TMEM132C, transmembrane protein 132C, has been implicated in multiple biological functions and disease-related processes. Although its exact essential function remains to be fully elucidated, it has been associated with pathways relevant to various physiological and pathological conditions. Its study via genetic models could potentially shed light on its detailed mechanisms [7,9].

The TMEM132C rs7296262 single-nucleotide polymorphism (SNP) is significantly associated with nausea induced by opioids used for cancer pain and postoperative pain. The distribution of nausea-prone genotypes for this SNP is reversed between chronic and acute phases of opioid use [1]. In triple-negative breast cancer, methylation-expression correlations suggest that TMEM132C (cg03530754) may serve as a diagnostic and prognostic marker [2]. Also, TMEM132C, along with LIPE, may drive synovial hyperplasia via the PPARγ signaling axis in rheumatoid arthritis [3]. Moreover, prenatal exposure to endocrine-disrupting chemicals (EDCs) may be associated with childhood obesity, and DNA methylation at TMEM132C may act as a partial mediator [4]. Additionally, it has been identified as a potential biomarker during cortical aging, a possible independent risk factor in breast cancer prognosis, a candidate gene for pulmonary function in Northeast Asians, a novel prognostic biomarker in breast cancer, a gene with a strong signal of selection in Tibetans potentially related to cardio-pulmonary function adaptation, and associated with nicotine metabolism biomarker genetics in African American females [5,6,7,8,9,10].

In conclusion, TMEM132C is involved in a wide range of biological and disease-related processes. Its associations with nausea during opioid use, various cancer prognoses, rheumatoid arthritis, childhood obesity, cortical aging, pulmonary function, high-altitude adaptation, and nicotine metabolism highlight its importance in multiple disease areas. Further studies using genetic models such as KO/CKO mouse models could potentially uncover more detailed functions and mechanisms of TMEM132C in these processes.

References:

1. Kang, Yuna, Nishizawa, Daisuke, Ohka, Seii, Ichinohe, Tatsuya, Ikeda, Kazutaka. 2024. TMEM132C rs7296262 Single-Nucleotide Polymorphism Is Significantly Associated with Nausea Induced by Opioids Administered for Cancer Pain and Postoperative Pain. In International journal of molecular sciences, 25, . doi:10.3390/ijms25168845. https://pubmed.ncbi.nlm.nih.gov/39201532/

2. Zhang, Xiaoyu, Kang, Xiaoning, Jin, Lijun, Liu, Wei, Wang, Zunyi. 2020. ABCC9, NKAPL, and TMEM132C are potential diagnostic and prognostic markers in triple-negative breast cancer. In Cell biology international, 44, 2002-2010. doi:10.1002/cbin.11406. https://pubmed.ncbi.nlm.nih.gov/32544280/

3. Cheng, Fangyue, Dai, Zhen, Zhang, Jinling. 2025. TMEM132C and LIPE protein molecules drive synovial hyperplasia via the PPARγ signaling axis: Mechanistic insights into core pathogenic proteins in rheumatoid arthritis. In International journal of biological macromolecules, 309, 143027. doi:10.1016/j.ijbiomac.2025.143027. https://pubmed.ncbi.nlm.nih.gov/40216124/

4. Lv, Yiqing, Jia, Zhenxian, Wang, Yin, Xu, Shunqing, Li, Yuanyuan. 2024. Prenatal EDC exposure, DNA Methylation, and early childhood growth: A prospective birth cohort study. In Environment international, 190, 108872. doi:10.1016/j.envint.2024.108872. https://pubmed.ncbi.nlm.nih.gov/38986426/

5. Niu, Rui-Ze, Feng, Wan-Qing, Yu, Qing-Shan, Qin, Qing-Min, Liu, Jia. 2023. Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging. In Frontiers in aging neuroscience, 15, 1063861. doi:10.3389/fnagi.2023.1063861. https://pubmed.ncbi.nlm.nih.gov/37539343/

6. Wan, Xiaohui, Hao, Shuhong, Hu, Chunmei, Qu, Rongfeng. 2022. Identification of a novel lncRNA-miRNA-mRNA competing endogenous RNA network associated with prognosis of breast cancer. In Journal of biochemical and molecular toxicology, 36, e23089. doi:10.1002/jbt.23089. https://pubmed.ncbi.nlm.nih.gov/35532246/

7. Son, Ho-Young, Sohn, Seong-Wook, Im, Sun-Hwa, Seo, Jeong-Sun, Kim, Jong-Il. 2015. Family-Based Association Study of Pulmonary Function in a Population in Northeast Asia. In PloS one, 10, e0139716. doi:10.1371/journal.pone.0139716. https://pubmed.ncbi.nlm.nih.gov/26430897/

8. de Almeida, Bernardo P, Apolónio, Joana Dias, Binnie, Alexandra, Castelo-Branco, Pedro. 2019. Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers. In BMC cancer, 19, 219. doi:10.1186/s12885-019-5403-0. https://pubmed.ncbi.nlm.nih.gov/30866861/

9. Zheng, Wangshan, He, Yaoxi, Guo, Yongbo, Qi, Xuebin, Su, Bing. 2023. Large-scale genome sequencing redefines the genetic footprints of high-altitude adaptation in Tibetans. In Genome biology, 24, 73. doi:10.1186/s13059-023-02912-1. https://pubmed.ncbi.nlm.nih.gov/37055782/

10. Chenoweth, Meghan J, Cox, Lisa Sanderson, Nollen, Nikki L, Knight, Jo, Tyndale, Rachel F. 2021. Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans. In Scientific reports, 11, 19572. doi:10.1038/s41598-021-98883-z. https://pubmed.ncbi.nlm.nih.gov/34599228/