SYN1

synapsin I, the group of Synapsins

Basic information

Region (hg38): X:47571901-47619857

Previous symbols: [ "MRX50" ]

Links

ENSG00000008056 ∙ NCBI:6853 ∙ OMIM:313440 ∙ HGNC:11494 ∙ Uniprot:P17600 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (Moderate), mode of inheritance: XL
• epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (Supportive), mode of inheritance: XL
• epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (Moderate), mode of inheritance: XL
• epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (Strong), mode of inheritance: XL
• epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (Strong), mode of inheritance: XL
• X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, X-linked, with variable learning disabilities and behavior disorders; Intellectual developmental disorder, X-linked 50	XL	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	Neurologic	14985377; 28973667

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SYN1 gene.

• Epilepsy,_X-linked_1,_with_variable_learning_disabilities_and_behavior_disorders (458 variants)
• not_provided (145 variants)
• Inborn_genetic_diseases (70 variants)
• not_specified (58 variants)
• SYN1-related_disorder (24 variants)
• Intellectual_disability,_X-linked_50 (18 variants)
• History_of_neurodevelopmental_disorder (6 variants)
• Intellectual_disability (3 variants)
• Neurodevelopmental_disorder (1 variants)
• Epilepsy (1 variants)
• Autism_spectrum_disorder (1 variants)
• See_cases (1 variants)
• SYN1-related_neurodevelopmental_disorder (1 variants)
• Seizure (1 variants)
• X-linked_complex_neurodevelopmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006950.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	6	142	4	153
missense	1	5	239	23	2	270
nonsense	11	4				15
start loss		1	1			2
frameshift	31	9				40
splice donor/acceptor (+/-2bp)	2	5				7
Total	45	25	246	165	6

Highest pathogenic variant AF is 0.00000635851

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SYN1	protein_coding	protein_coding	ENST00000295987	13	47950

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00784	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.97	116	247	0.469	0.0000196	4477
Missense in Polyphen		17	57.239	0.297		1005
Synonymous	1.44	91	110	0.826	0.00000964	1513
Loss of Function	3.82	1	18.9	0.0529	0.00000133	320

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: Neuronal phosphoprotein that coats synaptic vesicles, binds to the cytoskeleton, and is believed to function in the regulation of neurotransmitter release. The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxid functions at a presynaptic level.
• Disease: DISEASE: Epilepsy X-linked, with variable learning disabilities and behavior disorders (XELBD) [MIM:300491]: A neurologic disorder characterized by variable combinations of epilepsy, learning difficulties, macrocephaly, and aggressive behavior. {ECO:0000269|PubMed:14985377}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Synaptic Vesicle Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Monoamine Transport;Neuronal System;Dopamine Neurotransmitter Release Cycle;Neurotransmitter release cycle;Transmission across Chemical Synapses;Serotonin Neurotransmitter Release Cycle (Consensus)

Recessive Scores

• pRec: 0.628

Haploinsufficiency Scores

• pHI: 0.668
• hipred: Y
• hipred_score: 0.739
• ghis: 0.659

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Syn1
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: chemical synaptic transmission;neurotransmitter secretion;regulation of neurotransmitter secretion;neuron development;synapse organization;synaptic vesicle clustering;regulation of synaptic vesicle exocytosis
• Cellular component: synaptonemal complex;Golgi apparatus;cytosol;cytoskeleton;synaptic vesicle;postsynaptic density;cell junction;axon;dendrite;synaptic vesicle membrane;myelin sheath;presynaptic active zone;Schaffer collateral - CA1 synapse;extrinsic component of synaptic vesicle membrane;anchored component of synaptic vesicle membrane
• Molecular function: actin binding;transporter activity;protein binding;ATP binding;protein kinase binding;calcium-dependent protein binding