Intellectual disability
Gene: NSF

NSF (N-ethylmaleimide sensitive factor, vesicle fusing ATPase)
EnsemblGeneIds (GRCh38): ENSG00000073969
EnsemblGeneIds (GRCh37): ENSG00000073969
OMIM: 601633, Gene2Phenotype
NSF is in 2 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Red List (low evidence)

Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Created: 17 May 2023, 10:29 a.m. | Last Modified: 17 May 2023, 10:29 a.m.

Panel Version: 5.127

Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Created: 17 May 2023, 10:28 a.m. | Last Modified: 17 May 2023, 10:28 a.m.

Panel Version: 5.127

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental and epileptic encephalopathy 96, OMIM:619340

Publications

36645181

Created: 17 May 2023, 10:25 a.m.
Last Modified: 17 May 2023, 10:25 a.m.
Panel version: 5.125

Sarah Leigh (Genomics England Curator)

I don't know

Not associated with relevant phenotype in OMIM or Gen2Phen (11/05/2021). At least two variants reported in two unrelated cases with epileptic encephalopathy of early infantile onset, one proband died at day 36 after birth of respirative failure, the other proband has profound intellectual disability, severe motor developmental delay, and no spontaneous respiration. Supportive functional studies in Drosophila were also presented (PMID 31675180).
Created: 11 May 2021, 6:15 p.m. | Last Modified: 11 May 2021, 6:15 p.m.

Panel Version: 3.1075

Created: 11 May 2021, 6:15 p.m.
Last Modified: 11 May 2021, 6:15 p.m.
Panel version: 3.1075

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene submitted by expert reviewed. Based on the evidence provided it was decided that there is currently not enough evidence to establish a gene-phenotype association. Therefore, this gene has been given a Red rating.
Created: 26 Nov 2019, 2:58 p.m. | Last Modified: 26 Nov 2019, 2:58 p.m.

Panel Version: 2.1117

Created: 26 Nov 2019, 2:58 p.m.
Last Modified: 26 Nov 2019, 2:58 p.m.
Panel version: 2.1117

Konstantinos Varvagiannis (Other)

I don't know

Suzuki et al. (2019 - PMID: 31675180) report on 2 unrelated individuals with de novo missense NSF variants. Overall the phenotype corresponded to an early infantile epileptic encephalopathy. The first patient developed vomiting and tonic seizures immediately after birth, with burst-suppression pattern upon EEG. Trio exome sequencing, followed by Sanger sequencing of proband and parents, revealed a de novo missense variant (NM_006178.3:c.1375G>A / p.Ala459Thr), absent from public databases and predicted in silico to be deleterious (CADD score of 30). The girl died 36 days after birth due to respiratory failure. Another subject, having necessitated mechanical ventilation due to absence of spontaneous respiration after birth, developed myoclonic seizures. EEG showed a burst-suppression pattern. At the age of 3, she was noted to have persistence of seizures and profound ID. Trio exome sequencing identified a missense NSF variant (c.1688C>T / p.Pro563Leu) also confirmed and shown to be de novo by Sanger sequencing. Again the variant was absent from public datasets and had a CADD score of 34. While expression of wt NSF allele in the developing eye of Drosophila had no effect, expression of mutants severely affected eye development - suggesting a dominant negative effect. NSF encodes a homo-hexameric AAA ATPase, which is recruited by SNAPs (Soluble NSF Attachment Proteins) - and the latter by SNAREs (SNAP REceptors) - thus having a role in vesicular transport and membrane fusion. There is currently no associated phenotype in OMIM/G2P. Overall, this gene could be considered for inclusion probably with amber/red rating pending further evidence (eg. additional work-up or alternative causes/explanations not discussed).
Sources: Literature
Created: 11 Nov 2019, 5:36 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability

Publications

31675180

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Created: 11 Nov 2019, 5:36 p.m.

Panel version: 2.1098

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Red

Phenotypes

Developmental and epileptic encephalopathy 96, OMIM:619340

OMIM

601633

Clinvar variants

Variants in NSF

Penetrance

unknown

Publications

Mode of Pathogenicity

Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Panels with this gene