RIC3: RIC3 Acetylcholine Receptor Chaperone
A key regulator of nicotinic acetylcholine receptor assembly and function
Gene Information Card
| Symbol | RIC3 |
|---|---|
| Full Name | RIC3 acetylcholine receptor chaperone |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.4 |
| NCBI Gene ID | 79608 ncbi.nlm.nih.gov/gene/79608 |
| Ensembl ID | ENSG00000166479 |
| UniProt ID | Q7Z5H4 |
| OMIM ID | 610509 |
| HGNC ID | 23495 |
| Aliases | RIC-3, RIC3A, RIC3B, UNQ5838/PRO19637 |
Description
RIC3 (RIC3 acetylcholine receptor chaperone) encodes a protein that acts as a chaperone specifically for nicotinic acetylcholine receptors (nAChRs). It is required for the proper folding, assembly, and surface expression of certain nAChR subtypes, particularly those containing alpha7 subunits. RIC3 is expressed in the brain and other tissues and plays a critical role in cholinergic signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered nAChR assembly and function due to RIC3 variants may contribute to cholinergic dysfunction in schizophrenia. | ClinVar, OMIM |
| Nicotine dependence | Variants in RIC3 have been associated with nicotine dependence and smoking behavior in genome-wide association studies. | NCBI Gene, ClinVar |
| Autism spectrum disorder | Rare RIC3 variants have been reported in individuals with ASD, potentially affecting nAChR-mediated synaptic transmission. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.2 | Low |
| Lung | 6.1 | Low |
| Heart | 4.3 | Low |
| Liver | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.3 | Neuroblastoma cell line, high expression |
| HEK293 | 2.1 | Low expression |
| HeLa | 1.5 | Low expression |
| HepG2 | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4C>T (p.Pro2Ser) | missense | 0.001% | Reduced chaperone activity for alpha7 nAChR |
| c.217G>A (p.Gly73Arg) | missense | 0.002% | Impaired nAChR surface expression |
| c.538C>T (p.Arg180Trp) | missense | 0.005% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
p.Pro2Ser and p.Gly73Arg reduce RIC3 chaperone activity, leading to decreased surface expression of alpha7 nAChRs.
Gain of Function (GOF)
No gain-of-function mutations have been reported.
Dominant Negative (DN)
No dominant-negative mutations have been described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nicotinic acetylcholine receptor signaling (Reactome: R-HSA-629587)
• Cholinergic synapse (KEGG: hsa04725)
Protein Summary
The RIC3 protein is a 368-amino acid chaperone localized to the endoplasmic reticulum and Golgi apparatus. It contains a conserved RIC3 domain and interacts with nAChR subunits to promote their proper folding, assembly, and trafficking to the cell surface. RIC3 is essential for functional expression of homomeric alpha7 nAChRs and also modulates heteromeric nAChRs. Its expression is enriched in the brain, particularly in regions involved in cognition and reward.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RIC3 Knockout HEK293 Cell Line | EDJ-KQ15069 | Human | 79608 | Details Get a Quote |
| RIC3 Knockout A-549 Cell Line | EDJ-KQ44379 | Human | 79608 | Details Get a Quote |
| RIC3 Knockout HeLa Cell Line | EDJ-KQ45625 | Human | 79608 | Details Get a Quote |
| RIC3 Knockout HCT 116 Cell Line | EDJ-KQ74123 | Human | 79608 | Details Get a Quote |
