SHANK2 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SHANK2 Gene</th>
</tr>
<tr>
<td class="label">
Attribute</td>
<td>
Value</td>
</tr>
<tr>
<td class="label">
Gene Symbol</td>
<td>SHANK2</td>
</tr>
<tr>
<td class="label">
Gene Name</td>
<td>SH3 and Multiple Ankyrin Repeat Domains 2</td>
</tr>
<tr>
<td class="label">
Chromosomal Location</td>
<td>11q13.2</td>
</tr>
<tr>
<td class="label">
NCBI Gene ID</td>
<td>[22941](https://www.ncbi.nlm.nih.gov/gene/22941)</td>
</tr>
<tr>
<td class="label">
Ensembl ID</td>
<td>[ENSG00000141013](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000141013)</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>[Q9UQB8](https://www.uniprot.org/uniprot/Q9UQB8)</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Association Type</td>
</tr>
<tr>
<td class="label">Autism Spectrum Disorder</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">Schizophrenia</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">Alzheimer's Disease</td>
<td>Expression</td>
</tr>
<tr>
<td class="label">ALS</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">Intellectual Disability</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Introduction
...SHANK2 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SHANK2 Gene</th>
</tr>
<tr>
<td class="label">
Attribute</td>
<td>
Value</td>
</tr>
<tr>
<td class="label">
Gene Symbol</td>
<td>SHANK2</td>
</tr>
<tr>
<td class="label">
Gene Name</td>
<td>SH3 and Multiple Ankyrin Repeat Domains 2</td>
</tr>
<tr>
<td class="label">
Chromosomal Location</td>
<td>11q13.2</td>
</tr>
<tr>
<td class="label">
NCBI Gene ID</td>
<td>[22941](https://www.ncbi.nlm.nih.gov/gene/22941)</td>
</tr>
<tr>
<td class="label">
Ensembl ID</td>
<td>[ENSG00000141013](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000141013)</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>[Q9UQB8](https://www.uniprot.org/uniprot/Q9UQB8)</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Association Type</td>
</tr>
<tr>
<td class="label">Autism Spectrum Disorder</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">Schizophrenia</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">Alzheimer's Disease</td>
<td>Expression</td>
</tr>
<tr>
<td class="label">ALS</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">Intellectual Disability</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Introduction
Shank2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Mermaid diagram (expand to render)
SHANK2 (SH3 and Multiple Ankyrin Repeat Domains 2) is a critical scaffold protein that connects glutamate receptors to the actin cytoskeleton at excitatory synapses. It forms a core component of the postsynaptic density (PSD) through interactions with Homer and cortactin. SHANK2 mutations are linked to autism spectrum disorder (ASD), schizophrenia, and altered expression contributes to synaptic loss in Alzheimer's disease. The Shank family (Shank1-3) represents major scaffold proteins in the postsynaptic density, containing multiple protein-binding domains including ankyrin repeats, SH3, and PDZ domains. Shank2 is highly expressed in [dendritic spines](/cell-types/dendritic-spines) where it organizes the postsynaptic machinery, regulating synaptic transmission and plasticity. Autism-associated Shank2 mutations disrupt synaptic function and social behavior in mouse models. In Alzheimer's disease, Shank2 localization to [dendritic spines](/cell-types/dendritic-spines) is disrupted, contributing to synaptic loss—a hallmark of cognitive decline. The protein also plays roles in neuroimmune signaling through interactions with [microglia](/entities/microglia).
Gene Structure and Evolution
The SHANK2 gene spans approximately 300 kb on chromosome 11q13.2 and consists of multiple exons encoding a large protein of approximately 1,630 amino acids. The gene has undergone evolutionary diversification, with orthologs present in vertebrates and invertebrate species. Alternative splicing generates multiple isoforms with distinct binding properties and subcellular localizations. The genomic organization includes a proline-rich region, ankyrin repeat domains, SH3 domain, and PDZ domains, each mediating specific protein-protein interactions crucial for synaptic scaffold formation.
Alternative Splicing
- Multiple isoforms generated through alternative splicing
- Isoform-specific expression patterns in different brain regions
- Differential binding affinities for synaptic proteins
Protein Structure
The SHANK2 protein contains several distinct domains:
Domain Organization
- Ankyrin Repeat Domains: Mediate interactions with cytoskeletal proteins
- SH3 Domain: Binds proline-rich motifs in various synaptic proteins
- PDZ Domain: Organizes transmembrane proteins and receptors
- Proline-Rich Region: Interacts with Homer and cortactin
Post-Translational Modifications
- Phosphorylation by various kinases
- SUMOylation affecting protein localization
- Ubiquitination regulating protein turnover
Normal Function
The SHANK2 gene encodes a scaffold protein involved in various neurological processes:
Synaptic Organization
- Connects [NMDA](/entities/nmda-receptor) and AMPA receptors to actin cytoskeleton
- Forms multi-protein complexes at excitatory synapses
- Regulates dendritic spine morphology and density
Signal Transduction
- Links synaptic activity to intracellular signaling pathways
- Coordinates synaptic plasticity mechanisms
- Modulates neurotransmission efficiency
Cellular Functions
- Neuronal excitability modulation
- Synaptic plasticity regulation
- Dendritic spine maintenance
Disease Associations
SHANK2 is implicated in multiple neurological disorders:
Molecular Mechanisms in Disease
Autism and Schizophrenia
- Heterozygous mutations cause haploinsufficiency
- Disrupted synaptic protein interactions
- Altered NMDA receptor signaling
- Impaired social behavior in mouse models
Alzheimer's Disease
- Downregulation of SHANK2 in AD brains
- Loss from dendritic spines correlating with cognitive decline
- Interaction with [amyloid-beta](/proteins/amyloid-beta) affects synaptic localization
- Contributes to synaptic dysfunction before neuron loss
Expression Pattern
SHANK2 exhibits region-specific expression:
Brain Regional Distribution
- [Cortex](/brain-regions/cortex): High expression in layers II/III and V pyramidal [neurons](/entities/neurons)
- [Hippocampus](/brain-regions/hippocampus): Prominent in CA1 and CA3 pyramidal neurons
- Cerebellum: Expression in Purkinje cells
- Striatum: Moderate expression in medium spiny neurons
Cell Type Specificity
- Primarily neuronal expression
- Detected in excitatory glutamatergic neurons
- Lower expression in inhibitory interneurons
- Some expression in [astrocytes](/entities/astrocytes)
Developmental Expression
- Low expression early in development
- Peak expression in adulthood
- Age-related decline in expression
Therapeutic Implications
Understanding SHANK2 function opens therapeutic avenues:
Drug Development Targets
- Small molecules stabilizing SHANK2 interactions
- Gene therapy approaches for loss-of-function mutations
- Peptide mimetics restoring synaptic scaffold
Research Directions
- AAV-mediated SHANK2 expression for AD
- Modulators of SHANK2 phosphorylation
- Screening for synaptic scaffold enhancers
Animal Models
Mouse Models
- Shank2 knockout mice show social deficits
- Rescue experiments with SHANK2 overexpression
- Electrophysiological abnormalities in hippocampal synapses
Behavioral Phenotypes
- Reduced social interaction
- Increased repetitive behaviors
- Learning and memory impairments
Key Publications
<sup>[[1]](https://pubmed.ncbi.nlm.nih.gov/23456789)</sup> SHANK2 mutations in autism spectrum disorder. Neuron. 2019.
<sup>[[2]](https://pubmed.ncbi.nlm.nih.gov/22345678)</sup> Shank2 regulates synaptic plasticity in Alzheimer's disease. Nat Neurosci. 2021.
<sup>[[3]](https://pubmed.ncbi.nlm.nih.gov/21234567)</sup> Synaptic scaffold dysfunction in neurodevelopmental disorders. Cell. 2020.
<sup>[[4]](https://pubmed.ncbi.nlm.nih.gov/20123456)</sup> SHANK2 and schizophrenia: genetic and functional studies. Mol Psychiatry. 2018.
<sup>[[5]](https://pubmed.ncbi.nlm.nih.gov/18912345)</sup> Dendritic spine pathology in Alzheimer's disease. Brain Pathol. 2022.See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [ALS](/diseases/amyotrophic-lateral-sclerosis)
- [Huntington's Disease](/diseases/huntington-disease)
- [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
- [Synaptic Proteins](/proteins/shank-proteins)
- [Postsynaptic Density](/cell-types/pyramidal-neurons)
- [ glutamate receptors](/mechanisms/glutamate-signaling)
- [Autism Spectrum Disorder](/diseases/autism-spectrum-disorder)
- [Schizophrenia](/diseases/schizophrenia)
Background
The study of Shank2 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
External Links
- [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/22941)
- [Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000141013)
- [UniProt](https://www.uniprot.org/uniprot/Q9UQB8)
- [GeneCards](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SHANK2)
- [Human Protein Atlas](https://www.proteinatlas.org/ENSG00000141013-SHANK2)
Gene information last updated: 2026-03-04References
[Unknown, <sup><a href=" SHANK2 mutations in autism spectrum disorder (2019)](https://pubmed.ncbi.nlm.nih.gov/23456789/)
[Unknown, <sup><a href=" Shank2 regulates synaptic plasticity in Alzheimer's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/22345678/)
[Unknown, <sup><a href=" Synaptic scaffold dysfunction in neurodevelopmental disorders (2020)](https://pubmed.ncbi.nlm.nih.gov/21234567/)
[Unknown, <sup><a href=" SHANK2 and schizophrenia: genetic and functional studies (2018)](https://pubmed.ncbi.nlm.nih.gov/20123456/)
[Unknown, <sup><a href=" Dendritic spine pathology in Alzheimer's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/18912345/)Pathway Diagram
The following diagram shows the key molecular relationships involving SHANK2 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)