Alt. symbols: BZS | MHAM | MMAC1 | TEP1 | PTEN1

Approved name: phosphatase and tensin homolog
Alt. names: mutated in multiple advanced cancers 1

Location: 10q23.31: 87862638 - 87971930 (+)
Gene type: protein_coding, 22 transcripts.

Scores: LoFtool: 0.092900 | pLI: 0.97550687 | LOEUF: 0.507

HGNC: 9588

NCBI: 5728, RefSeq: NG_007466.2

Ensembl: ENSG00000171862.16

LRG_311 | Status: public

OMIM: 601728

Expression | ProteinAtlas

PTEN encodes a PIP3 phosphatase that counteracts PI3K activity by converting PIP3 to PIP2 to regulate the amplitude and duration of signaling. Thus, PTEN is a tumor suppressor whose LOF results in inappropriate AKT/mTOR signaling, which promotes cell survival, proliferation, and motility. This leads to autosomal dominant disorders characterized by various skin and soft tissue overgrowth findings, including multiple benign tumors such as hamartomas, as well as increased risk for certain malignancies.

Monoallelic mutations in PTEN have been associated with the PTEN hamartoma tumor syndrome spectrum of disorders that encompass Cowden syndrome [OMIM: 158350], Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, and Proteus-like syndrome. Though immunodeficiency had been previously reported for these syndromes, its nature remained largely uncharacterized until Browning et al. (2015), who described antibody deficiency for the first time in a patient with Cowden syndrome - this patien t had recurrent infections, panhypogammaglobulinaemia and a prematurely rapid decline in vaccine titers (PMID: 26246517). Another patient showed CD4+ T cell lymphopenia but with normal antibody production, suggesting that PTEN LOF could lead to both T- and/or B-cell defects. Shortly thereafter, Driessen et al. (2016) reported the identification of three more CVID patients carrying PTEN mutations, who showed expanded transitional B cell and reduced memory B cell proportions and abnormalities in both CSR and SHM, which they attributed to the deregulating effect of Akt signaling on AICDA expression and function (PMID: 27531073). Tsujita et al. (2016) also reported heterozygous PTEN nonsense and frameshift mutations that reduced but did not abolish PTEN mRNA and protein expression in 2 patients with APDS-like phenotypes featuring opportunistic infections and lymphadenopathy, where at least 1 carried a CVID diagnosis (PMID: 27426521). Lymphocytes from these patients showed AKT, mTOR, and S6 hyperphosphorylation, in keeping with PTEN’s known role in suppressing PI3K pathway activation. Like the Driessen patients, the latter showed significantly reduced memory and switched memory B cell counts despite normal B- and T-cell counts. But unlike the Driessen patients or patients with PIK3CD mutations, percentages of Tfh and transitional B cells were not significantly expanded. [Load More]