PTEN across dismech

PTEN (phosphatase and tensin homolog) is named by 21 disorder entries.

Normal function

ai-gene-review gives PTEN's core molecular functions as phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity; and protein serine/threonine phosphatase activity, acting in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; phosphatidylinositol dephosphorylation; and protein dephosphorylation.

Causative records

Two entries type PTEN as causative: Bannayan-Riley-Ruvalcaba Syndrome; and Familial Nonmedullary Thyroid Carcinoma, and both record the variants as germline (Bannayan-Riley-Ruvalcaba Syndrome; and Familial Nonmedullary Thyroid Carcinoma). In Bannayan-Riley-Ruvalcaba Syndrome the gene sits on the node Germline PTEN Loss of Function.

The two entries most closely identified with the gene record it differently. Cowden Syndrome's genetic record is untyped, as is PTEN Hamartoma Tumor Syndrome's (untyped): both say "Causative" only in the free-text association field, and neither records a variant origin (unrecorded). ClinGen rates PTEN definitive for PTEN hamartoma tumor syndrome, so that entry's record could be typed causative without any new evidence. Cowden Syndrome nonetheless places PTEN on 6 pathophysiology nodes, including PTEN Loss and PI3K/AKT/mTOR Pathway Activation and PTEN Genome Integrity Defect. Nodes naming PTEN in these syndromes conform to the module germline_two_hit_tumor_predisposition.

Somatic driver and untyped records

Three entries type PTEN as a somatic driver: Chromophobe Renal Cell Carcinoma; Endometriosis; and Thyroid Follicular Carcinoma. Two of them record the variant origin as somatic (Chromophobe Renal Cell Carcinoma; and Endometriosis); Thyroid Follicular Carcinoma's is unrecorded. Several carcinoma entries carry PTEN with no relationship type, among them Endometrial Carcinoma; Prostate Adenocarcinoma; and Glioblastoma, IDH-Wildtype; for example Endometrial Carcinoma is untyped.

Where the layers disagree

ClinGen classifies PTEN for 1 disease, and the dismech entries matched to it that do not type the gene are PTEN Hamartoma Tumor Syndrome.

Of the disorders that name PTEN, 14 have a genetic record for it with no relationship_type. That is the main curation gap this page exposes.

The KB's PTEN nodes are annotated with the PI3K/AKT process itself, while ai-gene-review annotates PTEN with the negative regulation of that process, so the two share 0 GO terms by exact identifier. Reading the KB annotation as "PTEN loss increases PI3K/AKT signalling" and the ai-gene-review one as "PTEN normally restrains it" reconciles them; a closure-aware comparison would need the GO hierarchy.