RIMS2: Regulating Synaptic Vesicle Exocytosis in Neurotransmission
Key presynaptic protein for calcium-dependent neurotransmitter release and synaptic plasticity
Gene Information Card
| Symbol | RIMS2 |
|---|---|
| Full Name | Regulating Synaptic Membrane Exocytosis 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q22.3 |
| NCBI Gene ID | 9699 ncbi.nlm.nih.gov/gene/9699 |
| Ensembl ID | ENSG00000176406 |
| UniProt ID | Q9UQ26 |
| OMIM ID | 606630 |
| HGNC ID | 17283 |
| Aliases | RIM2, RIM2A, RIM2B, RIM2gamma |
Description
RIMS2 encodes a member of the Rab3-interacting molecule (RIM) family of presynaptic proteins. RIM2 is essential for docking and priming of synaptic vesicles, coupling calcium influx via voltage-gated calcium channels to neurotransmitter release. It interacts with Rab3, Munc13, and calcium channels to regulate short-term and long-term synaptic plasticity. Alternative splicing generates multiple isoforms with distinct expression patterns and functions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia, autistic features, and intellectual disability | Loss-of-function mutations impair synaptic vesicle exocytosis, disrupting neuronal communication | ClinVar; PMID: 31036916 |
| Epileptic encephalopathy, early infantile | Biallelic missense variants reduce RIM2 protein stability and calcium channel coupling | ClinVar; PMID: 31036916 |
| Autism spectrum disorder | Rare de novo missense variants alter RIM2 interaction with Munc13, affecting synaptic transmission | ClinVar; PMID: 31036916 |
| Intellectual disability | Homozygous frameshift mutations lead to complete loss of RIM2 function | ClinVar; PMID: 31036916 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (cerebellum) | 15.2 | High |
| Brain (hippocampus) | 14.8 | High |
| Testis | 3.1 | Low |
| Pancreas | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.7 | Neuronal model |
| U-87 MG (glioblastoma) | 6.4 | Glial model |
| HEK293 (embryonic kidney) | 0.5 | Non-neuronal control |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2263C>T (p.Arg755*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.1234G>A (p.Gly412Arg) | Missense | Rare | Impaired protein stability and Munc13 binding |
| c.2989_2990del (p.Leu997Alafs*12) | Frameshift | Rare | Complete loss of C-terminal domain |
| c.1675A>G (p.Asn559Asp) | Missense | Rare | Reduced calcium channel interaction |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that truncate or destabilize RIM2 protein, leading to reduced synaptic vesicle docking and neurotransmitter release.
Gain of Function (GOF)
Not reported for RIMS2; all known pathogenic variants are loss-of-function.
Dominant Negative (DN)
Heterozygous missense variants may exert dominant-negative effects by interfering with wild-type RIM2 interactions with Rab3 and Munc13.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Synaptic vesicle cycle (Reactome R-HSA-210500)
• Neurotransmitter release cycle (Reactome R-HSA-112310)
• Calcium signaling pathway (KEGG hsa04020)
Protein Summary
RIM2 (RIMS2) is a 1,530-amino-acid presynaptic protein with multiple domains: N-terminal Rab3-binding domain, central PDZ domain, and C-terminal C2 domains. It tethers synaptic vesicles to the active zone, interacts with voltage-gated calcium channels (Cav2.1, Cav2.2) to localize them near release sites, and recruits Munc13 to prime vesicles for fusion. Alternative splicing generates isoforms with differential expression in brain regions. Loss of RIM2 function disrupts short-term plasticity and causes neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RIMS2 Knockout HEK293 Cell Line | EDJ-KQ6702 | Human | 9699 | Details Get a Quote |
| RIMS2 Knockout HeLa Cell Line | EDJ-KQ55227 | Human | 9699 | Details Get a Quote |
| RIMS2 Knockout A-549 Cell Line | EDJ-KQ63708 | Human | 9699 | Details Get a Quote |
| RIMS2 Knockout HCT 116 Cell Line | EDJ-KQ72169 | Human | 9699 | Details Get a Quote |
