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.
| Attribute | Value | [1]
|---|---| [2]
| Gene Symbol | SHANK2 | [3]
| Gene Name | SH3 and Multiple Ankyrin Repeat Domains 2 | [4]
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 22941 |
| Ensembl ID | ENSG00000141013 |
| UniProt ID | Q9UQB8 |
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 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 is disrupted, contributing to synaptic loss—a hallmark of cognitive decline. The protein also plays roles in neuroimmune signaling through interactions with microglia.
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.
The SHANK2 protein contains several distinct domains:
The SHANK2 gene encodes a scaffold protein involved in various neurological processes:
SHANK2 is implicated in multiple neurological disorders:
| Disease | Association Type | Notes |
|---|---|---|
| Autism Spectrum Disorder | Genetic | Multiple mutations identified; disrupt synaptic function |
| Schizophrenia | Genetic | Risk gene; altered expression in patients |
| Alzheimer's Disease | Expression | Reduced expression; contributes to synaptic loss |
| ALS | Genetic | Some mutations associated |
| Intellectual Disability | Genetic | De novo mutations cause ID |
SHANK2 exhibits region-specific expression:
Understanding SHANK2 function opens therapeutic avenues:
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.
Gene information last updated: 2026-03-04
<a href=" Shank2 regulates synaptic plasticity in Alzheimer's disease. Nat Neurosci. 2021. ↩︎
<a href=" Synaptic scaffold dysfunction in neurodevelopmental disorders. Cell. 2020. ↩︎
<a href=" SHANK2 and schizophrenia: genetic and functional studies. Mol Psychiatry. 2018. ↩︎
<a href=" Dendritic spine pathology in Alzheimer's disease. Brain Pathol. 2022. ↩︎