GALNT12, also known as polypeptide N-acetylgalactosaminyltransferase 12, belongs to the uridine diphosphate N-acetylgalactosamine gene family. It is involved in initiating O-glycans through mucin-type O-glycosylation, an important process in numerous biological functions [1,2,3]. This glycosylation process impacts various cellular functions and is associated with multiple biological pathways, potentially influencing disease-related processes.

GALNT12 has been found to play diverse roles in different diseases. In prostate cancer, it suppresses bone-specific metastasis by activating the BMP pathway via O-glycosylation of BMPR1A, inhibiting integrin αVβ3 expression and remodeling the immune microenvironment [1]. In fibrosarcoma, its upregulated expression promotes cell proliferation and migration by accelerating YAP1 nuclear localization [2]. In glioblastoma multiforme, it facilitates malignancy by influencing the PI3K/Akt/mTOR axis, as genetic knockdown and knockout in U87 MG cells led to decreased cell proliferation, migration, and invasion [3]. Also, there are associations with colorectal cancer, where some studies suggest it may be a moderate-penetrance susceptibility gene [6,7], though one study ruled it out as a major high-risk gene for a specific type of familial CRC [4]. In IgA nephropathy, GALNT12 has a genetic interaction with C1GALT1, and its mRNA expression is lower in patients, suggesting a role in the dysregulation of galactose-deficient IgA1 [5].

In conclusion, GALNT12 is crucial in regulating O-glycosylation-related functions. Model-based research, such as gene knockdown and knockout studies in cell lines, has revealed its significant roles in various cancers and IgA nephropathy. Understanding GALNT12's functions provides insights into disease mechanisms, potentially offering new targets for therapeutic interventions in these disease areas.

References:

1. Yang, Yang, Ding, Meng, Yin, Haoli, Qiu, Xuefeng, Guo, Hongqian. 2024. GALNT12 suppresses the bone-specific prostate cancer metastasis by activating BMP pathway via the O-glycosylation of BMPR1A. In International journal of biological sciences, 20, 1297-1313. doi:10.7150/ijbs.91925. https://pubmed.ncbi.nlm.nih.gov/38385080/

2. Yu, Site, Feng, Wenjie, Zeng, Jizhang, Peng, Yinghua, Zhang, Pihong. 2023. GALNT12 promotes fibrosarcoma growth by accelerating YAP1 nuclear localization. In Oncology letters, 26, 543. doi:10.3892/ol.2023.14131. https://pubmed.ncbi.nlm.nih.gov/38020290/

3. Zheng, Yongjia, Liang, Minting, Wang, Bowen, Mao, Yang, Wang, Shengjun. 2022. GALNT12 is associated with the malignancy of glioma and promotes glioblastoma multiforme in vitro by activating Akt signaling. In Biochemical and biophysical research communications, 610, 99-106. doi:10.1016/j.bbrc.2022.04.052. https://pubmed.ncbi.nlm.nih.gov/35461073/

4. Seguí, Nuria, Pineda, Marta, Navarro, Matilde, Capellá, Gabriel, Valle, Laura. 2013. GALNT12 is not a major contributor of familial colorectal cancer type X. In Human mutation, 35, 50-2. doi:10.1002/humu.22454. https://pubmed.ncbi.nlm.nih.gov/24115450/

5. Wang, Yan-Na, Zhou, Xu-Jie, Chen, Pei, Lv, Ji-Cheng, Zhang, Hong. 2021. Interaction between GALNT12 and C1GALT1 Associates with Galactose-Deficient IgA1 and IgA Nephropathy. In Journal of the American Society of Nephrology : JASN, 32, 545-552. doi:10.1681/ASN.2020060823. https://pubmed.ncbi.nlm.nih.gov/33593824/

6. Evans, Daniel R, Venkitachalam, Srividya, Revoredo, Leslie, Woods, Michael O, Guda, Kishore. 2018. Evidence for GALNT12 as a moderate penetrance gene for colorectal cancer. In Human mutation, 39, 1092-1101. doi:10.1002/humu.23549. https://pubmed.ncbi.nlm.nih.gov/29749045/

7. Clarke, Erica, Green, Roger C, Green, Jane S, Younghusband, H Banfield, Woods, Michael O. 2012. Inherited deleterious variants in GALNT12 are associated with CRC susceptibility. In Human mutation, 33, 1056-8. doi:10.1002/humu.22088. https://pubmed.ncbi.nlm.nih.gov/22461326/