AGRN (Agrin) Gene
Key Regulator of Neuromuscular Junction Formation and Synaptic Signaling
Gene Information Card
| Symbol | AGRN |
|---|---|
| Full Name | Agrin |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.33 |
| NCBI Gene ID | 375790 ncbi.nlm.nih.gov/gene/375790 |
| Ensembl ID | ENSG00000188157 |
| UniProt ID | O00468 |
| OMIM ID | 103320 |
| HGNC ID | 328 |
| Aliases | CMS8, CMSPD, agrin |
Description
The AGRN gene encodes agrin, a large heparan sulfate proteoglycan that is critical for the formation and maintenance of the neuromuscular junction (NMJ). Agrin is released by motor neurons and induces clustering of acetylcholine receptors (AChRs) on the postsynaptic muscle membrane, ensuring efficient synaptic transmission. Mutations in AGRN are associated with congenital myasthenic syndromes and other neuromuscular disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital Myasthenic Syndrome 8 (CMS8) | Loss-of-function mutations in AGRN impair agrin-mediated AChR clustering, leading to defective neuromuscular transmission and muscle weakness. | ClinVar, OMIM |
| Congenital Myasthenic Syndrome with Post-Synaptic Defect (CMSPD) | Mutations disrupt agrin binding to LRP4 or MuSK, preventing proper AChR aggregation at the NMJ. | OMIM, PubMed |
| Myasthenia Gravis (autoimmune) | Autoantibodies against agrin can block its function, contributing to NMJ dysfunction in some patients. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 12.5 | Medium |
| Brain | 8.3 | Low |
| Heart | 6.1 | Low |
| Liver | 1.2 | Not detected |
| Kidney | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal Muscle Myotubes | 15.0 | High expression; key for NMJ studies |
| SH-SY5Y (neuroblastoma) | 7.8 | Moderate expression; neuronal model |
| HEK293 | 2.1 | Low expression; used for recombinant agrin studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.5125C>T (p.Arg1709*) | Nonsense | Rare | Loss of function; truncates agrin, causing CMS8 |
| c.740G>A (p.Gly247Asp) | Missense | Rare | Impairs agrin-LRP4 interaction |
| c.1000_1001del (p.Val334fs) | Frameshift | Rare | Loss of function; leads to premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Most AGRN mutations are loss-of-function, reducing agrin secretion or its ability to cluster AChRs, leading to congenital myasthenic syndromes.
Gain of Function (GOF)
No gain-of-function mutations reported in AGRN.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005201 (extracellular matrix structural constituent) | • GO:0005515 (protein binding) |
| • GO:0007169 (transmembrane receptor protein tyrosine kinase signaling pathway) | • GO:0007528 (neuromuscular junction development) |
| • GO:0016358 (dendrite development) | • GO:0030154 (cell differentiation) |
| • GO:0045202 (synapse) |
Pathways
• Agrin in neuromuscular junction (Reactome: R-HSA-374919)
• LRP4-MuSK signaling in NMJ (Reactome: R-HSA-8851882)
• Synaptic signaling pathway (KEGG: hsa04724)
Protein Summary
Agrin is a ~400 kDa heparan sulfate proteoglycan composed of multiple domains, including follistatin-like, laminin-binding, and EGF-like repeats. It is secreted by motor neurons and binds to the LRP4 receptor on muscle cells, activating MuSK kinase to cluster AChRs. Alternative splicing generates isoforms with varying activity; the neural-specific Z+ isoform is most potent for NMJ formation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AGRN Knockout HEK293 Cell Line | EDJ-KQ4025 | Human | 375790 | Details Get a Quote |
| AGRN Knockout A-549 Cell Line | EDJ-KQ26364 | Human | 375790 | Details Get a Quote |
| AGRN Knockout HCT 116 Cell Line | EDJ-KQ26365 | Human | 375790 | Details Get a Quote |
| AGRN Knockout HeLa Cell Line | EDJ-KQ26366 | Human | 375790 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
