PPP2R1B

This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes a beta isoform of the constant regulatory subunit A. Defects in this gene could be the cause of some lung and colon cancers. At least two transcript variants encoding different isoforms have been found for this gene.^[7]

The PPP2R1B gene was discovered as part of the Human Genome Project research center focused on chromosome 11.^[8][9]

Somatic alterations in PPP2R1B have been identified in colorectal and lung cancer tumors and cell lines,^[8] with evidence that these alterations affect protein function, supporting a role for PPP2R1B as a candidate tumor suppressor gene in these cancers. Experimental studies have shown that suppression of PPP2R1B expression enables immortalized human cells to become tumorigenic, and that the wild-type protein forms a complex with the small GTPase RalA. These findings support the role of PPP2R1B as a tumor suppressor involved in regulating RalA function.^[10]

A case series described nine cancer patients with germline loss-of-function (LOF) variants in PPP2R1B, with breast cancer being the most frequently observed diagnosis.^[11] In all documented cases, individuals also had a family history of cancers including breast, ovarian, prostate, uterine, renal, and colorectal cancer, suggesting that PPP2R1B may function as a predisposition gene in breast and potentially other cancers.^[6]

PPP2R1B has been shown to interact with: