MPHOSPH9, also known as CDK2AP1, is a gene with diverse functions. It has been associated with multiple biological pathways and disease-related processes. Some evidence suggests it may be involved in cell cycle regulation as its risk allele in the MPHOSPH9/CDK2AP1 locus correlates with diminished RNA expression of the cell cycle regulator CDK2AP1 [1]. It also appears to play a role in inflammation-related pathways, as seen in its association with multiple sclerosis (MS) susceptibility, suggesting its importance in immune-related biological functions [1].

MPHOSPH9 has been implicated in several diseases. In gastric cancer, its upregulation is associated with poor prognosis, and it activates the mTOR signaling pathway, enhancing cancer cell proliferation [2]. In uterine fibroids, high MPHOSPH9 expression is an independent risk factor for postoperative re-intervention after high-intensity focused ultrasound treatment [3]. It has also been associated with type 2 diabetes susceptibility, although the effects in the Japanese population were not significant [6]. In addition, it is among the genes associated with venous thromboembolism susceptibility [4], and may be related to schizophrenia as potential regulatory variants in MPHOSPH9 were identified in a cross-ancestry analysis of brain QTLs [5]. A prognostic model in low-grade glioma was established based on 4 SUMOylation regulator-related signatures, including MPHOSPH9 [7].

In conclusion, MPHOSPH9 is a gene involved in various biological processes, especially those related to cell cycle, inflammation, and disease susceptibility. Its dysregulation is associated with multiple diseases such as gastric cancer, uterine fibroids, type 2 diabetes, venous thromboembolism, schizophrenia, and low-grade glioma. Research on MPHOSPH9 contributes to understanding disease mechanisms and may potentially lead to new diagnostic and therapeutic strategies for these diseases.

References:

1. . 2010. IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci. In Genes and immunity, 11, 397-405. doi:10.1038/gene.2010.28. https://pubmed.ncbi.nlm.nih.gov/20555355/

2. Xu, Ling-Ling, Shang, Yu, Qu, Xiao-Na, He, Hong-Mei. 2020. M-Phase Phosphoprotein 9 upregulation associates with poor prognosis and activates mTOR signaling in gastric cancer. In The Kaohsiung journal of medical sciences, 37, 208-214. doi:10.1002/kjm2.12319. https://pubmed.ncbi.nlm.nih.gov/33174370/

3. Wang, Jing, Xie, Yingjie, Zeng, Chaoqiang, Nie, Lin, Yang, Yang. . Predictive value of abnormal expression of MPHOSPH9 in reintervention after high intensity focused ultrasound treatment of uterine fibroids. In The journal of obstetrics and gynaecology research, 51, e16205. doi:10.1111/jog.16205. https://pubmed.ncbi.nlm.nih.gov/39780408/

4. Lindström, Sara, Wang, Lu, Smith, Erin N, Trégouët, David-Alexandre, Smith, Nicholas L. . Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism. In Blood, 134, 1645-1657. doi:10.1182/blood.2019000435. https://pubmed.ncbi.nlm.nih.gov/31420334/

5. Chen, Yu, Liu, Sihan, Ren, Zongyao, Liu, Chunyu, Chen, Chao. 2024. Cross-ancestry analysis of brain QTLs enhances interpretation of schizophrenia genome-wide association studies. In American journal of human genetics, 111, 2444-2457. doi:10.1016/j.ajhg.2024.09.001. https://pubmed.ncbi.nlm.nih.gov/39362218/

6. Matsuba, Ren, Imamura, Minako, Tanaka, Yasushi, Kawamori, Ryuzo, Maeda, Shiro. 2016. Replication Study in a Japanese Population of Six Susceptibility Loci for Type 2 Diabetes Originally Identified by a Transethnic Meta-Analysis of Genome-Wide Association Studies. In PloS one, 11, e0154093. doi:10.1371/journal.pone.0154093. https://pubmed.ncbi.nlm.nih.gov/27115357/

7. Li, Xiaozhi, Meng, Yutong. 2021. Construction of a SUMOylation regulator-based prognostic model in low-grade glioma. In Journal of cellular and molecular medicine, 25, 5434-5442. doi:10.1111/jcmm.16553. https://pubmed.ncbi.nlm.nih.gov/33951297/