AGRN [The Human Chemical-Genetic Interaction Map Project]

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======= AGRN =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: AGRN
  * **<color #00a2e8>Official Name</color>**: agrin
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=375790|375790]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O00468|O00468]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=AGRN&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20AGRN|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/103320|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Isoform 1: heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Component of the AGRN-LRP4 receptor complex that induces the phosphorylation and activation of MUSK. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Calcium ions are required for maximal AChR clustering. AGRN function in neurons is highly regulated by alternative splicing, glycan binding and proteolytic processing. Modulates calcium ion homeostasis in neurons, specifically by inducing an increase in cytoplasmic calcium ions. Functions differentially in the central nervous system (CNS) by inhibiting the alpha(3)- subtype of Na+/K+-ATPase and evoking depolarization at CNS synapses. This secreted isoform forms a bridge, after release from motor neurons, to basal lamina through binding laminin via the NtA domain. Isoform 1, isoform 4 and isoform 5: neuron-specific (z+) isoforms that contain C-terminal insertions of 8-19 AA are potent activators of AChR clustering. Isoform 5, agrin (z+8), containing the 8-AA insert, forms a receptor complex in myotubules containing the neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of the LDL receptor family. The splicing factors, NOVA1 and NOVA2, regulate AGRN splicing and production of the 'z' isoforms. Agrin N-terminal 110 kDa subunit: is involved in regulation of neurite outgrowth probably due to the presence of the glycosaminoglcan (GAG) side chains of heparan and chondroitin sulfate attached to the Ser/Thr- and Gly/Ser-rich regions. Also involved in modulation of growth factor signaling (By similarity). {ECO:0000250, ECO:0000269|PubMed:19631309, ECO:0000269|PubMed:21969364}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|NtA|
|Kazal 2|
|Laminin G 1|
|SEA|
|Laminin G 2|
|Kazal 1|
|Laminin EGF|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|positive regulation of synaptic growth at neuromuscular junction|
|positive regulation of neuromuscular junction development|
|regulation of synaptic growth at neuromuscular junction|
|clustering of voltage-gated sodium channels|
|chondroitin sulfate binding|
|dystroglycan binding|
|regulation of neuromuscular junction development|
|sialic acid binding|
|neuronal ion channel clustering|
|heparan sulfate proteoglycan binding|
|G protein-coupled acetylcholine receptor signaling pathway|
|laminin binding|
|acetylcholine receptor signaling pathway|
|positive regulation of filopodium assembly|
|cellular response to acetylcholine|
|response to acetylcholine|
|neuron maturation|
|postsynaptic signal transduction|
|neuromuscular junction development|
|regulation of filopodium assembly|
|receptor clustering|
|glycosaminoglycan catabolic process|
|aminoglycan catabolic process|
|positive regulation of synapse assembly|
|localization within membrane|
|basement membrane|
|signal transduction involved in cellular response to ammonium ion|
|lysosomal lumen|
|Golgi lumen|
|positive regulation of plasma membrane bounded cell projection assembly|
|structural constituent of cytoskeleton|
|retinoid metabolic process|
|glycosaminoglycan biosynthetic process|
|regulation of synapse assembly|
|aminoglycan biosynthetic process|
|diterpenoid metabolic process|
|terpenoid metabolic process|
|cellular response to ammonium ion|
|extracellular matrix structural constituent|
|anatomical structure maturation|
|isoprenoid metabolic process|
|glycosaminoglycan metabolic process|
|cell maturation|
|aminoglycan metabolic process|
|positive regulation of developmental growth|
|response to ammonium ion|
|carbohydrate derivative catabolic process|
|regulation of plasma membrane bounded cell projection assembly|
|regulation of cell projection assembly|
|regulation of synapse organization|
|regulation of synapse structure or activity|
|developmental maturation|
|positive regulation of growth|
|axon guidance|
|neuron projection guidance|
|synapse|
|synapse organization|
|regulation of developmental growth|
|extracellular matrix organization|
|collagen-containing extracellular matrix|
|axonogenesis|
|positive regulation of cell projection organization|
|extracellular structure organization|
|cellular response to drug|
|axon development|
|positive regulation of GTPase activity|
|cell morphogenesis involved in neuron differentiation|
|synaptic signaling|
|neuron projection morphogenesis|
|protein localization to membrane|
|regulation of GTPase activity|
|plasma membrane bounded cell projection morphogenesis|
|cell projection morphogenesis|
|cell part morphogenesis|
|positive regulation of cellular component biogenesis|
|positive regulation of nervous system development|
|cell junction|
|chemotaxis|
|taxis|
|cell morphogenesis involved in differentiation|
|cellular response to hormone stimulus|
|carbohydrate derivative biosynthetic process|
|cellular response to nitrogen compound|
|neuron projection development|
|regulation of growth|
|regulation of plasma membrane bounded cell projection organization|
|regulation of cell projection organization|
|calcium ion binding|
|cell morphogenesis|
|positive regulation of hydrolase activity|
|neuron development|
|cellular component morphogenesis|
|membrane organization|
|response to hormone|
|regulation of nervous system development|
|cellular lipid metabolic process|
|animal organ morphogenesis|
|regulation of cellular component biogenesis|
|neuron differentiation|
|response to drug|
|carbohydrate derivative metabolic process|
|macromolecule catabolic process|
|cellular response to oxygen-containing compound|
|organonitrogen compound catabolic process|
|response to nitrogen compound|
|cytoskeleton organization|
|cell-cell signaling|
|plasma membrane bounded cell projection organization|
|cell projection organization|
|positive regulation of cellular component organization|
|lipid metabolic process|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|regulation of hydrolase activity|
|locomotion|
|G protein-coupled receptor signaling pathway|
|positive regulation of developmental process|
|organonitrogen compound biosynthetic process|
|positive regulation of catalytic activity|
|response to endogenous stimulus|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|cellular protein localization|
|cellular macromolecule localization|
|neurogenesis|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|cell development|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|macromolecule biosynthetic process|
|organic substance catabolic process|
|positive regulation of molecular function|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|extracellular region|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp59|UMK57 1μM R01 exp59]]|-1.71|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 12880
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.58 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='AGRN Expression in NALM6 Cells: 4.58'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>