Premature ovarian failure 8

Summary

Premature ovarian failure 8 (MONDO:0014321) is a disease caused by STAG3 (GenCC Strong), with 1 cohort gene and 2 clinical trials.

At a glance

• Causal gene: STAG3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 20
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 8
Mondo ID	MONDO:0014321
OMIM	615723
DOID	DOID:0080865
UMLS	C3810367
MedGen	816697
GARD	0024985
Is cancer (heuristic)	no

Also known as: POF8 · premature ovarian failure 8 · premature ovarian failure type 8 · primary ovarian failure caused by mutation in STAG3 · STAG3 primary ovarian failure

Data availability: 20 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited primary ovarian failure › premature ovarian failure 8

Related subtypes (40): blepharophimosis, ptosis, and epicanthus inversus syndrome, congenital lipoid adrenal hyperplasia due to STAR deficency, ataxia telangiectasia, classic galactosemia, 46 XX gonadal dysgenesis, premature ovarian failure 2A, premature ovarian failure 2B, premature ovarian failure 1, Satoyoshi syndrome, premature ovarian failure 3, osteosclerosis-ichthyosis-premature ovarian failure syndrome, premature ovarian failure 5, premature ovarian failure 6, premature ovarian failure 7, aromatase deficiency, premature ovarian failure 9, 46,XX ovarian dysgenesis-short stature syndrome, premature ovarian failure 11, premature ovarian failure 12, Perrault syndrome, trisomy X, Turner syndrome, tetrasomy X, X small rings, premature ovarian failure 17, premature ovarian failure 18, premature ovarian failure 20, premature ovarian failure 19, premature ovarian failure 16, premature ovarian failure 13, premature ovarian failure 10, premature ovarian failure 14, premature ovarian failure 15, premature ovarian failure 4, premature ovarian failure 21, premature ovarian failure 22, premature ovarian failure 23, premature ovarian failure 24, premature ovarian failure 25, premature ovarian failure 26

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

20 retrieved; paginated sample, class counts are floors:

7 pathogenic, 6 benign, 5 likely pathogenic, 1 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
126427	NM_001282717.2(STAG3):c.562del (p.Gln188fs)	STAG3	Pathogenic	no assertion criteria provided
1328922	NM_001282717.2(STAG3):c.291dup (p.Asn98fs)	STAG3	Pathogenic	no assertion criteria provided
1328923	NM_001282717.2(STAG3):c.1950C>A (p.Tyr650Ter)	STAG3	Pathogenic	no assertion criteria provided
224903	NM_001282717.2(STAG3):c.1947_1948dup (p.Tyr650fs)	STAG3	Pathogenic	no assertion criteria provided
4293889	NM_001282717.2(STAG3):c.2821C>T (p.Gln941Ter)	STAG3	Pathogenic	criteria provided, single submitter
430588	NM_001282717.2(STAG3):c.1573+5G>A	STAG3	Pathogenic	no assertion criteria provided
4813861	NM_001282717.2(STAG3):c.2773del (p.Ser925fs)	STAG3	Pathogenic	criteria provided, single submitter
692153	NM_001282717.2(STAG3):c.962G>A (p.Arg321His)	STAG3	Pathogenic/Likely pathogenic	no assertion criteria provided
1709457	NM_001282717.2(STAG3):c.3369_3381del (p.Glu1124fs)	STAG3	Likely pathogenic	criteria provided, single submitter
1802231	NM_001282717.2(STAG3):c.2221-1_2225delinsAC	STAG3	Likely pathogenic	criteria provided, single submitter
3062323	NM_001282717.2(STAG3):c.3550G>T (p.Glu1184Ter)	STAG3	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
869148	NM_001282717.2(STAG3):c.1571del (p.Gln524fs)	STAG3	Likely pathogenic	criteria provided, single submitter
1214010	NM_001282717.2(STAG3):c.2627G>A (p.Gly876Glu)	STAG3	Uncertain significance	no assertion criteria provided
1183740	NM_001282717.2(STAG3):c.106A>C (p.Thr36Pro)	STAG3	Benign	criteria provided, multiple submitters, no conflicts
1229759	NM_001282717.2(STAG3):c.1245-26T>C	STAG3	Benign	criteria provided, multiple submitters, no conflicts
1230818	NM_001282717.2(STAG3):c.2445T>A (p.Ile815=)	STAG3	Benign	criteria provided, multiple submitters, no conflicts
1236675	NM_001282717.2(STAG3):c.48G>T (p.Leu16Phe)	STAG3	Benign	criteria provided, multiple submitters, no conflicts
1243986	NM_001282717.2(STAG3):c.1293A>C (p.Pro431=)	STAG3	Benign	criteria provided, multiple submitters, no conflicts
1287786	NM_001282717.2(STAG3):c.1573+41C>G	STAG3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
STAG3	Strong	Autosomal recessive	premature ovarian failure 8	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

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
STAG3	HGNC:11356	ENSG00000066923	Q9UJ98	Cohesin subunit SA-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STAG3	Cohesin subunit SA-3	Meiosis specific component of cohesin complex.

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)
STAG3	Other/Unknown	no		STAG, ARM-type_fold, SCD

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
left testis	1
oocyte	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STAG3	185	broad	marker	oocyte, right testis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAG3	1,232

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STAG3	Q9UJ98	78.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Meiosis	1	285.5×	0.009	STAG3
Reproduction	1	190.3×	0.009	STAG3
Meiotic synapsis	1	141.0×	0.009	STAG3
Cell Cycle	1	36.0×	0.028	STAG3

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
establishment of meiotic sister chromatid cohesion	1	4213.0×	7e-04	STAG3
sister chromatid cohesion	1	766.0×	0.002	STAG3
synaptonemal complex assembly	1	648.1×	0.002	STAG3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STAG3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	STAG3

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)
STAG3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials