Female infertility

Summary

Female infertility (MONDO:0021124) is a disease with 4 cohort genes (33 GWAS associations across 28 studies) and 106 clinical trials. Top therapeutic interventions include clomiphene, follitropin alfa, and sildenafil.

At a glance

• Cohort genes: 4
• GWAS associations: 33
• ClinVar variants: 3
• Clinical trials: 106

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	female infertility
Mondo ID	MONDO:0021124
EFO	EFO:0008560
MeSH	D007247
ICD-10-CM	N97
ICD-11	1237004558
SNOMED CT	6738008
UMLS	C0021361
MedGen	5795
Anatomy (UBERON)	UBERON:0000474
Is cancer (heuristic)	no

Also known as: female infertility · female reproductive system infertility · female reproductive system infertility disorder · female sterility · female sub-fertility · female subfertility · infertility disorder of female reproductive system · postpartum sterility · sterility, female · sterility, postpartum · sub fertility, female · sub-fertility, female · subfertility, female

Data availability: 3 ClinVar variants · 33 GWAS associations (28 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (33): 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 reproductive system neoplasm, polyp of vulva, vulval varices, vulvodynia, menstrual cycle-dependent periodic fever, Bartholin’s gland disease, delayed puberty, self-limited, menstrual disorder

Subtypes (4): female infertility of uterine origin, female infertility due to zona pellucida defect, inherited primary ovarian failure, female infertility due to oocyte meiotic arrest

Genetics & variants

GWAS landscape

33 GWAS associations across 28 studies. Top hits map to 19 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs61768001	4e-21	WNT4	C	1.1
rs9643050	4e-15	PKHD1L1	C	1.13
rs1422	2e-12	EBAG9	C	0.82
rs528780676	6e-12	RPSAP37 - LINC02039	T	2.76
rs17803970	5e-11	SYNE1	T	0.91
rs10929759	1e-10	GREB1	G	0.95
rs17879961	2e-10	CHEK2	G	1.35
rs17378154	2e-10	EBAG9	A	1.13
rs192462512	5e-10	LINC01283 - MIR3937	C	0.23
rs9696009	7e-10	DENND1A	A	1.21
rs72665317	8e-10	CDC42-AS1	G	1.14
rs1852684	9e-10	TEX41	T	1.12
rs12037376	7e-09	WNT4	G	0.9
rs190290095	8e-09	UBE2K - PDS5A	A	0.23
rs851982	8e-09	ESR1	C	1.08
rs111749498	1e-08	SLC47A2	T	2.29
rs143459581	1e-08	TTC28	T	1.3
rs111597692	2e-08	TMEM74 - TRHR	T	1.16
rs75045132	3e-08	WDR4P2 - FBXO48	C	0.89
rs552953683	3e-08	MAILR	C	2.93
rs11692588	3e-08	GREB1	A	0.92
rs4944654	4e-08	FZD4-DT	C	0.88
rs6938404	4e-08	RNU6-300P - AKAP12	T	0.96
rs72827480	4e-08	INHBB - LINC01101	C	1.1
rs9902027	4e-08	Y_RNA - TNFSF12	C	1.12
rs340879	5e-08	PROX1, PROX1-AS1	T	0.91
rs74156208	5e-08	TMEM26-AS1 - CABCOCO1	A	1.1
rs4404647	1e-07	ADCY2	?
rs10917151	2e-07	CDC42	A	1.21
rs10122243	2e-07	CDKN2B-AS1	T	1.16

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90483463	Venkatesh SS	2025	40,024	665,658	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90483472	Venkatesh SS	2025	24,282	797,909	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90483466	Venkatesh SS	2025	23,358	681,351	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90454225	Pujol Gualdo N	2025	13,289	216,463	Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.
GCST90483473	Venkatesh SS	2025	10,872	694,433	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90483467	Venkatesh SS	2025	10,864	694,441	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90483464	Venkatesh SS	2025	7,684	667,460	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90483470	Venkatesh SS	2025	7,359	580,284	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90483471	Venkatesh SS	2025	6,865	805,653	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90483465	Venkatesh SS	2025	6,271	783,723	Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	26

MAF distribution

Bucket	Variants
common (>=0.05)	21
low_freq (0.01-0.05)	5
rare (<0.01)	4
unknown	0

Functional consequences

Consequence	Count
intron_variant	21
intergenic_variant	5
3_prime_UTR_variant	2
missense_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs61768001	1	22139327	T>A,C,G	0.165	intron_variant	WNT4	4e-21	Tier 4: intronic/intergenic
rs9643050	8	109458129	T>C	0.06	intron_variant	PKHD1L1	4e-15	Tier 4: intronic/intergenic
rs1422	8	109551075	C>G	0.05	intron_variant	EBAG9	2e-12	Tier 4: intronic/intergenic
rs528780676	5	125969147	T>C	0.001	intron_variant	RPSAP37 - LINC02039	6e-12	Tier 4: intronic/intergenic
rs17803970	6	152232583	A>T	0.083	intron_variant	SYNE1	5e-11	Tier 4: intronic/intergenic
rs10929759	2	11581886	C>G	0.456	intron_variant	GREB1	1e-10	Tier 4: intronic/intergenic
rs17879961	22	28725099	A>C,G,T	0.039	missense_variant	CHEK2	2e-10	Tier 1: coding
rs17378154	8	109568721	G>A,T	0.059	3_prime_UTR_variant	EBAG9	2e-10	Tier 2: splice/UTR
rs192462512	X	39653668	T>C	0.002	intron_variant	LINC01283 - MIR3937	5e-10	Tier 4: intronic/intergenic
rs9696009	9	123856954	G>A	0.078	intron_variant	DENND1A	7e-10	Tier 4: intronic/intergenic
rs72665317	1	22040580	T>A,G	0.19	intron_variant	CDC42-AS1	8e-10	Tier 4: intronic/intergenic
rs1852684	2	145068818	G>C,T	0.367	intron_variant	TEX41	9e-10	Tier 4: intronic/intergenic
rs12037376	1	22135618	G>A,C	0.05	intron_variant	WNT4	7e-09	Tier 4: intronic/intergenic
rs190290095	4	39786858	G>A	0.002	intergenic_variant	UBE2K - PDS5A	8e-09	Tier 4: intronic/intergenic
rs851982	6	151703850	T>C	0.428	intron_variant	ESR1	8e-09	Tier 4: intronic/intergenic
rs111749498	17	19714694	C>T	0.027	intron_variant	SLC47A2	1e-08	Tier 4: intronic/intergenic
rs143459581	22	28068862	C>T	0.042	intron_variant	TTC28	1e-08	Tier 4: intronic/intergenic
rs111597692	8	109039973	C>T	0.032	intron_variant	TMEM74 - TRHR	2e-08	Tier 4: intronic/intergenic
rs75045132	2	68456386	G>C	0.033	intergenic_variant	WDR4P2 - FBXO48	3e-08	Tier 4: intronic/intergenic
rs552953683	8	102898586	T>C	0.002	intron_variant	MAILR	3e-08	Tier 4: intronic/intergenic
rs11692588	2	11544358	A>C,G	0.358	intron_variant	GREB1	3e-08	Tier 4: intronic/intergenic
rs4944654	11	87003155	C>A,G	0.05	intron_variant	FZD4-DT	4e-08	Tier 4: intronic/intergenic
rs6938404	6	151222906	C>T	0.452	intron_variant	RNU6-300P - AKAP12	4e-08	Tier 4: intronic/intergenic
rs72827480	2	120388925	T>A,C,G	0.401	intergenic_variant	INHBB - LINC01101	4e-08	Tier 4: intronic/intergenic
rs9902027	17	7537667	C>G,T	0.255	intergenic_variant	Y_RNA - TNFSF12	4e-08	Tier 4: intronic/intergenic
rs340879	1	213983171	T>A,C	0.418	intron_variant	PROX1, PROX1-AS1	5e-08	Tier 4: intronic/intergenic
rs74156208	10	61509370	G>A	0.184	intergenic_variant	TMEM26-AS1 - CABCOCO1	5e-08	Tier 4: intronic/intergenic
rs4404647	5	7751356	T>C	0.05	intron_variant	ADCY2	1e-07	Tier 4: intronic/intergenic
rs10917151	1	22096228	G>A,C,T	0.17	3_prime_UTR_variant	CDC42	2e-07	Tier 2: splice/UTR
rs10122243	9	22158925	C>T	0.41	regulatory_region_variant	CDKN2B-AS1	2e-07	Tier 3: regulatory

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3062225	NM_001282322.3(RNF212B):c.448C>T (p.Arg150Ter)	RNF212B	Likely pathogenic	criteria provided, single submitter
374000	NM_001282717.2(STAG3):c.2776C>T (p.Arg926Ter)	STAG3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
522599	NM_177987.3(TUBB8):c.600T>G (p.Phe200Leu)	TUBB8	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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.

Gene	Classification	Inheritance	Disease	Records
BTG4	Moderate	Autosomal recessive	female infertility	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STAG3	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
TUBB8	Orphanet:488191	Female infertility due to oocyte meiotic arrest

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BTG4	HGNC:13862	ENSG00000137707	Q9NY30	Protein BTG4	gencc
STAG3	HGNC:11356	ENSG00000066923	Q9UJ98	Cohesin subunit SA-3	clinvar
RNF212B	HGNC:20438	ENSG00000215277	A8MTL3	E3 ubiquitin-protein ligase RNF212B	clinvar
TUBB8	HGNC:20773	ENSG00000261456	Q3ZCM7	Tubulin beta-8 chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BTG4	Protein BTG4	Adapter protein that bridges CNOT7, a catalytic subunit of the CCR4-NOT complex, to EIF4E.
STAG3	Cohesin subunit SA-3	Meiosis specific component of cohesin complex.
RNF212B	E3 ubiquitin-protein ligase RNF212B	Ubiquitin E3 ligase that acts as a crucial factor for crossing-over (CO) formation during meiosis.
TUBB8	Tubulin beta-8 chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.0

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
Transcription factor	1	2.1×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BTG4	Other/Unknown	no		Anti_prolifrtn, BTG, BTG-like_sf
STAG3	Other/Unknown	no		STAG, ARM-type_fold, SCD
RNF212B	Transcription factor	no		Znf_RING_CS, Zip3/RNF212-like
TUBB8	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase

Expression context

Cohort genes with no expression data: 0.

3 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	2
sperm	2
primordial germ cell in gonad	2
secondary oocyte	1
left testis	1
right testis	1
kidney epithelium	1
cortical plate	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BTG4	54	tissue_specific	yes	oocyte, secondary oocyte, sperm
STAG3	185	broad	marker	oocyte, right testis, left testis
RNF212B	157	tissue_specific	marker	kidney epithelium, sperm, primordial germ cell in gonad
TUBB8	107		marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUBB8	4,732
STAG3	1,232
BTG4	608
RNF212B	192

Structural data

PDB: 0 · AlphaFold-only: 4 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TUBB8	Q3ZCM7	91.99
BTG4	Q9NY30	79.62
STAG3	Q9UJ98	78.46
RNF212B	A8MTL3	67.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 82. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Maternal to zygotic transition (MZT)	1	237.9×	0.049	BTG4
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	181.3×	0.049	TUBB8
Transport of connexons to the plasma membrane	1	181.3×	0.049	TUBB8
Gap junction trafficking and regulation	1	158.6×	0.049	TUBB8
Gap junction trafficking	1	158.6×	0.049	TUBB8
Activation of AMPK downstream of NMDARs	1	126.9×	0.049	TUBB8
RHO GTPases activate IQGAPs	1	115.3×	0.049	TUBB8
Sealing of the nuclear envelope (NE) by ESCRT-III	1	115.3×	0.049	TUBB8
HCMV Infection	1	108.8×	0.049	TUBB8
M-decay: degradation of maternal mRNAs by maternally stored factors	1	108.8×	0.049	BTG4
Gap junction assembly	1	97.6×	0.049	TUBB8
Nuclear Envelope (NE) Reassembly	1	97.6×	0.049	TUBB8
Meiosis	1	95.2×	0.049	STAG3
Selective autophagy	1	92.8×	0.049	TUBB8
Assembly and cell surface presentation of NMDA receptors	1	84.6×	0.049	TUBB8
Cargo trafficking to the periciliary membrane	1	82.8×	0.049	TUBB8
Aggrephagy	1	82.8×	0.049	TUBB8
Carboxyterminal post-translational modifications of tubulin	1	79.3×	0.049	TUBB8
Recycling pathway of L1	1	74.6×	0.049	TUBB8
COPI-independent Golgi-to-ER retrograde traffic	1	69.2×	0.049	TUBB8
Post NMDA receptor activation events	1	68.0×	0.049	TUBB8
Antimicrobial mechanism of IFN-stimulated genes	1	65.6×	0.049	TUBB8
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	64.5×	0.049	TUBB8
Reproduction	1	63.4×	0.049	STAG3
Activation of NMDA receptors and postsynaptic events	1	61.4×	0.049	TUBB8
Kinesins	1	59.5×	0.049	TUBB8
Cell Cycle	2	24.0×	0.049	STAG3, TUBB8
Developmental Biology	2	9.6×	0.049	BTG4, TUBB8
The role of GTSE1 in G2/M progression after G2 checkpoint	1	53.6×	0.051	TUBB8
Translocation of SLC2A4 (GLUT4) to the plasma membrane	1	51.4×	0.051	TUBB8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
establishment of meiotic sister chromatid cohesion	1	1053.2×	0.009	STAG3
spindle assembly involved in female meiosis	1	468.1×	0.009	TUBB8
chiasma assembly	1	468.1×	0.009	RNF212B
sister chromatid cohesion	1	191.5×	0.012	STAG3
synaptonemal complex assembly	1	162.0×	0.012	STAG3
oocyte maturation	1	150.5×	0.012	TUBB8
homologous chromosome pairing at meiosis	1	150.5×	0.012	RNF212B
mitotic cell cycle	1	33.4×	0.047	TUBB8
microtubule cytoskeleton organization	1	30.3×	0.047	TUBB8
neuron differentiation	1	25.1×	0.051	BTG4
regulation of cell cycle	1	18.6×	0.062	BTG4
negative regulation of cell population proliferation	1	10.5×	0.093	BTG4
protein ubiquitination	1	10.3×	0.093	RNF212B

Therapeutics

Drugs indicated or in trials for this disease

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

Drug	Status
Choriogonadotropin Alfa	Approved (phase 4)
Follitropin Alfa	Approved (phase 4)
Ganirelix	Approved (phase 4)
Lutropin Alfa	Approved (phase 4)

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

Drug	Highest phase
Acetylcysteine	Phase 3
Dydrogesterone	Phase 3
Progesterone	Phase 3

Drug target analysis

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

Druggability breadth: 1 of 4 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
TUBB8	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBB8	21	4
BTG4	0	0
STAG3	0	0
RNF212B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBB8
VINBLASTINE	4	TUBB8
LEVOFLOXACIN ANHYDROUS	4	TUBB8
DOCETAXEL	4	TUBB8
NOSCAPINE	4	TUBB8
VINBLASTINE SULFATE	4	TUBB8
PACLITAXEL	4	TUBB8
LEVOFLOXACIN	4	TUBB8
VINORELBINE	4	TUBB8
TIRBANIBULIN	4	TUBB8
PODOFILOX	4	TUBB8
VINCRISTINE	4	TUBB8
DOCETAXEL ANHYDROUS	4	TUBB8
PATUPILONE	3	TUBB8
ABT-751	2	TUBB8
MAYTANSINE	2	TUBB8
DOLASTATIN-10	2	TUBB8
INDIBULIN	2	TUBB8
PARBENDAZOLE	2	TUBB8
NOCODAZOLE	2	TUBB8
COMBRETASTATIN	1	TUBB8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TUBB8	1,757	Binding:1717, Functional:34, ADMET:6

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TUBB8	1,757

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

21 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)
COLCHICINE	4	TUBB8
VINBLASTINE	4	TUBB8
LEVOFLOXACIN ANHYDROUS	4	TUBB8
DOCETAXEL	4	TUBB8
NOSCAPINE	4	TUBB8
VINBLASTINE SULFATE	4	TUBB8
PACLITAXEL	4	TUBB8
LEVOFLOXACIN	4	TUBB8
VINORELBINE	4	TUBB8
TIRBANIBULIN	4	TUBB8
PODOFILOX	4	TUBB8
VINCRISTINE	4	TUBB8
DOCETAXEL ANHYDROUS	4	TUBB8
PATUPILONE	3	TUBB8
ABT-751	2	TUBB8
MAYTANSINE	2	TUBB8
DOLASTATIN-10	2	TUBB8
INDIBULIN	2	TUBB8
PARBENDAZOLE	2	TUBB8
NOCODAZOLE	2	TUBB8
COMBRETASTATIN	1	TUBB8

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TUBB8
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	BTG4, STAG3, RNF212B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BTG4	0	—
STAG3	0	—
RNF212B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 106.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	71
PHASE4	13
PHASE3	9
PHASE1	5
PHASE2/PHASE3	3
PHASE1/PHASE2	3
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06434233	PHASE4	RECRUITING	Opioid Use After Laparoscopic Salpingectomy
NCT06921395	PHASE4	RECRUITING	Phase IV Study to Evaluate the Efficacy and Safety of Fang Le Shu Compared to Guo Na Fen for Controlled Ovarian Stimulation in Infertile Women Undergoing in Vitro Fertilization-embryo Transfer (IVF-ET).
NCT01577472	PHASE4	COMPLETED	Efficacy Study Comparing the Effect of Clomiphencitrate to an Antagonist Protocol
NCT01791751	PHASE4	COMPLETED	Impact of Clomiphene Citrate Administration During the Early Luteal Phase on Endocrine Profile in IVF Cycles
NCT02070198	PHASE4	UNKNOWN	Long Acting FSH Plus Antagonist Versus Daily FSH Plus Antagonist Versus Short Agonist Protocol in Poor Responders Undergoing IVF
NCT02328924	PHASE4	COMPLETED	There is a Value of Luteinizing Hormone Predictive of in Vitro Fertilization Treatment Outcome in Antagonist Protocols?
NCT03057574	PHASE4	UNKNOWN	Gonapure® in Multifollicular Stimulation in Egyptian Women Undergoing IVF/ICSI
NCT05197374	PHASE4	COMPLETED	Effect of Estradiol Pretreatment on Antagonist ICSI Cycles
NCT05281341	PHASE4	COMPLETED	Effect of GH Administration in Poor Responders Undergoing Intracytoplasmic Sperm Injection (ICSI)
NCT05286554	PHASE4	COMPLETED	Addition of Gonadotropin Releasing Hormone Agonist to Luteal Phase Support
NCT05608590	PHASE4	UNKNOWN	What is the Best Moment for Performing an HSG in Women With a Unfulfilled Childwish
NCT05753098	PHASE4	COMPLETED	Effect of Sildenafil Citrate Compared to Estrogen as Adjuvant Therapy for Unexplained Infertility
NCT06684951	PHASE4	COMPLETED	Effects of Intrauterine Flushing With Human Chorionic Gonadotropin on ICSI Outcome
NCT02741102	PHASE2/PHASE3	RECRUITING	Uterine Transplant in Absolute Uterine Infertility (AUIF)
NCT01850030	PHASE3	COMPLETED	A Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Intravaginal Micronized Progesterone Capsules 600 mg Daily for Luteal Support in In-Vitro Fertilization
NCT02175498	PHASE3	COMPLETED	Effectiveness of Homeopathic Treatment in Female Infertility
NCT02237755	PHASE2/PHASE3	UNKNOWN	Clomiphene Citrate in Combination With Gonadotropins for Ovarian Stimulation in Women With Poor Ovarian Response.
NCT02237781	PHASE2/PHASE3	UNKNOWN	Levels of Anti-Mullerian Hormone (AMH) During Ovarian Stimulation With Gonadotropins
NCT02491437	PHASE3	COMPLETED	A Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Crinone 8% Intravaginal Progesterone Gel 90 mg Daily for Luteal Support in In-Vitro Fertilization (LOTUS II)
NCT03429621	PHASE3	COMPLETED	Effect of Simethicone on Reducing Bowel Interference During Tubal Resection
NCT03542331	PHASE3	UNKNOWN	Endometrial Effects of Lipiodol
NCT03767569	PHASE3	UNKNOWN	Myo-inositol as Pretreatment in Hyperandrogenic PCOS Patients
NCT03862586	PHASE3	COMPLETED	NAC Effect on Hox Genes Expressions in RIF
NCT05266924	PHASE3	UNKNOWN	Recombinant Follicle-stimulating Hormone in Treatment for Infertility
NCT05460858	PHASE3	UNKNOWN	NAC Effect on Infertile Women With Endometrioma
NCT06896747	PHASE1/PHASE2	RECRUITING	Evaluating Mechanically Engineered Stem Cell Exosomes for Treating Endometrial Injury: A Clinical Study
NCT03881904	PHASE1/PHASE2	UNKNOWN	OCP Pretreatment in PCOS Patients Undergoing ICSI Using Antagonist Protocol
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT06599528	PHASE1	RECRUITING	A Comparing Study Between SJ04 and Ovidrel® in Healthy Subjects
NCT01354886	PHASE1	COMPLETED	Single Dose FSH-GEX™ in Healthy Volunteers
NCT01477073	PHASE1	COMPLETED	Multiple Dose FSH-GEX(TM) in Healthy Volunteers
NCT01604044	PHASE1	COMPLETED	Highly Purified Menotropin (HP-hMG) Versus Recombinant FSH (rFSH) Plus Recombinant LH (rLH) in Intrauterine Insemination Cycles in Women ≥35 Years: a Prospective Randomized Trial.
NCT03755037	PHASE1	COMPLETED	Clomiphene Citrate, Estradiol and Sildenafil for Induction of Ovulation in Unexplained Infertility
NCT03237117	EARLY_PHASE1	UNKNOWN	Effect of Growth Hormone on Uterine Receptivity in Women With RIF in an Oocyte Donation Program
NCT06778733	EARLY_PHASE1	COMPLETED	Effectiveness of Low Dose Gonadotropin Stimulation Protocol Vs High Dose Gonadotropin Protocol in Poor Responders
NCT03496636	Not specified	RECRUITING	Autologous Ovarian Tissue Transplantation
NCT04866329	Not specified	RECRUITING	Female Fertility, Environmental Agents and Stress Oxidant
NCT05179993	Not specified	ACTIVE_NOT_RECRUITING	Detection of Microplastics in Human Granulosa Cells and in the Follicular Fluid of Women Undergoing ICSI Treatment
NCT05279560	Not specified	ACTIVE_NOT_RECRUITING	Ovarian PRP (Platelet Rich Plasma) Injection for Follicular Activation
NCT05421364	Not specified	RECRUITING	Effects of Intrauterine Administration of Autologous PBMC on the Endometrial Cells Populations

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CLOMIPHENE	4	9
FOLLITROPIN ALFA	4	4
SILDENAFIL	4	3
DYDROGESTERONE	4	2
ESTRADIOL VALERATE	4	2
ETHIODIZED OIL	4	2
TRIPTORELIN	4	2
CITRIC ACID	4	1
ESTRADIOL	4	1
ETHINYL ESTRADIOL	4	1
FOLIC ACID	4	1
GONADORELIN ACETATE	4	1
GONADOTROPIN, CHORIONIC	4	1
GUAIFENESIN	4	1
PROGESTERONE	4	1
SIMETHICONE	4	1
SOMATROPIN	4	1
UROFOLLITROPIN	4	1
ENCLOMIPHENE	3	4
ESTROGEN	3	1
GESTODENE	3	1
INOSITOL	3	1
CHEMBL1233255	0	1
CHEMBL1950780	0	1
CHEMBL2370644	0	1
CHEMBL2392189	0	1
CHEMBL259100	0	1