pogo transposable element derived with ZNF domain
The POGZ gene provides instructions for making a protein that is found in the cell nucleus, including in brain cells before and just after birth. The POGZ protein is part of a group known as zinc finger proteins, which contain one or more short regions called zinc finger domains. These regions include a specific pattern of protein building blocks (amino acids) and one or more charged atoms of zinc (zinc ions). The folded configuration of the zinc finger domain stabilizes the protein and allows it to attach (bind) to other molecules.
The POGZ protein binds to complexes called chromatin, the network of DNA and proteins that packages DNA into chromosomes. Binding with the POGZ protein helps change the structure of chromatin (chromatin remodeling) to alter how tightly regions of DNA are packaged. Chromatin remodeling is one way gene activity (expression) is regulated; when DNA is tightly packed gene expression is lower than when DNA is loosely packed. Regulation of gene expression by the POGZ protein is thought to be important to brain development, but the specific role of POGZ is unknown.
At least 14 POGZ gene mutations have been identified in people with autism spectrum disorder (ASD), a varied condition characterized by impaired social skills, communication problems, and repetitive behaviors. These mutations add or remove genetic material from the POGZ gene, change single amino acids in the POGZ protein sequence, or introduce a premature stop signal, resulting in an abnormally short, nonfunctional protein.
While the exact disease mechanism is unknown, studies suggest that the POGZ gene mutations associated with ASD result in a POGZ protein with impaired ability to bind to chromatin. Lack of chromatin binding likely results in abnormal chromatin remodeling, altering the normal expression of genes involved in brain development and leading to ASD.
POGZ gene mutations have also been found in people with intellectual disability, often with other signs and symptoms affecting various parts of the body. POGZ gene mutations are thought to impair the chromatin binding function of the POGZ protein, leading to abnormal gene expression that affects development of the brain and other body systems, but the specific connection between the mutations and development of intellectual disability and other signs and symptoms in affected individuals is unknown.
- putative protein product of Nbla00003
- zinc finger protein 280E
- zinc finger protein 635