Pigx, short for phosphatidylinositol glycan anchor biosynthesis, class X, encodes the regulatory subunit of GPI-mannose-transferase I (MT-I) enzyme, which is crucial in the glycosylphosphatidylinositol (GPI)-glycan biosynthesis pathway. GPI-anchored proteins (APs) play diverse roles as cell co-receptors, enzymes, and adhesion molecules. Pigx's function in GPI synthesis is vital for maintaining the presence of GPI-APs on the cell surface and their secretion, thus having overall biological importance in cell biology [1].

Mutations in Pigx-related genes are associated with various diseases. For example, in some PDGFRA/B-negative hypereosinophilic syndromes, PAK2::PIGX fusions were identified in responders to imatinib treatment, suggesting a potential molecular basis related to Pigx in this disorder [2,3]. In breast cancer cells, PIGX is highly and frequently up-regulated. Knockdown of PIGX significantly suppressed the growth of breast cancer cells, and it was found to be part of an RCN1/PIGX/RCN2 complex that may negatively regulate the expression of putative tumor suppressor genes ZIC1 and EHD2, contributing to breast carcinogenesis [4]. In paroxysmal nocturnal hemoglobinuria (PNH), ultradeep sequencing analysis of small PNH clones detected by flow cytometry aimed to determine the presence of PIGX gene mutations, though only a small portion of small PNH clones harbored PIGX mutations without significant correlation to variant allele frequency or the presence/absence of a PIG mutation [5].

In conclusion, Pigx is essential in GPI-anchor biosynthesis, with its dysregulation being implicated in diseases such as certain hematological disorders and breast cancer. Studies on Pigx, especially those related to its mutation and expression changes, contribute to understanding the molecular mechanisms underlying these diseases, potentially providing new insights for diagnosis and treatment.

References:

1. Torres-Valdetano, Ángeles, Vallejo-Ruiz, Verónica, Milflores-Flores, Lorena, Martínez-Morales, Patricia. 2024. Role of PIGM and PIGX in glycosylphosphatidylinositol biosynthesis and human health (Review). In Biomedical reports, 20, 57. doi:10.3892/br.2024.1746. https://pubmed.ncbi.nlm.nih.gov/38414627/

2. Loscocco, Giuseppe G, Helbig, Grzegorz. 2024. Imatinib is effective in some PDGFRA/B-negative hypereosinophilic syndromes: A step closer to unveiling underlying mechanisms. In British journal of haematology, 205, 2136-2138. doi:10.1111/bjh.19853. https://pubmed.ncbi.nlm.nih.gov/39468717/

3. Kim, Dong Hyun, Kim, Seokhyeon, Park, Seonyang, Koh, Youngil, Yoon, Sung-Soo. 2024. Phase II trial of imatinib mesylate in patients with PDGFRA/B-negative hypereosinophilic syndrome. In British journal of haematology, 205, 2305-2314. doi:10.1111/bjh.19828. https://pubmed.ncbi.nlm.nih.gov/39389908/

4. Nakakido, Makoto, Tamura, Kenji, Chung, Suyoun, Kiyotani, Kazuma, Nakamura, Yusuke. 2016. Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors. In International journal of oncology, 49, 868-76. doi:10.3892/ijo.2016.3607. https://pubmed.ncbi.nlm.nih.gov/27572108/

5. Jeong, Dajeong, Park, Hee Sue, Kim, Sung-Min, Yoon, Sung-Soo, Lee, Dong Soon. . Ultradeep Sequencing Analysis of Paroxysmal Nocturnal Hemoglobinuria Clones Detected by Flow Cytometry: PIG Mutation in Small PNH Clones. In American journal of clinical pathology, 156, 72-85. doi:10.1093/ajcp/aqaa211. https://pubmed.ncbi.nlm.nih.gov/33347536/