BNC2

protein-coding

basonuclin 2, the group of Zinc fingers C2H2-type

Gene summary

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]

MANE transcript

NM_017637.6

Inheritance

AD, AR

ClinVar variants

P:1U:224B:84

Top phenotype

Lower urinary tract obstruction, congenital

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr9:16,409,503-16,870,843

External References & Databases

Ensembl (ENSG00000173068)

Transcript & Mutation Effects

hg38 • Region Span ~461.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lower urinary tract obstruction, congenitalSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032833

Submitter: Labcorp Genetics (formerly Invitae)

lower urinary tract obstruction, congenitalMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0032833

Submitter: Ambry Genetics

posterior urethral valveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019640

Submitter: Orphanet

lower urinary tract obstruction, congenitalSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032833

Submitter: PanelApp Australia

lower urinary tract obstruction, congenitalDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0032833

Submitter: G2P

Clinical Genomic Database (CGD)

Lower urinary tract obstruction, congenitalAD

Manifestation: Renal

Intervention: Renal

Rationale: The condition may involve occult urinary tract obstruction, which may manifest as frequent urinary tract infections and other sequelae, leading to renal damage, and awareness may allow interventions to preserve kidney function

Refs: 31051115

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BNC2 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 185

Inborn genetic diseasesTotal: 153

BNC2-related disorderTotal: 44

HypotensionTotal: 17

Lower urinary tract obstruction, congenitalTotal: 10

not specifiedTotal: 9

Lower Urinary Tract ObstructionTotal: 2

Amelogenesis imperfectaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017637.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	50 clinvar	8 clinvar	62
missense	1 clinvar		216 clinvar	16 clinvar	10 clinvar	243
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	224	66	18	309

Highest pathogenic variant AF is 0.000023339995

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017637.6	RefSeq	NP_060107.3	7	MANE Select
ENST00000380672.9	Ensembl	ENSP00000370047.3	7	MANE Select
NM_001317939.2	RefSeq	NP_001304868.1	7	Standard
NM_001317940.2	RefSeq	NP_001304869.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
bnc2	Danio rerio	Structure: xanthophore Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

bnc2

Danio rerio

Structure: xanthophore

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

endochondral bone growth
regulation of transcription by RNA polymerase II
tongue development
roof of mouth development
mesenchyme development

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
metal ion binding

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380672
Coding exons: 7
Length: 461341
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.360	584	609	0.959	0.0000350	7327
Missense (PolyPhen)		157	222.8	0.70467		2747
Synonymous	-1.64	268	236	1.14	0.0000143	2145
Loss of Function	4.53	6	34.8	0.172	0.00000242	415

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable transcription factor specific for skin keratinocytes. May play a role in the differentiation of spermatozoa and oocytes.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.168
RVIS EVS: 0.63
RVIS percentile EVS: 83.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.330

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium