SHANK3

SH3 and multiple ankyrin repeat domains 3

The SHANK3 gene provides instructions for making a protein that is found in many of the body's tissues but is most abundant in the brain. The SHANK3 protein plays a role in the functioning of synapses, which are the connections between nerve cells (neurons) where cell-to-cell communication occurs. Within synapses, the SHANK3 protein acts as a scaffold that connects neurons, ensuring that the signals sent by one neuron are received by another.

The SHANK3 protein is also involved in the formation and maturation of dendritic spines. Dendrites are specialized extensions from neurons that are essential for the transmission of nerve impulses. Dendritic spines are small outgrowths from dendrites that further help transmit nerve impulses and increase communication between neurons.

The characteristic signs and symptoms of 22q13.3 deletion syndrome, which is also commonly known as Phelan-McDermid syndrome, are caused by a deletion near the end of the long (q) arm of chromosome 22. The chromosomal region that is typically deleted is thought to contain many genes, including the SHANK3 gene. As a result of the deletion, people with this condition have only one copy of the SHANK3 gene in each cell instead of the usual two copies.

Researchers believe that a deletion of the SHANK3 gene and a reduction in the amount of SHANK3 protein produced is responsible for many of the features of 22q13.3 deletion syndrome. A decrease in the functioning of synapses and cell-to-cell communication between neurons caused by a lack of SHANK3 protein is thought to contribute to the developmental delay, intellectual disability, and absent or severely delayed speech characteristic of people with 22q13.3 deletion syndrome.

At least seven SHANK3 gene mutations have been found in people who have the features of autism or similar conditions known as autism spectrum disorders. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. Most of these mutations disrupt the function of the SHANK3 protein or lead to the production of an abnormally short version of the protein. It is unclear how changes in the SHANK3 gene are related to the risk of developing autism. Researchers suspect that a disruption in nerve cell communication contributes to the development of autism.

Cytogenetic Location: 22q13.3, which is the long (q) arm of chromosome 22 at position 13.3

Molecular Location: base pairs 50,674,642 to 50,733,212 on chromosome 22 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 22q13.3, which is the long (q) arm of chromosome 22 at position 13.3
  • proline-rich synapse-associated protein 2
  • ProSAP2
  • SPANK-2