Uterine corpus leiomyoma

Summary

Uterine corpus leiomyoma (MONDO:0007886) is a disease (an umbrella term covering 11 Mondo subtypes) with 74 cohort genes (1,070 GWAS associations across 30 studies) and 246 clinical trials. The dominant Reactome pathway is Transcriptional regulation of testis differentiation (3 cohort genes). Top therapeutic interventions include elagolix, relugolix, and norethindrone acetate.

At a glance

• Umbrella term: 11 Mondo subtypes
• Cohort genes: 74
• GWAS associations: 1,070
• ClinVar variants: 32
• Clinical trials: 246

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	uterine corpus leiomyoma
Mondo ID	MONDO:0007886
EFO	EFO:0000731
OMIM	150699
DOID	DOID:13223
ICD-10-CM	D25
NCIT	C3434
SNOMED CT	95315005
UMLS	C0042133
MedGen	21801
GARD	0024585
Anatomy (UBERON)	UBERON:0009853
Is cancer (heuristic)	no

Also known as: body of uterus fibroid · body of uterus leiomyoma · corpus uteri fibroid · corpus uteri leiomyoma · fibroid of body of uterus · fibroid of corpus uteri · fibroid of the body of uterus · fibroid of the corpus uteri · fibroid of the uterine body · fibroid of the uterine corpus · fibroid of uterine body · fibroid of uterine corpus · leiomyoma of body of uterus · leiomyoma of corpus uteri · leiomyoma of the body of uterus · leiomyoma of the corpus uteri · leiomyoma of the uterine body · leiomyoma of the uterine corpus · leiomyoma of uterine body · leiomyoma of uterine corpus (+10 more)

Data availability: 32 ClinVar variants · 1,070 GWAS associations (30 studies) · 1 GenCC gene-disease record · 1 HPO phenotype · 13 cell lines.

Disease family

An umbrella term covering 11 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › musculoskeletal system benign neoplasm › benign muscle neoplasm › benign smooth muscle neoplasm › leiomyoma › uterine corpus leiomyoma

Related subtypes (29): laryngeal leiomyoma, gastric leiomyoma, ureter leiomyoma, vaginal leiomyoma, bladder leiomyoma, breast leiomyoma, small intestine leiomyoma, urethra leiomyoma, trachea leiomyoma, prostate leiomyoma, mediastinum leiomyoma, fallopian tube leiomyoma, central nervous system leiomyoma, bizarre leiomyoma, deep leiomyoma, leiomyoma cutis, lung leiomyoma, pericardium leiomyoma, leiomyomatosis, cellular leiomyoma, gallbladder leiomyoma, vulvar leiomyoma, colorectal leiomyoma, liver leiomyoma, esophagus leiomyoma, renal leiomyoma, myofibroma, leiomyoma of ciliary body, benign metastasizing leiomyoma

Subtypes (11): submucous uterine fibroid, subserous uterine fibroid, uterine corpus epithelioid leiomyoma, uterine corpus dissecting leiomyoma, uterus interstitial leiomyoma, uterine corpus myxoid leiomyoma, uterine corpus lipoleiomyoma, uterine corpus bizarre leiomyoma, uterine corpus diffuse leiomyomatosis, uterine corpus apoplectic leiomyoma, uterine corpus cellular leiomyoma

Genetics & variants

GWAS landscape

1,070 GWAS associations across 30 studies. Top hits map to 24 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11740768	2e-171	UIMC1	A
rs78378222	3e-132	TP53	T	0.64
rs58415480	6e-115	SYNE1	C	0.19
rs3820282	6e-87	WNT4	T	0.15
rs79342925	6e-86	STN1	T	0.32
rs13211170	1e-81	SYNE1	A	0.14
rs9479289	3e-64	SYNE1	T	0.12
rs141244868	1e-62	PSMD13	G	0.25
rs7106353	2e-58	THEM7P - WT1	T	0.15
rs61768001	7e-55	WNT4	T	0.15
rs73392700	5e-53	SIRT3	C	0.27
rs11031728	1e-52	THEM7P - WT1	C	0.16
rs733381	2e-51	TNRC6B	A	0.1
rs117245733	1e-50	LINC00598	A	0.33
rs805698	7e-49	COL17A1	T	0.31
rs150037725	3e-48	CFAP43	A	0.31
rs10069690	3e-48	TERT	T	0.1
rs12392108	6e-46	RAP2C-AS1	A	1.13
rs12225799	3e-45	PSMD13	G	0.3
rs5930554	3e-43	RAP2C-AS1	C	0.15
rs1265002	3e-43	COL17A1 - SFR1	A	0.29
rs4472361	9e-43	SYNE1	T	0.1
rs7726159	5e-42	TERT	A	0.09
rs11031005	2e-41	ARL14EP-DT	T
rs142959056	3e-38	SH3PXD2A	G	0.25
rs9479275	2e-37	SYNE1	A	0.09
rs633891	2e-37	SYNE1	T	0.08
rs111929914	7e-37	ATM	T	0.12
rs1519074	2e-36	NPAT	A	0.12
rs13211693	5e-36	SYNE1	T	0.1

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90461957	Kim J	2025	53,711	380,441	Genome-wide meta-analysis identifies novel risk loci for uterine fibroids within and across multiple ancestry groups.
GCST90461958	Kim J	2025	53,711	380,441	Genome-wide meta-analysis identifies novel risk loci for uterine fibroids within and across multiple ancestry groups.
GCST90483502	Venkatesh SS	2025	42,446	588,955	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90693145	Kiewa J	2023	39,454	197,153	A common genetic factor underlies genetic risk for gynaecological and reproductive disorders and is correlated with risk to depression.
GCST90428286	Xiao C	2024	35,474	267,505	Genetic contribution of reproductive traits to risk of uterine leiomyomata: a large-scale genome-wide cross-trait analysis.
GCST90428287	Xiao C	2024	35,474	267,505	Genetic contribution of reproductive traits to risk of uterine leiomyomata: a large-scale genome-wide cross-trait analysis.
GCST90428288	Xiao C	2024	35,474	267,505	Genetic contribution of reproductive traits to risk of uterine leiomyomata: a large-scale genome-wide cross-trait analysis.
GCST90018934	Sakaue S	2021	21,024	237,694	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST009158	Gallagher CS	2019	20,406	223,918	Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.
GCST006462	Rafnar T	2018	16,595	523,330	Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	2
Tier 3: regulatory	0
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	40
intergenic_variant	4
missense_variant	2
non_coding_transcript_exon_variant	2
3_prime_UTR_variant	1
splice_polypyrimidine_tract_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs16991615	20	5967581	G>A	0.05	missense_variant	MCM8		Tier 1: coding
rs11740768	5	176912498	G>A,C,T	0.05	intron_variant	UIMC1	2e-171	Tier 4: intronic/intergenic
rs78378222	17	7668434	T>A,G		3_prime_UTR_variant	TP53	3e-132	Tier 2: splice/UTR
rs58415480	6	152241136	C>G,T	0.05	intron_variant	SYNE1	6e-115	Tier 4: intronic/intergenic
rs3820282	1	22141722	C>A,G,T	0.05	intron_variant	WNT4	6e-87	Tier 4: intronic/intergenic
rs79342925	10	103911925	C>T	0.05	intron_variant	STN1	6e-86	Tier 4: intronic/intergenic
rs13211170	6	152289837	A>C,G	0.05	intron_variant	SYNE1	1e-81	Tier 4: intronic/intergenic
rs9479289	6	152307964	C>A,T	0.05	intron_variant	SYNE1	3e-64	Tier 4: intronic/intergenic
rs141244868	11	244818	GAA>G,GA,GAAA	0.05	intron_variant	PSMD13	1e-62	Tier 4: intronic/intergenic
rs7106353	11	32329881	C>A,T	0.05	intron_variant	THEM7P - WT1	2e-58	Tier 4: intronic/intergenic
rs61768001	1	22139327	T>A,C,G	0.05	intron_variant	WNT4	7e-55	Tier 4: intronic/intergenic
rs73392700	11	224845	G>C	0.05	intron_variant	SIRT3	5e-53	Tier 4: intronic/intergenic
rs11031728	11	32342070	C>G	0.05	intron_variant	THEM7P - WT1	1e-52	Tier 4: intronic/intergenic
rs733381	22	40273644	A>G	0.05	intron_variant	TNRC6B	2e-51	Tier 4: intronic/intergenic
rs117245733	13	40149807	G>A	0.05	intron_variant	LINC00598	1e-50	Tier 4: intronic/intergenic
rs805698	10	104057158	C>G,T	0.05	missense_variant	COL17A1	7e-49	Tier 1: coding
rs150037725	10	104132892	A>C,G		intron_variant	CFAP43	3e-48	Tier 4: intronic/intergenic
rs10069690	5	1279675	C>T	0.05	intron_variant	TERT	3e-48	Tier 4: intronic/intergenic
rs12392108	X	132180234	T>A,C	0.31	intergenic_variant	RAP2C-AS1	6e-46	Tier 4: intronic/intergenic
rs12225799	11	241124	C>G	0.129	intron_variant	PSMD13	3e-45	Tier 4: intronic/intergenic
rs5930554	X	132178061	T>C	0.05	intergenic_variant	RAP2C-AS1	3e-43	Tier 4: intronic/intergenic
rs1265002	10	104095898	A>T	0.05	intron_variant	COL17A1 - SFR1	3e-43	Tier 4: intronic/intergenic
rs4472361	6	152320471	G>A,T	0.05	intron_variant	SYNE1	9e-43	Tier 4: intronic/intergenic
rs7726159	5	1282204	C>A	0.05	intron_variant	TERT	5e-42	Tier 4: intronic/intergenic
rs11031005	11	30204809	T>C	0.05	intron_variant	ARL14EP-DT	2e-41	Tier 4: intronic/intergenic
rs142959056	10	103703795	GACAGT>G	0.05	intron_variant	SH3PXD2A	3e-38	Tier 4: intronic/intergenic
rs9479275	6	152239781	G>A,T	0.05	intron_variant	SYNE1	2e-37	Tier 4: intronic/intergenic
rs633891	6	152271616	C>G,T	0.05	intron_variant	SYNE1	2e-37	Tier 4: intronic/intergenic
rs111929914	11	108275572	C>G,T	0.05	intron_variant	ATM	7e-37	Tier 4: intronic/intergenic
rs1519074	11	108177255	A>G	0.05	intron_variant	NPAT	2e-36	Tier 4: intronic/intergenic

ClinVar germline variants

32 retrieved; paginated sample, class counts are floors:

26 not provided, 2 uncertain significance, 2 other, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
393560	NM_000143.4(FH):c.322C>T (p.Gln108Ter)	FH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1326290	NM_005220.3(DLX3):c.263A>G (p.Tyr88Cys)	DLX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
800987	NM_003483.6(HMGA2):c.283-2A>G	HMGA2	Uncertain significance	no assertion criteria provided
92217	NM_005120.3(MED12):c.130G>A (p.Gly44Ser)	MED12	other	no assertion criteria provided
92220	NM_005120.3(MED12):c.131G>A (p.Gly44Asp)	MED12	other	no assertion criteria provided
523402	NM_001083603.3(PTCH1):c.109del (p.Cys37fs)	PTCH1	Uncertain significance	criteria provided, single submitter
92197	NM_005120.3(MED12):c.100-1_139del	MED12	not provided	no classification provided
92198	NM_005120.3(MED12):c.100_141del (p.Asp34_Asn47del)	MED12	not provided	no classification provided
92199	NM_005120.3(MED12):c.100-8T>A	MED12	not provided	no classification provided
92200	NM_005120.3(MED12):c.103_138del (p.Glu35_Asn46del)	MED12	not provided	no classification provided
92201	NM_005120.3(MED12):c.107T>G (p.Leu36Arg)	MED12	not provided	no classification provided
92202	NM_005120.3(MED12):c.107_111delinsGC (p.Leu36_Thr37delinsArg)	MED12	not provided	no classification provided
92203	NM_005120.3(MED12):c.111_155del (p.Ala38_Ser52del)	MED12	not provided	no classification provided
92204	NM_005120.3(MED12):c.113_121del (p.Ala38_Asn40del)	MED12	not provided	no classification provided
92205	NM_005120.3(MED12):c.117_122del (p.Asn40_Val41del)	MED12	not provided	no classification provided
92206	NM_005120.3(MED12):c.118_132del (p.Asn40_Gly44del)	MED12	not provided	no classification provided
92207	NM_005120.3(MED12):c.118_134delinsTA (p.Asn40_Phe45delinsTyr)	MED12	not provided	no classification provided
92208	NM_005120.3(MED12):c.118_146delinsTT (p.Asn40_Pro49delinsPhe)	MED12	not provided	no classification provided
92209	NM_005120.3(MED12):c.122_148del (p.Val41_Pro49del)	MED12	not provided	no classification provided
92210	NM_005120.3(MED12):c.122_163del (p.Val41_Asp54del)	MED12	not provided	no classification provided
92211	NM_005120.3(MED12):c.123_152del (p.Lys42_Val51del)	MED12	not provided	no classification provided
92212	NM_005120.3(MED12):c.126_131del (p.Lys42_Gly44delinsAsn)	MED12	not provided	no classification provided
92213	NM_005120.3(MED12):c.126_140del (p.Lys42_Asn46del)	MED12	not provided	no classification provided
92214	NM_005120.3(MED12):c.128A>C (p.Gln43Pro)	MED12	not provided	no classification provided
92215	NM_005120.3(MED12):c.129_137del (p.Gln43_Asn46delinsHis)	MED12	not provided	no classification provided
92216	NM_005120.3(MED12):c.129_143del (p.Gly44_Gln48del)	MED12	not provided	no classification provided
92218	NM_005120.3(MED12):c.130G>C (p.Gly44Arg)	MED12	not provided	no classification provided
92219	NM_005120.3(MED12):c.130G>T (p.Gly44Cys)	MED12	not provided	no classification provided
92221	NM_005120.3(MED12):c.131G>C (p.Gly44Ala)	MED12	not provided	no classification provided
92222	NM_005120.3(MED12):c.131G>T (p.Gly44Val)	MED12	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 106 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
MED12	MED12	GWAS, Orphanet

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
HMGA2	No Known Disease Relationship	Unknown	uterine corpus leiomyoma	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MED12	Orphanet:1415	Hardikar syndrome
MED12	Orphanet:293707	Blepharophimosis-intellectual disability syndrome, MKB type
MED12	Orphanet:776	Lujan-Fryns syndrome
MED12	Orphanet:777	X-linked non-syndromic intellectual disability
MED12	Orphanet:93932	FG syndrome type 1
HMGA2	Orphanet:276148	Benign epithelial tumor of salivary glands
HMGA2	Orphanet:397590	Silver-Russell syndrome due to a point mutation
HMGA2	Orphanet:94063	12q14 microdeletion syndrome
HMGA2	Orphanet:99970	Dedifferentiated liposarcoma
HMGA2	Orphanet:99971	Well-differentiated liposarcoma
SALL1	Orphanet:857	Townes-Brocks syndrome
ZEB1	Orphanet:98973	Posterior polymorphous corneal dystrophy
ZEB1	Orphanet:98974	Fuchs endothelial corneal dystrophy
TERC	Orphanet:1775	Dyskeratosis congenita
TERC	Orphanet:2032	Idiopathic pulmonary fibrosis
TERC	Orphanet:88	Idiopathic aplastic anemia
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
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
WNT4	Orphanet:139466	SERKAL syndrome
WNT4	Orphanet:247768	Müllerian aplasia and hyperandrogenism
WNT4	Orphanet:2578	Mayer-Rokitansky-Küster-Hauser syndrome type 2
WT1	Orphanet:220	Denys-Drash syndrome
WT1	Orphanet:242	46,XY complete gonadal dysgenesis

Cohort genes → proteins

74 cohort genes, 71 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	69
gwas_and_clinvar	1
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MED12	HGNC:11957	ENSG00000184634	Q93074	Mediator of RNA polymerase II transcription subunit 12	gwas,clinvar
HMGA2	HGNC:5009	ENSG00000149948	P52926	High mobility group protein HMGI-C	gencc,clinvar
SALL1	HGNC:10524	ENSG00000103449	Q9NSC2	Sal-like protein 1	gwas
SHBG	HGNC:10839	ENSG00000129214	P04278	Sex hormone-binding globulin	gwas
SLC4A7	HGNC:11033	ENSG00000033867	Q9Y6M7	Sodium bicarbonate cotransporter 3	gwas
BABAM2	HGNC:1106	ENSG00000158019	Q9NXR7	BRISC and BRCA1-A complex member 2	gwas
SLK	HGNC:11088	ENSG00000065613	Q9H2G2	STE20-like serine/threonine-protein kinase	gwas
ZEB1	HGNC:11642	ENSG00000148516	P37275	Zinc finger E-box-binding homeobox 1	gwas
TERC	HGNC:11727	ENSG00000270141		telomerase RNA component	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gwas
WNT2	HGNC:12780	ENSG00000105989	P09544	Protein Wnt-2	gwas
WNT4	HGNC:12783	ENSG00000162552	P56705	Protein Wnt-4	gwas
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	gwas
SLC38A2	HGNC:13448	ENSG00000134294	Q96QD8	Sodium-coupled neutral amino acid symporter 2	gwas
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas
JPH1	HGNC:14201	ENSG00000104369	Q9HDC5	Junctophilin-1	gwas
NLGN2	HGNC:14290	ENSG00000169992	Q8NFZ4	Neuroligin-2	gwas
MRTFA	HGNC:14334	ENSG00000196588	Q969V6	Myocardin-related transcription factor A	gwas
SIRT3	HGNC:14931	ENSG00000142082	Q9NTG7	NAD-dependent protein deacetylase sirtuin-3, mitochondrial	gwas
MCM8	HGNC:16147	ENSG00000125885	Q9UJA3	DNA helicase MCM8	gwas
ARHGAP12	HGNC:16348	ENSG00000165322	Q8IWW6	Rho GTPase-activating protein 12	gwas
ZNF346	HGNC:16403	ENSG00000113761	Q9UL40	Zinc finger protein 346	gwas
CD44	HGNC:1681	ENSG00000026508	P16070	CD44 antigen	gwas
SYNE1	HGNC:17089	ENSG00000131018	Q8NF91	Nesprin-1	gwas
CDC42	HGNC:1736	ENSG00000070831	P60953	Cell division control protein 42 homolog	gwas
PDLIM5	HGNC:17468	ENSG00000163110	Q96HC4	PDZ and LIM domain protein 5	gwas
SULT1B1	HGNC:17845	ENSG00000173597	O43704	Sulfotransferase 1B1	gwas
SCGB1C1	HGNC:18394	ENSG00000188076	Q8TD33	Secretoglobin family 1C member 1	gwas
NEK10	HGNC:18592	ENSG00000163491	Q6ZWH5	Serine/threonine-protein kinase Nek10	gwas
EDEM1	HGNC:18967	ENSG00000134109	Q92611	ER degradation-enhancing alpha-mannosidase-like protein 1	gwas
KANK1	HGNC:19309	ENSG00000107104	Q14678	KN motif and ankyrin repeat domain-containing protein 1	gwas
BET1L	HGNC:19348	ENSG00000177951	Q9NYM9	BET1-like protein	gwas
PGBD2	HGNC:19399	ENSG00000185220	Q6P3X8	PiggyBac transposable element-derived protein 2	gwas
CIMAP1A	HGNC:19905	ENSG00000177947	Q96PU9	Ciliary microtubule associated protein 1A	gwas
TRMT6	HGNC:20900	ENSG00000089195	Q9UJA5	tRNA (adenine(58)-N(1))-methyltransferase non-catalytic subunit TRM6	gwas
PITPNM2	HGNC:21044	ENSG00000090975	Q9BZ72	Membrane-associated phosphatidylinositol transfer protein 2	gwas
RAP2C	HGNC:21165	ENSG00000123728	Q9Y3L5	Ras-related protein Rap-2c	gwas
PDHX	HGNC:21350	ENSG00000110435	O00330	Pyruvate dehydrogenase protein X component, mitochondrial	gwas
KCTD8	HGNC:22394	ENSG00000183783	Q6ZWB6	BTB/POZ domain-containing protein KCTD8	gwas
HOOK3	HGNC:23576	ENSG00000168172	Q86VS8	Protein Hook homolog 3	gwas
GREB1	HGNC:24885	ENSG00000196208	Q4ZG55	Protein GREB1	gwas
HEATR3	HGNC:26087	ENSG00000155393	Q7Z4Q2	HEAT repeat-containing protein 3	gwas
CWH43	HGNC:26133	ENSG00000109182	Q9H720	PGAP2-interacting protein	gwas
STN1	HGNC:26200	ENSG00000107960	Q9H668	CST complex subunit STN1	gwas
NIPAL1	HGNC:27194	ENSG00000163293	Q6NVV3	Magnesium transporter NIPA3	gwas
POGLUT3	HGNC:28496	ENSG00000178202	Q7Z4H8	Protein O-glucosyltransferase 3	gwas
C11orf65	HGNC:28519	ENSG00000166323	Q8NCR3	Protein MFI	gwas
DNM3	HGNC:29125	ENSG00000197959	Q9UQ16	Dynamin-3	gwas
DLX3	HGNC:2916	ENSG00000064195	O60479	Homeobox protein DLX-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MED12	Mediator of RNA polymerase II transcription subunit 12	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
HMGA2	High mobility group protein HMGI-C	Functions as a transcriptional regulator.
SALL1	Sal-like protein 1	Transcriptional repressor involved in organogenesis.
SHBG	Sex hormone-binding globulin	Functions as an androgen transport protein, but may also be involved in receptor mediated processes.
SLC4A7	Sodium bicarbonate cotransporter 3	Electroneutral sodium- and bicarbonate-dependent cotransporter with a Na(+):HCO3(-) 1:1 stoichiometry.
BABAM2	BRISC and BRCA1-A complex member 2	Component of the BRCA1-A complex, a complex that specifically recognizes ‘Lys-63’-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks…
SLK	STE20-like serine/threonine-protein kinase	Mediates apoptosis and actin stress fiber dissolution.
ZEB1	Zinc finger E-box-binding homeobox 1	Acts as a transcriptional repressor.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
WNT2	Protein Wnt-2	Ligand for members of the frizzled family of seven transmembrane receptors.
WNT4	Protein Wnt-4	Ligand for members of the frizzled family of seven transmembrane receptors.
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
SLC38A2	Sodium-coupled neutral amino acid symporter 2	Symporter that cotransports neutral amino acids and sodium ions from the extracellular to the intracellular side of the cell membrane.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
JPH1	Junctophilin-1	Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells.
NLGN2	Neuroligin-2	Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members.
MRTFA	Myocardin-related transcription factor A	Transcription coactivator that associates with the serum response factor (SRF) transcription factor to control expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration.
SIRT3	NAD-dependent protein deacetylase sirtuin-3, mitochondrial	NAD-dependent protein deacetylase.
MCM8	DNA helicase MCM8	Component of the MCM8-MCM9 complex, which is involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR).
ARHGAP12	Rho GTPase-activating protein 12	GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
ZNF346	Zinc finger protein 346	Binds with low affinity to dsDNA and ssRNA, and with high affinity to dsRNA, with no detectable sequence specificity.
CD44	CD44 antigen	Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment.
SYNE1	Nesprin-1	Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization.
CDC42	Cell division control protein 42 homolog	Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state.
PDLIM5	PDZ and LIM domain protein 5	May play an important role in the heart development by scaffolding PKC to the Z-disk region.
SULT1B1	Sulfotransferase 1B1	Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of dopamine, small phenols such as 1-naphthol and p-nitrophenol and thyroid hormones, including 3,3’-diiodothyronin…
NEK10	Serine/threonine-protein kinase Nek10	Plays a role in the cellular response to UV irradiation.
EDEM1	ER degradation-enhancing alpha-mannosidase-like protein 1	Extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle.
KANK1	KN motif and ankyrin repeat domain-containing protein 1	Adapter protein that links structural and signaling protein complexes positioned to guide microtubule and actin cytoskeleton dynamics during cell morphogenesis.
BET1L	BET1-like protein	Vesicle SNARE required for targeting and fusion of retrograde transport vesicles with the Golgi complex.
CIMAP1A	Ciliary microtubule associated protein 1A	Outer dense fibers are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail.
TRMT6	tRNA (adenine(58)-N(1))-methyltransferase non-catalytic subunit TRM6	Substrate-binding subunit of tRNA (adenine-N(1)-)-methyltransferase, which catalyzes the formation of N(1)-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA.
PITPNM2	Membrane-associated phosphatidylinositol transfer protein 2	Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes (in vitro).
RAP2C	Ras-related protein Rap-2c	Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form.
PDHX	Pyruvate dehydrogenase protein X component, mitochondrial	Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes.
KCTD8	BTB/POZ domain-containing protein KCTD8	Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response.
HOOK3	Protein Hook homolog 3	Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin.
GREB1	Protein GREB1	May play a role in estrogen-stimulated cell proliferation.
HEATR3	HEAT repeat-containing protein 3	Plays a role in ribosome biogenesis and in nuclear import of the 60S ribosomal protein L5/large ribosomal subunit protein uL18 (RPL5).
CWH43	PGAP2-interacting protein	Involved in lipid remodeling during GPI-anchor maturation.
STN1	CST complex subunit STN1	Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex.
NIPAL1	Magnesium transporter NIPA3	Acts as a Mg(2+) transporter.
POGLUT3	Protein O-glucosyltransferase 3	Protein glucosyltransferase that catalyzes the transfer of glucose from UDP-glucose to a serine residue within the consensus sequence peptide C-X-N-T-X-G-S-F-X-C.
C11orf65	Protein MFI	Acts as an inhibitor of mitochondrial fission.
DNM3	Dynamin-3	Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP.
DLX3	Homeobox protein DLX-3	Transcriptional activator.
TNRC6B	Trinucleotide repeat-containing gene 6B protein	Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs).
SLAIN2	SLAIN motif-containing protein 2	Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization.
DMRT1	Doublesex- and mab-3-related transcription factor 1	Transcription factor that plays a key role in male sex determination and differentiation by controlling testis development and male germ cell proliferation.

Protein-family classification

Druggable: 16 · Difficult: 13 · Unknown: 45 · Druggable fraction: 0.22

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	5.2×	0.763
Complement	1	3.6×	0.763
Kinase	4	1.5×	0.763
Other/Unknown	45	1.1×	0.763
Ion channel	1	1.5×	0.766
Phosphatase	1	1.1×	0.766
Transcription factor	9	1.0×	0.766
Enzyme (other)	6	1.0×	0.766
Scaffold/PPI	4	0.9×	0.766
Antibody/Immunoglobulin	1	0.4×	0.958
GPCR	1	0.3×	0.958

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MED12	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
HMGA2	Other/Unknown	no		HMGA, HMGI/Y_DNA-bd_CS, AT_hook_DNA-bd_motif
SALL1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger
SHBG	Other/Unknown	no		Laminin_G, ConA-like_dom_sf, GAS-SHBG-PROS
SLC4A7	Other/Unknown	no		HCO3_transpt_euk, HCO3_transpt-like_TM_dom, Band3_cytoplasmic_dom
BABAM2	Other/Unknown	no		BRE
SLK	Kinase	yes		Prot_kinase_dom, UVR_dom, Ser/Thr_kinase_AS
ZEB1	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf
TERC	Other/Unknown	no
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
WNT2	Other/Unknown	no		Wnt, Wnt2, Wnt_CS
WNT4	Other/Unknown	no		Wnt, Wnt4, Wnt_CS
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
SLC38A2	Other/Unknown	no		AA_transpt_TM
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
JPH1	Other/Unknown	no		MORN, Junctophilin
NLGN2	Other/Unknown	no		Nlgn, CarbesteraseB, Carboxylesterase_B_CS
MRTFA	Other/Unknown	no		SAP_dom, RPEL_repeat, SAP_dom_sf
SIRT3	Enzyme (other)	yes	2.3.1.24	Sirtuin, Ssirtuin_cat_dom, Sirtuin_cat_small_dom_sf
MCM8	Other/Unknown	no		MCM_dom, AAA+_ATPase, NA-bd_OB-fold
ARHGAP12	Scaffold/PPI	no		RhoGAP_dom, WW_dom, SH3_domain
ZNF346	Transcription factor	no		Matrin/U1-like-C_Znf_C2H2, Znf_C2H2_type, Znf_C2H2_sf
CD44	Other/Unknown	no		Link_dom, CD44_antigen, C-type_lectin-like/link_sf
SYNE1	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
CDC42	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTPase_Rho, Small_GTP-bd
PDLIM5	Transcription factor	no		PDZ, Znf_LIM, PDZ_sf
SULT1B1	Enzyme (other)	yes	2.8.2.1	Sulfotransferase_dom, P-loop_NTPase
SCGB1C1	Other/Unknown	no		Secretoglobin, Secretoglobin_sf, Secretoglobin_1C-like
NEK10	Kinase	yes		Prot_kinase_dom, Tyr_kinase_AS, Kinase-like_dom_sf
EDEM1	Other/Unknown	no		Glyco_hydro_47, 6hp_glycosidase-like_sf, Seven-hairpin_glycosidases
KANK1	Scaffold/PPI	no		Ankyrin_rpt, KN_motif, Ankyrin_rpt-contain_sf
BET1L	Other/Unknown	no		T_SNARE_dom, BET1_SNARE
PGBD2	Other/Unknown	no		PGBD, PiggyBac_TE-derived
CIMAP1A	Other/Unknown	no		SHIPPO-rpt, CIMAP
TRMT6	Enzyme (other)	yes	2.1.1.220	TRM6
PITPNM2	Other/Unknown	no		PI_transfer, DDHD_dom, HAD_sf
RAP2C	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
PDHX	Enzyme (other)	yes	1.2.1.104	Biotin_lipoyl, 2-oxoacid_DH_actylTfrase, 2-oxoA_DH_lipoyl-BS
KCTD8	Other/Unknown	no		BTB/POZ_dom, T1-type_BTB, SKP1/BTB/POZ_sf
HOOK3	Other/Unknown	no		CH_dom, Hook_C, CH_dom_sf
GREB1	Other/Unknown	no		GREB1, GREB1_N, GREB1-like_C
HEATR3	Other/Unknown	no		ARM-like, ARM-type_fold, SYO1-like
CWH43	Other/Unknown	no		Endo/exonu/phosph_ase_sf, GPI-anchor_lipid_remodeler, PGAP2IP_TM_2nd
STN1	Other/Unknown	no		NA-bd_OB_tRNA, NA-bd_OB-fold, Stn1
NIPAL1	Other/Unknown	no		Mg_trans_NIPA, EmrE-like
POGLUT3	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, CAP10, Ig-like_fold
C11orf65	Other/Unknown	no
DNM3	Scaffold/PPI	no	3.6.5.5	Dynamin_stalk, Dynamin_GTPase, PH_domain
DLX3	Transcription factor	no		HTH_motif, HD, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

63 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)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	7
buccal mucosa cell	6
stromal cell of endometrium	5
male germ line stem cell (sensu Vertebrata) in testis	5
monocyte	5
left testis	5
granulocyte	5
sural nerve	4
endothelial cell	4
tendon	4
mononuclear cell	4
ventricular zone	3
oocyte	3
colonic epithelium	3
decidua	3
tibia	3
tibialis anterior	3
cortical plate	3
right hemisphere of cerebellum	3
leukocyte	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MED12	281	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left ovary
HMGA2	149	ubiquitous	marker	sural nerve, embryo, stromal cell of endometrium
SALL1	195	broad	marker	ventricular zone, inferior vagus X ganglion, renal medulla
SHBG	162	tissue_specific	yes	right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis, cervix squamous epithelium
SLC4A7	284	ubiquitous	marker	oocyte, duodenum, calcaneal tendon
BABAM2	286	ubiquitous	marker	right adrenal gland, left adrenal gland cortex, right adrenal gland cortex
SLK	293	ubiquitous	marker	esophagus squamous epithelium, endothelial cell, amniotic fluid
ZEB1	287	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
TERC	113	ubiquitous	yes	bone marrow cell, colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
WNT2	154	broad	marker	stromal cell of endometrium, placenta, lower lobe of lung
WNT4	177	broad	marker	islet of Langerhans, decidua, type B pancreatic cell
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
SLC38A2	296	ubiquitous	marker	tibia, visceral pleura, parietal pleura
CSMD1	179	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, primary visual cortex
JPH1	213	broad	marker	quadriceps femoris, vastus lateralis, tibialis anterior
NLGN2	138	ubiquitous	yes	cortical plate, right hemisphere of cerebellum, superior frontal gyrus
MRTFA	260	ubiquitous	marker	monocyte, leukocyte, mononuclear cell
SIRT3	270	ubiquitous	marker	right frontal lobe, apex of heart, left testis
MCM8	226	ubiquitous	marker	primordial germ cell in gonad, buccal mucosa cell, oocyte
ARHGAP12	294	ubiquitous	marker	buccal mucosa cell, calcaneal tendon, tendon
ZNF346	217	ubiquitous	marker	pancreatic ductal cell, buccal mucosa cell, cortical plate
CD44	294	ubiquitous	marker	parotid gland, stromal cell of endometrium, mammalian vulva
SYNE1	275	ubiquitous	marker	cerebellar hemisphere, right hemisphere of cerebellum, calcaneal tendon
CDC42	301	ubiquitous	marker	cortical plate, monocyte, mononuclear cell
PDLIM5	295	ubiquitous	marker	biceps brachii, skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis
SULT1B1	161	broad	marker	rectum, mucosa of transverse colon, jejunal mucosa
SCGB1C1	99	tissue_specific	yes	monocyte, leukocyte, granulocyte
NEK10	178	broad	marker	olfactory segment of nasal mucosa, right uterine tube, left testis

Protein interactions among cohort

Intra-cohort edges: 31.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
ESR1	12,382
ATM	7,383
CD44	6,810
TERT	5,717
FOXO1	5,714
LNX1	5,295
PDGFRA	5,186
ZEB1	4,171
WT1	3,938

Intra-cohort edges

A	B	Sources
ATM	BABAM2	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
ATM	ZEB1	biogrid_interaction
BABAM2	UIMC1	string_interaction
BET1L	CIMAP1A	string_interaction
BET1L	PGBD2	string_interaction
BET1L	RIC8A	string_interaction
BET1L	SCGB1C1	string_interaction
BET1L	SLK	string_interaction
BET1L	TNRC6B	string_interaction
C11orf65	POGLUT3	string_interaction
CDC42	SLC38A2	intact
CIMAP1A	RIC8A	string_interaction
CIMAP1A	SIRT3	string_interaction
CIMAP1A	SLK	string_interaction
DMRT1	KANK1	string_interaction
DNAH2	ESR1	intact
ESR1	GREB1	biogrid_interaction, string_interaction
ESR1	RAP2C	intact
ESR1	SLAIN2	intact
GABRG1	KCTD8	string_interaction
GREB1	WNT4	string_interaction
HMGA2	TP53	biogrid_interaction
JPH1	NIPAL1	biogrid_interaction, intact
LNX1	SCFD2	string_interaction
LNX1	ZNF346	intact
NEK10	SLC4A7	string_interaction
PDGFRA	POGLUT3	intact
RAP2C	WNT4	string_interaction
SIRT3	TP53	string_interaction
TP53	WT1	intact, string_interaction

Structural data

PDB: 44 · AlphaFold-only: 27 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ESR1	P03372	478
TP53	P04637	313
CDC42	P60953	48
SIRT3	Q9NTG7	44
WT1	P19544	28
TERT	O14746	23
PTCH1	Q13635	16
PDGFRA	P16234	15
NLGN2	Q8NFZ4	14
ATM	Q13315	14
SHBG	P04278	13
FOXO1	Q12778	11
STN1	Q9H668	8
GRM4	Q14833	8
SLK	Q9H2G2	7
MCM8	Q9UJA3	7
FH	P07954	7
CD44	P16070	6
FSHB	P01225	6
KANK1	Q14678	5
PDHX	O00330	5
HOOK3	Q86VS8	5
HMGA1	P17096	5
BABAM2	Q9NXR7	4
UIMC1	Q96RL1	4
MED12	Q93074	3
SYNE1	Q8NF91	3
PDLIM5	Q96HC4	3
TRMT6	Q9UJA5	3
LNX1	Q8TBB1	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
POGLUT3	Q7Z4H8	93.16
SCFD2	Q8WU76	92.33
CWH43	Q9H720	91.45
WNT4	P56705	91.41
RAP2C	Q9Y3L5	91.23
RIC8A	Q9NPQ8	90.37
BET1L	Q9NYM9	89.02
WNT2	P09544	88.89
CYTH4	Q9UIA0	87.17
EDEM1	Q92611	84.73
PGBD2	Q6P3X8	83.55
HEATR3	Q7Z4Q2	83.07
NIPAL1	Q6NVV3	80.98
SLC38A2	Q96QD8	79.11
GABRG1	Q8N1C3	79.06
SCGB1C1	Q8TD33	78.35
SPATA18	Q8TC71	75.51
C11orf65	Q8NCR3	74.69
CIMAP1A	Q96PU9	74.04
GREB1	Q4ZG55	71.10
NEK10	Q6ZWH5	70.23
PITPNM2	Q9BZ72	67.96
ARHGAP12	Q8IWW6	67.68
HMGA2	P52926	65.46
SALL1	Q9NSC2	49.54
TNRC6B	Q9UPQ9	39.58
ITPR1	Q14643

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 389. Enrichment computed across 74 evidence-associated genes (49 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 49 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transcriptional regulation of testis differentiation	3	43.7×	0.009	WNT4, WT1, DMRT1
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	3	41.1×	0.009	HMGA2, TP53, HMGA1
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	4	11.9×	0.044	BABAM2, TP53, UIMC1, ATM
G2/M Checkpoints	4	11.0×	0.046	BABAM2, TP53, MCM8, ATM
Regulation of FOXO transcriptional activity by acetylation	2	46.6×	0.051	SIRT3, FOXO1
G2/M DNA damage checkpoint	4	9.8×	0.051	BABAM2, TP53, UIMC1, ATM
TP53 Regulates Transcription of Caspase Activators and Caspases	2	38.8×	0.064	TP53, ATM
Nephron development	2	35.9×	0.066	WNT4, WT1
Imatinib-resistant PDGFR mutants	1	233.1×	0.073	PDGFRA
Sunitinib-resistant PDGFR mutants	1	233.1×	0.073	PDGFRA
Regorafenib-resistant PDGFR mutants	1	233.1×	0.073	PDGFRA
Sorafenib-resistant PDGFR mutants	1	233.1×	0.073	PDGFRA
PDGFR mutants bind TKIs	1	233.1×	0.073	PDGFRA
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	233.1×	0.073	TP53
Stabilization of p53	2	31.1×	0.073	TP53, ATM
Extension of Telomeres	2	24.5×	0.073	TERT, STN1
Mitochondrial unfolded protein response (UPRmt)	2	24.5×	0.073	SIRT3, ESR1
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	2	22.2×	0.073	TP53, ATM
Regulation of TP53 Activity through Methylation	2	22.2×	0.073	TP53, ATM
Class B/2 (Secretin family receptors)	3	11.7×	0.073	WNT2, WNT4, PTCH1
Nonhomologous End-Joining (NHEJ)	3	10.3×	0.073	BABAM2, UIMC1, ATM
Estrogen-dependent gene expression	4	6.2×	0.073	KANK1, GREB1, TNRC6B, ESR1
Cell Cycle	6	4.4×	0.073	BABAM2, TERT, MCM8, SYNE1, STN1, ATM
DNA Double Strand Break Response	2	19.4×	0.076	BABAM2, ATM
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	2	18.6×	0.079	CD44, ESR1
WNT ligand biogenesis and trafficking	2	17.3×	0.082	WNT2, WNT4
Citric acid cycle (TCA cycle)	2	17.3×	0.082	SIRT3, FH
MAPK6/MAPK4 signaling	3	8.3×	0.082	CDC42, TNRC6B, FOXO1
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	2	15.5×	0.097	SIRT3, FOXO1
Telomere Maintenance	2	15.0×	0.100	TERT, STN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 67 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
adrenal gland development	5	50.3×	4e-05	HMGA2, SALL1, WNT4, WT1, PDGFRA
positive regulation of epithelial cell proliferation involved in lung morphogenesis	3	107.8×	9e-04	HMGA2, WNT2, CDC42
replicative senescence	3	44.4×	0.007	TERT, TP53, ATM
oocyte development	3	41.9×	0.007	WNT4, DMRT1, ATM
branching involved in ureteric bud morphogenesis	4	21.9×	0.007	SALL1, WNT4, WT1, PTCH1
positive regulation of transcription by RNA polymerase II	15	3.3×	0.007	MED12, HMGA2, SALL1, ZEB1, TP53, WNT2, WT1, MRTFA (+7 more)
positive regulation of fibroblast proliferation	4	17.6×	0.008	HMGA2, WNT2, ESR1, PDGFRA
positive regulation of miRNA transcription	4	17.4×	0.008	TERT, TP53, WT1, MRTFA
male gonad development	5	11.6×	0.008	HMGA2, WNT4, WT1, CSMD1, ESR1
mammary gland branching involved in pregnancy	2	125.8×	0.008	CSMD1, ESR1
positive regulation of DNA-templated transcription	10	4.2×	0.010	MED12, HMGA2, SALL1, TP53, WNT4, WT1, ESR1, FOXO1 (+2 more)
heart development	6	7.0×	0.014	MED12, SALL1, TERT, WT1, PDLIM5, ATM
negative regulation of DNA-templated transcription	9	4.2×	0.016	HMGA2, SALL1, ZEB1, TP53, WNT4, WT1, UIMC1, FOXO1 (+1 more)
oncogene-induced cell senescence	2	71.9×	0.018	HMGA2, HMGA1
regulation of cell cycle G2/M phase transition	2	71.9×	0.018	TP53, NEK10
double-strand break repair	4	12.1×	0.018	BABAM2, TP53, UIMC1, ATM
mitotic G2 DNA damage checkpoint signaling	3	19.9×	0.023	BABAM2, UIMC1, ATM
mammary gland epithelium development	2	55.9×	0.026	WNT2, WNT4
response to ionizing radiation	3	18.4×	0.026	BABAM2, UIMC1, ATM
positive regulation of male gonad development	2	50.3×	0.027	WT1, DMRT1
fibroblast proliferation	3	17.6×	0.027	HMGA2, TP53, ESR1
positive regulation of Wnt signaling pathway	3	17.1×	0.027	SALL1, TERT, KANK1
Sertoli cell differentiation	2	45.7×	0.030	WNT4, DMRT1
mesenchymal to epithelial transition	2	45.7×	0.030	WNT4, WT1
cytoplasmic microtubule organization	3	15.4×	0.033	SLK, HOOK3, SLAIN2
protein import into nucleus	4	8.6×	0.039	TERT, TP53, HEATR3, CWH43
stem cell proliferation	3	14.0×	0.040	HMGA2, TP53, PTCH1
gonad development	2	33.5×	0.045	SALL1, WT1
wound healing, spreading of cells	2	33.5×	0.045	MRTFA, CD44
DNA damage response	6	4.8×	0.045	BABAM2, TP53, MCM8, FH, FOXO1, ATM

Therapeutics

Drugs indicated for this disease

1 approved, 14 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ulipristal Acetate	Approved (phase 4)
Ascorbic Acid	Phase 3 (in late-stage trials)
Asoprisnil	Phase 3 (in late-stage trials)
Epigalocatechin Gallate	Phase 3 (in late-stage trials)
Goserelin	Phase 3 (in late-stage trials)
Leuprolide	Phase 3 (in late-stage trials)
Linzagolix	Phase 3 (in late-stage trials)
Mifepristone	Phase 3 (in late-stage trials)
Misoprostol	Phase 3 (in late-stage trials)
Progesterone	Phase 3 (in late-stage trials)
Relugolix	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Telapristone Acetate	Phase 3 (in late-stage trials)
Tranexamic Acid	Phase 3 (in late-stage trials)
Vilaprisan	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetylcysteine, Dienogest, Pirfenidone, Simvastatin.

Drug target analysis

Approved (phase 4): 11 · Phase ≥3: 13 · Phased (≥1): 14 · Undrugged: 60

Druggability breadth: 30 of 74 evidence-associated genes (41%) 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
SHBG	PROGESTERONE
SLK	AFATINIB
TERT	BERBERINE
TP53	NITROFURANTOIN
SIRT3	CAFFEINE
CDC42	KETOROLAC
ESR1	CANDESARTAN CILEXETIL
FOXO1	PANOBINOSTAT
GABRG1	ENZALUTAMIDE
ATM	AMIODARONE HYDROCHLORIDE
PDGFRA	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ESR1	162	4
SLK	81	4
PDGFRA	77	4
ATM	35	4
SHBG	30	4
GABRG1	15	4
TERT	10	4
SIRT3	5	4
CDC42	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PROGESTERONE	4	SHBG
NORETHINDRONE	4	ESR1, SHBG
ESTRADIOL	4	ESR1, SHBG
METHYLTESTOSTERONE	4	SHBG
ESTRONE	4	ESR1, SHBG
DANAZOL	4	ESR1, SHBG
ETONOGESTREL	4	ESR1, SHBG
DESOGESTREL	4	ESR1, SHBG
ESTRIOL	4	ESR1, SHBG
NORGESTREL	4	SHBG
MESTEROLONE	4	SHBG
TESTOSTERONE	4	SHBG
HYDROCORTISONE	4	SHBG
ETHINYL ESTRADIOL	4	ESR1, SHBG
MEDROXYPROGESTERONE ACETATE	4	ESR1, SHBG
PRASTERONE	4	SHBG
AFATINIB	4	SLK
FEDRATINIB	4	PDGFRA, SLK
LENVATINIB	4	ESR1, PDGFRA, SLK
AXITINIB	4	PDGFRA, SLK
SORAFENIB	4	PDGFRA, SLK
NERATINIB	4	SLK
ENTRECTINIB	4	SLK
VANDETANIB	4	PDGFRA, SLK
BOSUTINIB	4	PDGFRA, SLK
FILGOTINIB	4	SLK
GILTERITINIB	4	SLK
PAZOPANIB	4	PDGFRA, SLK
NINTEDANIB	4	PDGFRA, SLK
SUNITINIB	4	PDGFRA, SLK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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

Symbol	Assays	Type breakdown
ESR1	2,435	Binding:2037, Functional:363, ADMET:35
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
TERT	391	Binding:389, Functional:2
SIRT3	286	Binding:277, Functional:6, ADMET:3
SLK	280	Binding:279, Functional:1
GRM4	252	Functional:161, Binding:91
ATM	240	Binding:233, Functional:5, ADMET:2
GABRG1	188	Binding:169, Functional:15, Toxicity:3, ADMET:1
CDC42	76	Binding:76
NEK10	40	Binding:40
SHBG	34	Binding:26, ADMET:7, Functional:1
FOXO1	27	Binding:27
ITPR1	13	Binding:12, Functional:1
CD44	9	Binding:9
MED12	6	Binding:6
HMGA1	6	Binding:6
PTCH1	4	Binding:4
SULT1B1	3	ADMET:3
PTPRR	3	Binding:3
WNT2	2	Binding:2
SLC38A2	2	Binding:2
KCTD8	2	Binding:2
SLC4A7	1	Binding:1
PDLIM5	1	Binding:1
RAP2C	1	Binding:1
PDHX	1	Binding:1
RIC8A	1	Binding:1
FH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SIRT3	2.3.1.24, 2.3.1.286	sphingosine N-acyltransferase, protein acetyllysine N-acetyltransferase
CDC42	3.6.5.2	small monomeric GTPase
SULT1B1	2.8.2.1, 2.8.2.2	aryl sulfotransferase, alcohol sulfotransferase
TRMT6	2.1.1.220	tRNA (adenine58-N1)-methyltransferase
PDHX	1.2.1.104	pyruvate dehydrogenase system
DNM3	3.6.5.5	dynamin GTPase
FH	4.2.1.2	fumarate hydratase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
PTPRR	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
SLK	280
TERT	391
TP53	869
SIRT3	286
ESR1	2,435
GABRG1	188
GRM4	252
ATM	240
PDGFRA	1,172

Pharmacogenomics

Cohort genes with a PharmGKB record: 73; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

28 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)
PROGESTERONE	4	SHBG
ESTRADIOL	4	ESR1, SHBG
METHYLTESTOSTERONE	4	SHBG
ESTRONE	4	ESR1, SHBG
DANAZOL	4	ESR1, SHBG
ETONOGESTREL	4	ESR1, SHBG
ESTRIOL	4	ESR1, SHBG
NORGESTREL	4	SHBG
MESTEROLONE	4	SHBG
TESTOSTERONE	4	SHBG
HYDROCORTISONE	4	SHBG
ETHINYL ESTRADIOL	4	ESR1, SHBG
MEDROXYPROGESTERONE ACETATE	4	ESR1, SHBG
PRASTERONE	4	SHBG
AFATINIB	4	SLK
FEDRATINIB	4	PDGFRA, SLK
LENVATINIB	4	ESR1, PDGFRA, SLK
AXITINIB	4	PDGFRA, SLK
SORAFENIB	4	PDGFRA, SLK
NERATINIB	4	SLK
ENTRECTINIB	4	SLK
VANDETANIB	4	PDGFRA, SLK
BOSUTINIB	4	PDGFRA, SLK
FILGOTINIB	4	SLK
GILTERITINIB	4	SLK
PAZOPANIB	4	PDGFRA, SLK
NINTEDANIB	4	PDGFRA, SLK
SUNITINIB	4	PDGFRA, SLK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	11	SHBG, SLK, TERT, TP53, SIRT3, CDC42, ESR1, FOXO1, GABRG1, ATM (+1 more)
B	Phased (≥1) drug, not yet approved	3	MED12, NEK10, GRM4
C	Druggable family + PDB, no drug	6	CSMD1, SULT1B1, TRMT6, PDHX, FH, PTPRR
D	Druggable family + AlphaFold only, no drug	2	POGLUT3, ITPR1
E	Difficult family or no structure, no drug	52	HMGA2, SALL1, SLC4A7, BABAM2, ZEB1, TERC, WNT2, WNT4, WT1, SLC38A2 (+42 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC4A7	1	NEK10
WT1	0	TP53
GREB1	0	ESR1
HMGA2	0	—
SALL1	0	—
BABAM2	0	—
ZEB1	0	—
TERC	0	—
WNT2	2	—
WNT4	0	—
SLC38A2	2	—
CSMD1	0	—
JPH1	0	—
NLGN2	0	—
MRTFA	0	—
MCM8	0	—
ARHGAP12	0	—
ZNF346	0	—
CD44	9	—
SYNE1	0	—
PDLIM5	1	—
SULT1B1	3	—
SCGB1C1	0	—
EDEM1	0	—
KANK1	0	—
BET1L	0	—
PGBD2	0	—
CIMAP1A	0	—
TRMT6	0	—
PITPNM2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 246.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	143
PHASE3	44
PHASE2	19
PHASE4	18
PHASE1	8
PHASE2/PHASE3	7
EARLY_PHASE1	6
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06143631	PHASE4	RECRUITING	Prescription of Letrozole for Uterine Myoma
NCT00159328	PHASE4	COMPLETED	Efficacy Study of Magnetic Resonance (MR) Guided Focused Ultrasound in the Treatment of Large Fibroids
NCT00180739	PHASE4	WITHDRAWN	Safety Trial of Magnetic Resonance (MR) Guided Focused Ultrasound Surgery (FUS) in Women With Uterine Fibroids Wishing to Pursue Pregnancy in the Future
NCT00628901	PHASE4	COMPLETED	A Prospective Study Comparing Contour SE™ Microspheres to Embosphere® Microspheres for Treating Symptomatic Uterine Fibroids With Uterine Fibroid Embolization (UFE)
NCT00995878	PHASE4	COMPLETED	The FIRSTT: Comparing MRgFUS(MR-guided Focused Ultrasound) Versus UAE (Uterine Artery Embolization)for Uterine Fibroids.
NCT01239641	PHASE4	UNKNOWN	High Intensity Focused Ultrasound Ablation Virus Myomectomy to Treat Uterine Fibroids
NCT01388907	PHASE4	COMPLETED	Efficacity Assessment of PREVADH® in Adhesion Prevention in Gynaecologic Surgery
NCT01555073	PHASE4	TERMINATED	Preemptive Analgesia Following Uterine Artery Embolization
NCT01738724	PHASE4	TERMINATED	Study of the Efficacy of Dienogest in the Treatment of Uterine Leiomyomas When Compared to Desogestrel and Goserelin
NCT02293447	PHASE4	COMPLETED	Intra-arterial Lidocaine for Pain Control Post Uterine Fibroid Embolization
NCT02440750	PHASE4	UNKNOWN	Endometrial Preparation Before Operative Hysteroscopy in Premenopausal Women
NCT02470741	PHASE4	COMPLETED	Pilot of Letrozole for Uterine Myomas
NCT03210324	PHASE4	TERMINATED	A Study on the Mifepristone Tablets in the Treatment of Symptomatic Uterine Fibroids With Safety and Efficacy
NCT03317795	PHASE4	COMPLETED	Treatment of Heavy Menstrual Bleeding in Women With Uterine Fibroids
NCT03500367	PHASE4	UNKNOWN	Efficacy and Safety of Rapamycin (Sirolimus) in the Treatment of Symptomatic Uterine Fibroids and Leiomyomatosis
NCT03886220	PHASE4	COMPLETED	A Study to Evaluate the Safety and Efficacy of Elagolix for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women
NCT04132349	PHASE4	TERMINATED	Ulipristal Acetate in Symptomatic Uterine Fibroid
NCT04832906	PHASE4	COMPLETED	UA Versus UAE in Treatment of Fibroids
NCT03948789	PHASE3	ACTIVE_NOT_RECRUITING	Phase III Study of MR-Guided Focused Ultrasound Surgery for the Treatment of Uterine Fibroids Compared to Myomectomy
NCT05364008	PHASE3	ACTIVE_NOT_RECRUITING	FRIEND: Fibroids and Unexplained Infertility Treatment With Epigallocatechin Gallate; A Natural CompounD in Green Tea
NCT05862272	PHASE3	RECRUITING	A Phase 3B Study to Evaluate Bone Mineral Density With Long-Term Use of Relugolix Combination Tablet in Women With Uterine Fibroids or Endometriosis
NCT06671548	PHASE3	RECRUITING	Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
NCT07378098	PHASE3	RECRUITING	to Evaluate the Efficacy and Safety of KLH-2109 in Patients With Uterine Fibroids and Menorrhagia
NCT00152256	PHASE3	COMPLETED	A Study to Evaluate of the Safety and Effectiveness of Asoprisnil in Treating Women With Uterine Fibroids
NCT00156156	PHASE3	COMPLETED	Study of Asoprisnil in the Treatment of Uterine Fibroids.
NCT00156208	PHASE3	COMPLETED	Safety of Treatment of Uterine Fibroids With Asoprisnil
NCT00295217	PHASE3	COMPLETED	MR Guided Focused Ultrasound Surgery in the Treatment of Uterine Fibroids: Software V4.2 Validation
NCT00365989	PHASE3	COMPLETED	MR Guided Focused Ultrasound Treatment of Uterine Fibroids With Enhanced Sonication
NCT00702702	PHASE3	TERMINATED	Safety and Efficacy of Proellex in Pre-menopausal Anemic Women With Symptomatic Uterine Fibroids
NCT00712595	PHASE2/PHASE3	COMPLETED	Mifepristone for Treatment of Uterine Fibroids
NCT00735553	PHASE3	TERMINATED	Evaluating the Safety and Efficacy of Proellex® (CDB-4124) in Premenopausal Women With Symptomatic Uterine Fibroids
NCT00737282	PHASE3	TERMINATED	Multicenter Study Evaluating the Safety of Proellex® in Premenopausal Women With Uterine Fibroids
NCT00785356	PHASE3	TERMINATED	Safety and Efficacy of Proellex in Pre-Menopausal Anemic Women With Symptomatic Uterine Fibroids
NCT00853567	PHASE3	TERMINATED	Evaluating the Safety and Efficacy of Proellex® in Premenopausal Women With Symptomatic Uterine Fibroids
NCT00874302	PHASE3	WITHDRAWN	Safety and Efficacy of 25 and 50 mg Doses of Proellex® in Treating the Recurrence of Uterine Fibroid Symptoms
NCT00886873	PHASE2/PHASE3	COMPLETED	Mifepristone 10 or 5 mg for 6 Months to Treat Uterine Fibroids
NCT01064960	PHASE3	COMPLETED	Therapeutic MRI-HIFU Ablation of Uterine Fibroids in a 3T MRI Scanner
NCT01069120	PHASE3	TERMINATED	Safety of 25 and 50 mg Proellex® in the Treatment of Women With Symptomatic Uterine Fibroids
NCT01141062	PHASE3	COMPLETED	Therapeutic MRI Guided High Intensity Focused Ultrasound Ablation of Uterine Fibroids
NCT01156857	PHASE3	COMPLETED	PGL4001 Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ELAGOLIX	4	14
RELUGOLIX	4	9
NORETHINDRONE ACETATE	4	8
ULIPRISTAL ACETATE	4	6
MIFEPRISTONE	4	4
NORETHINDRONE	4	4
DIENOGEST	4	3
LEUPROLIDE	4	3
LINZAGOLIX	4	3
ULIPRISTAL	4	3
CLOMIPHENE	4	2
LETROZOLE	4	2
ASCORBIC ACID	4	1
CARBETOCIN	4	1
CARBOPROST TROMETHAMINE	4	1
CELECOXIB	4	1
DESOGESTREL	4	1
GOSERELIN	4	1
IOHEXOL	4	1
IOPAMIDOL	4	1
LIDOCAINE	4	1
PIRFENIDONE	4	1
PREGABALIN	4	1
PYRIDOXINE	4	1
SIROLIMUS	4	1
TRANEXAMIC ACID	4	1
TRIAMCINOLONE	4	1
VASOPRESSIN	4	1
ZALEPLON	4	1
TELAPRISTONE ACETATE	3	15