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    SHANK3 SH3 and multiple ankyrin repeat domains 3 [ Homo sapiens (human) ]

    Gene ID: 85358, updated on 21-May-2024

    Summary

    Official Symbol
    SHANK3provided by HGNC
    Official Full Name
    SH3 and multiple ankyrin repeat domains 3provided by HGNC
    Primary source
    HGNC:HGNC:14294
    See related
    Ensembl:ENSG00000251322 MIM:606230; AllianceGenome:HGNC:14294
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PSAP2; SCZD15; PROSAP2; SPANK-2; DEL22q13.3
    Summary
    This gene is a member of the Shank gene family. Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation. Mutations in this gene are a cause of autism spectrum disorder (ASD), which is characterized by impairments in social interaction and communication, and restricted behavioral patterns and interests. Mutations in this gene also cause schizophrenia type 15, and are a major causative factor in the neurological symptoms of 22q13.3 deletion syndrome, which is also known as Phelan-McDermid syndrome. Additional isoforms have been described for this gene but they have not yet been experimentally verified. [provided by RefSeq, Mar 2012]
    Annotation information
    Annotation category: suggests misassembly
    Annotation category: partial on reference assembly
    Expression
    Broad expression in spleen (RPKM 33.0), fat (RPKM 32.0) and 15 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See SHANK3 in Genome Data Viewer
    Location:
    22q13.33
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (50672823..50733212)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (51186790..51246792)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (51111251..51171640)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:51064758-51065540 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14004 Neighboring gene uncharacterized LOC124905149 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:51073690-51074206 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:51074207-51074721 Neighboring gene arylsulfatase A Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:51079931-51080494 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:51080495-51081059 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr22:51081781-51082282 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr22:51082283-51082782 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:51094338-51095537 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:51113751-51114554 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:51133481-51133981 Neighboring gene RNA, U6 small nuclear 409, pseudogene Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:51142004-51143203 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:51143385-51144035 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19333 Neighboring gene uncharacterized LOC105373100 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:51178129-51178925 Neighboring gene acrosin

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Phelan-McDermid syndrome
    MedGen: C1853490 OMIM: 606232 GeneReviews: Phelan-McDermid Syndrome
    Compare labs
    Schizophrenia 15
    MedGen: C3151380 OMIM: 613950 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2018-08-14)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2018-08-14)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • KIAA1650

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables SH3 domain binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables actin binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables ionotropic glutamate receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables ionotropic glutamate receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables scaffold protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables synaptic receptor adaptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables synaptic receptor adaptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables zinc ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Process Evidence Code Pubs
    involved_in AMPA glutamate receptor clustering ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in MAPK cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in NMDA glutamate receptor clustering ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in adult behavior IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in brain morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in dendritic spine morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in guanylate kinase-associated protein clustering ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in learning IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in learning ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in memory ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of actin filament bundle assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of cell volume ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in neuromuscular process controlling balance ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of dendritic spine development ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in positive regulation of excitatory postsynaptic potential ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in positive regulation of glutamate receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in positive regulation of long-term neuronal synaptic plasticity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of long-term synaptic potentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of synapse structural plasticity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of synaptic transmission, glutamatergic ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in postsynaptic density assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of dendritic spine morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in regulation of long-term synaptic depression ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in regulation of long-term synaptic potentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in social behavior IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in social behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in striatal medium spiny neuron differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in synapse assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in vocal learning IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in vocalization behavior IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in vocalization behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in ciliary membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    is_active_in dendritic spine IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in neuron projection ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in neuron spine ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in postsynaptic density IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in postsynaptic density ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    colocalizes_with postsynaptic membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     

    General protein information

    Preferred Names
    SH3 and multiple ankyrin repeat domains protein 3
    Names
    proline rich synapse associated protein 2
    shank postsynaptic density protein
    shank3 postsynaptic density protein

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_070230.1 RefSeqGene

      Range
      5001..68996
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001372044.2NP_001358973.1  SH3 and multiple ankyrin repeat domains protein 3

      Status: REVIEWED

      Source sequence(s)
      AB569469, AC000036, AC000050
      UniProtKB/Swiss-Prot
      D7UT47, Q8TET3, Q9BYB0
      Related
      ENSP00000510794.2, ENST00000692848.2
      Conserved Domains (8) summary
      cd09506
      Location:17391804
      SAM_Shank1,2,3; SAM domain of Shank1,2,3 family proteins
      cd11984
      Location:549600
      SH3_Shank3; Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3
      COG0666
      Location:200392
      ANKYR; Ankyrin repeat [Signal transduction mechanisms]
      PRK12323
      Location:12081412
      PRK12323; DNA polymerase III subunit gamma/tau
      cd00992
      Location:648737
      PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
      sd00045
      Location:257288
      ANK; ANK repeat [structural motif]
      cd17177
      Location:83169
      FERM_F0_SHANK3; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in SH3 and multiple ankyrin repeat domains protein 3 (SHANK3)
      pfam12796
      Location:329410
      Ank_2; Ankyrin repeats (3 copies)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

      Range
      50672823..50733212
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_015148969.2 Reference GRCh38.p14 PATCHES

      Range
      8917..69331
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060946.1 Alternate T2T-CHM13v2.0

      Range
      51186790..51246792
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NG_008607.2: Suppressed sequence

      Description
      NG_008607.2: This RefSeq was removed because currently there is insufficient support for the genomic sequence in this region.
    2. NM_001080420.1: Suppressed sequence

      Description
      NM_001080420.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein. Exon 11 was based on ab initio prediction and is not supported by transcript data.