Ovarian granulosa cell tumor

Summary

Ovarian granulosa cell tumor (MONDO:0023283) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 2 ClinVar predisposition records) and 5 clinical trials. Top therapeutic interventions include bevacizumab, bleomycin sulfate, and etoposide phosphate.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian granulosa cell tumor
Mondo ID	MONDO:0023283
MeSH	C537296
NCIT	C6261
SNOMED CT	254863004
UMLS	C1370419
MedGen	277970
GARD	0027911
Anatomy (UBERON)	UBERON:0000992
Is cancer (heuristic)	yes

Also known as: adult granulosa cell tumor of the ovary · adult granulosa cell tumour of the ovary · GCT of the ovary · granulosa cell neoplasm of ovary · granulosa cell neoplasm of the ovary · granulosa cell tumor of ovary · granulosa cell tumor of the ovary · granulosa cell tumour of ovary · granulosa cell tumour of the ovary · granulosa theca cell tumor · granulosa theca cell tumor of the ovary · granulosa theca cell tumour · granulosa theca cell tumour of the ovary · ovarian granulosa cell neoplasm · ovarian granulosa cell tumor · ovary granulosa cell tumor · ovary granulosa cell tumour

Data availability: 2 ClinVar variants · 8 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › endocrine gland neoplasm › granulosa cell tumor › ovarian granulosa cell tumor

Related subtypes (1): testicular granulosa cell tumor

Subtypes (1): maligant granulosa cell tumor of ovary

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

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
15904	NM_002070.4(GNAI2):c.536G>A (p.Arg179His)	GNAI2	Pathogenic	criteria provided, single submitter
15903	NM_002070.4(GNAI2):c.535C>T (p.Arg179Cys)	GNAI2	Conflicting classifications of pathogenicity	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
GNAI2	Act	NHL	CIViC #2312

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
GNAI2	HGNC:4385	ENSG00000114353	P04899	Guanine nucleotide-binding protein G(i) subunit alpha-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNAI2	Guanine nucleotide-binding protein G(i) subunit alpha-2	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNAI2	Other/Unknown	no		Gprotein_alpha_su, Gprotein_alpha_I, GproteinA_insert

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
granulocyte	1
monocyte	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNAI2	291	ubiquitous	marker	granulocyte, monocyte, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNAI2	3,311

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAI2	P04899	34

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Adenylate cyclase inhibitory pathway	1	761.3×	0.007	GNAI2
ADP signalling through P2Y purinoceptor 12	1	496.5×	0.007	GNAI2
Adrenaline,noradrenaline inhibits insulin secretion	1	393.8×	0.007	GNAI2
ADORA2B mediated anti-inflammatory cytokines production	1	253.8×	0.007	GNAI2
GPER1 signaling	1	248.3×	0.007	GNAI2
G alpha (z) signalling events	1	233.1×	0.007	GNAI2
Regulation of insulin secretion	1	219.6×	0.007	GNAI2
Extra-nuclear estrogen signaling	1	170.4×	0.007	GNAI2
G alpha (s) signalling events	1	73.2×	0.015	GNAI2
G alpha (i) signalling events	1	39.0×	0.026	GNAI2

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
G protein-coupled adenosine receptor signaling pathway	1	2407.4×	0.003	GNAI2
negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway	1	2407.4×	0.003	GNAI2
negative regulation of calcium ion-dependent exocytosis	1	1872.4×	0.003	GNAI2
negative regulation of synaptic transmission	1	1685.2×	0.003	GNAI2
negative regulation of adenylate cyclase activity	1	1404.3×	0.003	GNAI2
positive regulation of urine volume	1	1296.3×	0.003	GNAI2
G protein-coupled acetylcholine receptor signaling pathway	1	1053.2×	0.003	GNAI2
positive regulation of superoxide anion generation	1	887.0×	0.003	GNAI2
regulation of calcium ion transport	1	802.5×	0.003	GNAI2
positive regulation of neural precursor cell proliferation	1	766.0×	0.003	GNAI2
negative regulation of apoptotic signaling pathway	1	561.7×	0.004	GNAI2
gamma-aminobutyric acid signaling pathway	1	543.6×	0.004	GNAI2
positive regulation of vascular associated smooth muscle cell proliferation	1	432.1×	0.004	GNAI2
response to nutrient	1	295.6×	0.006	GNAI2
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1	218.9×	0.007	GNAI2
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	113.1×	0.013	GNAI2
cell population proliferation	1	102.8×	0.013	GNAI2
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.015	GNAI2
positive regulation of cell migration	1	61.7×	0.020	GNAI2
cell division	1	46.2×	0.025	GNAI2
G protein-coupled receptor signaling pathway	1	36.2×	0.030	GNAI2
positive regulation of cell population proliferation	1	33.6×	0.031	GNAI2
signal transduction	1	16.1×	0.062	GNAI2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GNAI2	2	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ALISERTIB	3	GNAI2
MOLIBRESIB	2	GNAI2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GNAI2	9	Binding:9

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).

Drug repurposing candidates

2 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
ALISERTIB	3	GNAI2
MOLIBRESIB	2	GNAI2

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	1	GNAI2
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: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	4
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00748657	PHASE2	COMPLETED	Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary
NCT01042522	PHASE2	UNKNOWN	Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors
NCT01584297	PHASE2	TERMINATED	Ketoconazole as Inhibitor of the Enzyme CYP17 in Locally Advanced or Disseminated Granulosa Cell Tumour of Ovary
NCT05348356	PHASE2	COMPLETED	Nirogacestat in Ovarian Granulosa Cell Tumors
NCT06254781	Not specified	COMPLETED	Luspatercept in Metastatic AGCT of the Ovary

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BEVACIZUMAB	4	1
BLEOMYCIN SULFATE	4	1
ETOPOSIDE PHOSPHATE	4	1
KETOCONAZOLE	4	1
LEVOKETOCONAZOLE	4	1
LUSPATERCEPT	4	1
NIROGACESTAT	4	1
CHEMBL328863	0	1
CHEMBL75	0	1