SYT1

synaptotagmin 1, the group of Synaptotagmins|MicroRNA protein coding host genes

Basic information

Region (hg38): 12:78863992-79452008

Previous symbols: [ "SYT", "SVP65" ]

Links

ENSG00000067715 ∙ NCBI:6857 ∙ OMIM:185605 ∙ HGNC:11509 ∙ Uniprot:P21579 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: AD
• infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome (Moderate), mode of inheritance: AD
• infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome (Moderate), mode of inheritance: AD
• infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Baker-Gordon syndrome	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	25705886; 30107533

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SYT1 gene.

• not provided (25 variants)
• Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome (16 variants)
• Inborn genetic diseases (14 variants)
• SYT1-associated neurodevelopmental disorder (6 variants)
• Syndromic intellectual disability (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYT1 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	3	7
missense	1	10	27	2		40
nonsense						0
start loss						0
frameshift			2			2
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	1	11	30	6	4

Variants in SYT1

This is a list of pathogenic ClinVar variants found in the SYT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-79217494-C-G			Benign (Apr 01, 2024)
12-79217524-T-C		Inborn genetic diseases	Uncertain significance (Nov 01, 2022)
12-79217529-G-A		Inborn genetic diseases	Uncertain significance (Aug 03, 2022)
12-79217594-C-T		Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome	Benign (Jul 15, 2021)
12-79217602-AG-A			Uncertain significance (Jul 01, 2022)
12-79217662-T-C		Inborn genetic diseases	Uncertain significance (Feb 09, 2022)
12-79285813-G-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
12-79285844-G-T		SYT1-associated neurodevelopmental disorder	Uncertain significance (Jan 16, 2019)
12-79285886-A-G		Inborn genetic diseases	Uncertain significance (Jul 05, 2023)
12-79285910-G-C			Uncertain significance (Feb 02, 2023)
12-79285934-A-G		Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
12-79285960-A-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
12-79292017-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)
12-79292034-T-C		SYT1-related disorder	Benign (Dec 31, 2019)
12-79292056-AAAG-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2020)
12-79292060-A-G			Uncertain significance (Jun 25, 2020)
12-79292061-A-C			Uncertain significance (Apr 29, 2022)
12-79292078-A-T		Inborn genetic diseases	Uncertain significance (Jun 23, 2023)
12-79292133-C-A		Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome • SYT1-related disorder	Benign (Jul 15, 2021)
12-79296070-T-G		Neurodevelopmental disorder	Likely pathogenic (Oct 27, 2020)
12-79296074-G-A			Likely benign (Sep 01, 2022)
12-79296114-A-G		Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome	Uncertain significance (Feb 07, 2022)
12-79296116-G-T			Uncertain significance (Jun 28, 2022)
12-79296126-T-A			Uncertain significance (Apr 13, 2023)
12-79296130-A-G			Uncertain significance (Oct 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SYT1	protein_coding	protein_coding	ENST00000261205	8	588016

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.600	0.400	125741	0	6	125747	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.84	109	230	0.474	0.0000118	2791
Missense in Polyphen		11	73.827	0.149		918
Synonymous	0.229	89	91.8	0.970	0.00000536	780
Loss of Function	3.35	4	20.3	0.197	0.00000111	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000268	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:23999003}.
• Disease: DISEASE: Note=A SYT1 rare mutation has been found in a child with a severe neuro-developmental disorder. The individual harboring this variant shows early onset dyskinetic movement disorder, severe motor delay and profound cognitive impairment, suggesting that SYT1 may play a role in the pathogenesis of this neuro- developmental disorder. {ECO:0000269|PubMed:25705886}.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Synaptic Vesicle Pathway;Disease;Vesicle-mediated transport;Membrane Trafficking;Effects of Botulinum toxin;Uptake and actions of bacterial toxins;Toxicity of botulinum toxin type G (BoNT/G);Neurotoxicity of clostridium toxins;Infectious disease;Neuronal System;Clathrin-mediated endocytosis;Glutamate Neurotransmitter Release Cycle;Dopamine Neurotransmitter Release Cycle;Acetylcholine Neurotransmitter Release Cycle;Toxicity of botulinum toxin type B (BoNT/B);GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Neurexins and neuroligins;Cargo recognition for clathrin-mediated endocytosis;Transmission across Chemical Synapses;Protein-protein interactions at synapses;Serotonin Neurotransmitter Release Cycle;Norepinephrine Neurotransmitter Release Cycle (Consensus)

Recessive Scores

• pRec: 0.466

Intolerance Scores

• loftool: 0.484
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

• pHI: 0.408
• hipred: Y
• hipred_score: 0.825
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.786

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Syt1
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; 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); muscle 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype

Gene ontology

• Biological process: detection of calcium ion;chemical synaptic transmission;neurotransmitter secretion;brain development;glutamate secretion;regulation of dopamine secretion;synaptic vesicle exocytosis;vesicle-mediated transport;calcium ion regulated exocytosis;regulation of exocytosis;regulation of calcium ion-dependent exocytosis;vesicle docking;synaptic vesicle endocytosis;calcium ion-regulated exocytosis of neurotransmitter;positive regulation of synaptic transmission;protein homooligomerization;protein heterooligomerization;regulation of synaptic transmission, glutamatergic;membrane organization;cellular response to calcium ion;fast, calcium ion-dependent exocytosis of neurotransmitter;calcium-dependent activation of synaptic vesicle fusion;regulation of regulated secretory pathway;positive regulation of dendrite extension
• Cellular component: cytoplasm;Golgi apparatus;plasma membrane;synaptic vesicle;cell junction;integral component of synaptic vesicle membrane;axon;clathrin-coated vesicle membrane;synaptic vesicle membrane;dense core granule;SNARE complex;chromaffin granule membrane;presynaptic membrane;neuron projection;neuron projection terminus;excitatory synapse;clathrin-sculpted acetylcholine transport vesicle membrane;clathrin-sculpted glutamate transport vesicle membrane;clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane;clathrin-sculpted monoamine transport vesicle membrane;exocytic vesicle;hippocampal mossy fiber to CA3 synapse;glutamatergic synapse
• Molecular function: SNARE binding;phosphatidylserine binding;calcium ion binding;protein binding;calmodulin binding;calcium-dependent phospholipid binding;1-phosphatidylinositol binding;phosphatidylinositol-4,5-bisphosphate binding;protein C-terminus binding;syntaxin-1 binding;syntaxin binding;clathrin binding;syntaxin-3 binding;identical protein binding;protein heterodimerization activity;calcium-dependent protein binding;low-density lipoprotein particle receptor binding