INPP4B

Overview

INPP4B encodes inositol polyphosphate 4-phosphatase type II, a lipid phosphatase that converts PIP3 to PIP2, opposing the PI3K/AKT signaling pathway. INPP4B functions as a tumor suppressor by limiting AKT activation and is frequently deleted in prostate cancer, complementing PTEN loss in deregulating phosphoinositide signaling.

Alterations observed in the corpus

• INPP4B was identified as a recurrently deleted tumor suppressor in prostate cancer by integrative genomic profiling of the MSKCC cohort PMID:20579941
• Deleted (homozygous and heterozygous) in breast cancer (TCGA, 510 tumors); loss associated with PI3K pathway activation in luminal B subtype PMID:23000897

Cancer types (linked)

• PRAD: Focal deletion of INPP4B identified in the MSKCC cohort, representing an alternative mechanism of PI3K pathway activation alongside PTEN loss PMID:20579941

Co-occurrence and mutual exclusivity

• INPP4B deletion may co-occur or overlap with PTEN deletion in prostate cancer, both converging on PI3K/AKT pathway hyperactivation PMID:20579941

Therapeutic relevance

• PI3K/AKT pathway inhibitors may have activity in tumors with INPP4B loss, similar to PTEN-deleted tumors.

Open questions

• Whether INPP4B loss is an independent driver or cooperates with PTEN loss in prostate cancer progression is not fully resolved.

Sources

• PMID:20579941 — Integrative genomic profiling of prostate cancer (MSKCC cohort)

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