SYN1

Chr X

synapsin I

Also known as: EPILX, EPILX1, MRX50, SYN1a, SYN1b, SYNI

NCBI Gene: 6853 ENSG00000008056 UniProt: P17600

Synapsin I is a neuronal phosphoprotein that coats synaptic vesicles and regulates neurotransmitter release at presynaptic terminals, while also controlling axon outgrowth and synaptogenesis. Mutations cause X-linked epilepsy with variable learning disabilities and behavior disorders, as well as X-linked intellectual developmental disorder. Disease predominantly results from loss-of-function mutations, consistent with the gene's high intolerance to such variants.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family plays a role in regulation of axonogenesis and synaptogenesis. The protein encoded serves as a substrate for several different protein kinases and phosphorylation may function in the regulation of this protein in the nerve terminal. Mutations in this gene may be associated with X-linked disorders with primary neuronal degeneration such as Rett syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEpilepsy, X-linked 1, with variable learning disabilities and behavior disorders

UniProtIntellectual developmental disorder, X-linked 50

Clinical highlights

Gene-disease validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

106

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)