Ovarian dysgenesis 1

Summary

Ovarian dysgenesis 1 (MONDO:0024463) is a disease caused by FSHR (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FSHR (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 74

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian dysgenesis 1
Mondo ID	MONDO:0024463
OMIM	233300
DOID	DOID:0080493
UMLS	C0949595
MedGen	215397
GARD	0018039
Is cancer (heuristic)	no

Also known as: ODG1 · ovarian dysgenesis 1 · XXGD

Data availability: 74 ClinVar variants · 2 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 1

Related subtypes (10): ovarian dysgenesis 2, SERKAL syndrome, ovarian dysgenesis 3, ovarian dysgenesis 7, ovarian dysgenesis 9, ovarian dysgenesis 10, ovarian dysgenesis 8, 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

74 retrieved; paginated sample, class counts are floors:

38 uncertain significance, 11 likely pathogenic, 10 conflicting classifications of pathogenicity, 5 pathogenic, 4 benign, 3 likely benign, 1 not provided, 1 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
16243	NM_000145.4(FSHR):c.566C>T (p.Ala189Val)	FSHR	Pathogenic	no assertion criteria provided
16245	NM_000145.4(FSHR):c.1717C>T (p.Arg573Cys)	FSHR	Pathogenic	no assertion criteria provided
16248	NM_000145.4(FSHR):c.1255G>A (p.Ala419Thr)	FSHR	Pathogenic	no assertion criteria provided
16251	NM_000145.4(FSHR):c.1555C>A (p.Pro519Thr)	FSHR	Pathogenic	no assertion criteria provided
29704	NM_000145.4(FSHR):c.1760C>A (p.Pro587His)	FSHR	Pathogenic/Likely pathogenic	no assertion criteria provided
3381984	NM_000145.4(FSHR):c.564_565del (p.Ala189fs)	FSHR	Pathogenic	criteria provided, single submitter
3381987	NM_000145.4(FSHR):c.1255G>C (p.Ala419Pro)	FSHR	Likely pathogenic	criteria provided, single submitter
3779679	NM_000145.4(FSHR):c.507del (p.Phe170fs)	FSHR	Likely pathogenic	criteria provided, single submitter
3892624	NM_000145.4(FSHR):c.1109G>A (p.Trp370Ter)	FSHR	Likely pathogenic	criteria provided, single submitter
4849477	NM_000145.4(FSHR):c.580C>T (p.Gln194Ter)	FSHR	Likely pathogenic	criteria provided, single submitter
56030	NM_000145.4(FSHR):c.1043C>G (p.Pro348Arg)	FSHR	Likely pathogenic	no assertion criteria provided
56031	NM_000145.4(FSHR):c.1724C>T (p.Ala575Val)	FSHR	Likely pathogenic	no assertion criteria provided
56032	NM_000145.4(FSHR):c.1801C>G (p.Leu601Val)	FSHR	Likely pathogenic	no assertion criteria provided
56033	NM_000145.4(FSHR):c.662T>G (p.Val221Gly)	FSHR	Likely pathogenic	no assertion criteria provided
56034	NM_000145.4(FSHR):c.671A>T (p.Asp224Val)	FSHR	Likely pathogenic	no assertion criteria provided
996017	NM_000145.4(FSHR):c.1384G>C (p.Ala462Pro)	FSHR	Likely pathogenic	criteria provided, single submitter
996018	NM_000145.4(FSHR):c.1862C>T (p.Ala621Val)	FSHR	Likely pathogenic	criteria provided, single submitter
16244	NM_000145.4(FSHR):c.479T>C (p.Ile160Thr)	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
255348	NM_000145.4(FSHR):c.24G>T (p.Leu8Phe)	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
336482	NM_000145.4(FSHR):c.1330G>A (p.Ala444Thr)	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
336485	NM_000145.4(FSHR):c.786C>T (p.Val262=)	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
336489	NM_000145.4(FSHR):c.485G>A (p.Arg162Lys)	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
336490	NM_000145.4(FSHR):c.446+10T>C	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
757090	NM_000145.4(FSHR):c.1572C>G (p.Ser524Arg)	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
897606	NM_000145.4(FSHR):c.*321A>T	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
898832	NM_000145.4(FSHR):c.1022T>C (p.Val341Ala)	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
898896	NM_000145.4(FSHR):c.496G>T (p.Val166Leu)	FSHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1339879	NM_000145.4(FSHR):c.1669C>T (p.Arg557Trp)	FSHR	Uncertain significance	criteria provided, single submitter
1709277	NM_000145.4(FSHR):c.43G>T (p.Gly15Cys)	FSHR	Uncertain significance	criteria provided, single submitter
3097194	NM_000145.4(FSHR):c.986C>A (p.Thr329Lys)	FSHR	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
FSHR	Strong	Autosomal recessive	ovarian dysgenesis 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FSHR	Orphanet:243	46,XX gonadal dysgenesis
FSHR	Orphanet:64739	Ovarian hyperstimulation syndrome

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
FSHR	HGNC:3969	ENSG00000170820	P23945	Follicle-stimulating hormone receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FSHR	Follicle-stimulating hormone receptor	G protein-coupled receptor for follitropin, the follicle-stimulating hormone.

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FSHR	GPCR	yes		GPCR_Rhodpsn, LRRNT, Gphrmn_rcpt_fam

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
lower esophagus mucosa	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
FSHR	98	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, lower esophagus mucosa, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FSHR	1,667

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FSHR	P23945	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Hormone ligand-binding receptors	1	951.7×	0.002	FSHR
G alpha (s) signalling events	1	73.2×	0.014	FSHR

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
regulation of acetylcholine metabolic process	1	16852.0×	0.001	FSHR
primary ovarian follicle growth	1	8426.0×	0.001	FSHR
regulation of platelet-derived growth factor receptor signaling pathway	1	8426.0×	0.001	FSHR
follicle-stimulating hormone signaling pathway	1	5617.3×	0.001	FSHR
obsolete regulation of protein kinase A signaling	1	4213.0×	0.002	FSHR
regulation of hormone metabolic process	1	3370.4×	0.002	FSHR
Sertoli cell proliferation	1	2808.7×	0.002	FSHR
intracellular water homeostasis	1	2407.4×	0.002	FSHR
transcytosis	1	1685.2×	0.002	FSHR
regulation of osteoclast differentiation	1	1532.0×	0.002	FSHR
cellular response to follicle-stimulating hormone stimulus	1	1404.3×	0.002	FSHR
positive regulation of intracellular estrogen receptor signaling pathway	1	1203.7×	0.002	FSHR
gonad development	1	1123.5×	0.002	FSHR
Sertoli cell development	1	1123.5×	0.002	FSHR
regulation of systemic arterial blood pressure	1	1053.2×	0.002	FSHR
negative regulation of bone resorption	1	991.3×	0.002	FSHR
regulation of chromosome organization	1	936.2×	0.002	FSHR
sperm DNA condensation	1	887.0×	0.002	FSHR
female gamete generation	1	802.5×	0.002	FSHR
female gonad development	1	802.5×	0.002	FSHR
uterus development	1	802.5×	0.002	FSHR
basement membrane organization	1	510.7×	0.003	FSHR
hormone-mediated signaling pathway	1	401.2×	0.004	FSHR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1	218.9×	0.006	FSHR
locomotory behavior	1	179.3×	0.007	FSHR
male gonad development	1	156.0×	0.008	FSHR
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.009	FSHR
neuron projection development	1	122.1×	0.010	FSHR
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	113.1×	0.010	FSHR
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.013	FSHR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FSHR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FSHR	43	Functional:26, Binding:17

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

0 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.

Druggability pyramid

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

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

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FSHR	43	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.