ARC Gene: Activity-Regulated Cytoskeleton-Associated Protein
ARC (Activity-Regulated Cytoskeleton-Associated Protein) is a protein-coding gene involved in synaptic plasticity, long-term potentiation, and memory formation. It encodes a protein that regulates AMPA receptor trafficking and actin cytoskeleton dynamics in neurons.
Gene Information Card
| Symbol | ARC |
|---|---|
| Full Name | Activity-Regulated Cytoskeleton-Associated Protein |
| Gene Type | Protein-coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 23237 ncbi.nlm.nih.gov/gene/23237 |
| Ensembl ID | ENSG00000198576 |
| UniProt ID | Q7LC44 |
| OMIM ID | 612461 |
| HGNC ID | HGNC:24068 |
| Aliases | ARG3.1, KIAA0278 |
Description
The ARC gene encodes the activity-regulated cytoskeleton-associated protein, a member of the immediate-early gene family that is rapidly induced by neuronal activity. ARC protein is localized to the postsynaptic density and plays a critical role in synaptic plasticity by regulating AMPA receptor endocytosis and trafficking. It is essential for long-term potentiation (LTP), long-term depression (LTD), and memory consolidation. ARC is also involved in actin cytoskeleton remodeling at synapses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual Disability | Loss-of-function mutations in ARC impair synaptic plasticity and AMPA receptor trafficking, leading to cognitive deficits. | ClinVar, OMIM |
| Autism Spectrum Disorder | ARC variants may disrupt synaptic signaling and neuronal connectivity, contributing to ASD pathogenesis. | ClinVar, NCBI |
| Schizophrenia | Altered ARC expression is associated with synaptic dysfunction and glutamate signaling abnormalities in schizophrenia. | NCBI, OMIM |
| Alzheimer's Disease | Reduced ARC levels are linked to synaptic loss and cognitive decline in Alzheimer's disease. | NCBI, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 45.2 | High |
| Cerebral Cortex | 52.1 | High |
| Hippocampus | 48.7 | High |
| Cerebellum | 30.5 | Medium |
| Testis | 8.3 | Low |
| Heart | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 35.6 | High expression; used in neuronal differentiation studies |
| SK-N-SH (neuroblastoma) | 28.4 | Moderate expression |
| HEK293 (embryonic kidney) | 1.2 | Low expression; not neuronal |
| HeLa (cervical carcinoma) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2T>C (p.Met1?) | Missense | Rare | Loss of start codon; likely loss of function |
| c.166C>T (p.Arg56*) | Nonsense | Rare | Premature stop; loss of function |
| c.434G>A (p.Arg145Gln) | Missense | Rare | Impaired AMPA receptor binding; dominant negative effect |
| c.637_639del (p.Lys213del) | In-frame deletion | Rare | Altered protein stability; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated or unstable ARC protein, impairing synaptic plasticity.
Gain of Function (GOF)
Not reported for ARC; gain-of-function mutations are not documented in current databases.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg145Gln) that disrupt ARC's interaction with AMPA receptors, interfering with normal protein function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Synaptic plasticity pathway (Reactome: R-HSA-9627250)
• AMPA receptor trafficking (Reactome: R-HSA-399719)
• Long-term potentiation (KEGG: hsa04720)
• Long-term depression (KEGG: hsa04730)
• Glutamatergic synapse (KEGG: hsa04724)
Protein Summary
The ARC protein is a 396-amino acid, 45 kDa cytosolic protein that shuttles to the postsynaptic density in an activity-dependent manner. It contains a C-terminal domain that binds to endocytic machinery, facilitating AMPA receptor internalization. ARC also interacts with actin and regulates dendritic spine morphology. Its expression is tightly regulated by neuronal activity and is critical for synaptic plasticity and memory.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARC Knockout HEK293 Cell Line | EDJ-KQ7906 | Human | 23237 | Details Get a Quote |
| ARC Knockout HCT 116 Cell Line | EDJ-KQ33524 | Human | 23237 | Details Get a Quote |
| ARC Knockout HeLa Cell Line | EDJ-KQ55707 | Human | 23237 | Details Get a Quote |
| ARC Knockout A-549 Cell Line | EDJ-KQ64205 | Human | 23237 | Details Get a Quote |
