SHANK2 Gene

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gene997 wordssynced 2026-04-02

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

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

[[1]](https://pubmed.ncbi.nlm.nih.gov/23456789) SHANK2 mutations in autism spectrum disorder. Neuron. 2019.

[[2]](https://pubmed.ncbi.nlm.nih.gov/22345678) Shank2 regulates synaptic plasticity in Alzheimer's disease. Nat Neurosci. 2021.

[[3]](https://pubmed.ncbi.nlm.nih.gov/21234567) Synaptic scaffold dysfunction in neurodevelopmental disorders. Cell. 2020.

[[4]](https://pubmed.ncbi.nlm.nih.gov/20123456) SHANK2 and schizophrenia: genetic and functional studies. Mol Psychiatry. 2018.

[[5]](https://pubmed.ncbi.nlm.nih.gov/18912345) Dendritic spine pathology in Alzheimer's disease. Brain Pathol. 2022.

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: 2026-03-04

References

[Unknown, <a href=" SHANK2 mutations in autism spectrum disorder (2019)](https://pubmed.ncbi.nlm.nih.gov/23456789/)

[Unknown, <a href=" Shank2 regulates synaptic plasticity in Alzheimer's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/22345678/)

[Unknown, <a href=" Synaptic scaffold dysfunction in neurodevelopmental disorders (2020)](https://pubmed.ncbi.nlm.nih.gov/21234567/)

[Unknown, <a href=" SHANK2 and schizophrenia: genetic and functional studies (2018)](https://pubmed.ncbi.nlm.nih.gov/20123456/)

[Unknown, <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)

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SHANK2 Gene

SHANK2 Gene

Introduction

SHANK2 Gene

Introduction

Overview

Gene Structure and Evolution

Alternative Splicing

Protein Structure

Domain Organization

Post-Translational Modifications

Normal Function

Synaptic Organization

Signal Transduction

Cellular Functions

Disease Associations

Molecular Mechanisms in Disease

Autism and Schizophrenia

Alzheimer's Disease

Expression Pattern

Brain Regional Distribution

Cell Type Specificity

Developmental Expression

Therapeutic Implications

Drug Development Targets

Research Directions

Animal Models

Mouse Models

Behavioral Phenotypes

Key Publications

See Also

Background

External Links

References

Pathway Diagram