POGZ

Molecular characteristics

POGZ (Pogo transposable element with ZNF domain) encodes a heterochromatin protein 1 α-binding protein containing a cluster of multiple C2H2-type zinc fingers, a centromere protein (CENP) B-like DNA-binding domain, and a DDE domain that might regulate gene expression. POGZ is involved in mitosis and is expressed in the human fetal and adult brain (BrainSpan Atlas and GTEx). It is hypothesized to function as a transcriptional regulator in molecular networks crucial for neuronal function.

The first few mutations in POGZ were detected by whole exome/genome sequencing in cohorts of individuals with autism spectrum disorders (ASD), developmental delay (DD)/intellectual disability (ID) or schizophrenia. Mutations in POGZ can be identified using targeted or genome-wide sequencing technology. Most mutations are de novo truncating or frameshift mutations. Though, several missense mutations have been reported as well. In contrast to the truncating or frameshift mutations, the missense mutations are not clearly associated with impaired intellectual capacity. However, the missense variants seem to be associated with a behavioral phenotype, including ASD or autistic-like features, reminiscent of that seen in individuals carrying LGD variants.

Prenatal testing is technically feasible, but the likelihood of recurrence in families who have had an affected child is considered low based upon the current knowledge.