUTYNIN	4	ESR1
MILTEFOSINE	4	ESR1
MIFEPRISTONE	4	ESR1
LENVATINIB	4	ESR1, KDR
CLOFAZIMINE	4	ESR1
BUTOCONAZOLE	4	ESR1
MOLSIDOMINE	4	ESR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
KDR	2,687	Binding:2594, Functional:64, ADMET:27, Toxicity:2
ESR1	2,435	Binding:2037, Functional:363, ADMET:35
IGF1R	1,091	Binding:1037, Functional:53, ADMET:1
TNF	193	Binding:162, Functional:31
PDE1C	185	Binding:175, ADMET:5, Functional:5
MAP3K4	131	Binding:131
KSR2	28	Binding:28
IL1B	26	Binding:26
CDC73	8	Binding:8
ITPK1	6	Binding:6
MEIS1	5	Binding:5
C2	4	Binding:4
ZBTB40	3	Binding:3
CDKN2A	2	Binding:2
DEFA1	2	Binding:2
IL33	1	Binding:1
CHLSN	1	Binding:1
IL1A	1	Binding:1
PTPRD	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KSR2	2.7.11.25	mitogen-activated protein kinase kinase kinase
IGF1R	2.7.10.1	receptor protein-tyrosine kinase
ITPK1	2.7.1.134, 2.7.1.159	inositol-tetrakisphosphate 1-kinase, inositol-1,3,4-trisphosphate 5/6-kinase
KDR	2.7.10.1	receptor protein-tyrosine kinase
MAP3K4	2.7.12.2	mitogen-activated protein kinase kinase
PDE1C	3.1.4.17	3’,5’-cyclic-nucleotide phosphodiesterase
PTPRD	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TNF	193
ESR1	2,435
IGF1R	1,091
KDR	2,687
MAP3K4	131
PDE1C	185

Pharmacogenomics

Cohort genes with a PharmGKB record: 55; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 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)
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	IL1B, TNF
PENTOXIFYLLINE	4	TNF
MESALAMINE	4	KDR, TNF
LENALIDOMIDE	4	IL1B, TNF
CANDESARTAN CILEXETIL	4	ESR1
DIENESTROL	4	ESR1
BEXAROTENE	4	ESR1
VARENICLINE	4	ESR1
ACETOPHENAZINE	4	ESR1
ARIPIPRAZOLE	4	ESR1
RALOXIFENE HYDROCHLORIDE	4	ESR1
TRIMETREXATE	4	ESR1
ESTRADIOL ACETATE	4	ESR1
ETHYLESTRENOL	4	ESR1
ETHYNODIOL DIACETATE	4	ESR1
CHLOROTRIANISENE	4	ESR1
ESTRADIOL CYPIONATE	4	ESR1
MESTRANOL	4	ESR1
QUINESTROL	4	ESR1
RIBOFLAVIN 5’-PHOSPHATE	4	ESR1
ESTETROL ANHYDROUS	4	ESR1
OXYBUTYNIN	4	ESR1
MILTEFOSINE	4	ESR1
MIFEPRISTONE	4	ESR1
LENVATINIB	4	ESR1, KDR
CLOFAZIMINE	4	ESR1
BUTOCONAZOLE	4	ESR1
MOLSIDOMINE	4	ESR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	TNF, ESR1, IGF1R, IL1B, KDR, MAP3K4, PDE1C
B	Phased (≥1) drug, not yet approved	1	CDC73
C	Druggable family + PDB, no drug	7	C2, CSMD1, KSR2, ALCAM, HLA-DRA, ITPK1, PTPRD
D	Druggable family + AlphaFold only, no drug	5	CAPN14, SORCS1, NAALADL2, OR1D2, OR1G1
E	Difficult family or no structure, no drug	36	WNT4, HNRNPA3P1, FOXP2, TFAP2D, TLR10, IL33, KLF3, MOAP1, SYNE1, CDH20 (+26 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CCDC170	0	ESR1
GREB1	0	ESR1
C2	4	—
WNT4	0	—
HNRNPA3P1	0	—
FOXP2	0	—
CSMD1	0	—
TFAP2D	0	—
TLR10	0	—
IL33	1	—
KLF3	0	—
MOAP1	0	—
CAPN14	0	—
SORCS1	0	—
SYNE1	0	—
CDH20	0	—
RHOU	0	—
CDKN2A	2	—
CDKN2B	0	—
VEZT	0	—
KSR2	28	—
C14orf132	0	—
RNF144B	0	—
CHLSN	1	—
NAALADL2	0	—
ETAA1	0	—
RBM43	0	—
PARP1P2	0	—
DEFA1	2	—
FAM163A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 705.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	493
PHASE2	78
PHASE3	47
PHASE4	38
PHASE1	22
PHASE1/PHASE2	10
EARLY_PHASE1	9
PHASE2/PHASE3	8

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04554693	PHASE4	ACTIVE_NOT_RECRUITING	The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery
NCT05059626	PHASE4	RECRUITING	Endometriosis and Microvascular Dysfunction; Simvastatin and Duavee
NCT05962034	PHASE4	RECRUITING	Thromboxane Function in Women With Endometriosis
NCT06523530	PHASE4	RECRUITING	Effect of a GnRH Analog on Hepatic Steatosis
NCT06543550	PHASE4	RECRUITING	Comparison Between the Effects of Implantable Gestrinone and Oral Dienogest in the Treatment of Endometriosis
NCT06577233	PHASE4	RECRUITING	Superior Hypogastric Nerve Plexus Block With Bupivacaine After Robotic Resection of Endometriosis
NCT06951802	PHASE4	RECRUITING	Endometriosis and Pain Treatment by Intraoperative Administration of Low-dose Ketamine
NCT07144904	PHASE4	NOT_YET_RECRUITING	Assessing the Efficacy of Indocyanine Green for Ureter Identification During Robot-Assisted Surgery in Advanced-Stage Endometriosis
NCT07532876	PHASE4	ENROLLING_BY_INVITATION	Comparison of Elagolix and OCPs in Reducing Endometriosis Associated Pelvic Pain
NCT00286351	PHASE4	COMPLETED	Use of Arimidex and Zoladex as Pretreatment to IVF in Women With Ovarian Endometriosis
NCT00621179	PHASE4	COMPLETED	Endometrial Markers and Response of Endometriosis Patients to Prolonged GnRH Agonist Prior to IVF
NCT00625950	PHASE4	COMPLETED	Endometriosis Patients Undergoing Quinagolide Treatment
NCT00654524	PHASE4	UNKNOWN	Randomized Study of Gonadotropin-releasing-hormone Agonist (GnRH-a) or Expectant Management for Endometriosis
NCT00735852	PHASE4	COMPLETED	Decapeptyl SR With Livial Add Back Therapy in the Management of Chronic Cyclical Pelvic Pain in Pre Menopausal Women
NCT00844012	PHASE4	UNKNOWN	Continuous Postoperative Use of Low-Dose Combined Oral Contraceptivesfor for Endometriosis-Related Chronic Pelvic Pain
NCT01056042	PHASE4	COMPLETED	Efficacy of Injectable Contraceptive and Oral Contraceptive Administered After Surgical Treatment of Endometriosis With Pain
NCT01581359	PHASE4	COMPLETED	The Effect of Pre-treatment With GnRH Analogues Prior in Vitro Fertilization in Patients With Endometriosis
NCT01682642	PHASE4	COMPLETED	The Influence of Adjuvant Medical Treatment of Peritoneal Endometriosis on the Outcome of IVF. A Prospective Randomized Analysis.
NCT01769781	PHASE4	COMPLETED	Anastrazole Plus GnRH-agonist in the Treatment of Endometriosis Recurrence
NCT01779232	PHASE4	COMPLETED	Danazol Treatment in Endometriosis Women Before IVF
NCT02158845	PHASE4	COMPLETED	Levonorgestrel-releasing Intrauterine System in Patients With Endometriosis
NCT02165917	PHASE4	UNKNOWN	Study to Compare Peritoneal Ablation by Excision Only and Excision With the Use of an Adhesion Barrier
NCT02213081	PHASE4	COMPLETED	Ulipristal for Endometriosis-related Pelvic Pain
NCT02214550	PHASE4	COMPLETED	Chronic Pain Risk Associated With Menstrual Period Pain
NCT02385448	PHASE4	UNKNOWN	Comparing the Use of Dienogest and Combined Oral Contraceptive Pills (Microgynon) to Reduce the Risk of Recurrence of Endometriotic Cyst After Conservative Surgery
NCT02387931	PHASE4	COMPLETED	Supplementation in Adolescent Girls With Endometriosis
NCT02393482	PHASE4	UNKNOWN	Psychological Impact of Amenorrhea in Women With Endometriosis
NCT02427386	PHASE4	COMPLETED	Homeopathic Treatment of Chronic Pelvic Pain in Women With Endometriosis
NCT02475564	PHASE4	COMPLETED	Resveratrol for Pain Due to Endometriosis
NCT02480647	PHASE4	COMPLETED	Clinical Trial the Use of Levonorgestrel-releasing Intrauterine System Versus Etonogestrel Implant in Endometriosis
NCT02534688	PHASE4	COMPLETED	Effectiveness of Levonorgestrel-intrauterine System (LNG-IUS) Versus Depot Medroxyprogesterone Acetate (DMPA) in Treatment of Pelvic Pain in Clinically Diagnosed Endometriotic Patients
NCT02812186	PHASE4	COMPLETED	Deep Versus Moderate Neuromuscular Blockade During Laparoscopic Surgery
NCT04218487	PHASE4	UNKNOWN	Xuefu-Zhuyu Capsule for the Treatment of Qizhi Xueyu Zheng (Qi Stagnation and Blood Stasis Syndrome)
NCT04942015	PHASE4	UNKNOWN	Honghuaruyi Wan for Endometriosis Dysmenorrhea
NCT05013242	PHASE4	UNKNOWN	Goserline Acetate VS Dienogest in Endometriosi
NCT05331053	PHASE4	TERMINATED	MicroRNA Activation of LOX-1 Mechanisms in Endometriosis
NCT05560230	PHASE4	COMPLETED	Intraoperative Clonidine for Postoperative Pain Management in Patients Undergoing Surgical Treatment for Endometriosis
NCT07182032	PHASE4	WITHDRAWN	Ketamine in Central Sensitization
NCT04333576	PHASE3	ACTIVE_NOT_RECRUITING	Study Of Oral Elagolix Tablets In Combination With Combined Oral Contraceptive Capsules/Tablets To Assess Dysmenorrhea Response In Adult Female Participants With Endometriosis And Associated Moderate To Severe Pain
NCT04356664	PHASE2/PHASE3	RECRUITING	Benefit of GnRH Agonist Before Frozen Embryo Transfer in Patients With Endometriosis and/or Adenomyosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ELAGOLIX	4	36
LEUPROLIDE	4	19
DIENOGEST	4	16
LINZAGOLIX	4	10
NORETHINDRONE ACETATE	4	6
TRIPTORELIN	4	6
NORETHINDRONE	4	5
RELUGOLIX	4	5
DANAZOL	4	4
LEVONORGESTREL	4	4
ROSIGLITAZONE	4	4
DYDROGESTERONE	4	3
CABERGOLINE	4	2
CLONIDINE	4	2
GONADORELIN ACETATE	4	2
GOSERELIN ACETATE	4	2
AFATINIB	4	1
ANASTROZOLE	4	1
ATOSIBAN	4	1
AXITINIB	4	1
BUPIVACAINE HYDROCHLORIDE	4	1
CETRORELIX	4	1
CETRORELIX ACETATE	4	1
CHOLECALCIFEROL	4	1
DEGARELIX	4	1
DESOGESTREL	4	1
DRONABINOL	4	1
ESKETAMINE HYDROCHLORIDE	4	1
ESTRADIOL	4	1
ETHINYL ESTRADIOL	4	1