Premature ovarian failure 5

disease

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Also known as NOBOX primary ovarian failurePof5premature ovarian failure type 5primary ovarian failure caused by mutation in NOBOX

Summary

Premature ovarian failure 5 (MONDO:0012689) is a disease caused by NOBOX (GenCC Strong), with 1 cohort gene and 2 clinical trials.

At a glance

Causal gene: NOBOX (GenCC Strong)
Cohort genes: 1
ClinVar variants: 71
Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 5
Mondo ID	MONDO:0012689
MeSH	C566921
OMIM	611548
DOID	DOID:0080862
UMLS	C1969060
MedGen	409743
GARD	0024882
Is cancer (heuristic)	no

Also known as: NOBOX primary ovarian failure · Pof5 · premature ovarian failure 5 · premature ovarian failure type 5 · primary ovarian failure caused by mutation in NOBOX

Data availability: 71 ClinVar variants · 3 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 5

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

71 retrieved; paginated sample, class counts are floors:

32 uncertain significance, 18 benign, 7 conflicting classifications of pathogenicity, 6 likely benign, 4 pathogenic, 2 benign/likely benign, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
167873	NM_001436401.1(NOBOX):c.652C>T (p.Arg218Ter)	NOBOX	Pathogenic	criteria provided, multiple submitters, no conflicts
167876	NM_001436401.1(NOBOX):c.696+74G>C	NOBOX	Pathogenic	no assertion criteria provided
167877	NM_001436401.1(NOBOX):c.697G>T (p.Val233Leu)	NOBOX	Pathogenic	no assertion criteria provided
3376873	NM_001436401.1(NOBOX):c.958del (p.Val320fs)	NOBOX	Pathogenic	criteria provided, single submitter
4081552	NM_001080413.3(NOBOX):c.120T>A (p.Cys40Ter)	NOBOX	Likely pathogenic	criteria provided, single submitter
812129	NM_001436401.1(NOBOX):c.727C>T (p.Arg243Ter)	NOBOX	Likely pathogenic	criteria provided, single submitter
1083	NM_001436401.1(NOBOX):c.713G>A (p.Arg238His)	NOBOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
167874	NM_001436401.1(NOBOX):c.38-293G>T	NOBOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359139	NM_001436401.1(NOBOX):c.1347C>T (p.Ser449=)	NOBOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359140	NM_001436401.1(NOBOX):c.1195C>T (p.Pro399Ser)	NOBOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359148	NM_001436401.1(NOBOX):c.107C>T (p.Pro36Leu)	NOBOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
791163	NM_001436401.1(NOBOX):c.1475C>T (p.Pro492Leu)	NOBOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908266	NM_001436401.1(NOBOX):c.1132C>A (p.Pro378Thr)	NOBOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030082	NM_001436401.1(NOBOX):c.1118+5G>A	NOBOX	Uncertain significance	criteria provided, single submitter
1709933	NM_001436401.1(NOBOX):c.76G>A (p.Gly26Arg)	NOBOX	Uncertain significance	criteria provided, multiple submitters, no conflicts
2664232	NM_001436401.1(NOBOX):c.986C>T (p.Pro329Leu)	NOBOX	Uncertain significance	criteria provided, single submitter
3251988	NM_001080413.3(NOBOX):c.48G>C (p.Trp16Cys)	NOBOX	Uncertain significance	criteria provided, single submitter
359132	NM_001436401.1(NOBOX):c.1587A>G (p.Ser529=)	NOBOX	Uncertain significance	criteria provided, single submitter
359133	NM_001436401.1(NOBOX):c.1549C>A (p.Pro517Thr)	NOBOX	Uncertain significance	criteria provided, single submitter
359136	NM_001436401.1(NOBOX):c.1423+11G>A	NOBOX	Uncertain significance	criteria provided, single submitter
359137	NM_001436401.1(NOBOX):c.1400T>G (p.Met467Arg)	NOBOX	Uncertain significance	criteria provided, single submitter
359141	NM_001436401.1(NOBOX):c.1156C>G (p.Leu386Val)	NOBOX	Uncertain significance	criteria provided, multiple submitters, no conflicts
359143	NM_001436401.1(NOBOX):c.971C>G (p.Pro324Arg)	NOBOX	Uncertain significance	criteria provided, single submitter
359145	NM_001436401.1(NOBOX):c.696+80G>A	NOBOX	Uncertain significance	criteria provided, single submitter
359146	NM_001436401.1(NOBOX):c.424C>T (p.Arg142Cys)	NOBOX	Uncertain significance	criteria provided, multiple submitters, no conflicts
359149	NM_001436401.1(NOBOX):c.107C>G (p.Pro36Arg)	NOBOX	Uncertain significance	criteria provided, single submitter
359151	NM_001436401.1(NOBOX):c.38-299G>C	NOBOX	Uncertain significance	criteria provided, single submitter
359153	NM_001436401.1(NOBOX):c.38-357G>C	NOBOX	Uncertain significance	criteria provided, single submitter
359156	NM_001080413.3(NOBOX):c.130C>T (p.Arg44Trp)	NOBOX	Uncertain significance	criteria provided, multiple submitters, no conflicts
359158	NM_001080413.3(NOBOX):c.85+10T>C	NOBOX	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
NOBOX	Strong	Autosomal dominant	premature ovarian failure 5	3

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
NOBOX	HGNC:22448	ENSG00000106410	O60393	Homeobox protein NOBOX	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NOBOX	Homeobox protein NOBOX	Transcription factor which may play a role in oogenesis.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NOBOX	Transcription factor	no		HD, Homeodomain-like_sf, NOBOX

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	1
broad (>20)	0
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
granulocyte	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NOBOX	8		yes	primordial germ cell in gonad, colonic epithelium, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOBOX	855

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NOBOX	O60393	48.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
M-decay: degradation of maternal mRNAs by maternally stored factors	1	326.3×	0.003	NOBOX

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
oogenesis	1	383.0×	0.005	NOBOX
regulation of transcription by RNA polymerase II	1	11.7×	0.086	NOBOX

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
NOBOX	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	NOBOX

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)
NOBOX	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

Cohort genes: NOBOX