Premature ovarian failure 16

Summary

Premature ovarian failure 16 (MONDO:0032881) is a disease caused by BNC1 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: BNC1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 16
Mondo ID	MONDO:0032881
OMIM	618723
DOID	DOID:0080873
UMLS	C5231474
MedGen	1684679
GARD	0018044
Is cancer (heuristic)	no

Also known as: POF16

Data availability: 6 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 16

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 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 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

6 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
800707	NM_001717.4(BNC1):c.1065_1069del (p.Arg356fs)	BNC1	Pathogenic	no assertion criteria provided
1396950	NM_006876.3(B4GAT1):c.1240C>T (p.Arg414Cys)	B4GAT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1030363	NM_001717.4(BNC1):c.2917C>T (p.Arg973Ter)	BNC1	Uncertain significance	criteria provided, single submitter
2351907	NM_001717.4(BNC1):c.1925T>C (p.Leu642Ser)	BNC1	Uncertain significance	criteria provided, single submitter
3382993	NM_001717.4(BNC1):c.132_133del (p.Ser45fs)	BNC1	Uncertain significance	criteria provided, single submitter
3392493	NM_001717.4(BNC1):c.564AGA[1] (p.Glu190del)	BNC1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
ASIC2	Strong	Autosomal dominant	premature ovarian failure 16	4
BNC1	Strong	Autosomal dominant	premature ovarian failure 16	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BNC1	Orphanet:243	46,XX gonadal dysgenesis
B4GAT1	Orphanet:899	Walker-Warburg syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BNC1	HGNC:1081	ENSG00000169594	Q01954	Zinc finger protein basonuclin-1	gencc,clinvar
ASIC2	HGNC:99	ENSG00000108684	Q16515	Acid-sensing ion channel 2	gencc,clinvar
B4GAT1	HGNC:15685	ENSG00000174684	O43505	Beta-1,4-glucuronyltransferase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BNC1	Zinc finger protein basonuclin-1	Transcriptional activator.
ASIC2	Acid-sensing ion channel 2	Forms pH-gated trimeric sodium channels that act as postsynaptic excitatory sensors in the nervous system.
B4GAT1	Beta-1,4-glucuronyltransferase 1	Beta-1,4-glucuronyltransferase involved in O-mannosylation of alpha-dystroglycan (DAG1).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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	4.0×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BNC1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Disconnected-like
ASIC2	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
B4GAT1	Enzyme (other)	yes	2.4.1.149	B4GAT1

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
germinal epithelium of ovary	1
parietal pleura	1
primordial germ cell in gonad	1
anterior cingulate cortex	1
cingulate cortex	1
prefrontal cortex	1
endothelial cell	1
middle temporal gyrus	1
pons	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BNC1	117	broad	marker	germinal epithelium of ovary, parietal pleura, primordial germ cell in gonad
ASIC2	131	tissue_specific	marker	prefrontal cortex, cingulate cortex, anterior cingulate cortex
B4GAT1	285	ubiquitous	marker	endothelial cell, middle temporal gyrus, pons

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ASIC2	1,493
B4GAT1	823
BNC1	471

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ASIC2	Q16515	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
B4GAT1	O43505	88.46
BNC1	Q01954	54.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 3 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
Defective LARGE causes MDDGA6 and MDDGB6	1	1903.3×	0.009	B4GAT1
Matriglycan biosynthesis on DAG1	1	407.9×	0.021	B4GAT1
Keratan sulfate/keratin metabolism	1	248.3×	0.022	B4GAT1
Keratan sulfate biosynthesis	1	190.3×	0.022	B4GAT1
Glycosaminoglycan metabolism	1	109.8×	0.026	B4GAT1
Diseases associated with O-glycosylation of proteins	1	107.7×	0.026	B4GAT1
O-linked glycosylation	1	72.3×	0.028	B4GAT1
Stimuli-sensing channels	1	68.0×	0.028	ASIC2
Diseases of glycosylation	1	65.6×	0.028	B4GAT1
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.028	B4GAT1
Ion channel transport	1	48.0×	0.032	ASIC2
Diseases of metabolism	1	40.2×	0.035	B4GAT1
Transport of small molecules	1	12.6×	0.102	ASIC2
Post-translational protein modification	1	9.6×	0.123	B4GAT1
Disease	1	6.5×	0.165	B4GAT1
Metabolism of proteins	1	6.2×	0.165	B4GAT1
Metabolism	1	5.8×	0.165	B4GAT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of systemic arterial blood pressure by aortic arch baroreceptor feedback	1	2808.7×	0.006	ASIC2
positive regulation of oocyte maturation	1	1872.4×	0.006	BNC1
regulation of transcription by RNA polymerase I	1	1404.3×	0.006	BNC1
detection of mechanical stimulus involved in sensory perception	1	936.2×	0.007	ASIC2
sensory perception of sour taste	1	561.7×	0.010	ASIC2
keratan sulfate proteoglycan biosynthetic process	1	330.4×	0.010	B4GAT1
protein O-linked glycosylation via mannose	1	312.1×	0.010	B4GAT1
regulation of vasoconstriction	1	267.5×	0.010	ASIC2
protein localization to synapse	1	255.3×	0.010	ASIC2
regulation of monoatomic ion transmembrane transport	1	244.2×	0.010	ASIC2
cellular response to acidic pH	1	244.2×	0.010	ASIC2
positive regulation of transcription by RNA polymerase I	1	216.1×	0.010	BNC1
phototransduction	1	165.2×	0.013	ASIC2
regulation of postsynapse assembly	1	114.6×	0.017	ASIC2
positive regulation of synapse assembly	1	81.4×	0.019	ASIC2
cellular response to xenobiotic stimulus	1	80.2×	0.019	ASIC2
synapse assembly	1	77.0×	0.019	ASIC2
regulation of membrane potential	1	77.0×	0.019	ASIC2
epidermis development	1	70.2×	0.020	BNC1
sodium ion transmembrane transport	1	67.7×	0.020	ASIC2
establishment of localization in cell	1	53.5×	0.024	ASIC2
sensory perception of sound	1	33.6×	0.036	ASIC2
axon guidance	1	30.2×	0.038	B4GAT1
spermatogenesis	1	11.7×	0.090	BNC1
negative regulation of apoptotic process	1	11.6×	0.090	ASIC2
positive regulation of cell population proliferation	1	11.2×	0.090	BNC1
cell differentiation	1	9.7×	0.100	BNC1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
BNC1	0	0
ASIC2	0	0
B4GAT1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
B4GAT1	2.4.1.149	N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	B4GAT1
E	Difficult family or no structure, no drug	2	BNC1, ASIC2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BNC1	0	—
ASIC2	0	—
B4GAT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.