Granulosa cell tumor

Summary

Granulosa cell tumor (MONDO:0006036) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers) and 1 clinical trial. Top therapeutic interventions include nivolumab.

At a glance

• Classification: Cancer
• Cohort genes: 2
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	granulosa cell tumor
Mondo ID	MONDO:0006036
EFO	EFO:1000032
MeSH	D006106
DOID	DOID:2999
NCIT	C3070
UMLS	C0018206
MedGen	6676
Is cancer (heuristic)	yes

Also known as: granulosa cell neoplasm · granulosa cell neoplasm (disease) · granulosa cell tumor · granulosa cell tumor, adult type (morphologic abnormality) · granulosa cell tumor, sarcomatoid · GRCT · neoplasm of granulosa cell · tumor of granulosa cell · tumour of granulosa cell

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (13): benign endocrine neoplasm, thymus neoplasm, thyroid tumor, pituitary tumor, familial tumoral calcinosis, neuroendocrine neoplasm, malignant endocrine neoplasm, non-functioning endocrine neoplasm, functioning endocrine neoplasm, adrenal gland neoplasm, pineal body neoplasm, tumor of parathyroid gland, liver and intrahepatic bile duct neoplasm

Subtypes (2): testicular granulosa cell tumor, ovarian granulosa cell tumor

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
FOXL2	Act	OVT	CIViC #72
DICER1	LoF	COADREAD,CSCC,MEL,UCEC	CIViC #9533

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FOXL2	Orphanet:572333	Blepharophimosis-ptosis-epicanthus inversus syndrome plus
FOXL2	Orphanet:572354	Blepharophimosis-ptosis-epicanthus inversus syndrome type 1
FOXL2	Orphanet:572361	Blepharophimosis-ptosis-epicanthus inversus syndrome type 2
FOXL2	Orphanet:99915	Malignant granulosa cell tumor of the ovary
DICER1	Orphanet:276399	Familial multinodular goiter
DICER1	Orphanet:284343	DICER1 tumor-predisposition syndrome
DICER1	Orphanet:404476	Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome
DICER1	Orphanet:99757	Embryonal rhabdomyosarcoma
DICER1	Orphanet:99914	Gynandroblastoma
DICER1	Orphanet:99915	Malignant granulosa cell tumor of the ovary
DICER1	Orphanet:99916	Malignant Sertoli-Leydig cell tumor of the ovary

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FOXL2	HGNC:1092	ENSG00000183770	P58012	Forkhead box protein L2	civic_evidence
DICER1	HGNC:17098	ENSG00000100697	Q9UPY3	Endoribonuclease Dicer	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FOXL2	Forkhead box protein L2	Transcriptional regulator.
DICER1	Endoribonuclease Dicer	Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.228
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FOXL2	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
DICER1	Enzyme (other)	yes	3.1.26.3	RNase_III_dom, Helicase_C-like, PAZ_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
ovary	1
stromal cell of endometrium	1
caput epididymis	1
cauda epididymis	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FOXL2	84	broad	marker	left ovary, stromal cell of endometrium, ovary
DICER1	295	ubiquitous	marker	cauda epididymis, caput epididymis, tongue squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DICER1	8,268
FOXL2	1,727

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DICER1	Q9UPY3	21
FOXL2	P58012	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis	1	1903.3×	0.004	DICER1
Small interfering RNA (siRNA) biogenesis	1	571.0×	0.005	DICER1
Transcriptional regulation of testis differentiation	1	356.9×	0.005	FOXL2
Regulation of MITF-M-dependent genes involved in apoptosis	1	317.2×	0.005	DICER1
SUMOylation of transcription factors	1	285.5×	0.005	FOXL2
MicroRNA (miRNA) biogenesis	1	228.4×	0.005	DICER1
M-decay: degradation of maternal mRNAs by maternally stored factors	1	163.1×	0.006	DICER1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
apoptotic DNA fragmentation	2	1203.7×	2e-05	FOXL2, DICER1
female somatic sex determination	1	8426.0×	0.001	FOXL2
granulosa cell differentiation	1	8426.0×	0.001	FOXL2
positive regulation of Schwann cell differentiation	1	4213.0×	0.002	DICER1
peripheral nervous system myelin formation	1	2808.7×	0.002	DICER1
global gene silencing by mRNA cleavage	1	2808.7×	0.002	DICER1
oocyte growth	1	2106.5×	0.002	FOXL2
tRNA decay	1	1685.2×	0.002	DICER1
positive regulation of luteinizing hormone secretion	1	1685.2×	0.002	FOXL2
extraocular skeletal muscle development	1	1404.3×	0.002	FOXL2
positive regulation of follicle-stimulating hormone secretion	1	1404.3×	0.002	FOXL2
negative regulation of Schwann cell proliferation	1	1203.7×	0.002	DICER1
siRNA processing	1	936.2×	0.003	DICER1
embryonic eye morphogenesis	1	766.0×	0.003	FOXL2
RISC complex assembly	1	766.0×	0.003	DICER1
miRNA metabolic process	1	702.2×	0.003	DICER1
pre-miRNA processing	1	561.7×	0.004	DICER1
miRNA processing	1	526.6×	0.004	DICER1
nerve development	1	468.1×	0.004	DICER1
uterus development	1	401.2×	0.004	FOXL2
positive regulation of myelination	1	383.0×	0.004	DICER1
negative regulation of transcription by RNA polymerase II	2	17.7×	0.005	FOXL2, DICER1
negative regulation of tumor necrosis factor-mediated signaling pathway	1	227.7×	0.006	DICER1
ovarian follicle development	1	195.9×	0.007	FOXL2
neuron projection morphogenesis	1	138.1×	0.010	DICER1
negative regulation of tumor necrosis factor production	1	125.8×	0.010	DICER1
single fertilization	1	91.6×	0.014	FOXL2
anatomical structure morphogenesis	1	69.6×	0.017	FOXL2
negative regulation of gene expression	1	34.5×	0.034	DICER1
positive regulation of apoptotic process	1	28.4×	0.040	FOXL2

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Darolutamide, Exemestane.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FOXL2	0	0
DICER1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DICER1	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DICER1	3.1.26.3	ribonuclease III

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 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.

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	DICER1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FOXL2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FOXL2	0	—
DICER1	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NIVOLUMAB	4	1