PIK3R1是抑癌基因，编码蛋白是磷脂酰肌醇-3-激酶（PI3K）的调节亚基又称为p85α。在没有上游受体酪氨酸激酶（RTK）激活的情况下，PIK3R1蛋白既稳定又抑制PI3K的催化亚基p110α的活性。在RTK活化后，PIK3R1蛋白与RTK的磷酸化酪氨酸残基结合。随后，这将PI3K酶复合物募集到细胞膜并允许p110α催化亚基产生磷脂酰肌醇-3,4,5-三磷酸（PIP3）。PIP3的产生导致丝氨酸/苏氨酸激酶AKT的募集和活化，其反过来激活参与细胞生长，增殖和存活的许多下游靶标（例如mTOR）。PIK3R1突变最常发生在其两个SRC同源性2（SH2）结构域，nSH2和iSH2中。这些突变破坏p85α抑制PI3K催化亚基的能力，从而导致AKT-mTOR信号传导的异常激活。在所有肿瘤类型中，PIK3R1突变倾向于与TP53，PIK3CA，SETD2和WT1的改变相互排斥。PIK3R1突变在胶质母细胞瘤中普遍存在，在子宫内膜癌，乳腺癌和结直肠癌中较少见。

PIK3R1, the regulatory subunit of PI3-kinase, is mutated in various cancers, most frequently in glioma, endometrial and colorectal cancers. PIK3R1 encodes p85α, the regulatory subunit of phosphatidylinositol-3-kinase (PI3K). In the absence of upstream receptor tyrosine kinase (RTK) activation, p85α both stabilizes and inhibits the activity of p110α, the catalytic subunit of PI3K. Upon RTK activation, p85α binds to phosphorylated tyrosine residues on the cytoplasmic tails of RTKs. Subsequently, this recruits the PI3K enzymatic complex to the cell membrane and allows the p110α catalytic subunit to generate phosphatidylinositol-3, 4, 5-trisphosphate (PIP3). The production of PIP3 results in recruitment and activation of the serine/threonine kinase, AKT, which in turn activates numerous downstream targets (e.g. mTOR) involved in cell growth, proliferation and survival. PIK3R1 mutations occur most frequently in its two SRC Homology 2 (SH2) domains, nSH2 and iSH2. These mutations disrupt the ability of p85α to inhibit the PI3K catalytic subunit, thus resulting in aberrant activation of AKT-mTOR signaling. Across all tumor types, PIK3R1 mutations tend to be mutually exclusive with alterations in TP53, PIK3CA, SETD2 and WT1. PIK3R1 mutations are prevalent in glioblastoma and to a lesser extent in endometrial, breast and colorectal cancers.

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