BNC1

protein-coding

basonuclin 1, the group of Zinc fingers C2H2-type

Gene summary

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]

Previous symbols:

MANE transcript

NM_001717.4

Inheritance

ClinVar variants

P:4U:127B:16

Top phenotype

Premature ovarian failure 16

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr15:83,255,884-83,284,664

External References & Databases

Ensembl (ENSG00000169594)

Transcript & Mutation Effects

hg38 • Region Span ~28.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

premature ovarian failure 16MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0032881

Submitter: Ambry Genetics

premature ovarian failure 16LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032881

Submitter: Labcorp Genetics (formerly Invitae)

premature ovarian failure 16STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032881

Submitter: PanelApp Australia

46 XX gonadal dysgenesisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0009299

Submitter: Orphanet

Clinical Genomic Database (CGD)

Premature ovarian failure 16AD

Manifestation: Obstetric

Intervention: Obstetric

Rationale: Genetic knowledge may allow reproductive capabilities such as via egg preservation

Refs: 30010909

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BNC1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 131

not providedTotal: 7

Premature ovarian failure 16Total: 5

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 2

Premature ovarian failureTotal: 1

46 XX gonadal dysgenesisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001717.4. 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				6 clinvar	1 clinvar	7
missense		1 clinvar	123 clinvar	8 clinvar	1 clinvar	133
nonsense			2 clinvar			2
start loss						0
frameshift	1 clinvar	2 clinvar	2 clinvar			5
splice donor/acceptor (+/-2bp)						0
Total	1	3	127	14	2	147

Highest pathogenic variant AF is 0.0000020564341

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001717.4	RefSeq	NP_001708.3	5	MANE Select
ENST00000345382.7	Ensembl	ENSP00000307041.2	5	MANE Select
NM_001301206.2	RefSeq	NP_001288135.1	5	Standard
ENST00000569704.2	Ensembl	ENSP00000456727.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
spermatogenesis
positive regulation of cell population proliferation
epidermis development
cell differentiation

Molecular Function

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

Cellular Component

nucleus
nucleoplasm
cytoplasm
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000345382
Coding exons: 5
Length: 28812
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125740
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.20	446	524	0.852	0.0000284	6646
Missense (PolyPhen)		150	191.66	0.78265		2344
Synonymous	-0.165	199	196	1.01	0.0000107	1903
Loss of Function	4.21	4	28.0	0.143	0.00000135	379

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
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	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional activator (By similarity). Likely specific for squamous epithelium and for the constituent keratinocytes at a stage either prior to or at the very beginning of terminal differentiation (PubMed:8034748). Required for the maintenance of spermatogenesis (By similarity). May also play a role in the differentiation of oocytes and the early development of embryos (By similarity). {ECO:0000250|UniProtKB:O35914, ECO:0000269|PubMed:8034748}.;

Recessive Scores

pRec: 0.144

Intolerance Scores

LoFtool: 0.0259
RVIS EVS: -1.28
RVIS percentile EVS: 5.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.747

Gene Damage Prediction

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