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AGRN Gene

protein-coding   GIFtS: 67
GCID: GC01P000946

Agrin

  See AGRN-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
agrin1 2
AGRIN3
Agrin Proteoglycan1 2

External Ids:    HGNC: 3291   Entrez Gene: 3757902   Ensembl: ENSG000001881577   OMIM: 1033205   UniProtKB: O004683   

Export aliases for AGRN gene to outside databases

Previous GC identifers: GC01P000484 GC01P000708 GC01U900219 GC00P9W0144 GC01P000996 GC01P000226


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for AGRN Gene:
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. (provided by RefSeq, Aug 2011)

GeneCards Summary for AGRN Gene:
AGRN (agrin) is a protein-coding gene. Diseases associated with AGRN include agrn-related congenital myasthenic syndrome, and myasthenic syndrome, congenital, with pre- and postsynaptic defects. GO annotations related to this gene include laminin binding and calcium ion binding. An important paralog of this gene is EYS.

UniProtKB/Swiss-Prot: AGRIN_HUMAN, O00468
Function: 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 homestasis 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
Function: Isoform 2: transmembrane form that is the predominate form in neurons of the brain, induces dendritic
filopodia and synapse formation in mature hippocampal neurons in large part due to the attached glycosaminoglycan
chains and the action of Rho-family GTPases
Function: 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
Function: Isoform 3 and isoform 6: lack any 'z' insert, are muscle-specific and may be involved in endothelial
cell differentiation
Function: 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)
Function: Agrin C-terminal 22 kDa fragment: this released fragment is important for agrin signaling and to exert a
maximal dendritic filopodia-inducing effect. All 'z' splice variants (z+) of this fragment also show an increase
in the number of filopodia

Gene Wiki entry for AGRN (Agrin) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000001.10  NT_032977.10  NC_018912.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the AGRN gene promoter:
         CREB   p53   deltaCREB   MyoD   STAT3   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidAGRN promoter sequence
   Search Chromatin IP Primers for AGRN

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat AGRN


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1p36.33   Ensembl cytogenetic band:  1p36.33   HGNC cytogenetic band: 1p36.33

AGRN Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
AGRN gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01P000946:  view genomic region     (about GC identifiers)

Start:
955,503 bp from pter      End:
991,496 bp from pter
Size:
35,994 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: AGRIN_HUMAN, O00468 (See protein sequence)
Recommended Name: Agrin precursor  
Size: 2067 amino acids; 217232 Da
Subunit: Monomer (By similarity). Interacts (N-terminal subunit) with TGF-beta family members, BMP2 AND BMP4; the
interactions inhibit the activity of these growth factors. Interacts with TGFB1; the interaction enhances the
activity of TGFB1 (By similarity). Component of the AGRN-LRP4 complex that consists of a tetramer of two
AGRN-LRP4 heterodimers. Interacts (via the laminin G-like 3 domain) directly with LRP4; the interaction is
required for activation of MUSK and clustering of AChR and requires the 'z8' insert present in the z(+8)
isoforms. Interacts with DAG1; the interaction is influenced by cell surface glycosaminoglycans and by
alternative splicing of AGRN
Miscellaneous: Cleaved C-terminal fragments may be used as a biomarker for sarcopenia, age-related progressive
loss of skeletal muscle (PubMed:22683512)
Caution: The unknown residue 'x' in the transmembrane isoform is probably a proline residue by similarity to mouse
and rat sequences
Secondary accessions: Q5SVA1 Q5SVA2 Q60FE1 Q7KYS8 Q8N4J5 Q96IC1 Q9BTD4
Alternative splicing: 7 isoforms:  O00468-1   O00468-2   O00468-3   O00468-4   O00468-5   O00468-6   O00468-7   (Produced by usage of an alternative first exon)

Explore the universe of human proteins at neXtProt for AGRN: NX_O00468

Explore proteomics data for AGRN at MOPED

Post-translational modifications: 

  • Contains heparan and chondroitin sulfate chains and alpha-dystroglycan as well as N-linked and O-linked
    oligosaccharides. Glycosaminoglycans (GAGs), present in the N-terminal 110 kDa fragment, are required for
    induction of filopodia in hippocampal neurons. The first cluster (Gly/Ser-rich) for GAG attachment contains
    heparan sulfate (HS) chains and the second cluster (Ser/Thr-rich), contains chondroitin sulfate (CS) chains.
    Heparin and heparin sulfate binding in the G3 domain is independent of calcium ions. Binds heparin with a
    stoichiometry of 2:1. Binds sialic acid with a stoichiometry of 1:1 and binding requires calcium ions (By
    similarity)1
  • At synaptic junctions, cleaved at two conserved sites, alpha and beta, by neurotrypsin. Cleavage at the alpha-site
    produces the agrin N-terminal 110-kDa subunit and the agrin C-terminal 110-kDa subunit. Further cleavage of agrin
    C-terminal 110-kDa subunit at the beta site produces the C-terminal fragments, agrin C-terminal 90 kDa fragment
    and agrin C-terminal 22 kDa fragment. Excessive cleavage at the beta-site releases large amounts of the agrin
    C-terminal 22 kDa fragment leading to destabilization at the neuromuscular junction (NMJ)1
  • Glycosylation2 at Asn135, Thr159, Thr162, Thr167, Asn250, Thr754, Asn777, Asn932, Thr1274, Thr1275,
                                 Ser1277, Ser1281, Ser1282, Thr1285, Ser1292, Thr1294, Ser1295, Thr1301, Thr1302, Thr1306 (see all 35)
  • Modification sites at PhosphoSitePlus

  • See AGRN Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_940978.2  
    ENSEMBL proteins: 
     ENSP00000368678   ENSP00000400771  
    Reactome Protein details: O00468

    AGRN Human Recombinant Protein Products:

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    antibodies-online antibodies for AGRN (36 products) 

    AGRN Assay Products:

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    ECMPG: Proteoglycans / Extracellular Matrix : Other

    Selected InterPro protein domains (see all 11):
     IPR008993 TIMP-like_OB-fold
     IPR002350 Kazal_dom
     IPR000742 EG-like_dom
     IPR013320 ConA-like_subgrp
     IPR001791 Laminin_G

    Graphical View of Domain Structure for InterPro Entry O00468

    ProtoNet protein and cluster: O00468

    Selected Blocks protein domains (see all 7):
    IPB000082 SEA domain
    IPB001455 Protein of unknown function UPF0033
    IPB001791 Laminin G
    IPB001881 EGF-like calcium-binding
    IPB006210 Type I EGF


    UniProtKB/Swiss-Prot: AGRIN_HUMAN, O00468
    Domain: The NtA domain, absent in TM-agrin, is required for binding laminin and connecting to basal lamina
    Domain: Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan/DAG1
    binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding (By similarity)
    Similarity: Contains 4 EGF-like domains
    Similarity: Contains 9 Kazal-like domains
    Similarity: Contains 2 laminin EGF-like domains
    Similarity: Contains 3 laminin G-like domains
    Similarity: Contains 1 NtA (N-terminal agrin) domain
    Similarity: Contains 1 SEA domain


    Find genes that share domains with AGRN           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: AGRIN_HUMAN, O00468
    Function: 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 homestasis 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
    Function: Isoform 2: transmembrane form that is the predominate form in neurons of the brain, induces dendritic
    filopodia and synapse formation in mature hippocampal neurons in large part due to the attached glycosaminoglycan
    chains and the action of Rho-family GTPases
    Function: 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
    Function: Isoform 3 and isoform 6: lack any 'z' insert, are muscle-specific and may be involved in endothelial
    cell differentiation
    Function: 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)
    Function: Agrin C-terminal 22 kDa fragment: this released fragment is important for agrin signaling and to exert a
    maximal dendritic filopodia-inducing effect. All 'z' splice variants (z+) of this fragment also show an increase
    in the number of filopodia

         Genatlas biochemistry entry for AGRN:
    acetylcholine receptor aggregating factor,agrin,component of synaptic basal lamina on the surface of muscle fibers

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002162dystroglycan binding ISS--
    GO:0005200structural constituent of cytoskeleton TAS9652404
    GO:0005509calcium ion binding ISS--
    GO:0005515protein binding IPI--
    GO:0030548acetylcholine receptor regulator activity IEA--
         
    Find genes that share ontologies with AGRN           About GenesLikeMe


    Phenotypes:
         9 MGI mutant phenotypes (inferred from 7 alleles(MGI details for Agrn):
     behavior/neurological  growth/size/body  limbs/digits/tail  mortality/aging  muscle 
     nervous system  normal  renal/urinary system  respiratory system 

    Find genes that share phenotypes with AGRN           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for AGRN: Agrntm4Jrs Agrntm1Jrs Agrntm3Jrs Agrntm2Jrs

       genOway: Develop your customized and physiologically relevant rodent model for AGRN

    miRNA
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    miRTarBase miRNAs that target AGRN:
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    Block miRNA regulation of human, mouse, rat AGRN using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate AGRN (see all 20):
    hsa-miR-3910 hsa-miR-1321 hsa-miR-520d-5p hsa-miR-128 hsa-miR-16-1* hsa-miR-144 hsa-miR-1184 hsa-miR-4274
    SwitchGear 3'UTR luciferase reporter plasmidAGRN 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    AGRIN_HUMAN, O00468: Isoform 1: Secreted, extracellular space, extracellular matrix. Note=Synaptic basal lamina
    at the neuromuscular junction (By similarity)
    AGRIN_HUMAN, O00468: Isoform 2: Cell junction, synapse. Cell membrane; Single-pass type II membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    plasma membrane5
    golgi apparatus4
    lysosome4
    vacuole4
    cytosol1

    Gene Ontology (GO): Selected cellular component terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region TAS--
    GO:0005604basement membrane ----
    GO:0005605basal lamina IDA9405491
    GO:0005615extracellular space IEA--
    GO:0005737cytoplasm IDA--

    Find genes that share ontologies with AGRN           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for AGRN About   (see all 16)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1MPS VI - Maroteaux-Lamy syndrome
    MPS VI - Maroteaux-Lamy syndrome0.45
    MPS IIIB - Sanfilippo syndrome B0.45
    MPS IIIC - Sanfilippo syndrome C0.45
    MPS II - Hunter syndrome0.45
    MPS IV - Morquio syndrome A0.45
    Glycosaminoglycan metabolism0.45
    Mucopolysaccharidoses0.45
    MPS IV - Morquio syndrome B0.45
    2Heparan sulfate/heparin (HS-GAG) metabolism
    Heparan sulfate/heparin (HS-GAG) metabolism0.57
    HS-GAG degradation0.39
    HS-GAG biosynthesis0.57
    3Diseases associated with visual transduction
    Visual phototransduction0.44
    Diseases associated with visual transduction0.43
    Retinoid metabolism and transport0.44
    4L1CAM interactions
    Axon guidance0.63
    Developmental Biology0.63
    5NCAM signaling for neurite out-growth
    NCAM1 interactions0.59
    NCAM signaling for neurite out-growth0.59


    Find genes that share SuperPaths with AGRN           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for AGRN
        Muscular Dystrophies and Dystrophin-Glycoprotein Complex
    Agrin Interactions at Neuromuscular Junction

    Selected Reactome Pathways for AGRN (see all 8)
        Integrin cell surface interactions
    NCAM1 interactions
    A tetrasaccharide linker sequence is required for GAG synthesis
    ECM proteoglycans
    HS-GAG biosynthesis


    1 Kegg Pathway  (Kegg details for AGRN):
        ECM-receptor interaction

        Pathway & Disease-focused RT2 Profiler PCR Array including AGRN: 
              Skeletal Muscle: Myogenesis & Myopathy in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for AGRN

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for AGRN (O004681, 2, 3 ENSP000003686784) via UniProtKB, MINT, STRING, and/or I2D (see all 62)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ATXN7O152651, 3EBI-947482,EBI-708350 I2D: score=1 
    PDIA3P301012, 3MINT-4301502 I2D: score=1 
    GFI1BQ5VTD93, ENSP000003447824I2D: score=2 STRING: ENSP00000344782
    DAG1Q141183, ENSP000003124354I2D: score=1 STRING: ENSP00000312435
    ATN1P542593, ENSP000003490764I2D: score=2 STRING: ENSP00000349076
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 25):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001523retinoid metabolic process TAS--
    GO:0005975carbohydrate metabolic process TAS--
    GO:0006024glycosaminoglycan biosynthetic process TAS--
    GO:0006027glycosaminoglycan catabolic process TAS--
    GO:0007009plasma membrane organization IEA--

    Find genes that share ontologies with AGRN           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for AGRN (AGRIN)

    Selected Novoseek inferred chemical compound relationships for AGRN gene (see all 19)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    acetylcholine 84.8 131 9077444 (2), 12182759 (2), 16256100 (2), 18272689 (2) (see all 99)
    tyrosine 66.2 92 12399462 (4), 7965081 (2), 11278328 (2), 17452444 (2) (see all 58)
    heparan sulfate 63.4 5 9117266 (1), 11340306 (1), 14871397 (1), 9738008 (1) (see all 5)
    heparin 34.7 22 8693000 (5), 9215700 (3), 8607994 (3), 9294861 (2) (see all 11)
    alpha-bungarotoxin 29.6 1 8227074 (1)
    glycosaminoglycan 28.9 6 11761721 (2), 12009503 (1), 19166823 (1)
    sialic acid 11.5 10 10741468 (6)
    serine 8.29 3 15328353 (1), 14691009 (1)
    carbohydrates 6.12 3 17649979 (1), 11988021 (1)
    calcium 5.75 17 10440735 (3), 14622909 (3), 15389602 (3), 11748634 (2) (see all 9)



    Find genes that share compounds with AGRN           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for AGRN gene: 
    NM_198576.3  

    Unigene Cluster for AGRN:

    Agrin
    Hs.273330  [show with all ESTs]
    Unigene Representative Sequence: NM_198576
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000379370(uc001ack.2) ENST00000477585 ENST00000469403 ENST00000479707
    ENST00000466223 ENST00000478677 ENST00000492947 ENST00000419249 ENST00000461111

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    Selected qRT-PCR Assays for microRNAs that regulate AGRN (see all 20):
    hsa-miR-3910 hsa-miR-1321 hsa-miR-520d-5p hsa-miR-128 hsa-miR-16-1* hsa-miR-144 hsa-miR-1184 hsa-miR-4274
    SwitchGear 3'UTR luciferase reporter plasmidAGRN 3' UTR sequence
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    Predesigned siRNA for gene silencing in human, mouse, rat AGRN
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    GenScript: all cDNA clones in your preferred vector: AGRN (NM_198576)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for AGRN
    Search Vector BioLabs for ready-to-use adenovirus/AAV for human, mouse, rat AGRN
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    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat AGRN
      QuantiTect SYBR Green Assays in human, mouse, rat AGRN
      QuantiFast Probe-based Assays in human, mouse, rat AGRN

    Additional mRNA sequence: 

    AB191264.1 AF016903.1 AK021586.1 BC004220.2 BC007649.1 BC034009.1 BC063620.1 BC084578.1 
    S44195.1 U84406.1 

    13 DOTS entries:

    DT.97860457  DT.85105385  DT.100801920  DT.99984146  DT.102833761  DT.121400270  DT.97858399  DT.100038596 
    DT.65288538  DT.85105388  DT.91873136  DT.95317433  DT.101983424 

    Selected AceView cDNA sequences (see all 514):

    AA653992 BU684918 AI056761 BM974240 AW806729 BU631309 BU682541 BQ231016 
    AW273381 BE394344 R06917 AW590815 BQ277685 CA445048 AW614928 BU541184 
    AI921505 AA156776 N21168 AA991526 BF436634 BU734821 AW204172 BU553525 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for AGRN (see all 25)    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b · 16c ^ 17a · 17b ^ 18 ^ 19a · 19b ^
    SP1:                                                                                                                                                            
    SP2:                                                                                                                                                            
    SP3:                                                                                                                                                            
    SP4:                                                                                                                                                            
    SP5:                                                                                                                                                            

    ExUns: 20a · 20b ^ 21 ^ 22a · 22b ^ 23 ^ 24a · 24b ^ 25 ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29a · 29b ^ 30a · 30b ^ 31 ^ 32 ^ 33a · 33b ^ 34 ^ 35 ^ 36a · 36b ·
    SP1:                                                                                                                                      -                     
    SP2:                                                                                                                                                            
    SP3:                                                                                                                                                            
    SP4:                                                                                                                                                            
    SP5:                                                                                                                                                            

    ExUns: 36c ^ 37a · 37b · 37c ^ 38 ^ 39a · 39b ^ 40a · 40b · 40c ^ 41 ^ 42a · 42b ^ 43 ^ 44a · 44b
    SP1:                    -     -     -     -     -                                                   
    SP2:                                                                                                
    SP3:                                                                                                
    SP4:                    -           -     -     -                                                   
    SP5:                                                                                                


    ECgene alternative splicing isoforms for AGRN

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    AGRN expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TGTTGATTTT
    AGRN Expression
    About this image


    AGRN expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Heart (Cardiovascular System)    fully expand to see all 2 entries
             Cushion Mesenchymal Cells Endocardium
     
     Breast (Uncategorized)
     
     Epidermis (Integumentary System)
    AGRN Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    AGRN Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.273330

    UniProtKB/Swiss-Prot: AGRIN_HUMAN, O00468
    Tissue specificity: Expressed in basement membranes of lung and kidney. Muscle- and neuron-specific isoforms are
    found. Isoforms (y+) with the 4 AA insert and (z+8) isoforms with the 8 AA insert are all neuron-specific.
    Isoforms (z+11) are found in both neuronal and non-neuronal tissues

        Pathway & Disease-focused RT2 Profiler PCR Array including AGRN: 
              Skeletal Muscle: Myogenesis & Myopathy in human mouse rat

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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for AGRN

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for AGRN gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Agrn1 , 5 agrin1, 5 80.3(n)1
    82.57(a)1
      4 (88.55 cM)5
    116031  NM_021604.31  NP_067617.31 
     1561652905 
    chicken
    (Gallus gallus)
    Aves AGRN1 agrin 67.82(n)
    64.17(a)
      396538  NM_205527.1  NP_990858.1 
    lizard
    (Anolis carolinensis)
    Reptilia AGRN6
    agrin
    61(a)
    1 ↔ 1
    GL343925.1(2850-101730)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia agrn1 agrin 61.39(n)
    62.66(a)
      100492176  XM_002936384.2  XP_002936430.2 
    zebrafish
    (Danio rerio)
    Actinopterygii hm:gc121 hm:gc12 60.96(n)
    58.32(a)
      565373  NM_001177452.1  NP_001170923.1 
    worm
    (Caenorhabditis elegans)
    Secernentea agr-11 agr-1 41.94(n)
    34.94(a)
      3565243  NM_001026981.4  NP_001022152.3 


    ENSEMBL Gene Tree for AGRN (if available)
    TreeFam Gene Tree for AGRN (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for AGRN gene
    EYS2  EGFLAM2  HSPG22  
    16 SIMAP similar genes for AGRN using alignment to 6 protein entries:     AGRIN_HUMAN (see all proteins):
    SPOCK2    CPAMD8    SPOCK1    SLIT2    F9    SPINK1
    EGFLAM    LAMB4    FSTL1    tmp_locus_3    FSTL4    FSTL5
    DKFZp566D234    FST    FSTL3    WUGSC

    Find genes that share paralogs with AGRN           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for AGRN (see all 1933)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0690664
    Myasthenia, limb-girdle, familial (LGM)4--see VAR_0690662 V F mis40--------
    VAR_0687424
    Myasthenia, limb-girdle, familial (LGM)4--see VAR_0687422 G R mis40--------
    rs1994763961,2
    Cpathogenic1985955(+) GCAAGC/GGGGCA 2 R G mis10--------
    rs1843741121,2
    --919635(+) TTTCCC/TTGTTT 1 -- int10--------
    rs1876973571,2
    --919636(+) TTCCCC/TGTTTT 1 -- int10--------
    rs1470947731,2
    --919652(+) CTGAGA/GACAGA 1 -- int10--------
    rs1925947671,2
    --919683(+) CTCGCC/TCTCTG 1 -- int10--------
    rs1384656661,2
    --919731(+) AGCCTG/TCGGCA 1 -- int10--------
    rs1150461521,2
    F--919739(+) GCAGAT/CGGGAT 1 -- int11Minor allele frequency- C:0.02WA 118
    rs31281121,2
    C--919766(+) GGAAAG/CAAGGG 1 -- int113Minor allele frequency- C:0.02NA WA CSA 257

    HapMap Linkage Disequilibrium report for AGRN (955503 - 991496 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for AGRN (see all 38):    About this table    
    Variant IDTypeSubtypePubMed ID
    dgv2e201CNV Deletion23290073
    esv4415CNV Deletion18987735
    esv2736139CNV Deletion23290073
    esv2741694CNV Deletion23290073
    esv2740583CNV Deletion23290073
    esv2738361CNV Deletion23290073
    esv2674475CNV Deletion23128226
    esv2742805CNV Deletion23290073
    esv2733916CNV Deletion23290073
    esv2743474CNV Deletion23290073

    Human Gene Mutation Database (HGMD): AGRN
    Locus Specific Mutation Databases (LSDB): AGRN

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing AGRN
    DNA2.0 Custom Variant and Variant Library Synthesis for AGRN

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 103320   
    OMIM disorders: 254300  
    UniProtKB/Swiss-Prot: AGRIN_HUMAN, O00468
  • Myasthenia, limb-girdle, familial (LGM) [MIM:254300]: A congenital myasthenic syndrome characterized by a
    typical 'limb girdle' pattern of muscle weakness with small, simplified neuromuscular junctions but normal
    acetylcholine receptor and acetylcholinesterase function. Note=The disease is caused by mutations affecting the
    gene represented in this entry

  • 4 diseases for AGRN:    
    About MalaCards
    agrn-related congenital myasthenic syndrome    myasthenic syndrome, congenital, with pre- and postsynaptic defects    myasthenia, limb-girdle, familial    hereditary cerebral hemorrhage with amyloidosis

    1 disease from the University of Copenhagen DISEASES database for AGRN:
    Congenital myasthenic syndrome

    Find genes that share disorders with AGRN           About GenesLikeMe

    Selected Novoseek inferred disease relationships for AGRN gene (see all 14)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    muscular dystrophies 58.5 3 18957220 (1), 11565031 (1), 18537849 (1)
    myasthenia gravis 33.8 1 17081697 (1)
    senile plaques 32.4 5 10867220 (2), 10673326 (1), 10339611 (1), 11761721 (1)
    diabetic nephropathies 21.6 2 14694155 (1), 11340306 (1)
    brain diseases 19.1 4 10673326 (3), 12458045 (1)
    alzheimers disease 10.8 10 10673326 (3), 11041342 (1), 12270958 (1), 16037493 (1) (see all 8)
    proteinuria 8.48 1 11979342 (1)
    tumors 0.324 12 16983329 (2), 19068466 (2), 17640714 (1), 20519181 (1)
    albuminuria 0 1 10446936 (1)
    genetic disorder 0 1 11754179 (1)

    Genetic Association Database (GAD): AGRN
    Human Genome Epidemiology (HuGE) Navigator: AGRN (1 document)

    Export disorders for AGRN gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

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    PubMed articles for AGRN gene, integrated from 10 sources (see all 313):
    (articles sorted by number of sources associating them with AGRN)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Primary structure and high expression of human agrin in basement membranes of adult lung and kidney. (PubMed id 9652404)1, 2, 9 Groffen A.J.A.... Van den Heuvel L.P.W.J. (Eur. J. Biochem. 1998)
    2. Agrin binds to the nerve-muscle basal lamina via laminin. (PubMed id 9151673)1, 2, 9 Denzer A.J.... Ruegg M.A. (J. Cell Biol. 1997)
    3. Identification of an agrin mutation that causes congenital myasthenia and affects synapse function. (PubMed id 19631309)1, 2, 9 Huze C....Hantai D. (Am. J. Hum. Genet. 2009)
    4. Agrin in the developing CNS: new roles for a synapse organizer. (PubMed id 12270958)1, 3, 9 KrAPger S. and SchrAPder J.E. (News Physiol. Sci. 2002)
    5. LG2 agrin mutation causing severe congenital myasthenic syndrome mimics functional characteristics of non-neural (z-) agrin. (PubMed id 22205389)1, 2 Maselli R.A....Ferns M.J. (Hum. Genet. 2012)
    6. Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome. (PubMed id 19598235)1, 4 Chakrabarti B....Baron-Cohen S. (Autism Res 2009)
    7. Identification of agrinSN isoform and muscle-specific receptor tyrosine kinase (MuSK) in sperm. (PubMed id 16487930)1, 2 Kumar P.... Meizel S. (Biochem. Biophys. Res. Commun. 2006)
    8. Structure and expression of a rat agrin. (PubMed id 1851019)1, 3 Rupp F....Scheller R.H. (Neuron 1991)
    9. Comparison of the expression of agrin, a basement membrane heparan sulfate proteoglycan, in cholangiocarcinoma and hepatocellular carcinoma. (PubMed id 17640714)1, 9 Batmunkh E....Kovalszky I. (Hum. Pathol. 2007)
    10. Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue. (PubMed id 9417121)1, 9 Gesemann M....Ruegg M.A. (J. Biol. Chem. 1998)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section

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    Entrez Gene: 375790 HGNC: 329 AceView: AGRN Ensembl:ENSG00000188157 euGenes: HUgn375790
    ECgene: AGRN Kegg: 375790 H-InvDB: AGRN

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for AGRN Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for AGRN gene:
    Search GeneIP for patents involving AGRN

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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