Ovarian dysgenesis 8

Summary

Ovarian dysgenesis 8 (MONDO:0032590) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian dysgenesis 8
Mondo ID	MONDO:0032590
OMIM	618187
DOID	DOID:0080500
UMLS	C4748626
MedGen	1648455
GARD	0025708
Is cancer (heuristic)	no

Also known as: ODG8

Data availability: 3 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › hypogonadism › gonadal dysgenesis › 46 XX gonadal dysgenesis › ovarian dysgenesis 8

Related subtypes (10): ovarian dysgenesis 2, SERKAL syndrome, ovarian dysgenesis 3, ovarian dysgenesis 7, ovarian dysgenesis 1, ovarian dysgenesis 9, ovarian dysgenesis 10, ovarian dysgenesis 5, ovarian dysgenesis 6, ovarian dysgenesis 11

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
590785	NM_001437.3(ESR2):c.941A>G (p.Lys314Arg)	ESR2	Pathogenic	no assertion criteria provided
3383047	NM_001437.3(ESR2):c.1108G>A (p.Val370Ile)	ESR2	Uncertain significance	criteria provided, single submitter
3383124	NM_001437.3(ESR2):c.1220A>G (p.Asn407Ser)	ESR2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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
ESR2	Moderate	Autosomal dominant	ovarian dysgenesis 8	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ESR2	Orphanet:99361	Isolated familial medullary thyroid carcinoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ESR2	HGNC:3468	ENSG00000140009	Q92731	Estrogen receptor beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ESR2	Estrogen receptor beta	Nuclear hormone receptor.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Nuclear receptor	1	385.9×	0.003

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ESR2	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ESR2	170	broad	yes	right adrenal gland, right adrenal gland cortex, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ESR2	5,924

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ESR2	Q92731	39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nuclear Receptor transcription pathway	1	200.3×	0.012	ESR2
Extra-nuclear estrogen signaling	1	170.4×	0.012	ESR2
ESR-mediated signaling	1	128.3×	0.012	ESR2
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.012	ESR2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.012	ESR2
PIP3 activates AKT signaling	1	66.8×	0.015	ESR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
estrogen receptor signaling pathway	1	732.7×	0.009	ESR2
obsolete positive regulation of DNA-binding transcription factor activity	1	601.9×	0.009	ESR2
cellular response to estradiol stimulus	1	411.0×	0.009	ESR2
negative regulation of cell growth	1	144.0×	0.019	ESR2
cell-cell signaling	1	69.6×	0.032	ESR2
regulation of DNA-templated transcription	1	31.6×	0.056	ESR2
positive regulation of DNA-templated transcription	1	27.9×	0.056	ESR2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.074	ESR2
signal transduction	1	16.1×	0.074	ESR2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.074	ESR2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ESR2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
ESR2	RALOXIFENE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ESR2	44	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RALOXIFENE HYDROCHLORIDE	4	ESR2
CISPLATIN	4	ESR2
MIFEPRISTONE	4	ESR2
ESTRADIOL	4	ESR2
FULVESTRANT	4	ESR2
LASOFOXIFENE	4	ESR2
DIETHYLSTILBESTROL	4	ESR2
MEDROXYPROGESTERONE ACETATE	4	ESR2
RALOXIFENE	4	ESR2
TAMOXIFEN	4	ESR2
METHYSERGIDE	4	ESR2
DEMECLOCYCLINE HYDROCHLORIDE	4	ESR2
ESTETROL ANHYDROUS	4	ESR2
SPIRONOLACTONE	4	ESR2
ESTRONE	4	ESR2
ESTRIOL	4	ESR2
BITHIONOL	4	ESR2
ELACESTRANT	4	ESR2
BAZEDOXIFENE	4	ESR2
HEXACHLOROPHENE	4	ESR2
PHENOLPHTHALEIN	4	ESR2
ETHINYL ESTRADIOL	4	ESR2
TAMOXIFEN CITRATE	4	ESR2
ACOLBIFENE	3	ESR2
BENSERAZIDE	3	ESR2
ISOPHENOXODIOL	3	ESR2
ARZOXIFENE	3	ESR2
AMCENESTRANT	3	ESR2
AFIMOXIFENE	3	ESR2
STALLIMYCIN	2	ESR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ESR2	1,113	Binding:837, Functional:265, ADMET:11

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ESR2	1,113

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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.

Compound	Max phase	Cohort target (bioactivity)
RALOXIFENE HYDROCHLORIDE	4	ESR2
CISPLATIN	4	ESR2
MIFEPRISTONE	4	ESR2
ESTRADIOL	4	ESR2
FULVESTRANT	4	ESR2
LASOFOXIFENE	4	ESR2
DIETHYLSTILBESTROL	4	ESR2
MEDROXYPROGESTERONE ACETATE	4	ESR2
RALOXIFENE	4	ESR2
TAMOXIFEN	4	ESR2
METHYSERGIDE	4	ESR2
DEMECLOCYCLINE HYDROCHLORIDE	4	ESR2
ESTETROL ANHYDROUS	4	ESR2
SPIRONOLACTONE	4	ESR2
ESTRONE	4	ESR2
ESTRIOL	4	ESR2
BITHIONOL	4	ESR2
ELACESTRANT	4	ESR2
BAZEDOXIFENE	4	ESR2
HEXACHLOROPHENE	4	ESR2
PHENOLPHTHALEIN	4	ESR2
ETHINYL ESTRADIOL	4	ESR2
TAMOXIFEN CITRATE	4	ESR2
ACOLBIFENE	3	ESR2
BENSERAZIDE	3	ESR2
ISOPHENOXODIOL	3	ESR2
ARZOXIFENE	3	ESR2
AMCENESTRANT	3	ESR2
AFIMOXIFENE	3	ESR2
STALLIMYCIN	2	ESR2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ESR2
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.