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Intellectual disability

Gene: BSN

Amber List (moderate evidence)
BSN (bassoon presynaptic cytomatrix protein)
EnsemblGeneIds (GRCh38): ENSG00000164061
EnsemblGeneIds (GRCh37): ENSG00000164061
OMIM: 604020, Gene2Phenotype
BSN is in 4 panels

1 review

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As reviewed by Helen Lord, there are numerous individuals reported in literature with a neurodevelopmental disorder with monoallelic variants in BSN. The disorder includes a range of variably penetrant features, with DD/ID and epilepsy being the most common (PMID: 40393460 Guzman et al., 2025). There are 4 individuals reported with compound heterozygous variants in BSN with early onset epilepsy. However, only 1/4 of the biallelic cases presented with developmental delay (PMID: 36600631, Ye et al., 2023). Based on the available evidence this gene should be rated Green for Intellectual disability, with MOI set to BIALLELIC, autosomal or pseudoautosomal.

BSN is not yet associated with a phenotype in OMIM (accessed 17th Nov 2025).
Created: 17 Nov 2025, 4:26 p.m. | Last Modified: 17 Nov 2025, 4:26 p.m.
Panel Version: 9.185
Literature review by Helen Lord (Oxford Medical Genetics Laboratories) copied from the Epilepsy panel:

There are a lot of cases to support an AD phenotype but unsure as to whether there is also an AR pheontype associated with disease...

PMID:36600631 - Ye et al, 2023:
BSN gene encodes the Bsssoon protein which is highly expressed in the mammalian brain especially the cerebral cortex and the hippocampus.
WES in 313 trios with epilepsies of unknown causes novel BSN variants identifed in 5 cases and 3 additional variants identified in 3 cases from different centres:
Cases 1-4 compound het - variants shown to be inherited in trans
Cases 5-8 - het variants idenitied in case 5 & 6 inherited from affected parent (febrile seizure in these parents) and in cases 7 & 8 - arise de novo.
The 9 variants present in low or no allele freq in all populations or East Asian populations - no hom in gnomAD. No other pathogenic/likely pathogenic variants in other epilepsy genes identiifed.
Fig 3:
B:The 2 nonsense variants in exon 5 thought to result in the truncation of the basson protein and trigger NMD. Both de novo. They state LOF and haploinsuffucency of BSN are potentially pathogenic.
C: 6/9 missense variants led to hydrogen bond alterations - mostly creation of hydrogen bonds which were not predicted orignally. 5/9 missense variants clustered in the C-terminus. Among the 4 pairs of compound het variants at least 1 variant in each pair had hydrogen bond alterations.
In the discussion they state LOF of Bassoon is potentially the underlying mechanism of pathogenicity of BSN variants, which is consistent with the pathogenisi of other genes encoding CAZ proteins such as UNC13A and UNC13B; however, the functional effects of BSN variants warrants further investigation.
In het BSN knockout mice - no phenotype; however, hom knockout mice null led to spontaneous seizures and partial preamture lethality. Clinically the patients with monoallelic BSN missense variants achieved seizure free status without treatment or under monotherapy; whereas, the majority of patients with biallelic missense variants required combination therapy, possible correlation between genotype and phenotype severity.

PMID 39616287: Yacoub et al, 2025: WES in 10 JME (juvenille myoclonic epilepsy) patients - P4 found to have a het BSN missense variant - c.2534G>A p.(Arg845Gln), also identified in her affected brother who has GTCs, but also detected in an unaffected brother. Presumably also inherited from an unaffected pedogree (pedigree included - no mention of parental testing).

PMID: 40393460 Guzman et al, 2025: cohort of 29 individuals with BSN variants including 14 with de novo vairants, 13 individuals with PTVs (protein truncating variants) of unknown inheritance and 2 individuals with PTVs with paternal inheritance. Affected individuals had diverse neurodevelopmental phenotypes including behavioural abnormalities; delayed speech, learning difficulties and variable seizure types.
Recruitment: 2/29 - enrolled in the Epilepsy genetics research project at Childrens Hospital Philadelphia (CHOP) confirmed de novo; 14/29 identified via gene matcher - 9/14 confirmed de novo by respective institutions; 7/29 identified through Penn medicine biobank; 1/29 missense de novo BSN variant identified from birth defects biorepositary at CHOP; 3/29 BSN PTVs idenitifed through the center for applied genomics at CHOP and a lit review identified 2/29 previously reported individuals with de novo PTVs in BSN.
Table 1 details the 14 individuals with de novo BSN variants - 8/14 had seizures (different types); 12/14 had developmental features.
They suggest haploinsuffucency as as a likely mechanism.
Created: 17 Nov 2025, 4:10 p.m. | Last Modified: 17 Nov 2025, 4:27 p.m.
Panel Version: 9.185

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

Created: 17 Nov 2025, 4:10 p.m.
Last Modified: 17 Nov 2025, 4:27 p.m.
Panel version: 9.185

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
Phenotypes
  • neurodevelopmental disorder, MONDO:0700092
Tags
Q4_25_promote_green
OMIM
604020
Clinvar variants
Variants in BSN
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Nov 2025, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: bsn has been classified as Amber List (Moderate Evidence).

17 Nov 2025, Gel status: 1

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q4_25_promote_green tag was added to gene: BSN.

17 Nov 2025, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ida Ertmanska (Genomics England Curator)

gene: BSN was added gene: BSN was added to Intellectual disability. Sources: Other Mode of inheritance for gene: BSN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BSN were set to 36600631; 39616287; 40393460 Phenotypes for gene: BSN were set to neurodevelopmental disorder, MONDO:0700092 Review for gene: BSN was set to GREEN