MPPED2, the Metallophosphoesterase-domain-containing protein 2, encodes a metallophosphodiesterase protein conserved throughout evolution. While its exact associated pathways are not fully elaborated in the provided abstracts, its role in various biological processes is emerging. It has potential importance in understanding the molecular mechanisms underlying different diseases [1,5,7].

MPPED2 expression is downregulated in several malignancies such as glioblastoma, breast cancer, and colorectal cancer, likely due to promoter hypermethylation. In glioblastoma, restoring MPPED2 expression inhibits cell proliferation, migration, and enhances sensitivity to temozolomide [1]. In breast cancer, its restoration reduces cell proliferation, migration, and invasion [5]. In neuroblastoma, Mpped2 overexpression in mice improves survival rate, impairs tumor growth, and induces neuronal differentiation, indicating its tumor-suppressing function [7]. Also, in trauma survivors, the rs2065418 TT SNP in MPPED2 is associated with altered systemic inflammation and adverse outcomes [3]. In addition, in a Chinese hypertensive cohort, the rs10767873 variant of MPPED2 is associated with kidney function and risk of cardiovascular disease [6]. In migraine, MPPED2 has a subtype-specific risk allele [2]. And in dental caries, MPPED2 (rs11031093, G Allele) is marginally associated with caries susceptibility in primary dentition [4].

In conclusion, MPPED2 appears to function as a potential tumor suppressor in multiple cancer types, influencing cell proliferation, migration, and drug sensitivity. Its role extends to other conditions such as trauma-related systemic inflammation, kidney function and cardiovascular disease in hypertension, and migraine. The study of MPPED2 through various genetic models helps in understanding the biological mechanisms underlying these diseases, potentially providing new therapeutic strategies.

References:

1. Pellecchia, Simona, De Martino, Marco, Esposito, Francesco, Fusco, Alfredo, Pallante, Pierlorenzo. 2021. MPPED2 is downregulated in glioblastoma, and its restoration inhibits proliferation and increases the sensitivity to temozolomide of glioblastoma cells. In Cell cycle (Georgetown, Tex.), 20, 716-729. doi:10.1080/15384101.2021.1901042. https://pubmed.ncbi.nlm.nih.gov/33734003/

2. Hautakangas, Heidi, Winsvold, Bendik S, Ruotsalainen, Sanni E, Palotie, Aarno, Pirinen, Matti. 2022. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. In Nature genetics, 54, 152-160. doi:10.1038/s41588-021-00990-0. https://pubmed.ncbi.nlm.nih.gov/35115687/

3. Schimunek, Lukas, Namas, Rami A, Yin, Jinling, Billiar, Timothy R, Vodovotz, Yoram. 2019. MPPED2 Polymorphism Is Associated With Altered Systemic Inflammation and Adverse Trauma Outcomes. In Frontiers in genetics, 10, 1115. doi:10.3389/fgene.2019.01115. https://pubmed.ncbi.nlm.nih.gov/31781170/

4. Katifelis, Hector, Sioziou, Anna, Gazouli, Maria, Emmanouil, Dimitris. 2020. ACTN2 (rs6656267) and MPPED2 (rs11031093 and rs536007) polymorphisms in primary dentition caries: A case-control study. In International journal of paediatric dentistry, 30, 478-482. doi:10.1111/ipd.12627. https://pubmed.ncbi.nlm.nih.gov/32040219/

5. Pellecchia, Simona, Sepe, Romina, Federico, Antonella, Fusco, Alfredo, Pallante, Pierlorenzo. 2019. The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer. In Cancers, 11, . doi:10.3390/cancers11060797. https://pubmed.ncbi.nlm.nih.gov/31181813/

6. Zhong, Yixuan, Wu, Yiyi, Yang, Yunyun, Zhang, Mei, Zhang, Weili. 2023. Association of MPPED2 gene variant rs10767873 with kidney function and risk of cardiovascular disease in patients with hypertension. In Journal of human genetics, 68, 393-398. doi:10.1038/s10038-022-01118-w. https://pubmed.ncbi.nlm.nih.gov/36797372/

7. Liguori, Lucia, Andolfo, Immacolata, de Antonellis, Paqualino, Iolascon, Achille, Zollo, Massimo. 2012. The metallophosphodiesterase Mpped2 impairs tumorigenesis in neuroblastoma. In Cell cycle (Georgetown, Tex.), 11, 569-81. doi:10.4161/cc.11.3.19063. https://pubmed.ncbi.nlm.nih.gov/22262177/