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Atlas / Disease / Female reproductive system disorder

Female reproductive system disorder

disease
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Also known as disease of female reproductive systemdisease or disorder of female reproductive systemdisorder of female genital systemdisorder of female reproductive systemfemale reproductive diseasefemale reproductive system diseasefemale reproductive system disease or disordergynaecological disease

Summary

Female reproductive system disorder (MONDO:0002263) is a disease (an umbrella term covering 34 Mondo subtypes) with 13 cohort genes (34 GWAS associations across 119 studies) and 5 clinical trials. Top therapeutic interventions include cholecalciferol.

At a glance

  • Umbrella term: 34 Mondo subtypes
  • Cohort genes: 13
  • GWAS associations: 34
  • Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namefemale reproductive system disorder
Mondo IDMONDO:0002263
EFOEFO:0009549
MeSHD005831
DOIDDOID:229
NCITC27020
SNOMED CT310789003
UMLSC0236100
MedGen65928
Anatomy (UBERON)UBERON:0000474
Is cancer (heuristic)no

Also known as: disease of female reproductive system · disease or disorder of female reproductive system · disorder of female genital system · disorder of female reproductive system · female reproductive disease · female reproductive system disease · female reproductive system disease or disorder · female reproductive system disorder · gynaecological disease

Data availability: 34 GWAS associations (119 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 34 Mondo subtypes.

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

Related subtypes (29): pelvic organ prolapse, cortisone reductase deficiency, physiological sexual disorder, gonadal 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

Subtypes (34): ectopic pregnancy, pelvic inflammatory disease, endosalpingiosis, vaginal disorder, prolapse of female genital organ, Allen-Masters syndrome, fallopian tube disorder, vulvar disease, uterine disorder, gynatresia, Bartholin duct cyst, ovarian disorder, hymen, imperforate, preterm premature rupture of the membranes, mammary-digital-nail syndrome, Asherman syndrome, uterine cervical aplasia and agenesis, longitudinal vaginal septum, transverse vaginal septum, polycystic ovaries-urethral sphincter dysfunction syndrome, granulomatous mastitis, vaginal atresia, mullerian aplasia, vulvovaginal gingival syndrome, isolated partial vaginal agenesis, female infertility, female reproductive system neoplasm, polyp of vulva, vulval varices, vulvodynia, menstrual cycle-dependent periodic fever, Bartholin’s gland disease, delayed puberty, self-limited, menstrual disorder

Genetics & variants

GWAS landscape

34 GWAS associations across 119 studies. Top hits map to 15 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs122257994e-17PSMD13?
rs1380608718e-16PSMD13?
rs173323205e-13TNRC6B?
rs9373805534e-11NRXN1-DT?
rs74120105e-11CDC42 - WNT4?1.12
rs1176703752e-10TUBB?
rs3764826385e-10LINC01677 - MTATP6P14?
rs2022179932e-09OR5V1?
rs25079683e-09MICA?
rs1168329923e-09PPP1R17 - PDE1C?
rs1172195865e-09LINC00343 - RNA5SP38?
17:412001071e-08?
rs92712152e-08HLA-DRB1 - HLA-DQA1?
rs92579852e-08ZFP57 - HLA-F-AS1?
rs1451522093e-08BNC1 - SH3GL3?
rs1474276294e-08LINC02940?
17:700978514e-08?
rs734944865e-08GABBR2?
rs64322165e-08GREB1?
rs171798517e-08HLA-W, POLR1HASP, POLR1HASP?1.11
rs1506778041e-07GALNT9 - FBRSL1?
rs1407815162e-07LINC02328, LINC02316?
rs5689250973e-07LINC01809 - RPL37P10?
rs1884336381e-06RPS6KA2?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90080695Backman JD202110,065219,069Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST009823Masuda T20197,97539,556GWAS of five gynecologic diseases and cross-trait analysis in Japanese.
GCST009824Masuda T20197,97539,556GWAS of five gynecologic diseases and cross-trait analysis in Japanese.
GCST90044468Jiang L20217,694239,846A generalized linear mixed model association tool for biobank-scale data.
GCST009822Masuda T20197,31539,556GWAS of five gynecologic diseases and cross-trait analysis in Japanese.
GCST90044461Jiang L20217,013240,527A generalized linear mixed model association tool for biobank-scale data.
GCST90044441Jiang L20215,543450,805A generalized linear mixed model association tool for biobank-scale data.
GCST90080679Backman JD20215,496197,997Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90080682Backman JD20213,237205,577Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90080670Backman JD20212,734209,232Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic24

MAF distribution

BucketVariants
common (>=0.05)15
low_freq (0.01-0.05)0
rare (<0.01)0
unknown9

Functional consequences

ConsequenceCount
intron_variant12
intergenic_variant9
unknown2
non_coding_transcript_exon_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs1222579911241124C>G0.05intron_variantPSMD134e-17Tier 4: intronic/intergenic
rs13806087111241284G>A0.05intron_variantPSMD138e-16Tier 4: intronic/intergenic
rs173323202240315616G>A,T0.05intron_variantTNRC6B5e-13Tier 4: intronic/intergenic
rs937380553251836223A>Gintron_variantNRXN1-DT4e-11Tier 4: intronic/intergenic
rs7412010122109953G>C0.05intergenic_variantCDC42 - WNT45e-11Tier 4: intronic/intergenic
rs117670375630719695C>T0.05intergenic_variantTUBB2e-10Tier 4: intronic/intergenic
rs3764826381106418677A>Tintergenic_variantLINC01677 - MTATP6P145e-10Tier 4: intronic/intergenic
rs202217993629419199GT>G0.05intron_variantOR5V12e-09Tier 4: intronic/intergenic
rs2507968631404941G>A,C,T0.05intron_variantMICA3e-09Tier 4: intronic/intergenic
rs116832992731745141T>C0.05intergenic_variantPPP1R17 - PDE1C3e-09Tier 4: intronic/intergenic
rs11721958613105912102C>T0.05intergenic_variantLINC00343 - RNA5SP385e-09Tier 4: intronic/intergenic
17:412001071e-08Tier 4: intronic/intergenic
rs9271215632611500C>G,T0.05intergenic_variantHLA-DRB1 - HLA-DQA12e-08Tier 4: intronic/intergenic
rs9257985629684476A>G0.05intergenic_variantZFP57 - HLA-F-AS12e-08Tier 4: intronic/intergenic
rs1451522091583408460A>G0.05intron_variantBNC1 - SH3GL33e-08Tier 4: intronic/intergenic
rs1474276292139047396G>Aintron_variantLINC029404e-08Tier 4: intronic/intergenic
17:700978514e-08Tier 4: intronic/intergenic
rs73494486998579569C>A,T0.05intron_variantGABBR25e-08Tier 4: intronic/intergenic
rs6432216211562834T>C0.05intron_variantGREB15e-08Tier 4: intronic/intergenic
rs17179851629956663T>A,C0.05non_coding_transcript_exon_variantHLA-W, POLR1HASP, POLR1HASP7e-08Tier 4: intronic/intergenic
rs15067780412132360369C>Tintergenic_variantGALNT9 - FBRSL11e-07Tier 4: intronic/intergenic
rs1407815161486042426T>Gintron_variantLINC02328, LINC023162e-07Tier 4: intronic/intergenic
rs568925097283554152TA>Tintergenic_variantLINC01809 - RPL37P103e-07Tier 4: intronic/intergenic
rs1884336386166653330G>Cintron_variantRPS6KA21e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 24 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
HOXA10LimitedAutosomal dominantfemale reproductive system disorder

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BRCA1Orphanet:1331Familial prostate cancer
BRCA1Orphanet:1333Familial pancreatic carcinoma
BRCA1Orphanet:145Hereditary breast and/or ovarian cancer syndrome
BRCA1Orphanet:168829Primary peritoneal carcinoma
BRCA1Orphanet:227535Hereditary breast cancer
BRCA1Orphanet:667662Breast implant-associated anaplastic large cell lymphoma
BRCA1Orphanet:694963Inflammatory breast cancer
BRCA1Orphanet:70567Cholangiocarcinoma
BRCA1Orphanet:84Fanconi anemia
SOX9Orphanet:140Campomelic dysplasia
SOX9Orphanet:213846,XX ovotesticular difference of sex development
SOX9Orphanet:24246,XY complete gonadal dysgenesis
SOX9Orphanet:25151046,XY partial gonadal dysgenesis
SOX9Orphanet:39346,XX testicular difference of sex development
SOX9Orphanet:718Isolated Pierre Robin sequence
WNT4Orphanet:139466SERKAL syndrome
WNT4Orphanet:247768Müllerian aplasia and hyperandrogenism
WNT4Orphanet:2578Mayer-Rokitansky-Küster-Hauser syndrome type 2
CDC42Orphanet:487796Takenouchi-Kosaki syndrome
CDC42Orphanet:619363NOCARH syndrome
TNRC6BOrphanet:528084Non-specific syndromic intellectual disability
GABBR2Orphanet:3095Atypical Rett syndrome
GABBR2Orphanet:442835Non-specific early-onset epileptic encephalopathy
PDE1COrphanet:90635Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

13 cohort genes, 13 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only12
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
HOXA10HGNC:5100ENSG00000253293P31260Homeobox protein Hox-A10gencc
SH3GL3HGNC:10832ENSG00000140600Q99963Endophilin-A3gwas
BRCA1HGNC:1100ENSG00000012048P38398Breast cancer type 1 susceptibility proteingwas
SOX9HGNC:11204ENSG00000125398P48436Transcription factor SOX-9gwas
WNT4HGNC:12783ENSG00000162552P56705Protein Wnt-4gwas
CDC42HGNC:1736ENSG00000070831P60953Cell division control protein 42 homologgwas
BET1LHGNC:19348ENSG00000177951Q9NYM9BET1-like proteingwas
GREB1HGNC:24885ENSG00000196208Q4ZG55Protein GREB1gwas
TNRC6BHGNC:29190ENSG00000100354Q9UPQ9Trinucleotide repeat-containing gene 6B proteingwas
RIC8AHGNC:29550ENSG00000177963Q9NPQ8Chaperone Ric-8Agwas
GABBR2HGNC:4507ENSG00000136928O75899Gamma-aminobutyric acid type B receptor subunit 2gwas
PDE1CHGNC:8776ENSG00000154678Q14123Dual specificity calcium/calmodulin-dependent 3’,5’-cyclic nucleotide phosphodiesterase 1Cgwas
ASIC2HGNC:99ENSG00000108684Q16515Acid-sensing ion channel 2gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
HOXA10Homeobox protein Hox-A10Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
SH3GL3Endophilin-A3Implicated in endocytosis.
BRCA1Breast cancer type 1 susceptibility proteinE3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
SOX9Transcription factor SOX-9Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
WNT4Protein Wnt-4Ligand for members of the frizzled family of seven transmembrane receptors.
CDC42Cell division control protein 42 homologPlasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state.
BET1LBET1-like proteinVesicle SNARE required for targeting and fusion of retrograde transport vesicles with the Golgi complex.
GREB1Protein GREB1May play a role in estrogen-stimulated cell proliferation.
TNRC6BTrinucleotide repeat-containing gene 6B proteinPlays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs).
RIC8AChaperone Ric-8AChaperone that specifically binds and folds nascent G alpha proteins prior to G protein heterotrimer formation, promoting their stability and activity: folds GNAI1, GNAO1, GNA13 and GNAQ.
GABBR2Gamma-aminobutyric acid type B receptor subunit 2Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2.
PDE1CDual specificity calcium/calmodulin-dependent 3’,5’-cyclic nucleotide phosphodiesterase 1CCalmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
ASIC2Acid-sensing ion channel 2Forms pH-gated trimeric sodium channels that act as postsynaptic excitatory sensors in the nervous system.

Protein-family classification

Druggable: 2 · Difficult: 5 · Unknown: 6 · Druggable fraction: 0.15

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.

FamilyGenesFoldFDR
Transcription factor42.5×0.313
GPCR11.8×0.837
Scaffold/PPI11.3×0.837
Enzyme (other)10.9×0.837
Other/Unknown60.8×0.837

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
HOXA10Transcription factornoHD, Homeodomain-like_sf, Homeobox_CS
SH3GL3Scaffold/PPInoSH3_domain, BAR_dom, AH/BAR_dom_sf
BRCA1Transcription factorno2.3.2.27BRCT_dom, Znf_RING, BRCA1
SOX9Transcription factornoHMG_box_dom, Sox_N, HMG_box_dom_sf
WNT4Other/UnknownnoWnt, Wnt4, Wnt_CS
CDC42Enzyme (other)yes3.6.5.2Small_GTPase, Small_GTPase_Rho, Small_GTP-bd
BET1LOther/UnknownnoT_SNARE_dom, BET1_SNARE
GREB1Other/UnknownnoGREB1, GREB1_N, GREB1-like_C
TNRC6BOther/UnknownnoNucleotide-bd_a/b_plait_sf, Argonaute_hook_dom, TNRC6_PABC-bd
RIC8AOther/UnknownnoChaperone_Ric-8_A/B, ARM-like, ARM-type_fold
GABBR2GPCRyesGPCR_3, ANF_lig-bd_rcpt, GPCR3_GABA-B
PDE1CTranscription factorno3.1.4.17PDEase_catalytic_dom, HD/PDEase_dom, PDE1_N
ASIC2Other/UnknownnoENaC, ENaC_chordates, ENaC_CS

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)13
unknown0

Top tissues across cohort

TissueCohort genes
ventricular zone3
biceps brachii1
body of uterus1
skeletal muscle tissue of biceps brachii1
male germ cell1
middle frontal gyrus1
sperm1
male germ line stem cell (sensu Vertebrata) in testis1
primordial germ cell in gonad1
cranial nerve II1
hair follicle1
decidua1
islet of Langerhans1
type B pancreatic cell1
cortical plate1
monocyte1
mononuclear cell1
adenohypophysis1
body of pancreas1
pituitary gland1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
HOXA10190broadmarkerbiceps brachii, body of uterus, skeletal muscle tissue of biceps brachii
SH3GL3209broadmarkersperm, middle frontal gyrus, male germ cell
BRCA1208ubiquitousmarkerventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
SOX9274ubiquitousmarkerventricular zone, cranial nerve II, hair follicle
WNT4177broadmarkerislet of Langerhans, decidua, type B pancreatic cell
CDC42301ubiquitousmarkercortical plate, monocyte, mononuclear cell
BET1L241ubiquitousmarkerbody of pancreas, adenohypophysis, pituitary gland
GREB1219broadmarkerleft ovary, right ovary, ovary
TNRC6B289ubiquitousmarkerbuccal mucosa cell, epithelium of nasopharynx, nasopharynx
RIC8A274ubiquitousmarkerstromal cell of endometrium, ventricular zone, granulocyte
GABBR2193broadmarkerBrodmann (1909) area 23, lateral nuclear group of thalamus, middle temporal gyrus
PDE1C222broadmarkerendothelial cell, heart right ventricle, corpus callosum
ASIC2131tissue_specificmarkerprefrontal cortex, cingulate cortex, anterior cingulate cortex

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

SymbolInteractor count
BRCA19,064
SOX94,935
CDC422,537
WNT42,347
TNRC6B2,064
GABBR21,980
HOXA101,554
ASIC21,493
SH3GL31,461
RIC8A1,436

Intra-cohort edges

ABSources
BET1LRIC8Astring_interaction
BET1LTNRC6Bstring_interaction
GABBR2SH3GL3biogrid_interaction
GREB1WNT4string_interaction

Structural data

PDB: 6 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CDC42P6095348
BRCA1P3839833
GABBR2O7589926
SH3GL3Q999632
SOX9P484361
ASIC2Q165151

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
WNT4P5670591.41
RIC8AQ9NPQ890.37
BET1LQ9NYM989.02
PDE1CQ1412371.53
GREB1Q4ZG5571.10
HOXA10P3126061.37
TNRC6BQ9UPQ939.58

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 188. Enrichment computed across 13 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Transcriptional regulation of testis differentiation2129.8×0.019SOX9, WNT4
EGFR downregulation262.9×0.031SH3GL3, CDC42
Signaling by EGFR259.3×0.031SH3GL3, CDC42
Defective DNA double strand break response due to BRCA1 loss of function1519.1×0.072BRCA1
Defective DNA double strand break response due to BARD1 loss of function1519.1×0.072BRCA1
Cam-PDE 1 activation1259.6×0.082PDE1C
G-protein beta:gamma signalling1173.0×0.082CDC42
Post-transcriptional silencing by small RNAs1148.3×0.082TNRC6B
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence1148.3×0.082BRCA1
Inactivation of CDC42 and RAC11129.8×0.082CDC42
Competing endogenous RNAs (ceRNAs) regulate PTEN translation1129.8×0.082TNRC6B
Regulation of CDH11 mRNA translation by microRNAs1115.3×0.082TNRC6B
Regulation of NPAS4 mRNA translation1115.3×0.082TNRC6B
Regulation of PD-L1(CD274) translation1115.3×0.082TNRC6B
Regulation of PTEN mRNA translation1103.8×0.082TNRC6B
RHO GTPases activate KTN1194.4×0.082CDC42
Listeria monocytogenes entry into host cells194.4×0.082SH3GL3
Regulation of CDH1 mRNA translation by microRNAs194.4×0.082TNRC6B
Defective homologous recombination repair (HRR) due to PALB2 loss of function186.5×0.082BRCA1
CD28 dependent Vav1 pathway179.9×0.082CDC42
Nephron development179.9×0.082WNT4
Diseases of DNA Double-Strand Break Repair174.2×0.082BRCA1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function174.2×0.082BRCA1
InlB-mediated entry of Listeria monocytogenes into host cell169.2×0.082SH3GL3
Negative regulation of TCF-dependent signaling by WNT ligand antagonists164.9×0.082WNT4
DCC mediated attractive signaling164.9×0.082CDC42
Regulation of RUNX1 Expression and Activity161.1×0.082TNRC6B
Resolution of D-Loop Structures157.7×0.082BRCA1
Regulation of MITF-M-dependent genes involved in apoptosis157.7×0.082TNRC6B
Developmental Lineage of Multipotent Pancreatic Progenitor Cells154.6×0.082SOX9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
renal vesicle induction2648.1×0.001SOX9, WNT4
Sertoli cell differentiation2235.7×0.004SOX9, WNT4
prostate gland development2216.1×0.004SOX9, HOXA10
male gonad development336.0×0.005SOX9, WNT4, HOXA10
female sex determination11296.3×0.016WNT4
negative regulation of testicular blood vessel morphogenesis11296.3×0.016WNT4
cell-cell adhesion involved in gastrulation11296.3×0.016RIC8A
metanephric nephron morphogenesis11296.3×0.016WNT4
negative regulation of male gonad development11296.3×0.016WNT4
positive regulation of cortisol biosynthetic process11296.3×0.016WNT4
negative regulation of androgen biosynthetic process11296.3×0.016WNT4
branching involved in ureteric bud morphogenesis256.4×0.016SOX9, WNT4
morphogenesis of an epithelium252.9×0.016SOX9, GREB1
epithelial to mesenchymal transition248.0×0.016SOX9, WNT4
positive regulation of stress fiber assembly248.0×0.016WNT4, CDC42
embryonic epithelial tube formation1648.1×0.017WNT4
negative regulation of immune system process1648.1×0.017SOX9
regulation of systemic arterial blood pressure by aortic arch baroreceptor feedback1648.1×0.017ASIC2
epithelial cell proliferation involved in prostatic bud elongation1648.1×0.017SOX9
regulation of cell proliferation involved in tissue homeostasis1648.1×0.017SOX9
regulation of branching involved in lung morphogenesis1648.1×0.017SOX9
cell proliferation involved in heart morphogenesis1648.1×0.017SOX9
renal vesicle formation1648.1×0.017WNT4
metanephric tubule formation1648.1×0.017WNT4
regulation of retrograde vesicle-mediated transport, Golgi to ER1648.1×0.017BET1L
regulation of epithelial cell proliferation involved in lung morphogenesis1648.1×0.017SOX9
heart valve formation1432.1×0.017SOX9
neural crest cell fate specification1432.1×0.017SOX9
male germ-line sex determination1432.1×0.017SOX9
positive regulation of aldosterone biosynthetic process1432.1×0.017WNT4

Therapeutics

Drugs indicated for this disease

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

DrugDevelopment status
Clindamycin PhosphateApproved (phase 4)

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 4 · Undrugged: 9

Druggability breadth: 6 of 13 evidence-associated genes (46%) 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.

SymbolExample approved molecule
BRCA1RIBOFLAVIN
CDC42KETOROLAC
GABBR2BACLOFEN
PDE1CVARDENAFIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
PDE1C154
BRCA1124
GABBR244
CDC4234
HOXA1000
SH3GL300
SOX900
WNT400
BET1L00
GREB100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
RIBOFLAVIN4BRCA1
DAUNORUBICIN HYDROCHLORIDE4BRCA1
TOPOTECAN HYDROCHLORIDE4BRCA1
DAUNORUBICIN4BRCA1
DOXORUBICIN HYDROCHLORIDE4BRCA1
MESALAMINE4BRCA1
DIPYRIDAMOLE4BRCA1, PDE1C
KETOROLAC4CDC42
BACLOFEN4GABBR2
VARDENAFIL4PDE1C
SILDENAFIL4PDE1C
VINPOCETINE4PDE1C
NIMODIPINE4PDE1C
CURCUMIN3BRCA1
SURAMIN3BRCA1
SURAMIN HEXASODIUM3BRCA1
ARBACLOFEN3GABBR2
PAPAVERINE3PDE1C
NITRENDIPINE3PDE1C
SODIUM TANSHINONE IIA SULFONATE2BRCA1
HOMIDIUM BROMIDE2BRCA1
SANGUINARIUM CHLORIDE2CDC42
SGS-7422GABBR2
BUFROLIN2PDE1C
OXAGRELATE2PDE1C
ZAPRINAST2PDE1C
CILOSTAMIDE2PDE1C
ETAZOLATE2PDE1C
IDOXIFENE2PDE1C
ROLIPRAM2PDE1C

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

SymbolAssaysType breakdown
PDE1C185Binding:175, ADMET:5, Functional:5
CDC4276Binding:76
GABBR257Binding:35, Functional:21, ADMET:1
BRCA113Binding:9, Functional:4
SOX93Binding:3
RIC8A1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BRCA12.3.2.27RING-type E3 ubiquitin transferase
CDC423.6.5.2small monomeric GTPase
PDE1C3.1.4.173’,5’-cyclic-nucleotide phosphodiesterase

Cohort genes with high screening signal

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

SymbolChEMBL assays
PDE1C185

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
RIBOFLAVIN4BRCA1
DAUNORUBICIN HYDROCHLORIDE4BRCA1
TOPOTECAN HYDROCHLORIDE4BRCA1
DAUNORUBICIN4BRCA1
DOXORUBICIN HYDROCHLORIDE4BRCA1
MESALAMINE4BRCA1
DIPYRIDAMOLE4BRCA1, PDE1C
KETOROLAC4CDC42
BACLOFEN4GABBR2
VARDENAFIL4PDE1C
SILDENAFIL4PDE1C
VINPOCETINE4PDE1C
NIMODIPINE4PDE1C
CURCUMIN3BRCA1
SURAMIN3BRCA1
SURAMIN HEXASODIUM3BRCA1
ARBACLOFEN3GABBR2
PAPAVERINE3PDE1C
NITRENDIPINE3PDE1C
SODIUM TANSHINONE IIA SULFONATE2BRCA1
HOMIDIUM BROMIDE2BRCA1
SANGUINARIUM CHLORIDE2CDC42
SGS-7422GABBR2
BUFROLIN2PDE1C
OXAGRELATE2PDE1C
ZAPRINAST2PDE1C
CILOSTAMIDE2PDE1C
ETAZOLATE2PDE1C
IDOXIFENE2PDE1C
ROLIPRAM2PDE1C

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4BRCA1, CDC42, GABBR2, PDE1C
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug9HOXA10, SH3GL3, SOX9, WNT4, BET1L, GREB1, TNRC6B, RIC8A, ASIC2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
HOXA100—
SH3GL30—
SOX93—
WNT40—
BET1L0—
GREB10—
TNRC6B0—
RIC8A1—
ASIC20—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified5

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04678414Not specifiedACTIVE_NOT_RECRUITINGInfertility Survey Among Reproductive Age Women With Gynecological and Breast Cancer
NCT07472842Not specifiedRECRUITINGStudy on the Outcomes of Patients Treated in Gynecological Emergency Departments for Pelvic Endometriosis or Suspected Pelvic Endometriosis
NCT02233283Not specifiedCOMPLETEDEffect of Modifications of Nutritional Intake Upon Reproductive Hormones in Normal Women
NCT03584529Not specifiedUNKNOWNAssociation Between Vitamin D and the Development of Uterine Fibroids
NCT03586947Not specifiedUNKNOWNAssociation Between Vitamin D and the Risk of Uterine Fibroids

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
CHOLECALCIFEROL41

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 72

This page pulls from 72 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptuberonufeatureumlsuniprot