SNAP25

synaptosome associated protein 25, the group of SNAREs

Basic information

Region (hg38): 20:10172394-10308258

Previous symbols: [ "SNAP" ]

Links

ENSG00000132639 ∙ NCBI:6616 ∙ OMIM:600322 ∙ HGNC:11132 ∙ Uniprot:P60880 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 18 (Limited), mode of inheritance: AD
• presynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy (Moderate), mode of inheritance: AD
• congenital myasthenic syndrome 18 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital 18, with intellectual disability and ataxia	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	25381298
Treatment with cholinesterase inhibitor was not described as effective

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SNAP25 gene.

• Congenital myasthenic syndrome 18 (138 variants)
• not provided (43 variants)
• Early infantile epileptic encephalopathy with suppression bursts (25 variants)
• Inborn genetic diseases (14 variants)
• SNAP25-related disorder (2 variants)
• Unilateral Hypotonia;Intellectual disability;Epilepsy with generalized tonic-clonic seizures;Focal epilepsy (1 variants)
• Global developmental delay (1 variants)
• not specified (1 variants)
• Presynaptic congenital myasthenic syndrome (1 variants)
• SNAP25-related early-onset developmental and epileptic encephalopathy (1 variants)
• Global developmental delay;Optic atrophy;Stereotypic movement disorder;Seizure;Microcephaly (1 variants)
• SNAP25-related condition (1 variants)
• Intellectual disability, severe (1 variants)
• Developmental and epileptic encephalopathy, 2 (1 variants)
• SNAP25 related neurodevelopmental disorder (1 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SNAP25 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			2	30	1	33
missense	2	16	41	3	3	65
nonsense	1	2		1		4
start loss						0
frameshift		1	1			2
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)		2	1			3
splice region			3	13	1	17
non coding			2	42	19	63
Total	3	21	50	77	23

Variants in SNAP25

This is a list of pathogenic ClinVar variants found in the SNAP25 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-10244102-G-A			Benign (Jul 16, 2018)
20-10253609-G-A		Congenital myasthenic syndrome 18	Benign (Jan 29, 2024)
20-10275143-C-T			Likely benign (Mar 30, 2021)
20-10275458-C-A			Likely benign (Apr 08, 2021)
20-10275483-A-G		not specified	Likely benign (Mar 28, 2021)
20-10275495-G-A		Congenital myasthenic syndrome 18 • Inborn genetic diseases	Uncertain significance (Jun 27, 2022)
20-10275497-C-T		Congenital myasthenic syndrome 18 • Inborn genetic diseases • SNAP25-related disorder	Likely benign (Jan 14, 2024)
20-10275498-G-A		Congenital myasthenic syndrome 18	Uncertain significance (Nov 13, 2023)
20-10275502-A-G		Congenital myasthenic syndrome 18	Uncertain significance (May 10, 2021)
20-10275503-C-T		Congenital myasthenic syndrome 18	Likely benign (Dec 11, 2023)
20-10275504-G-A		Congenital myasthenic syndrome 18	Benign (Dec 09, 2023)
20-10275513-C-A		Congenital myasthenic syndrome 18	Uncertain significance (Oct 01, 2022)
20-10275514-G-A		Congenital myasthenic syndrome 18	Uncertain significance (Sep 22, 2023)
20-10275515-C-A		Inborn genetic diseases	Likely benign (Nov 05, 2018)
20-10275516-A-C		Congenital myasthenic syndrome 18	Uncertain significance (Jan 15, 2022)
20-10275517-A-G		Congenital myasthenic syndrome 18	Benign (Feb 04, 2021)
20-10275518-T-C		Congenital myasthenic syndrome 18	Likely benign (Oct 18, 2023)
20-10275523-TGGA-T		Congenital myasthenic syndrome 18	Uncertain significance (Nov 22, 2022)
20-10275538-G-A		Congenital myasthenic syndrome 18	Uncertain significance (Jul 14, 2022)
20-10275541-GGGCTGACCAGTT-G		Congenital myasthenic syndrome 18	Likely benign (Jan 17, 2022)
20-10275542-G-A		Congenital myasthenic syndrome 18	Likely benign (Jun 30, 2022)
20-10275548-C-A		Congenital myasthenic syndrome 18	Uncertain significance (Jun 30, 2022)
20-10275551-G-A		Congenital myasthenic syndrome 18	Likely benign (Apr 14, 2023)
20-10275552-T-C		Congenital myasthenic syndrome 18	Likely benign (Nov 11, 2023)
20-10275560-T-C		Congenital myasthenic syndrome 18	Likely benign (Jul 07, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SNAP25	protein_coding	protein_coding	ENST00000254976	7	88589

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.987	0.0135	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.96	36	131	0.274	0.00000806	1391
Missense in Polyphen		12	42.019	0.28559		416
Synonymous	1.93	26	41.9	0.621	0.00000251	348
Loss of Function	3.35	0	13.0	0.00	7.13e-7	140

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 in pancreatic beta cells. {ECO:0000250|UniProtKB:P60881}.
• Disease: DISEASE: Myasthenic syndrome, congenital, 18 (CMS18) [MIM:616330]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS18 is an autosomal dominant presynaptic disorder clinically characterized by early-onset muscle weakness and easy fatigability associated with delayed psychomotor development and ataxia. {ECO:0000269|PubMed:25381298}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Synaptic Vesicle Pathway;Insulin Signaling;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Neutrophil degranulation;Disease;Other interleukin signaling;Signaling by Interleukins;Cytokine Signaling in Immune system;Toxicity of botulinum toxin type A (BoNT/A);Effects of Botulinum toxin;Toxicity of botulinum toxin type C (BoNT/C);Uptake and actions of bacterial toxins;Neurotoxicity of clostridium toxins;Infectious disease;Innate Immune System;Immune System;Neuronal System;Glutamate Neurotransmitter Release Cycle;Dopamine Neurotransmitter Release Cycle;Acetylcholine Neurotransmitter Release Cycle;GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Toxicity of botulinum toxin type E (BoNT/E);Transmission across Chemical Synapses;Serotonin Neurotransmitter Release Cycle;Norepinephrine Neurotransmitter Release Cycle (Consensus)

Recessive Scores

• pRec: 0.394

Intolerance Scores

• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.85

Haploinsufficiency Scores

• pHI: 0.409
• hipred: Y
• hipred_score: 0.783
• ghis: 0.656

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.907

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Snap25
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; skeleton phenotype; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; normal 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: snap25a
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: structure

Gene ontology

• Biological process: neurotransmitter uptake;exocytosis;vesicle fusion;chemical synaptic transmission;locomotory behavior;associative learning;regulation of neuron projection development;synaptic vesicle exocytosis;synaptic vesicle docking;synaptic vesicle priming;synaptic vesicle fusion to presynaptic active zone membrane;neutrophil degranulation;regulation of insulin secretion;long-term synaptic potentiation;potassium ion transmembrane transport;exocytic insertion of neurotransmitter receptor to postsynaptic membrane;neurotransmitter receptor internalization
• Cellular component: cytoplasm;trans-Golgi network;cytosol;cytoskeleton;plasma membrane;synaptic vesicle;voltage-gated potassium channel complex;membrane;cell junction;growth cone;BLOC-1 complex;SNARE complex;extrinsic component of cytoplasmic side of plasma membrane;vesicle;specific granule membrane;somatodendritic compartment;presynaptic membrane;neuron projection;myelin sheath;perinuclear region of cytoplasm;synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex;tertiary granule membrane;postsynapse;glutamatergic synapse
• Molecular function: voltage-gated potassium channel activity;SNAP receptor activity;protein binding;syntaxin-1 binding;syntaxin binding;calcium-dependent protein binding