Shank3 Gene Summary [Mouse]
Enables ionotropic glutamate receptor binding activity and scaffold protein binding activity. A structural constituent of postsynaptic density. Involved in several processes, including learning or memory; modulation of chemical synaptic transmission; and postsynapse organization. Acts upstream of or within several processes, including MAPK cascade; negative regulation of actin filament bundle assembly; and regulation of AMPA glutamate receptor clustering. Located in neuron spine and plasma membrane. Is active in glutamatergic synapse. Is expressed in central nervous system. Used to study Phelan-McDermid syndrome; autism spectrum disorder; and schizophrenia. Human ortholog(s) of this gene implicated in Phelan-McDermid syndrome and schizophrenia 15. Orthologous to human SHANK3 (SH3 and multiple ankyrin repeat domains 3). [provided by Alliance of Genome Resources, Jul 2025]
Details
| Type | Protein Coding |
| Official Symbol | Shank3 |
| Official Name | SH3 and multiple ankyrin repeat domains 3 [Source:MGI Symbol;Acc:MGI:1930016] |
| Ensembl ID | ENSMUSG00000022623 |
| Bio databases IDs | |
| Aliases | SH3 and multiple ankyrin repeat domains 3 |
| Synonyms | DEL22q13.3, LOC284940, PROSAP2, PSAP2, SCZD15, SH3 and multiple ankyrin repeat domains 3, SPANK-2 |
| Species | Mouse, Mus musculus |
| Orthologies |
Protein Domains
A protein domain is a distinct structural or functional region within a protein that can evolve, function, and exist independently of the rest of the protein chain. These domains in mouse Shank3 often fold into stable, three-dimensional structures and are associated with specific biological functions, such as binding to DNA, other proteins, or small molecules.
- Domain present in PSD-95, Dlg, and ZO-1/2
- Ankyrin repeats (many copies)
- SAM domain
- SAM (Sterile alpha motif )
- G-protein-coupled receptor binding
- canonical PDZ domain
- Ankyrin repeats (3 copies)
- GKAP/Homer scaffold
- protein binding
- SPN domain
- ionotropic glutamate receptor binding
- identical protein binding
- proline rich domain
- SH3-domain binding
- Ankyrin repeat
- Src Homology 3 domain superfamily
- Sterile alpha motif
- binding protein
- zinc ion binding
- Ubl1_cv_Nsp3_N-like
- SAM domain (Sterile alpha motif)
- structural molecule
- N-terminal or F0 domain of Talin-head FERM
- ankyrin repeats
Pathways
Biological processes and signaling networks where the Shank3 gene in mouse plays a role, providing insight into its function and relevance in health or disease.
Top Findings
The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
disease
- schizophrenia
- memory deficits
- mental retardation
- hereditary disorder
- chromosome 22q13.3 deletion syndrome
- autism-like behavioral deficit
- neurodevelopmental disorder
- pervasive developmental disorder
- hypersensitive reaction
- SHANK3-related disorder
phenotypes
- increased circulating phosphate level
- abnormal CNS synaptic transmission
- abnormal allogrooming behavior
- abnormal autopod morphology
- abnormal basal ganglion morphology
- abnormal behavior
- abnormal brain commissure morphology
- abnormal brain internal capsule morphology
- abnormal brain wave pattern
- abnormal brain white matter morphology
- abnormal cerebellar peduncle morphology
- abnormal cingulum morphology
- abnormal conditioned emotional response
- abnormal dendritic spine morphology
- abnormal ear development
- abnormal excitatory postsynaptic currents
- abnormal excitatory postsynaptic potential
- abnormal gait
- abnormal glutamate-mediated receptor currents
- abnormal habituation to a novel odor
- abnormal impulsive behavior control
- abnormal innate avoidance response
- abnormal learning/memory/conditioning
- abnormal locomotor activation
- abnormal long term depression
- abnormal long term object recognition memory
- abnormal medium spiny neuron morphology
- abnormal miniature excitatory postsynaptic currents
- abnormal miniature inhibitory postsynaptic currents
- abnormal motor capabilities/coordination/movement
- abnormal motor coordination/ balance
- abnormal motor learning
- abnormal nervous system electrophysiology
- abnormal nest building behavior
- abnormal neuron physiology
- abnormal object recognition memory
- abnormal odor adaptation
- abnormal olfactory lobe morphology
- abnormal paired-pulse inhibition
- abnormal postsynaptic density morphology
- abnormal reflex
- abnormal response to new environment
- abnormal response to novel object
- abnormal response to novelty
- abnormal response to social novelty
- abnormal sexual interaction
- abnormal single cell response
- abnormal social investigation
- abnormal social recognition
- abnormal social/conspecific interaction
- abnormal spatial learning
- abnormal spatial reference memory
- abnormal spinal cord commissure morphology
- abnormal startle reflex
- abnormal striatum morphology
- abnormal synapse morphology
- abnormal synaptic transmission
- abnormal vocalization
- altered righting response
- circling
- decreased amygdala size
- decreased anxiety-related response
- decreased body weight
- decreased excitatory postsynaptic current amplitude
- decreased exploration in new environment
- decreased grip strength
- decreased post-tetanic potentiation
- decreased prepulse inhibition
- decreased startle reflex
- decreased stereotypic behavior
- decreased susceptibility to pharmacologically induced seizures
- decreased synaptic depression
- decreased thermal nociceptive threshold
- decreased vertical activity
- decreased vocalization
- enhanced contextual conditioning behavior
- enhanced cued conditioning behavior
- environmentally induced seizures
- excessive vocalization
- hyperactivity
- hypoactivity
- hyporesponsive to tactile stimuli
- impaired contextual conditioning behavior
- impaired coordination
- impaired discrimination learning
- impaired learning
- impaired righting response
- impaired spatial learning
- impaired synaptic plasticity
- increased aggression towards mice
- increased anxiety-related response
- increased body weight
- increased fear-related response
- increased grooming behavior
- increased startle reflex
- increased stereotypic behavior
- increased thigmotaxis
- increased vertical activity
- induced hyperactivity
- lethality incomplete penetrance
- long stride length
- neonatal lethality incomplete penetrance
- photophobia
- postnatal growth retardation
- premature death
- premature suckling reflex loss
- reduced NMDA-mediated synaptic currents
- reduced long term depression
- reduced long term potentiation
- skin lesions
- small hippocampus
- social withdrawal
- thalamus hyperplasia
- weakness
role in cell
- expression in
- proliferation
- quantity
- differentiation
- response
- formation
- abnormal morphology
- synaptic transmission
- function
- trans-signaling
Subcellular Expression
Locations within the cell where the protein is known or predicted to be active, providing insight into its function and cellular context.
- Plasma Membrane
- membrane fraction
- glutaminergic synapse
- organelle
- Cytoplasm
- cilia
- cytosol
- basolateral cell surfaces
- dendritic spines
- neurites
- postsynaptic density
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the mouse Shank3 gene, providing context for its role in the cell.
Biological Process
Functions and activities the gene product is involved in
- regulation of long-term synaptic potentiation
- positive regulation of long-term synaptic potentiation
- regulation of long term synaptic depression
- positive regulation of glutamate receptor signaling pathway
- vocal learning
- brain morphogenesis
- learning
- memory
- striatal medium spiny neuron differentiation
- MAPK cascade
- negative regulation of cell volume
- postsynaptic density assembly
- positive regulation of synaptic transmission, glutamatergic
- social behavior
- regulation of dendritic spine morphogenesis
- positive regulation of dendritic spine development
- dendritic spine morphogenesis
- synapse assembly
- alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor clustering
- N-methyl-D-aspartate receptor clustering
- guanylate kinase-associated protein clustering
- positive regulation of synapse structural plasticity
- negative regulation of actin filament bundle assembly
- positive regulation of excitatory postsynaptic membrane potential
- adult behavior
- neuromuscular process controlling balance
- vocalization behavior
- positive regulation of long-term neuronal synaptic plasticity
Cellular Component
Where in the cell the gene product is active
- postsynaptic density
- neuron spine
- postsynaptic membrane
- dendritic spine
- cytosol
- cilium membrane
- neuron projection
- plasma membrane
Molecular Function
What the gene product does at the molecular level
- scaffold protein binding
- ionotropic glutamate receptor binding
- zinc ion binding
- protein binding
- actin binding
- GKAP/Homer scaffold activity
- SH3 domain binding