BSN

protein-coding

bassoon presynaptic cytomatrix protein, the group of Zinc fingers PCLO-type

Gene summary

Neurotransmitters are released from a specific site in the axon terminal called the active zone, which is composed of synaptic vesicles and a meshwork of cytoskeleton underlying the plasma membrane. The protein encoded by this gene is thought to be a scaffolding protein involved in organizing the presynaptic cytoskeleton. The gene is expressed primarily in neurons in the brain. A similar gene product in rodents is concentrated in the active zone of axon terminals and tightly associated with cytoskeletal structures, and is essential for regulating neurotransmitter release from a subset of synapses. [provided by RefSeq, Jul 2008]

Previous symbols:

ZNF231

MANE transcript

NM_003458.4

Inheritance

AD, AR

ClinVar variants

P:9U:748B:82

Top phenotype

epilepsy

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr3:49,554,477-49,671,549

External References & Databases

Ensembl (ENSG00000164061)

Transcript & Mutation Effects

hg38 • Region Span ~117.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epilepsyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005027

Submitter: G2P

epilepsySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0005027

Submitter: PanelApp Australia

epilepsySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0005027

Submitter: PanelApp Australia

epilepsyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005027

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BSN variants in ClinVar

14 Conditions Cataloged

not specifiedTotal: 636

not providedTotal: 152

BSN-related disorderTotal: 60

BSN related epilepsyTotal: 4

EpilepsyTotal: 3

BSN-associated neurodevelopmental disorderTotal: 2

BSN-associated seizure disorderTotal: 2

Parkinson diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003458.4. 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			5 clinvar	37 clinvar	6 clinvar	48
missense			705 clinvar	34 clinvar	5 clinvar	744
nonsense	1 clinvar	6 clinvar	16 clinvar			23
start loss						0
frameshift	2 clinvar		21 clinvar			23
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	3	6	748	71	11	839

Highest pathogenic variant AF is 6.8410964e-7

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_003458.4	RefSeq	NP_003449.2	10	MANE Select
ENST00000296452.5	Ensembl	ENSP00000296452.4	10	MANE Select
XM_047449149.1	RefSeq	XP_047305105.1	10	Standard
XM_047449150.1	RefSeq	XP_047305106.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

chemical synaptic transmission
synapse assembly
protein localization to synapse
maintenance of presynaptic active zone structure
regulation of synaptic vesicle cycle

Molecular Function

metal ion binding
structural constituent of presynaptic active zone

Cellular Component

nucleus
synaptic vesicle
cell surface
postsynaptic density
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296452
Coding exons: 10
Length: 117057
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.26	2095	2.26e+3	0.925	0.000149	24933
Missense (PolyPhen)		36	35.452	1.0155		383
Synonymous	0.638	925	950	0.974	0.0000595	8761
Loss of Function	8.97	13	118	0.110	0.00000684	1304

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00015	0.00013	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Is thought to be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. Seems to act through binding to ERC2/CAST1. Essential in regulated neurotransmitter release from a subset of brain glutamatergic synapses. Involved in the formation of the retinal photoreceptor ribbon synapses (By similarity). {ECO:0000250|UniProtKB:O88778}.;

Recessive Scores

pRec: 0.223

Intolerance Scores

LoFtool: 0.126
RVIS EVS: -3.96
RVIS percentile EVS: 0.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.805

Gene Damage Prediction

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