Premature ovarian failure 7

Summary

Premature ovarian failure 7 (MONDO:0013065) is a disease caused by NR5A1 (GenCC Strong), with 1 cohort gene and 3 clinical trials.

At a glance

• Causal gene: NR5A1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 7
Mondo ID	MONDO:0013065
MeSH	C567838
OMIM	612964
DOID	DOID:0080864
UMLS	C2751825
MedGen	414115
GARD	0024899
Is cancer (heuristic)	no

Also known as: adrenocortical insufficiency · NR5A1 primary ovarian failure · Pof7 · premature ovarian failure 7 · premature ovarian failure type 7 · primary ovarian failure caused by mutation in NR5A1

Data availability: 14 ClinVar variants · 1 GenCC gene-disease record.

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 7

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, aromatase deficiency, premature ovarian failure 8, 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

14 retrieved; paginated sample, class counts are floors:

7 pathogenic, 3 uncertain significance, 2 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
12809	NM_004959.4(NR5A1):c.[368G>C;386C>T]		Pathogenic	no assertion criteria provided
12804	NM_004959.5(NR5A1):c.666del (p.Asn222fs)	NR5A1	Pathogenic	no assertion criteria provided
12805	NM_004959.5(NR5A1):c.877G>A (p.Asp293Asn)	NR5A1	Pathogenic	no assertion criteria provided
12806	NM_004959.5(NR5A1):c.3G>A (p.Met1Ile)	NR5A1	Pathogenic	no assertion criteria provided
12807	NM_004959.5(NR5A1):c.390del (p.Pro131fs)	NR5A1	Pathogenic	no assertion criteria provided
12808	NM_004959.5(NR5A1):c.682CTGCAGCTG[1] (p.228LQL[1])	NR5A1	Pathogenic	no assertion criteria provided
3596432	NM_004959.5(NR5A1):c.247G>A (p.Val83Met)	NR5A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3895489	NM_004959.5(NR5A1):c.1114_1116del (p.Lys372del)	NR5A1	Pathogenic	criteria provided, single submitter
1299627	NM_004959.5(NR5A1):c.578T>A (p.Ile193Asn)	NR5A1	Likely pathogenic	criteria provided, single submitter
4294444	NM_004959.5(NR5A1):c.529del (p.His177fs)	NR5A1	Likely pathogenic	criteria provided, single submitter
981141	NM_004959.5(NR5A1):c.1063G>A (p.Val355Met)	NR5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1302227	NM_004959.5(NR5A1):c.205C>T (p.Arg69Cys)	NR5A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3383135	NM_004959.5(NR5A1):c.8A>G (p.Tyr3Cys)	NR5A1	Uncertain significance	criteria provided, single submitter
4796609	NM_004959.5(NR5A1):c.1358T>G (p.Ile453Ser)	NR5A1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 6 · 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
NR5A1	Strong	Autosomal dominant	premature ovarian failure 7	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NR5A1	Orphanet:2138	46,XX ovotesticular difference of sex development
NR5A1	Orphanet:242	46,XY complete gonadal dysgenesis
NR5A1	Orphanet:243	46,XX gonadal dysgenesis
NR5A1	Orphanet:251510	46,XY partial gonadal dysgenesis
NR5A1	Orphanet:393	46,XX testicular difference of sex development
NR5A1	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
NR5A1	HGNC:7983	ENSG00000136931	Q13285	Steroidogenic factor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NR5A1	Steroidogenic factor 1	Transcriptional activator.

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)
NR5A1	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
NR5A1	77	tissue_specific	yes	right adrenal gland cortex, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NR5A1	2,146

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NR5A1	Q13285	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Transcriptional regulation of testis differentiation	1	713.8×	0.011	NR5A1
Transcriptional regulation of pluripotent stem cells	1	543.8×	0.011	NR5A1
SUMOylation of intracellular receptors	1	335.9×	0.012	NR5A1
Nuclear Receptor transcription pathway	1	200.3×	0.012	NR5A1
SUMO E3 ligases SUMOylate target proteins	1	178.4×	0.012	NR5A1
SUMOylation	1	163.1×	0.012	NR5A1
RNA Polymerase II Transcription	1	22.5×	0.075	NR5A1
Post-translational protein modification	1	19.2×	0.075	NR5A1
Gene expression (Transcription)	1	17.8×	0.075	NR5A1
Generic Transcription Pathway	1	15.1×	0.075	NR5A1
Developmental Biology	1	14.5×	0.075	NR5A1
Metabolism of proteins	1	12.4×	0.081	NR5A1

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
primary sex determination	1	8426.0×	0.001	NR5A1
response to gonadotropin-releasing hormone	1	5617.3×	0.001	NR5A1
negative regulation of female gonad development	1	4213.0×	0.001	NR5A1
luteinization	1	1872.4×	0.001	NR5A1
tissue development	1	1872.4×	0.001	NR5A1
sex determination	1	1685.2×	0.001	NR5A1
positive regulation of male gonad development	1	1685.2×	0.001	NR5A1
regulation of steroid biosynthetic process	1	1532.0×	0.001	NR5A1
Sertoli cell differentiation	1	1532.0×	0.001	NR5A1
calcineurin-mediated signaling	1	1532.0×	0.001	NR5A1
male sex determination	1	1404.3×	0.001	NR5A1
Leydig cell differentiation	1	1203.7×	0.002	NR5A1
maintenance of protein location in nucleus	1	1123.5×	0.002	NR5A1
hormone metabolic process	1	887.0×	0.002	NR5A1
female gonad development	1	802.5×	0.002	NR5A1
adrenal gland development	1	674.1×	0.002	NR5A1
hormone-mediated signaling pathway	1	401.2×	0.003	NR5A1
male gonad development	1	156.0×	0.008	NR5A1
transcription by RNA polymerase II	1	70.5×	0.016	NR5A1
positive regulation of gene expression	1	38.7×	0.028	NR5A1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.070	NR5A1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	NR5A1

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
NR5A1	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
NR5A1	88	Binding:84, Functional:4

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	NR5A1
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)
NR5A1	88	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1
PHASE1	1
Not specified	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
NCT01053754	Not specified	TERMINATED	Optimization of the Evaluation of the Adrenal Function After Discontinuation of a Prolonged Therapy With Corticosteroids