PAG1

Overview

PAG1 (Phosphoprotein Membrane Anchor with Glycosphingolipid Microdomains 1) encodes a transmembrane adaptor protein that localizes to lipid rafts and regulates Src-family kinase activity in lymphocytes via recruitment of CSK. In B and T cells, PAG1 acts as a negative regulator of antigen receptor signaling; its dysregulation can alter kinase activation thresholds in hematologic malignancies.

Alterations observed in the corpus

• Observed as a mutated gene in hypodiploid acute lymphoblastic leukemia (near haploid and low hypodiploid subtypes) in the St. Jude WGS/WES cohort of 44 pediatric hypodiploid ALL tumors PMID:23334668.

Cancer types (linked)

• BLL (B-lymphoblastic leukemia/lymphoma): Detected in hypodiploid ALL in the St. Jude genomic landscape study; specific mutation frequency not reported in the primary Genes & alterations section PMID:23334668.

Co-occurrence and mutual exclusivity

• Observed in a cohort with high rates of RTK/Ras pathway alterations (NF1, NRAS, KRAS, FLT3, PTPN11, MAPK1) in near haploid ALL PMID:23334668.

Therapeutic relevance

• No direct therapeutic targeting reported in the corpus. The broader hypodiploid ALL context shows PI3K pathway dependence; whether PAG1 alterations modulate PI3K/Ras signaling response is unresolved PMID:23334668.

Open questions

• Specific mutation class, frequency, and functional consequence of PAG1 alterations in hypodiploid ALL have not been characterized in the corpus; validation in independent cohorts needed.

Sources

• PMID:23334668

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