BNC1

Chr 15AD

basonuclin zinc finger protein 1

Also known as: BNC, BSN1, HsT19447, POF16, bn1

NCBI Gene: 646 ENSG00000169594 OMIM: 601930

This gene encodes a zinc finger transcriptional activator that regulates keratinocyte differentiation in skin and hair follicles, maintains spermatogenesis, and controls oocyte maturation through BMP15 regulation and AKT signaling. Mutations cause premature ovarian failure with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.96), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a zinc finger protein present in the basal cell layer of the epidermis and in hair follicles. It is also found in abundance in the germ cells of testis and ovary. This protein is thought to play a regulatory role in keratinocyte proliferation and it may also be a regulator for rRNA transcription. Disruption of this gene has been implicated in premature ovarian failure as well as testicular premature aging. [provided by RefSeq, Sep 2020]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.331 OMIM phenotype

Clinical Summary— BNC1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 125 VUS of 141 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.965

Z-score 4.21

OE 0.14 (0.07–0.33)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.20Z-score

OE missense 0.85 (0.79–0.92)

446 obs / 523.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.07–0.33)

0≤0.351.4

Missense OE?0.85 (0.79–0.92)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 4 / 28.0Missense obs/exp: 446 / 523.5Syn Z: -0.16

This gene — mechanism propensity

0.3892th %ile

GOF

0.2796th %ile

LOF

0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.33

Literature Evidence

LOFWe report haploinsufficiency of BNC1 as an etiology of human autosomal dominant POI.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 30010909 ↗

ClinVar Variant Classifications

141 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS125

Likely Benign8

Benign2

Pathogenic

Likely Pathogenic

125

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	2	1	0	0	3
VUS	2	122	1	0	125
Likely Benign	0	6	0	2	8
Benign	0	1	0	1	2
Total	5	130	1	3	139

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

34 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap BNC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →