Pelvic organ prolapse

Summary

Pelvic organ prolapse (MONDO:0000082) is a disease with 75 cohort genes (210 GWAS associations across 33 studies) and 441 clinical trials. Top therapeutic interventions include tolterodine, solifenacin, and tamsulosin.

At a glance

• Cohort genes: 75
• GWAS associations: 210
• Clinical trials: 441

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pelvic organ prolapse
Mondo ID	MONDO:0000082
EFO	EFO:0004710
MeSH	D056887
ICD-11	148580117
SNOMED CT	237113009
UMLS	C0877015
MedGen	209090
Is cancer (heuristic)	no

Data availability: 210 GWAS associations (33 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › pelvic organ prolapse

Related subtypes (29): cortisone reductase deficiency, physiological sexual disorder, gonadal disorder, female reproductive system disorder, male reproductive system disorder, pituitary gland disorder, infertility disorder, hypospadias, reproductive system neoplasm, dysplasia of cervix, female genital tuberculosis, habitual spontaneous abortion, aromatase excess syndrome, hand-foot-genital syndrome, mullerian duct anomalies-limb anomalies syndrome, Currarino triad, double uterus-hemivagina-renal agenesis syndrome, congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency, classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency, congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency, spondylocostal dysostosis-anal and genitourinary malformations syndrome, congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, estrogen resistance syndrome, short stature, microcephaly, and endocrine dysfunction, diethylstilbestrol syndrome, sexually transmitted disease, NR5A1-related sex development disorder

Genetics & variants

GWAS landscape

210 GWAS associations across 33 studies. Top hits map to 23 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs3820282	4e-31	WNT4	T	0.86
rs9306894	5e-26	GDF7	G	1.11
rs28403275	2e-23	TMEM248P1 - LINC02379	C	1.12
rs1247943	5e-22	GLULP5 - LINC02459	G	1.09
rs12325192	1e-21	UNGP1 - HNRNPA1L3	T	0.89
rs10219425	5e-18	WT1-AS	A	1.1
rs11899888	4e-16	EFEMP1	G	1.11
rs7682992	5e-16	TMEM248P1 - LINC02379	T	1.13
rs11031796	2e-15	WT1-AS	A	0.93
rs2267372	1e-14	PLA2G6, MAFF	A	1.08
rs1802575	1e-14	EFEMP1	C	1.12
rs3791675	2e-14	EFEMP1	C	1.09
rs235929	6e-14	GPX1P2 - EIF4A1P1	G	1.07
rs72624976	4e-12	IMPDH1	C	1.25
rs4944936	5e-12	POLD3 - RN7SKP297	T	1.08
rs4779863	9e-12	KLF13	G	1.07
rs4779517	1e-11	KLF13	G	1.07
rs4331788	1e-11	H3P15 - RBM48P1	T	1.07
rs251217	1e-11	SLC12A2	G	1.07
rs42400	2e-11	LINC02114 - LINC01020	C	1.07
rs58170120	1e-10	MGLL	A	1.08
rs10013769	1e-10	H3P15 - RBM48P1	G	1.07
rs9855015	3e-10	RUVBL1	A	1.08
rs2031900	4e-10	DOCK9-AS1, DOCK9	?	6.28
rs1544637	4e-10	UNGP1 - HNRNPA1L3	C	1.06
rs9513499	6e-10	DOCK9	?	6.18
rs1430191	1e-09	PNPT1 - EFEMP1	T	1.09
rs34503674	2e-09	DOCK9	?	6.02
rs142692409	2e-09	CWC22 - SCHLAP1	?
rs12314243	4e-09	DUSP16	T	1.09

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90102470	Pujol-Gualdo N	2022	28,086	546,291	Advancing our understanding of genetic risk factors and potential personalized strategies for pelvic organ prolapse.
GCST010174	Olafsdottir T	2020	15,010	340,734	Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank.
GCST90436496	Zhou W	2018	11,966	396,730	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90436497	Zhou W	2018	7,462	396,730	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90080653	Backman JD	2021	5,753	205,179	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084639	Backman JD	2021	5,753	205,179	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90077800	Backman JD	2021	2,758	328,996	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081786	Backman JD	2021	2,758	328,996	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90077801	Backman JD	2021	2,633	175,261	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081787	Backman JD	2021	2,633	175,261	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	1
Tier 2: splice/UTR	5
Tier 3: regulatory	0
Tier 4: intronic/intergenic	44

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	28
intergenic_variant	16
3_prime_UTR_variant	5
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs3820282	1	22141722	C>A,G,T	0.16	intron_variant	WNT4	4e-31	Tier 4: intronic/intergenic
rs9306894	2	20678345	A>G	0.05	3_prime_UTR_variant	GDF7	5e-26	Tier 2: splice/UTR
rs28403275	4	126003529	G>A,C	0.05	intron_variant	TMEM248P1 - LINC02379	2e-23	Tier 4: intronic/intergenic
rs1247943	12	114235616	G>A,T	0.05	intergenic_variant	GLULP5 - LINC02459	5e-22	Tier 4: intronic/intergenic
rs12325192	16	51454218	C>T	0.18	intron_variant	UNGP1 - HNRNPA1L3	1e-21	Tier 4: intronic/intergenic
rs10219425	11	32463234	A>C	0.05	intron_variant	WT1-AS	5e-18	Tier 4: intronic/intergenic
rs11899888	2	55875609	A>G	0.11	intron_variant	EFEMP1	4e-16	Tier 4: intronic/intergenic
rs7682992	4	126037217	A>C,G,T	0.206	intergenic_variant	TMEM248P1 - LINC02379	5e-16	Tier 4: intronic/intergenic
rs11031796	11	32458261	G>A,C	0.31	intron_variant	WT1-AS	2e-15	Tier 4: intronic/intergenic
rs2267372	22	38202227	A>C,G,T	0.05	intron_variant	PLA2G6, MAFF	1e-14	Tier 4: intronic/intergenic
rs1802575	2	55866069	G>C	0.05	3_prime_UTR_variant	EFEMP1	1e-14	Tier 2: splice/UTR
rs3791675	2	55884174	C>A,G,T	0.05	intron_variant	EFEMP1	2e-14	Tier 4: intronic/intergenic
rs235929	21	27264365	G>A,C,T	0.05	intergenic_variant	GPX1P2 - EIF4A1P1	6e-14	Tier 4: intronic/intergenic
rs72624976	7	128392779	C>G,T	0.049	3_prime_UTR_variant	IMPDH1	4e-12	Tier 2: splice/UTR
rs4944936	11	74681469	T>C	0.05	intergenic_variant	POLD3 - RN7SKP297	5e-12	Tier 4: intronic/intergenic
rs4779863	15	31344472	C>G	0.05	intron_variant	KLF13	9e-12	Tier 4: intronic/intergenic
rs4779517	15	31344221	C>G,T	0.49	intron_variant	KLF13	1e-11	Tier 4: intronic/intergenic
rs4331788	4	126146934	G>A,T	0.05	intergenic_variant	H3P15 - RBM48P1	1e-11	Tier 4: intronic/intergenic
rs251217	5	128176372	A>G	0.05	intron_variant	SLC12A2	1e-11	Tier 4: intronic/intergenic
rs42400	5	4978582	C>A,G	0.05	intron_variant	LINC02114 - LINC01020	2e-11	Tier 4: intronic/intergenic
rs58170120	3	128002490	T>A,C	0.18	intergenic_variant	MGLL	1e-10	Tier 4: intronic/intergenic
rs10013769	4	126155033	A>C,G,T	0.35	intergenic_variant	H3P15 - RBM48P1	1e-10	Tier 4: intronic/intergenic
rs9855015	3	128089972	A>G,T	0.05	intron_variant	RUVBL1	3e-10	Tier 4: intronic/intergenic
rs2031900	13	98827749	A>G,T	0.05	intron_variant	DOCK9-AS1, DOCK9	4e-10	Tier 4: intronic/intergenic
rs1544637	16	51450926	T>C	0.05	intron_variant	UNGP1 - HNRNPA1L3	4e-10	Tier 4: intronic/intergenic
rs9513499	13	98861244	C>A,G,T	0.05	intron_variant	DOCK9	6e-10	Tier 4: intronic/intergenic
rs1430191	2	55806292	C>G,T	0.478	intergenic_variant	PNPT1 - EFEMP1	1e-09	Tier 4: intronic/intergenic
rs34503674	13	98861290	A>C	0.05	intron_variant	DOCK9	2e-09	Tier 4: intronic/intergenic
rs142692409	2	180552833	T>C	0.05	intergenic_variant	CWC22 - SCHLAP1	2e-09	Tier 4: intronic/intergenic
rs12314243	12	12515476	C>A,T	0.12	intron_variant	DUSP16	4e-09	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 55 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BIN1	Orphanet:169186	Autosomal recessive centronuclear myopathy
BIN1	Orphanet:169189	Autosomal dominant centronuclear myopathy
SALL1	Orphanet:857	Townes-Brocks syndrome
SLC12A2	Orphanet:633021	SLC12A2-related autosomal recessive neonatal-developmental delay-intellectual disability-feeding difficulty-sensorineural deafness syndrome
SLC12A2	Orphanet:633024	SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome
SOX5	Orphanet:313884	12p12.1 microdeletion syndrome
SOX5	Orphanet:313892	Developmental and speech delay due to SOX5 deficiency
SOX5	Orphanet:626	Large/giant congenital melanocytic nevus
TBX5	Orphanet:101016	Romano-Ward syndrome
TBX5	Orphanet:392	Holt-Oram syndrome
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
WT1	Orphanet:251510	46,XY partial gonadal dysgenesis
WT1	Orphanet:3097	Meacham syndrome
WT1	Orphanet:347	Frasier syndrome
WT1	Orphanet:654	Nephroblastoma
WT1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
WT1	Orphanet:83469	Desmoplastic small round cell tumor
WT1	Orphanet:893	WAGR syndrome
ZP2	Orphanet:404466	Female infertility due to zona pellucida defect
FOXP2	Orphanet:209908	Isolated childhood apraxia of speech
FOXP2	Orphanet:251061	7q31 microdeletion syndrome
RTL1	Orphanet:254525	Temple syndrome due to paternal 14q32.2 microdeletion
RTL1	Orphanet:254528	Kagami-Ogata syndrome due to maternal 14q32.2 microdeletion
RTL1	Orphanet:254531	Temple syndrome due to paternal 14q32.2 hypomethylation
RTL1	Orphanet:254534	Kagami-Ogata syndrome due to maternal 14q32.2 hypermethylation
RTL1	Orphanet:96184	Temple syndrome due to maternal uniparental disomy of chromosome 14
RTL1	Orphanet:96334	Kagami-Ogata syndrome due to paternal uniparental disomy of chromosome 14
AFG2A	Orphanet:457351	Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome
THAP1	Orphanet:98806	Primary dystonia, DYT6 type
CPE	Orphanet:633028	CPE-related Prader-Willi-like syndrome
FAT4	Orphanet:2136	Hennekam syndrome
FAT4	Orphanet:314679	Cerebrofacioarticular syndrome
CRYM	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
DCT	Orphanet:597733	Oculocutaneous albinism type 8
ABCA1	Orphanet:31150	Tangier disease
ABCA1	Orphanet:425	Apolipoprotein A-I deficiency
DPP6	Orphanet:228140	Idiopathic ventricular fibrillation
DPP6	Orphanet:2514	Autosomal dominant primary microcephaly
EFEMP1	Orphanet:75376	Familial drusen
EFEMP1	Orphanet:98977	Juvenile glaucoma
GPC6	Orphanet:93329	Autosomal recessive omodysplasia
GYPC	Orphanet:288	Hereditary elliptocytosis
ABCC1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
IMPDH1	Orphanet:65	Leber congenital amaurosis
IMPDH1	Orphanet:791	Retinitis pigmentosa
LAMA5	Orphanet:521450	LAMA5-related multisystemic syndrome

Cohort genes → proteins

75 cohort genes, 62 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF7	HGNC:10070	ENSG00000114125	Q9UBF6	RING-box protein 2	gwas
BIN1	HGNC:1052	ENSG00000136717	O00499	Myc box-dependent-interacting protein 1	gwas
SALL1	HGNC:10524	ENSG00000103449	Q9NSC2	Sal-like protein 1	gwas
SGK1	HGNC:10810	ENSG00000118515	O00141	Serine/threonine-protein kinase Sgk1	gwas
SLC12A2	HGNC:10911	ENSG00000064651	P55011	Solute carrier family 12 member 2	gwas
SOX5	HGNC:11201	ENSG00000134532	P35711	Transcription factor SOX-5	gwas
SPRY1	HGNC:11269	ENSG00000164056	O43609	Protein sprouty homolog 1	gwas
STAU2	HGNC:11371	ENSG00000040341	Q9NUL3	Double-stranded RNA-binding protein Staufen homolog 2	gwas
TBX5	HGNC:11604	ENSG00000089225	Q99593	T-box transcription factor TBX5	gwas
WNT4	HGNC:12783	ENSG00000162552	P56705	Protein Wnt-4	gwas
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	gwas
ZP2	HGNC:13188	ENSG00000103310	Q05996	Zona pellucida sperm-binding protein 2	gwas
FOXP2	HGNC:13875	ENSG00000128573	O15409	Forkhead box protein P2	gwas
RTL1	HGNC:14665	ENSG00000254656	A6NKG5	Retrotransposon-like protein 1	gwas
CHRNA6	HGNC:15963	ENSG00000147434	Q15825	Neuronal acetylcholine receptor subunit alpha-6	gwas
MAML2	HGNC:16259	ENSG00000184384	Q8IZL2	Mastermind-like protein 2	gwas
CDH9	HGNC:1768	ENSG00000113100	Q9ULB4	Cadherin-9	gwas
AFG2A	HGNC:18119	ENSG00000145375	Q8NB90	ATPase family gene 2 protein homolog A	gwas
SHC3	HGNC:18181	ENSG00000148082	Q92529	SHC-transforming protein 3	gwas
TRIM51	HGNC:19023	ENSG00000124900	Q9BSJ1	Tripartite motif-containing protein 51	gwas
PGBD5	HGNC:19405	ENSG00000177614	Q8N414	PiggyBac transposable element-derived protein 5	gwas
CHRNB3	HGNC:1963	ENSG00000147432	Q05901	Neuronal acetylcholine receptor subunit beta-3	gwas
FNDC3A	HGNC:20296	ENSG00000102531	Q9Y2H6	Fibronectin type-III domain-containing protein 3A	gwas
THAP1	HGNC:20856	ENSG00000131931	Q9NVV9	THAP domain-containing protein 1	gwas
TXNDC5	HGNC:21073	ENSG00000239264	Q8NBS9	Thioredoxin domain-containing protein 5	gwas
CALHM4	HGNC:21094	ENSG00000164451	Q5JW98	Calcium homeostasis modulator protein 4	gwas
CPE	HGNC:2303	ENSG00000109472	P16870	Carboxypeptidase E	gwas
FAT4	HGNC:23109	ENSG00000196159	Q6V0I7	Protocadherin Fat 4	gwas
CRAT	HGNC:2342	ENSG00000095321	P43155	Carnitine O-acetyltransferase	gwas
RPL31P4	HGNC:23546	ENSG00000213598		ribosomal protein L31 pseudogene 4	gwas
CRYM	HGNC:2418	ENSG00000103316	Q14894	Ketimine reductase mu-crystallin	gwas
ASCL4	HGNC:24311	ENSG00000187855	Q6XD76	Achaete-scute homolog 4	gwas
SPATS2L	HGNC:24574	ENSG00000196141	Q9NUQ6	SPATS2-like protein	gwas
LINC01181	HGNC:25533	ENSG00000250929		long intergenic non-protein coding RNA 1181	gwas
CEP20	HGNC:26435	ENSG00000133393	Q96NB1	Centrosomal protein 20	gwas
KCTD18	HGNC:26446	ENSG00000155729	Q6PI47	BTB/POZ domain-containing protein KCTD18	gwas
KLHDC7A	HGNC:26791	ENSG00000179023	Q5VTJ3	Kelch domain-containing protein 7A	gwas
ANKS4B	HGNC:26795	ENSG00000175311	Q8N8V4	Ankyrin repeat and SAM domain-containing protein 4B	gwas
DCT	HGNC:2709	ENSG00000080166	P40126	L-dopachrome tautomerase	gwas
BAALC-AS2	HGNC:28595	ENSG00000236939	P0C853	Putative uncharacterized protein BAALC-AS2	gwas
DISC1	HGNC:2888	ENSG00000162946	Q9NRI5	Disrupted in schizophrenia 1 protein	gwas
ABCA1	HGNC:29	ENSG00000165029	O95477	Phospholipid-transporting ATPase ABCA1	gwas
FHAD1	HGNC:29408	ENSG00000142621	B1AJZ9	Forkhead-associated domain-containing protein 1	gwas
DOLPP1	HGNC:29565	ENSG00000167130	Q86YN1	Dolichyldiphosphatase 1	gwas
DPP6	HGNC:3010	ENSG00000130226	P42658	A-type potassium channel modulatory protein DPP6	gwas
PSME2P2	HGNC:30160	ENSG00000225131		proteasome activator subunit 2 pseudogene 2	gwas
RPSAP10	HGNC:31460	ENSG00000224439		ribosomal protein SA pseudogene 10	gwas
MIR216A	HGNC:31593	ENSG00000207798		microRNA 216a	gwas
MIR217	HGNC:31594	ENSG00000207548		microRNA 217	gwas
MIR370	HGNC:31784	ENSG00000199005		microRNA 370	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF7	RING-box protein 2	Catalytic component of multiple cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes), which mediate the ubiquitination and subsequent proteasomal degradation of target proteins.
BIN1	Myc box-dependent-interacting protein 1	Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling.
SALL1	Sal-like protein 1	Transcriptional repressor involved in organogenesis.
SGK1	Serine/threonine-protein kinase Sgk1	Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration a…
SLC12A2	Solute carrier family 12 member 2	Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane.
SOX5	Transcription factor SOX-5	Transcription factor involved in chondrocytes differentiation and cartilage formation.
SPRY1	Protein sprouty homolog 1	Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2.
STAU2	Double-stranded RNA-binding protein Staufen homolog 2	RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite.
TBX5	T-box transcription factor TBX5	DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.
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.
ZP2	Zona pellucida sperm-binding protein 2	Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy.
FOXP2	Forkhead box protein P2	Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium.
RTL1	Retrotransposon-like protein 1	Plays an essential role in capillaries endothelial cells for the maintenance of feto-maternal interface and for development of the placenta.
CHRNA6	Neuronal acetylcholine receptor subunit alpha-6	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…
MAML2	Mastermind-like protein 2	Acts as a transcriptional coactivator for NOTCH proteins.
CDH9	Cadherin-9	Cadherins are calcium-dependent cell adhesion proteins.
AFG2A	ATPase family gene 2 protein homolog A	ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability.
SHC3	SHC-transforming protein 3	Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons.
PGBD5	PiggyBac transposable element-derived protein 5	Transposase that mediates sequence-specific genomic rearrangements.
CHRNB3	Neuronal acetylcholine receptor subunit beta-3	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…
FNDC3A	Fibronectin type-III domain-containing protein 3A	Mediates spermatid-Sertoli adhesion during spermatogenesis.
THAP1	THAP domain-containing protein 1	DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression.
TXNDC5	Thioredoxin domain-containing protein 5	Protein disulfide isomerase of the endoplasmic reticulum lumen involved in the formation of disulfide bonds in proteins.
CALHM4	Calcium homeostasis modulator protein 4	May assemble to form gap junction channel-like structures involved in intercellular communication.
CPE	Carboxypeptidase E	Sorting receptor that directs prohormones to the regulated secretory pathway.
FAT4	Protocadherin Fat 4	Cadherins are calcium-dependent cell adhesion proteins.
CRAT	Carnitine O-acetyltransferase	Catalyzes the reversible transfer of acyl groups from carnitine to coenzyme A (CoA) and regulates the acyl-CoA/CoA ratio.
CRYM	Ketimine reductase mu-crystallin	Catalyzes the NAD(P)H-dependent reduction of imine double bonds of a number of cyclic ketimine substrates, including sulfur-containing cyclic ketimines.
ASCL4	Achaete-scute homolog 4	Could be a transcriptional regulator involved in skin development.
CEP20	Centrosomal protein 20	Involved in the biogenesis of cilia.
ANKS4B	Ankyrin repeat and SAM domain-containing protein 4B	As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length.
DCT	L-dopachrome tautomerase	Plays a role in melanin biosynthesis.
DISC1	Disrupted in schizophrenia 1 protein	Involved in the regulation of multiple aspects of embryonic and adult neurogenesis.
ABCA1	Phospholipid-transporting ATPase ABCA1	Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP.
FHAD1	Forkhead-associated domain-containing protein 1	Regulator of sperm motility and spermatocyte meiosis.
DOLPP1	Dolichyldiphosphatase 1	Required for efficient N-glycosylation.
DPP6	A-type potassium channel modulatory protein DPP6	Promotes cell surface expression of the potassium channel KCND2.
EFEMP1	EGF-containing fibulin-like extracellular matrix protein 1	Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways.
FARP1	FERM, ARHGEF and pleckstrin domain-containing protein 1	Functions as a guanine nucleotide exchange factor for RAC1.
IQCJ-SCHIP1	IQCJ-SCHIP1 readthrough transcript protein	May play a role in action potential conduction in myelinated cells through the organization of molecular complexes at nodes of Ranvier and axon initial segments.
GDF7	Growth/differentiation factor 7	May play an active role in the motor area of the primate neocortex.
GFRA2	GDNF family receptor alpha-2	Receptor for neurturin (NRTN), a growth factor that supports the survival of sympathetic neurons.
NDUFC2-KCTD14	NADH dehydrogenase [ubiquinone] 1 subunit C2, isoform 2	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.
GPC6	Glypican-6	Cell surface proteoglycan that bears heparan sulfate.
GUCA1C	Guanylyl cyclase-activating protein 3	Stimulates guanylyl cyclase 1 (GC1) and GC2 when free calcium ions concentration is low and inhibits guanylyl cyclases when free calcium ions concentration is elevated.
GYPC	Glycophorin-C	This protein is a minor sialoglycoprotein in human erythrocyte membranes.
ABCC1	Multidrug resistance-associated protein 1	Mediates export of organic anions and drugs from the cytoplasm.
HOXD3	Homeobox protein Hox-D3	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
HOXD4	Homeobox protein Hox-D4	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Protein-family classification

Druggable: 13 · Difficult: 17 · Unknown: 45 · Druggable fraction: 0.17

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
Transporter	2	2.1×	0.757
Protease	3	1.5×	0.757
Transcription factor	12	1.3×	0.757
Other/Unknown	45	1.1×	0.757
Scaffold/PPI	5	1.1×	0.790
Phosphatase	1	1.1×	0.891
Enzyme (other)	5	0.8×	0.937
Antibody/Immunoglobulin	1	0.4×	0.937
Kinase	1	0.4×	0.937

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF7	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_H2
BIN1	Scaffold/PPI	no		SH3_domain, Amphiphysin, Amphiphysin_2
SALL1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger
SGK1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
SLC12A2	Other/Unknown	no		SLC12A1/SLC12A2, NKCC1, AA-permease/SLC12A_dom
SOX5	Transcription factor	no		HMG_box_dom, HMG_box_dom_sf, SOX/SOX-like_TF
SPRY1	Other/Unknown	no		Sprouty, Sprouty_domain
STAU2	Other/Unknown	no		dsRBD_dom, Staufen_C, STAU2_DSRM_2
TBX5	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
WNT4	Other/Unknown	no		Wnt, Wnt4, Wnt_CS
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
ZP2	Other/Unknown	no		ZP_dom, ZP_dom_CS, ZP-C_dom
FOXP2	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
RTL1	Protease	yes		Peptidase_aspartic_dom_sf, RTL1/1-8/LDOC_capsid-like, RTL1-rel
CHRNA6	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
MAML2	Other/Unknown	no		Mastermind-like_N, MAML1-3, MAML_N_sf
CDH9	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
AFG2A	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
SHC3	Scaffold/PPI	no		SH2, PID_Shc-like, PTB/PI_dom
TRIM51	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
PGBD5	Other/Unknown	no		PGBD, PGBD5
CHRNB3	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
FNDC3A	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
THAP1	Transcription factor	no		THAP_Znf, THAP1/10, THAP_Znf_sf
TXNDC5	Enzyme (other)	yes	5.3.4.1	PDI_thioredoxin-like_dom, Thioredoxin_domain, Thioredoxin_CS
CALHM4	Other/Unknown	no		CALHM
CPE	Protease	yes	3.4.17.10	Peptidase_M14, CarboxyPept-like_regulatory, M14_CPE_CPD
FAT4	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
CRAT	Enzyme (other)	yes	2.3.1.7	Carn_acyl_trans, CAT-like_dom_sf, Cho/carn_acyl_trans_1_2
RPL31P4	Other/Unknown	no
CRYM	Enzyme (other)	yes	1.5.1.21	ODC_Mu_crystall, ODC_N, NAD(P)-bd_dom_sf
ASCL4	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
SPATS2L	Other/Unknown	no		UBA-like_sf, SPATS2-like
LINC01181	Other/Unknown	no
CEP20	Other/Unknown	no		LisH, FOP_dimerisation-dom_N
KCTD18	Other/Unknown	no		T1-type_BTB, SKP1/BTB/POZ_sf, KCTD18_C
KLHDC7A	Other/Unknown	no		Kelch_1, Kelch-typ_b-propeller, Kelch/BTB_domain_protein
ANKS4B	Scaffold/PPI	no		SAM, Ankyrin_rpt, SAM/pointed_sf
DCT	Other/Unknown	no		Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
BAALC-AS2	Other/Unknown	no
DISC1	Other/Unknown	no		DISC1
ABCA1	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
FHAD1	Other/Unknown	no		FHA_dom, SMAD_FHA_dom_sf, CC-FHA_domain
DOLPP1	Phosphatase	yes		PAP2/HPO, PAP2/HPO_sf, Dolichyldiphosphatase_PAP2
DPP6	Protease	yes		Peptidase_S9_cat, Peptidase_S9B_N, AB_hydrolase_fold
PSME2P2	Other/Unknown	no
RPSAP10	Other/Unknown	no
MIR216A	Other/Unknown	no
MIR217	Other/Unknown	no
MIR370	Other/Unknown	no

Expression context

Cohort genes with no expression data: 1.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	4
broad (>20)	69
unknown	1

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	14
primordial germ cell in gonad	10
adrenal tissue	7
cortical plate	5
right uterine tube	5
calcaneal tendon	4
prefrontal cortex	4
buccal mucosa cell	4
endothelial cell	4
secondary oocyte	4
ventricular zone	3
mucosa of paranasal sinus	3
placenta	3
pancreatic ductal cell	3
middle temporal gyrus	3
corpus epididymis	3
duodenum	3
stromal cell of endometrium	3
mucosa of transverse colon	3
lower esophagus muscularis layer	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF7	292	ubiquitous	marker	left adrenal gland, left adrenal gland cortex, right adrenal gland
BIN1	287	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
SALL1	195	broad	marker	ventricular zone, inferior vagus X ganglion, renal medulla
SGK1	299	ubiquitous	marker	palpebral conjunctiva, eye, right lung
SLC12A2	277	ubiquitous	marker	palpebral conjunctiva, parotid gland, inferior vagus X ganglion
SOX5	221	ubiquitous	marker	cortical plate, calcaneal tendon, synovial joint
SPRY1	272	ubiquitous	marker	pericardium, omental fat pad, peritoneum
STAU2	279	ubiquitous	marker	cortical plate, ganglionic eminence, prefrontal cortex
TBX5	129	broad	marker	tendon of biceps brachii, cardiac muscle of right atrium, buccal mucosa cell
WNT4	177	broad	marker	islet of Langerhans, decidua, type B pancreatic cell
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
ZP2	63	tissue_specific	yes	cerebellar cortex, cerebellum, cerebellar hemisphere
FOXP2	237	broad	marker	buccal mucosa cell, tibialis anterior, mucosa of paranasal sinus
RTL1	44	tissue_specific	marker	adrenal tissue, male germ line stem cell (sensu Vertebrata) in testis, placenta
CHRNA6	80	tissue_specific	marker	pancreatic ductal cell, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell
MAML2	238	ubiquitous	marker	mucosa of paranasal sinus, cartilage tissue, mammary duct
CDH9	121	tissue_specific	marker	endothelial cell, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
AFG2A	211	ubiquitous	marker	tendon of biceps brachii, calcaneal tendon, tendon
SHC3	201	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, endothelial cell
TRIM51	3		marker	male germ line stem cell (sensu Vertebrata) in testis, oocyte, endothelial cell
PGBD5	215	broad	marker	frontal pole, entorhinal cortex, middle temporal gyrus
CHRNB3	71	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell, ileal mucosa
FNDC3A	291	ubiquitous	marker	corpus epididymis, caput epididymis, adrenal tissue
THAP1	260	ubiquitous	yes	secondary oocyte, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
TXNDC5	135	ubiquitous	marker	duodenum, rectum, stromal cell of endometrium
CALHM4	53	tissue_specific	yes	placenta, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
CPE	284	ubiquitous	marker	type B pancreatic cell, caudate nucleus, paraflocculus
FAT4	231	ubiquitous	marker	calcaneal tendon, cortical plate, blood vessel layer
CRAT	289	ubiquitous	marker	sperm, male germ cell, left testis
RPL31P4	124		marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, vermiform appendix

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WT1	3,938
MYH11	3,818
DISC1	3,573
BIN1	3,571
ABCA1	3,551
SGK1	3,422
AFG2A	3,394
PGBD5	3,234
IMPDH1	3,227
ABCC1	3,018

Intra-cohort edges

A	B	Sources
CHRNA6	CHRNB3	string_interaction
EFEMP1	LOXL1	string_interaction
EFEMP1	TXNDC5	biogrid_interaction
IMPDH1	TXNDC5	biogrid_interaction
KCTD18	SPATS2L	string_interaction
SALL1	TBX5	string_interaction

Structural data

PDB: 32 · AlphaFold-only: 30 · No structure: 13

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WT1	P19544	28
IMPDH1	P20839	18
SLC12A2	P55011	14
DPP6	P42658	8
RNF7	Q9UBF6	7
BIN1	O00499	7
TXNDC5	Q8NBS9	7
CALHM4	Q5JW98	7
ABCA1	O95477	7
FNDC3A	Q9Y2H6	6
LYPLA1	O75608	6
GFRA2	O00451	5
ABCC1	P33527	5
SGK1	O00141	4
TBX5	Q99593	4
THAP1	Q9NVV9	3
CRAT	P43155	3
ZP2	Q05996	2
FOXP2	O15409	2
CHRNA6	Q15825	2
AFG2A	Q8NB90	2
FAT4	Q6V0I7	2
LAMA5	O15230	2
CHRNB3	Q05901	1
CRYM	Q14894	1
DCT	P40126	1
DISC1	Q9NRI5	1
FARP1	Q9Y4F1	1
GUCA1C	O95843	1
GYPC	P04921	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT4	P56705	91.41
CPE	P16870	90.83
DOLPP1	Q86YN1	89.92
TRIM51	Q9BSJ1	86.80
NDUFC2-KCTD14	E9PQ53	84.85
GPC6	Q9Y625	82.67
PGBD5	Q8N414	81.78
EFEMP1	Q12805	77.67
CDH9	Q9ULB4	77.60
CEP20	Q96NB1	73.95
GDF7	Q7Z4P5	72.03
FHAD1	B1AJZ9	71.77
ASCL4	Q6XD76	71.48
ANKS4B	Q8N8V4	70.57
STAU2	Q9NUL3	70.34
MORC1	Q86VD1	69.88
HOXD4	P09016	66.73
SPATS2L	Q9NUQ6	63.72
SPRY1	O43609	61.99
KLHDC7A	Q5VTJ3	61.91
SHC3	Q92529	61.89
KCTD18	Q6PI47	60.83
LOXL1	Q08397	59.91
SOX5	P35711	58.95
RTL1	A6NKG5	58.74
IQCJ-SCHIP1	B3KU38	58.27
HOXD3	P31249	58.01
SALL1	Q9NSC2	49.54
MAML2	Q8IZL2	46.21
BAALC-AS2	P0C853	38.58

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 218. Enrichment computed across 76 evidence-associated genes (38 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 38 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Highly calcium permeable nicotinic acetylcholine receptors	2	66.8×	0.035	CHRNA6, CHRNB3
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	2	54.6×	0.035	CHRNA6, CHRNB3
Presynaptic nicotinic acetylcholine receptors	2	50.1×	0.035	CHRNA6, CHRNB3
Nephron development	2	46.2×	0.035	WNT4, WT1
Acetylcholine binding and downstream events	2	42.9×	0.035	CHRNA6, CHRNB3
Postsynaptic nicotinic acetylcholine receptors	2	42.9×	0.035	CHRNA6, CHRNB3
Transcriptional regulation of testis differentiation	2	37.6×	0.039	WNT4, WT1
Defective ABCA1 causes TGD	1	150.3×	0.145	ABCA1
Nucleotide biosynthesis	1	150.3×	0.145	IMPDH1
Signaling by Receptor Tyrosine Kinases	4	5.4×	0.145	SGK1, SPRY1, SHC3, LAMA5
RET signaling	2	13.7×	0.185	SHC3, GFRA2
Metabolism of nitric oxide: NOS3 activation and regulation	1	60.1×	0.198	LYPLA1
Melanin biosynthesis	1	60.1×	0.198	DCT
Cation-coupled Chloride cotransporters	1	42.9×	0.198	SLC12A2
Synthesis of dolichyl-phosphate	1	42.9×	0.198	DOLPP1
Metabolism of porphyrins	1	37.6×	0.198	ABCC1
HDL assembly	1	37.6×	0.198	ABCA1
Transport of RCbl within the body	1	37.6×	0.198	ABCC1
NFE2L2 regulating MDR associated enzymes	1	37.6×	0.198	ABCC1
Beta-oxidation of pristanoyl-CoA	1	30.1×	0.198	CRAT
Lysine catabolism	1	30.1×	0.198	CRYM
Interaction With Cumulus Cells And The Zona Pellucida	1	27.3×	0.198	ZP2
Purine ribonucleoside monophosphate biosynthesis	1	27.3×	0.198	IMPDH1
NOTCH2 intracellular domain regulates transcription	1	25.0×	0.198	MAML2
Positive Regulation of CDH1 Gene Transcription	1	25.0×	0.198	FOXP2
eNOS activation	1	23.1×	0.198	LYPLA1
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation	1	23.1×	0.198	SALL1
Heme degradation	1	21.5×	0.198	ABCC1
Defective EXT2 causes exostoses 2	1	21.5×	0.198	GPC6
Defective EXT1 causes exostoses 1, TRPS2 and CHDS	1	21.5×	0.198	GPC6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 57 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
branching involved in ureteric bud morphogenesis	4	25.7×	0.009	SALL1, WNT4, WT1, LAMA5
adrenal gland development	3	35.5×	0.022	SALL1, WNT4, WT1
negative regulation of Golgi to plasma membrane protein transport	2	98.5×	0.031	ANXA13, LYPLA1
ureteric bud development	3	24.0×	0.036	SALL1, SPRY1, WT1
export across plasma membrane	2	59.1×	0.048	ABCA1, ABCC1
mesenchymal to epithelial transition	2	53.8×	0.048	WNT4, WT1
camera-type eye development	3	18.9×	0.048	WT1, FOXP2, EFEMP1
roof plate formation	1	295.6×	0.051	GDF7
caudate nucleus development	1	295.6×	0.051	FOXP2
putamen development	1	295.6×	0.051	FOXP2
female sex determination	1	295.6×	0.051	WNT4
inductive cell-cell signaling	1	295.6×	0.051	SALL1
positive regulation of cell volume	1	295.6×	0.051	SLC12A2
antigen processing and presentation of lipid antigen via MHC class Ib	1	295.6×	0.051	ABCC1
negative regulation of cytoskeleton organization	1	295.6×	0.051	IQCJ-SCHIP1
cell migration involved in coronary vasculogenesis	1	295.6×	0.051	TBX5
negative regulation of testicular blood vessel morphogenesis	1	295.6×	0.051	WNT4
cyclic nucleotide transport	1	295.6×	0.051	ABCC1
metanephric nephron morphogenesis	1	295.6×	0.051	WNT4
negative regulation of metanephric glomerular mesangial cell proliferation	1	295.6×	0.051	WT1
non-replicative DNA transposition	1	295.6×	0.051	PGBD5
sphingolipid translocation	1	295.6×	0.051	ABCC1
intracellular nitrogen homeostasis	1	295.6×	0.051	ABCC1
positive regulation of cardiac conduction	1	295.6×	0.051	TBX5
negative regulation of ventricular cardiac muscle cell action potential	1	295.6×	0.051	BIN1
negative regulation of male gonad development	1	295.6×	0.051	WNT4
positive regulation of cortisol biosynthetic process	1	295.6×	0.051	WNT4
negative regulation of androgen biosynthetic process	1	295.6×	0.051	WNT4
embryonic epithelial tube formation	1	147.8×	0.051	WNT4
regulation of animal organ formation	1	147.8×	0.051	WT1

Therapeutics

Drugs indicated for this disease

0 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alfacalcidol	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Gabapentin	Phase 3 (in late-stage trials)
Tolterodine	Phase 3 (in late-stage trials)
Tranexamic Acid	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 6 · Undrugged: 69

Druggability breadth: 19 of 76 evidence-associated genes (25%) 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
SLC12A2	BUMETANIDE
CHRNA6	NICOTINE
CHRNB3	NICOTINE
ABCC1	RIMONABANT
IMPDH1	MYCOPHENOLIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC1	23	4
IMPDH1	2	4
SGK1	1	2
SLC12A2	1	4
CHRNA6	1	4
CHRNB3	1	4
RNF7	0	0
BIN1	0	0
SALL1	0	0
SOX5	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BUMETANIDE	4	SLC12A2
NICOTINE	4	CHRNA6, CHRNB3
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
MYCOPHENOLIC ACID	4	IMPDH1
VALSPODAR	3	ABCC1
TARIQUIDAR	3	ABCC1
QUERCETIN	3	ABCC1
UPROSERTIB	2	SGK1
DEXVERAPAMIL	2	ABCC1
VEDROPREVIR	2	ABCC1
VERLUKAST	2	ABCC1
BIRICODAR	2	ABCC1
CLESACOSTAT	2	ABCC1
BMS-754807	2	ABCC1
MERIMEPODIB	2	IMPDH1
KAEMPFEROL	1	ABCC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
SGK1	538	Binding:535, ADMET:2, Functional:1
ABCC1	459	Binding:270, Functional:166, ADMET:23
IMPDH1	46	Binding:40, Functional:6
CHRNA6	34	Binding:33, ADMET:1
CHRNB3	25	Binding:20, Functional:4, ADMET:1
LYPLA1	15	Binding:15
SLC12A2	13	Binding:9, Functional:4
ANXA13	6	Binding:6
AFG2A	2	Binding:2
TXNDC5	2	Binding:2
CRAT	2	Binding:2
ABCA1	2	Binding:2
GFRA2	2	Binding:2
TBX5	1	Binding:1
SPATS2L	1	Binding:1
LOXL1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SGK1	2.7.11.1	non-specific serine/threonine protein kinase
TXNDC5	5.3.4.1	protein disulfide-isomerase
CPE	3.4.17.10	carboxypeptidase E
CRAT	2.3.1.7	carnitine O-acetyltransferase
CRYM	1.5.1.21, 1.5.1.25	1-piperideine-2-carboxylate/1-pyrroline-2-carboxylate reductase (NADPH), thiomorpholine-carboxylate dehydrogenase
ABCC1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
IMPDH1	1.1.1.205	IMP dehydrogenase
LYPLA1	3.1.2.22	palmitoyl[protein] hydrolase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SGK1	538
ABCC1	459

Pharmacogenomics

Cohort genes with a PharmGKB record: 65; 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)
BUMETANIDE	4	SLC12A2
NICOTINE	4	CHRNA6, CHRNB3
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
MYCOPHENOLIC ACID	4	IMPDH1
VALSPODAR	3	ABCC1
TARIQUIDAR	3	ABCC1
QUERCETIN	3	ABCC1
UPROSERTIB	2	SGK1
DEXVERAPAMIL	2	ABCC1
VEDROPREVIR	2	ABCC1
VERLUKAST	2	ABCC1
BIRICODAR	2	ABCC1
CLESACOSTAT	2	ABCC1
BMS-754807	2	ABCC1
MERIMEPODIB	2	IMPDH1
KAEMPFEROL	1	ABCC1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	SLC12A2, CHRNA6, CHRNB3, ABCC1, IMPDH1
B	Phased (≥1) drug, not yet approved	1	SGK1
C	Druggable family + PDB, no drug	7	FNDC3A, TXNDC5, CRAT, CRYM, ABCA1, DPP6, LYPLA1
D	Druggable family + AlphaFold only, no drug	3	RTL1, CPE, DOLPP1
E	Difficult family or no structure, no drug	59	RNF7, BIN1, SALL1, SOX5, SPRY1, STAU2, TBX5, WNT4, WT1, ZP2 (+49 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RNF7	0	—
BIN1	0	—
SALL1	0	—
SOX5	0	—
SPRY1	0	—
STAU2	0	—
TBX5	1	—
WNT4	0	—
WT1	0	—
ZP2	0	—
FOXP2	0	—
RTL1	0	—
MAML2	0	—
CDH9	0	—
AFG2A	2	—
SHC3	0	—
TRIM51	0	—
PGBD5	0	—
FNDC3A	0	—
THAP1	0	—
TXNDC5	2	—
CALHM4	0	—
CPE	0	—
FAT4	0	—
CRAT	2	—
RPL31P4	0	—
CRYM	0	—
ASCL4	0	—
SPATS2L	1	—
LINC01181	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 441.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	384
PHASE4	29
PHASE3	15
PHASE2	6
PHASE2/PHASE3	3
PHASE1/PHASE2	2
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07600697	PHASE4	NOT_YET_RECRUITING	Suzetrigine for Opioid-Sparing Postoperative Analgesia Following Transvaginal Pelvic Reconstructive Surgery
NCT00557882	PHASE4	COMPLETED	Efficacy Study of Vaginal Mesh for Anterior Prolapse
NCT00697489	PHASE4	WITHDRAWN	Treatment of Urinary Stress Incontinence During or Following Correction of Pelvic Organ Prolapse
NCT00827528	PHASE4	COMPLETED	SIS Graft and Traditional Repair in Vaginal Wall Prolapse
NCT01092624	PHASE4	TERMINATED	Clinical Trial of Solifenacin Versus Placebo Plus Pessary for Women With Vaginal Prolapse
NCT01346436	PHASE4	UNKNOWN	Value of Robotic Rectopexy for the Treatment of Complex Pelvic Floor Dysfunction
NCT01497171	PHASE4	TERMINATED	The ELEGANT Trial: Elevate Transvaginal Mesh vs. Anterior Colporrhaphy
NCT01778985	PHASE4	COMPLETED	Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
NCT01805310	PHASE4	COMPLETED	Pre-operative Bowel Preparation Prior to Minimally Invasive Sacral Colpopexy
NCT02121977	PHASE4	TERMINATED	Study of the Elevate Anterior and Apical Prolapse Repair System Compared to Native Tissue Repair for Pelvic Organ Prolapse
NCT02123992	PHASE4	TERMINATED	Study of the Elevate Apical and Posterior Prolapse Repair System Compared to Native Tissue Repair for Pelvic Organ Prolapse
NCT02155738	PHASE4	COMPLETED	IV Acetaminophen for Postoperative Pain After Pelvic Organ Prolapse Repair
NCT02178735	PHASE4	COMPLETED	Clinical Outcomes and Urodynamic Effects After Vaginal Tailored Mesh Surgery for Pelvic Organ Prolapse
NCT02431897	PHASE4	COMPLETED	Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen
NCT02449915	PHASE4	COMPLETED	Improvement of Pain Following Robotic Sacrocolpopexy and Rectocele Repair for Pelvic Organ Prolapse
NCT02727322	PHASE4	COMPLETED	Nitrofurantoin Prophylaxis During Catheter-managed Acute Urinary Retention After Pelvic Reconstructive Surgery
NCT03032848	PHASE4	COMPLETED	Vaginal Estrogens Comparative Trial on Pelvic Organ Prolapse Patients
NCT03052816	PHASE4	COMPLETED	Ice T Postoperative Multimodal Pain Regimen in FPMRS Surgery
NCT03123861	PHASE4	COMPLETED	Gabapentin for Postop Pain After SSLF
NCT03779633	PHASE4	COMPLETED	Preoperative Oestrogen in Postmenopausal Women With Pelvic Organ Prolapse
NCT03939715	PHASE4	UNKNOWN	Surgical Intervention With DermaPure vs Native Tissue in Pelvic Organ Prolapse
NCT03995641	PHASE4	WITHDRAWN	The Effect of Local Analgesia on Postoperative Gluteal Pain in Patients Undergoing Sacrospinous Ligament Fixation
NCT04038099	PHASE4	COMPLETED	Lessons on Urethral Lidocaine in Urodynamics
NCT04444830	PHASE4	WITHDRAWN	Sprix for Postoperative Pain Control Following Gynecologic Surgery
NCT04807920	PHASE4	UNKNOWN	BOTOX® at the Time of Prolapse Surgery for OAB
NCT05658887	PHASE4	COMPLETED	Preoperative Gabapentin vs Placebo for Vaginal Prolapse Surgery
NCT06120530	PHASE4	COMPLETED	Intraperitoneal Bupivacaine for Pelvic Organ Prolapse
NCT06263985	PHASE4	UNKNOWN	Axis(TM) Solvent-dehydrate Dermal Allograft in the Treatment of Pelvic Organ Prolapse.
NCT06419075	PHASE4	WITHDRAWN	Tranexamic Acid in Vaginal Reconstructive Surgery
NCT06391372	PHASE3	ACTIVE_NOT_RECRUITING	Effect of Local Estriol Treatment Before Vaginal Repair Surgery
NCT07030426	PHASE3	NOT_YET_RECRUITING	Vaginal Estrogen for Improvement of Outcomes Following Pelvic Organ Prolapse Surgery
NCT00402844	PHASE2/PHASE3	COMPLETED	Safety Study of Pelvic Organ Prolapse Repair Using Transvaginal Mesh
NCT00506116	PHASE3	COMPLETED	Promoting Effective Recovery From Labor Urinary Incontinence (PERL)
NCT00695240	PHASE2/PHASE3	UNKNOWN	Post-Operative Pain Control Using Direct Continuous Bupivacaine Infusion After Pelvic Organ Prolapse Repair
NCT00803335	PHASE3	COMPLETED	The Effects of Local Vaginal Estrogen in Postmenopausal Women With Pelvic Organ Prolapse
NCT01182090	PHASE3	COMPLETED	Surgical Correction of Pelvic Organ Prolapse
NCT01384084	PHASE3	COMPLETED	Pelvic Organ Prolapse Repair Plus Mini-Sling Versus Pelvic Organ Prolapse Repair Alone
NCT02073734	PHASE3	COMPLETED	Effects of Preoperative Dexamethasone Study on QOL After Vaginal Reconstructive Surgery for POP
NCT02599311	PHASE3	UNKNOWN	the Indications and Clinical Efficacy of Pelvic Organ Prolapse Surgery
NCT02999724	PHASE3	UNKNOWN	Gabapentin Reduces Opioid Use Postoperatively (GROUP Study)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TOLTERODINE	4	4
SOLIFENACIN	4	3
TAMSULOSIN	4	3
ESTRADIOL	4	2
ESTRIOL	4	2
ALFACALCIDOL	4	1
BUPIVACAINE	4	1
ESTROGENS, CONJUGATED	4	1
GABAPENTIN	4	1
GENTAMICIN SULFATE	4	1
IBUPROFEN	4	1
METHENAMINE HIPPURATE	4	1
NITROFURANTOIN	4	1
ONABOTULINUMTOXINA	4	1
POLYTETRAFLUOROETHYLENE	4	1
TRIAMCINOLONE ACETONIDE	4	1
VASOPRESSIN	4	1
ESTROGEN	3	2
POWDERED CELLULOSE	3	1
PROMESTRIENE	3	1
REBOXETINE MESYLATE	3	1
SUZETRIGINE	3	1
CHEMBL1087542	0	1
POLYDIOXANONE	-1	1
POLYGLACTIN 370	-1	1