BNC2

Chr 9AD

basonuclin zinc finger protein 2

Also known as: BSN2, LUTO, bn2

NCBI Gene: 54796ENSG00000173068UniProt: Q6ZN30

This gene encodes a conserved zinc finger protein. The encoded protein functions in skin color saturation. Mutations in this gene are associated with facial pigmented spots. This gene is also associated with susceptibility to adolescent idiopathic scoliosis. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

Lower urinary tract obstruction, congenitalMIM #618612
AD
456
ClinVar variants
92
Pathogenic / LP
0.93
pLI score· haploinsufficient
0
Active trials
Clinical Summary— BNC2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
92 Pathogenic / Likely Pathogenic· 99 VUS of 456 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.928
Z-score 4.53
OE 0.17 (0.09–0.34)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.36Z-score
OE missense 0.96 (0.90–1.03)
584 obs / 609.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.09–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.90–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 6 / 34.8Missense obs/exp: 584 / 609.0Syn Z: -1.64

ClinVar Variant Classifications

456 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic89
Likely Pathogenic3
VUS99
Likely Benign38
Benign19
Conflicting4
89
Pathogenic
3
Likely Pathogenic
99
VUS
38
Likely Benign
19
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
88
0
89
Likely Pathogenic
0
0
3
0
3
VUS
1
84
14
0
99
Likely Benign
0
9
8
21
38
Benign
0
7
3
9
19
Conflicting
—4
Total110111630252

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

View in ClinVar →

Protein Context — Lollipop Plot

BNC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

BNC2-related congenital lower urinary tract obstruction

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
BASONUCLIN 2; BNC2
MIM #608669 · *

Lower urinary tract obstruction, congenital

MIM #618612

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare Variants in BNC2 Are Implicated in Autosomal-Dominant Congenital Lower Urinary-Tract Obstruction.
Kolvenbach CM et al.·Am J Hum Genet
2019
Genetic variant of BNC2 gene is functionally associated with adolescent idiopathic scoliosis in Chinese population.
Xu L et al.·Mol Genet Genomics
2017Functional
GWAS reveals loci associated with velopharyngeal dysfunction.
Chernus J et al.·Sci Rep
2018
Human skin color is influenced by an intergenic DNA polymorphism regulating transcription of the nearby BNC2 pigmentation gene.
Visser M et al.·Hum Mol Genet
2014
The Role of N6-Methyladenosine Methylation in the Progression of Endometrial Cancer.
Song K et al.·Cancer Biother Radiopharm
2022
Genetic Variants Can Predict the Outcome of Brace Treatment in Patients With Adolescent Idiopathic Scoliosis.
Dai Z et al.·Spine (Phila Pa 1976)
2025Cohort
Overexpression of Basonuclin Zinc Finger Protein 2 in stromal cell is related to mesenchymal phenotype and immunosuppression of mucinous colorectal adenocarcinoma.
Yin QZ et al.·Int Immunopharmacol
2024
Association between genetic polymorphisms and risk of adolescent idiopathic scoliosis in case-control studies: a systematic review.
Terhune E et al.·J Med Genet
2024Review
Development of a CAFs-related gene signature to predict survival and drug response in bladder cancer.
Zhang Z et al.·Hum Cell
2022
Combining Algorithms to Find Signatures That Predict Risk in Early-Stage Stomach Cancer.
Nation JB et al.·J Comput Biol
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools