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

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: mouse all
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Genomic context

Location:: 22q13.33

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (50672823..50733212)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (51186790..51246792)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (51111251..51171640)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Shank3 mutation impairs glutamate signaling and myelination in ASD mouse model and human iPSC-derived OPCs.
Title: Shank3 mutation impairs glutamate signaling and myelination in ASD mouse model and human iPSC-derived OPCs.
Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency.
Title: Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency.
Cardiovascular abnormalities in patients with SHANK3 pathogenic variants: Beyond neurodevelopmental disorders and epilepsy.
Title: Cardiovascular abnormalities in patients with SHANK3 pathogenic variants: Beyond neurodevelopmental disorders and epilepsy.
Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.
Title: Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.
Pharmacological modulation of developmental and synaptic phenotypes in human SHANK3 deficient stem cell-derived neuronal models.
Title: Pharmacological modulation of developmental and synaptic phenotypes in human SHANK3 deficient stem cell-derived neuronal models.
Evidence for common mechanisms of pathology between SHANK3 and other genes of Phelan-McDermid syndrome.
Title: Evidence for common mechanisms of pathology between SHANK3 and other genes of Phelan-McDermid syndrome.
EGR1 Regulates SHANK3 Transcription at Different Stages of Brain Development.
Title: EGR1 Regulates SHANK3 Transcription at Different Stages of Brain Development.
Expression profiles of the autism-related SHANK proteins in the human brain.
Title: Expression profiles of the autism-related SHANK proteins in the human brain.
Drugs prescribed for Phelan-McDermid syndrome differentially impact sensory behaviors in shank3 zebrafish models.
Title: Drugs prescribed for Phelan-McDermid syndrome differentially impact sensory behaviors in shank3 zebrafish models.
Role of the Autism Risk Gene Shank3 in the Development of Atherosclerosis: Insights from Big Data and Mechanistic Analyses.
Title: Role of the Autism Risk Gene Shank3 in the Development of Atherosclerosis: Insights from Big Data and Mechanistic Analyses.

Submit: New GeneRIF Correction See all GeneRIFs (92)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Phelan-McDermid syndrome MedGen: C1853490 OMIM: 606232 GeneReviews: Phelan-McDermid Syndrome-SHANK3 Related	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 &gt;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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D22S1726 (e-PCR)
- UniSTS:71686

NoName (e-PCR)
- UniSTS:146590

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

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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)

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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

NG_070230.1 RefSeqGene

Range

5001..68996

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Status: REVIEWED

Source sequence(s)

AB569469, AC000036, AC000050

UniProtKB/TrEMBL

A0A8I5KZC4, A0AAG2UY11

Related

ENSP00000510794.2, ENST00000692848.2

Conserved Domains (8) summary

cd09506
Location:1739 → 1804

SAM_Shank1,2,3; SAM domain of Shank1,2,3 family proteins

cd11984
Location:549 → 600

SH3_Shank3; Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3

COG0666
Location:200 → 392

ANKYR; Ankyrin repeat [Signal transduction mechanisms]

PRK12323
Location:1208 → 1412

PRK12323; DNA polymerase III subunit gamma/tau

cd00992
Location:648 → 737

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:257 → 288

ANK; ANK repeat [structural motif]

cd17177
Location:83 → 169

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:329 → 410

Ank_2; Ankyrin repeats (3 copies)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p14 Primary Assembly

Range

50672823..50733212

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GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 PATCHES

Genomic

NW_015148969.2 Reference GRCh38.p14 PATCHES

Range

8917..69331

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060946.1 Alternate T2T-CHM13v2.0

Range

51186790..51246792

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.
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.