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Protein SHANK3 PDB 2f3n.png
Aliases SHANK3, DEL22q13.3, PROSAP2, PSAP2, SCZD15, SPANK-2, SH3 and multiple ankyrin repeat domains 3
External IDs MGI: 1930016 HomoloGene: 75163 GeneCards: SHANK3
Gene location (Human)
Chromosome 22 (human)
Chr. Chromosome 22 (human)[1]
Chromosome 22 (human)
Genomic location for SHANK3
Genomic location for SHANK3
Band 22q13.33 Start 50,674,415 bp[1]
End 50,733,298 bp[1]
RNA expression pattern
PBB GE SHANK3 gnf1h02529 at fs.png

PBB GE SHANK3 gnf1h02526 x at fs.png

PBB GE SHANK3 gnf1h01748 s at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 22: 50.67 – 50.73 Mb Chr 22: 89.5 – 89.56 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

SH3 and multiple ankyrin repeat domains 3 (Shank3), also known as proline-rich synapse-associated protein 2 (ProSAP2), is a protein that in humans is encoded by the SHANK3 gene on chromosome 22.[5] Additional isoforms have been described for this gene but they have not yet been experimentally verified.


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.[6]

Clinical significance[edit]

Mutations in this gene are associated with autism spectrum disorder. This gene is often missing in patients with 22q13.3 deletion syndrome,[7] although not in all cases.[8]


SHANK3 has been shown to interact with ARHGEF7.[9]

Mouse models[edit]

Mouse models of Shank3 include N-terminal knock-outs[10][11] and a PDZ domain knock-out[12] all of which also show social interaction deficits and variable other phenotypes. Most of these mice are homozygous knock-outs whereas all the human Shank3 mutations have been heterozygous.

In an inducible knockout, restoration of Shank3 expression in adult mice promoted dendritic spine growth and recovered normal grooming behaviour and voluntary social interaction.[13] However, the reduced locomotion, anxiety and rotarod deficits remained. Germline restoration of the gene's expression rescued all measured phenotypes. Experiments on different developmental windows suggested that early intervention was more effective in restoring behavioural traits.


  1. ^ a b c ENSG00000283243 GRCh38: Ensembl release 89: ENSG00000251322, ENSG00000283243 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022623 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ "Entrez Gene: SHANK3 SH3 and multiple ankyrin repeat domains 3". 
  6. ^ Boeckers TM, Bockmann J, Kreutz MR, Gundelfinger ED (2002). "ProSAP/Shank proteins - a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease". J. Neurochem. 81 (5): 903–10. doi:10.1046/j.1471-4159.2002.00931.x. PMID 12065602. 
  7. ^ Sarasua SM, Dwivedi A, Boccuto L, Rollins JD, Chen CF, Rogers RC, Phelan K, DuPont BR, Collins JS (2011). "Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome)". J. Med. Genet. 48 (11): 761–6. doi:10.1136/jmedgenet-2011-100225. PMID 21984749. 
  8. ^ Simenson K, Õiglane-Shlik E, Teek R, Kuuse K, Õunap K (2014). "A patient with the classic features of Phelan-McDermid syndrome and a high immunoglobulin E level caused by a cryptic interstitial 0.72-Mb deletion in the 22q13.2 region". Am. J. Med. Genet. A. 164A (3): 806–9. doi:10.1002/ajmg.a.36358. PMID 24375995. 
  9. ^ Park E, Na M, Choi J, Kim S, Lee JR, Yoon J, Park D, Sheng M, Kim E (May 2003). "The Shank family of postsynaptic density proteins interacts with and promotes synaptic accumulation of the beta PIX guanine nucleotide exchange factor for Rac1 and Cdc42". J. Biol. Chem. 278 (21): 19220–9. doi:10.1074/jbc.M301052200. PMID 12626503. 
  10. ^ Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS, Roberts AC, Kim CJ, Berrios J, Colvin JS, Bousquet-Moore D, Lorenzo I, Wu G, Weinberg RJ, Ehlers MD, Philpot BD, Beaudet AL, Wetsel WC, Jiang YH (August 2011). "Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3". Hum. Mol. Genet. 20 (15): 3093–108. doi:10.1093/hmg/ddr212. PMC 3131048Freely accessible. PMID 21558424. 
  11. ^ Bozdagi O, Sakurai T, Papapetrou D, Wang X, Dickstein DL, Takahashi N, Kajiwara Y, Yang M, Katz AM, Scattoni ML, Harris MJ, Saxena R, Silverman JL, Crawley JN, Zhou Q, Hof PR, Buxbaum JD (2010). "Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication". Mol Autism. 1 (1): 15. doi:10.1186/2040-2392-1-15. PMC 3019144Freely accessible. PMID 21167025. 
  12. ^ Peça J, Feliciano C, Ting JT, Wang W, Wells MF, Venkatraman TN, Lascola CD, Fu Z, Feng G (April 2011). "Shank3 mutant mice display autistic-like behaviours and striatal dysfunction". Nature. 472 (7344): 437–42. doi:10.1038/nature09965. PMC 3090611Freely accessible. PMID 21423165. 
  13. ^ Mei Y, Monteiro P, Zhou Y, Kim JA, Gao X, Fu Z, Feng G (2016). "Adult restoration of Shank3 expression rescues selective autistic-like phenotypes". Nature. 530 (7591): 481–4. doi:10.1038/nature16971. PMID 26886798. 

Further reading[edit]

External links[edit]