BNC1

Chr 15

basonuclin zinc finger protein 1

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

NCBI Gene: 646 ENSG00000169594 UniProt: Q01954

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPremature ovarian failure 16

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.33

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in BNC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

1,206 rare PASS variants

Rare truncating (LoF)

1 in 4,100

44 rare PASS variants

Rare synonymous (reference)

1 in 120

511 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BNC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 69	1 in 8,200
South Asian	~43k	1 in 43	1 in 4,500
Remaining (unassigned)	~30k	1 in 52	1 in 2,900
European (Finnish)	~27k	1 in 130	1 in 690
Admixed American	~22k	1 in 48	1 in 1,600
African / African American	~21k	1 in 49	≈ 1 in 4,900
East Asian	~20k	1 in 62	1 in 1,900
Ashkenazi Jewish	~13k	1 in 210	none seen
Middle Eastern	~2,884	1 in 50	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 5.? see exons ↓