NSF

N-ethylmaleimide sensitive factor, vesicle fusing ATPase, the group of AAA ATPases

Basic information

Region (hg38): 17:46590669-46757679

Links

ENSG00000073969 ∙ NCBI:4905 ∙ OMIM:601633 ∙ HGNC:8016 ∙ Uniprot:P46459 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy 96 (Limited), mode of inheritance: AD
• developmental and epileptic encephalopathy 96 (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NSF gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSF gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4		4
missense		2	11	2		15
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	2	12	6	0

Variants in NSF

This is a list of pathogenic ClinVar variants found in the NSF region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-46692908-T-A			Likely benign (Jun 01, 2022)
17-46692988-C-T		not specified	Uncertain significance (Jan 06, 2023)
17-46692996-C-T		not specified	Uncertain significance (Mar 22, 2023)
17-46693035-G-T		Developmental and epileptic encephalopathy 96	Uncertain significance (Mar 06, 2023)
17-46694534-G-A		not specified	Uncertain significance (Aug 26, 2022)
17-46694563-C-T			Likely benign (Nov 01, 2024)
17-46694577-C-T			not provided (-)
17-46694579-G-A			Likely benign (Dec 01, 2022)
17-46694584-G-A			Likely benign (Jul 01, 2023)
17-46694643-C-A		not specified	Uncertain significance (Jul 09, 2024)
17-46694647-G-A		Developmental and epileptic encephalopathy 96	Uncertain significance (Oct 25, 2021)
17-46694654-C-T		not specified	Uncertain significance (Sep 24, 2024)
17-46704759-G-A		Developmental and epileptic encephalopathy 96	Pathogenic (May 28, 2021)
17-46711008-G-A			Likely benign (Dec 01, 2023)
17-46711081-A-ACAG		Developmental and epileptic encephalopathy 96	Uncertain significance (Jun 24, 2022)
17-46711107-G-A		not specified	Uncertain significance (Jun 11, 2024)
17-46713913-C-G		Developmental and epileptic encephalopathy 96	Likely pathogenic (Jul 24, 2023)
17-46713913-C-T		Developmental and epileptic encephalopathy 96	Pathogenic/Likely pathogenic (Nov 10, 2023)
17-46713956-T-C			Benign/Likely benign (Jul 01, 2023)
17-46726601-T-C		not specified	Uncertain significance (Jun 18, 2024)
17-46726612-C-T			Uncertain significance (May 01, 2022)
17-46728908-G-A		not specified	Uncertain significance (Dec 10, 2024)
17-46749801-C-G			Uncertain significance (Aug 01, 2022)
17-46749873-T-C		not specified	Uncertain significance (Nov 30, 2022)
17-46751530-C-T		not specified	Uncertain significance (Oct 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NSF	protein_coding	protein_coding	ENST00000398238	21	166796

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0183	0.981	124780	0	10	124790	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.58	107	213	0.502	0.0000112	4914
Missense in Polyphen		22	75.477	0.29148		1668
Synonymous	1.65	57	75.2	0.758	0.00000414	1376
Loss of Function	2.93	7	21.8	0.321	0.00000121	505

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000223	0.000223
Finnish	0.00	0.00
European (Non-Finnish)	0.0000536	0.0000530
Middle Eastern	0.000223	0.000223
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for vesicle-mediated transport. Catalyzes the fusion of transport vesicles within the Golgi cisternae. Is also required for transport from the endoplasmic reticulum to the Golgi stack. Seems to function as a fusion protein required for the delivery of cargo proteins to all compartments of the Golgi stack independent of vesicle origin. Interaction with AMPAR subunit GRIA2 leads to influence GRIA2 membrane cycling (By similarity). {ECO:0000250}.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);Synaptic Vesicle Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Vesicle-mediated transport;gamma-aminobutyric acid receptor life cycle pathway;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Neuronal System;BDNF;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Trafficking of GluR2-containing AMPA receptors;Trafficking of AMPA receptors;Intra-Golgi traffic;Glutamate binding, activation of AMPA receptors and synaptic plasticity;COPI-mediated anterograde transport;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport;Retrograde transport at the Trans-Golgi-Network;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.300

Haploinsufficiency Scores

• pHI: 0.544
• hipred: Y
• hipred_score: 0.819
• ghis: 0.666

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.570

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nsf
• Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype

Zebrafish Information Network

• Gene name: nsfb
• Affected structure: pigment cell
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: positive regulation of receptor recycling;potassium ion transport;intracellular protein transport;exocytosis;endoplasmic reticulum to Golgi vesicle-mediated transport;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;vesicle-mediated transport;regulation of exocytosis;SNARE complex disassembly;Golgi to plasma membrane protein transport;plasma membrane fusion;positive regulation of protein catabolic process;COPII vesicle coating;Golgi vesicle docking
• Cellular component: Golgi membrane;lysosomal membrane;Golgi stack;cytosol;plasma membrane;postsynaptic density;dendritic shaft;myelin sheath
• Molecular function: SNARE binding;protein binding;ATP binding;ATPase activity;syntaxin-1 binding;Rab GTPase binding;protein kinase binding;PDZ domain binding;ionotropic glutamate receptor binding;ATPase activity, coupled;protein-containing complex binding;metal ion binding