NSF

protein-coding

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

Gene summary

Enables PDZ domain binding activity and ionotropic glutamate receptor binding activity. Involved in intracellular protein transport; positive regulation of protein catabolic process; and positive regulation of receptor recycling. Located in cytosol and plasma membrane. Implicated in cocaine dependence and developmental and epileptic encephalopathy 96. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_006178.4

Inheritance

ClinVar variants

P:7U:51B:7

Top phenotype

Developmental and epileptic encephalopathy 96

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr17:46,590,669-46,757,679

External References & Databases

Ensembl (ENSG00000073969)

Transcript & Mutation Effects

hg38 • Region Span ~167.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy 96LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0023659

Submitter: Ambry Genetics

developmental and epileptic encephalopathy 96MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0023659

Submitter: PanelApp Australia

developmental and epileptic encephalopathy 96LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0023659

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NSF variants in ClinVar

6 Conditions Cataloged

not providedTotal: 29

not specifiedTotal: 24

Developmental and epileptic encephalopathy 96Total: 13

Alstrom syndromeTotal: 1

NSF-related conditionTotal: 1

Developmental and epileptic encephalopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006178.4. 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			1 clinvar	4 clinvar		5
missense	2 clinvar	5 clinvar	45 clinvar	3 clinvar		55
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	2	5	51	7	0	65

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006178.4	RefSeq	NP_006169.2	21	MANE Select
ENST00000398238.8	Ensembl	ENSP00000381293.4	21	MANE Select
ENST00000465370.2	Ensembl	ENSP00000467779.2	21	Standard
ENST00000465370.3	Ensembl	ENSP00000467779.2	21	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nsfb	Danio rerio	Structure: pigment cell Quality: quality abnormal

Gene / Model

Organism

Observed Phenotype

nsfb

Danio rerio

Structure: pigment cell

Quality: quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

positive regulation of receptor recycling
potassium ion transport
intracellular protein transport
exocytosis
endoplasmic reticulum to Golgi vesicle-mediated transport

Molecular Function

SNARE binding
protein binding
ATP binding
ATPase activity
syntaxin-1 binding

Cellular Component

Golgi membrane
lysosomal membrane
Golgi stack
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398238
Coding exons: 21
Length: 166796
Individuals with no LoFs: 124780
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 124790
p: 0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.58	107	213	0.502	0.0000112	4914
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.300

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.570

Gene Damage Prediction

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