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Aliases for SHANK3 Gene

Aliases for SHANK3 Gene

  • SH3 And Multiple Ankyrin Repeat Domains 3 2 3
  • PROSAP2 3 4 6
  • PSAP2 3 4 6
  • Proline Rich Synapse Associated Protein 2 2 3
  • Shank Postsynaptic Density Protein 2 3
  • DEL22q13.3 3 6
  • KIAA1650 4 6
  • SCZD15 3 6
  • SH3 And Multiple Ankyrin Repeat Domains Protein 3 3
  • Proline-Rich Synapse-Associated Protein 2 4
  • SPANK-2 3
  • Shank3 4

External Ids for SHANK3 Gene

Summaries for SHANK3 Gene

Entrez Gene Summary for SHANK3 Gene

  • 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]

GeneCards Summary for SHANK3 Gene

SHANK3 (SH3 And Multiple Ankyrin Repeat Domains 3) is a Protein Coding gene. Diseases associated with SHANK3 include phelan-mcdermid syndrome and schizophrenia 15. Among its related pathways are Signaling events regulated by Ret tyrosine kinase and Circadian entrainment. GO annotations related to this gene include protein C-terminus binding and scaffold protein binding. An important paralog of this gene is SHANK1.

UniProtKB/Swiss-Prot for SHANK3 Gene

  • Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation.

Gene Wiki entry for SHANK3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SHANK3 Gene

Genomics for SHANK3 Gene

Genomic Location for SHANK3 Gene

Start:
50,674,415 bp from pter
End:
50,733,298 bp from pter
Size:
58,884 bases
Orientation:
Plus strand

Genomic View for SHANK3 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SHANK3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SHANK3 Gene

Regulatory Elements for SHANK3 Gene

Proteins for SHANK3 Gene

  • Protein details for SHANK3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BYB0-SHAN3_HUMAN
    Recommended name:
    SH3 and multiple ankyrin repeat domains protein 3
    Protein Accession:
    Q9BYB0
    Secondary Accessions:
    • D7UT47
    • Q8TET3

    Protein attributes for SHANK3 Gene

    Size:
    1731 amino acids
    Molecular mass:
    184667 Da
    Quaternary structure:
    • May homomultimerize via its SAM domain. Interacts with BAIAP2, DBNL and SLC17A7/VGLUT1. Interacts with DLGAP1/GKAP, GRM1/MGLUR1, GRM5/MGLUR5 and LZTS3 C-termini via its PDZ domain. Interacts with ABI1, HOMER1, HOMER2, HOMER3 and CTTN/cortactin SH3 domain. Is part of a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts (via PDZ domain) with the GRIA1 subunit of the AMPA receptor (via PDZ-binding motif). Interacts with WASF1 and CYFIP2; the interactions mediate the association of SHANK3 with the WAVE1 complex. Interacts with ARPC2; the interaction probably mediates the association of SHANK3 with the Arp2/3 complex. Interacts (via ANK repeats) with SHARPIN and SPTAN1. Interacts (via PDZ domain) with ARHGAP44 (probably via PDZ-binding motif); the interaction takes place in dendritic spines and promotes GRIA1 exocytosis (By similarity).

    Alternative splice isoforms for SHANK3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SHANK3 Gene

Proteomics data for SHANK3 Gene at MOPED

Post-translational modifications for SHANK3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SHANK3 Gene

REFSEQ proteins:

No data available for DME Specific Peptides for SHANK3 Gene

Domains for SHANK3 Gene

Gene Families for SHANK3 Gene

HGNC:
  • ANKRD :Ankyrin repeat domain containing
  • SAMD :Sterile alpha motif (SAM) domain containing

Protein Domains for SHANK3 Gene

Graphical View of Domain Structure for InterPro Entry

Q9BYB0

UniProtKB/Swiss-Prot:

SHAN3_HUMAN
Domain:
  • In isoform 1, the N-terminal region preceding the ANK repeats interacts with the 6 ANK repeats in an intramolecular manner, thereby restricting access to ligands, such as SHARPIN and SPTAN1.:
    • Q9BYB0
  • Contains 1 PDZ (DHR) domain.:
    • Q9BYB0
  • Contains 1 SAM (sterile alpha motif) domain.:
    • Q9BYB0
  • Contains 1 SH3 domain.:
    • Q9BYB0
Similarity:
  • Contains 6 ANK repeats.:
    • Q9BYB0
genes like me logo Genes that share domains with SHANK3: view

Function for SHANK3 Gene

Molecular function for SHANK3 Gene

UniProtKB/Swiss-Prot Function: Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation.

Gene Ontology (GO) - Molecular Function for SHANK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003779 actin binding IEA --
GO:0005515 protein binding IPI 17474147
GO:0008022 protein C-terminus binding ISS --
GO:0008270 zinc ion binding ISS --
GO:0017124 SH3 domain binding ISS --
genes like me logo Genes that share ontologies with SHANK3: view
genes like me logo Genes that share phenotypes with SHANK3: view

Animal Models for SHANK3 Gene

MGI Knock Outs for SHANK3:

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targeting and HOMER Transcription for SHANK3 Gene

Localization for SHANK3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SHANK3 Gene

Cytoplasm. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density. Cell projection, dendritic spine. Note=In neuronal cells, extends into the region subjacent to the postsynaptic density (PSD). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SHANK3 Gene COMPARTMENTS Subcellular localization image for SHANK3 gene
Compartment Confidence
cytoskeleton 3
cytosol 3
plasma membrane 3
nucleus 2

Gene Ontology (GO) - Cellular Components for SHANK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane ISS --
GO:0030054 cell junction IEA --
GO:0043005 neuron projection ISS --
GO:0043197 dendritic spine IEA --
genes like me logo Genes that share ontologies with SHANK3: view

Pathways for SHANK3 Gene

genes like me logo Genes that share pathways with SHANK3: view

Pathways by source for SHANK3 Gene

1 BioSystems pathway for SHANK3 Gene
1 KEGG pathway for SHANK3 Gene

Gene Ontology (GO) - Biological Process for SHANK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade ISS --
GO:0007416 synapse assembly ISS --
GO:0007612 learning ISS --
GO:0007613 memory ISS --
GO:0021773 striatal medium spiny neuron differentiation ISS --
genes like me logo Genes that share ontologies with SHANK3: view

Compounds for SHANK3 Gene

(1) Novoseek inferred chemical compound relationships for SHANK3 Gene

Compound -log(P) Hits PubMed IDs
glutamate 20.6 1
genes like me logo Genes that share compounds with SHANK3: view

Transcripts for SHANK3 Gene

mRNA/cDNA for SHANK3 Gene

(2) REFSEQ mRNAs :
(6) Additional mRNA sequences :
(3) Selected AceView cDNA sequences:
(5) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for SHANK3 Gene

SH3 and multiple ankyrin repeat domains 3:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SHANK3 Gene

No ASD Table

Relevant External Links for SHANK3 Gene

GeneLoc Exon Structure for
SHANK3
ECgene alternative splicing isoforms for
SHANK3

Expression for SHANK3 Gene

mRNA expression in normal human tissues for SHANK3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB and MOPED for SHANK3 Gene

SOURCE GeneReport for Unigene cluster for SHANK3 Gene Hs.149035

mRNA Expression by UniProt/SwissProt for SHANK3 Gene

Q9BYB0-SHAN3_HUMAN
Tissue specificity: Expressed in the cerebral cortex and the cerebellum
genes like me logo Genes that share expressions with SHANK3: view

No data available for mRNA differential expression in normal tissues for SHANK3 Gene

Orthologs for SHANK3 Gene

This gene was present in the common ancestor of animals.

Orthologs for SHANK3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SHANK3 35
  • 96.64 (n)
  • 96.11 (a)
SHANK3 36
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SHANK3 35
  • 89.87 (n)
  • 94.91 (a)
SHANK3 36
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia -- 36
  • 72 (a)
OneToMany
-- 36
  • 89 (a)
OneToMany
-- 36
  • 80 (a)
OneToMany
SHANK3 35
  • 87.3 (n)
  • 91.19 (a)
mouse
(Mus musculus)
Mammalia Shank3 35
  • 87.79 (n)
  • 94.68 (a)
Shank3 16
Shank3 36
  • 95 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SHANK3 36
  • 82 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SHANK3 36
  • 66 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Shank3 35
  • 87.77 (n)
  • 93.87 (a)
chicken
(Gallus gallus)
Aves SHANK3 36
  • 46 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SHANK3 36
  • 69 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia shank3 35
  • 65.59 (n)
  • 70.92 (a)
zebrafish
(Danio rerio)
Actinopterygii shank3a 36
  • 59 (a)
OneToMany
shank3a 36
  • 55 (a)
OneToMany
shank3b 35
  • 62.34 (n)
  • 65.7 (a)
shank3b 36
  • 60 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Prosap 36
  • 24 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea shn-1 36
  • 31 (a)
OneToMany
Species with no ortholog for SHANK3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SHANK3 Gene

ENSEMBL:
Gene Tree for SHANK3 (if available)
TreeFam:
Gene Tree for SHANK3 (if available)

Paralogs for SHANK3 Gene

Paralogs for SHANK3 Gene

Pseudogenes.org Pseudogenes for SHANK3 Gene

genes like me logo Genes that share paralogs with SHANK3: view

Variants for SHANK3 Gene

Sequence variations from dbSNP and Humsavar for SHANK3 Gene

SNP ID Clin Chr 22 pos Sequence Context AA Info Type MAF
rs10451 -- 50,723,631(+) GGGAA(A/G)CTCAT intron-variant
rs131198 -- 50,697,755(-) tcccc(G/T)cgccg intron-variant
rs140067 -- 50,705,124(-) TTGGG(-/G)CACAG intron-variant
rs140068 -- 50,704,620(-) TGACC(-/C)GGGGC intron-variant
rs140069 -- 50,697,867(+) GTGAA(G/T)GGCTC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SHANK3 Gene

Variant ID Type Subtype PubMed ID
nsv915495 CNV Loss 21882294
nsv914543 CNV Loss 21882294
essv9884 CNV CNV 17122850
nsv459933 CNV Loss 19166990
dgv784n67 CNV Gain 20364138
nsv512665 CNV Loss 21212237
esv22211 CNV Gain+Loss 19812545
esv1366623 CNV Insertion 17803354
esv1007050 CNV Deletion 20482838
esv1327937 CNV Deletion 17803354
esv988358 CNV Deletion 20482838
esv1075589 CNV Deletion 17803354
esv2661079 CNV Deletion 23128226
nsv513599 CNV Insertion 21212237
esv1399411 CNV Deletion 17803354
esv1009137 CNV Deletion 20482838
nsv914570 CNV Loss 21882294
nsv518350 CNV Loss 19592680
dgv785n67 CNV Gain 20364138
nsv829354 CNV Loss 20364138
nsv829355 CNV Gain 20364138
nsv914571 CNV Loss 21882294
nsv191405 CNV Loss 16902084
essv13762 CNV CNV 17122850
nsv428394 CNV Loss 18775914
nsv9922 CNV Gain 18304495

Relevant External Links for SHANK3 Gene

HapMap Linkage Disequilibrium report
SHANK3
Human Gene Mutation Database (HGMD)
SHANK3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SHANK3 Gene

Disorders for SHANK3 Gene

(2) OMIM Diseases for SHANK3 Gene (606230)

UniProtKB/Swiss-Prot

SHAN3_HUMAN
  • Note=A chromosomal aberration involving SHANK3 is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with APPL2/DIP13B.
  • Note=Defects in SHANK3 are associated with neuropsychiatric disorders such as autism spectrum disorders (ASD), bipolar affective disorders and early dementia onset. ASD are characterized by impairments in reciprocal social interaction and communication as well as restricted and stereotyped patterns of interest and activities. ASD include forms with moderate to severe cognitive impairment and milder forms with higher cognitive ability (Asperger syndrome). Gene duplication is associated with hyperkinetic neuropsychiatric disorders (PubMed:24153177) such as hyperactivity, auditory overstimulation, epilepsy and bipolar affective disorders, among others. {ECO:0000269 PubMed:24153177}.
  • Phelan-McDermid syndrome (PHEDE) [MIM:606232]: A developmental disorder with variable features. Common features include neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behavior, and minor dysmorphic features. {ECO:0000269 PubMed:22892527, ECO:0000269 PubMed:23758760, ECO:0000269 PubMed:24132240}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Schizophrenia 15 (SCZD15) [MIM:613950]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269 PubMed:20385823}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(3) University of Copenhagen DISEASES for SHANK3 Gene

(1) Novoseek inferred disease relationships for SHANK3 Gene

Disease -log(P) Hits PubMed IDs
mental retardation 55.4 1

Relevant External Links for SHANK3

Genetic Association Database (GAD)
SHANK3
Human Genome Epidemiology (HuGE) Navigator
SHANK3
genes like me logo Genes that share disorders with SHANK3: view

Publications for SHANK3 Gene

  1. Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome. (PMID: 11431708) Bonaglia M.C. … Zuffardi O. (Am. J. Hum. Genet. 2001) 2 3 4 23
  2. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. (PMID: 17173049) Durand C.M. … Bourgeron T. (Nat. Genet. 2007) 2 3 4 23
  3. Association study of SHANK3 gene polymorphisms with autism in Chinese Han population. (PMID: 19566951) Qin J. … Zhang D. (BMC Med. Genet. 2009) 3 23 48
  4. The Shank family of scaffold proteins. (PMID: 10806096) Sheng M. … Kim E. (J. Cell Sci. 2000) 2 3 4
  5. Identification of novel transcribed sequences on human chromosome 22 by expressed sequence tag mapping. (PMID: 11258795) Hirosawa M. … Ohara O. (DNA Res. 2001) 2 3 4

Products for SHANK3 Gene

  • antibodies-online peptides for SHANK3
  • antibodies-online antibodies for SHANK3
  • antibodies-online kits for SHANK3

Sources for SHANK3 Gene

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