TMEM132D, a human gene, has been associated with multiple functions. It encodes a transmembrane protein, and its family proteins are thought to play roles in regulating NAP1 protein homologs to restrict inappropriate WAVE-regulatory complex (WRC) activity, thus influencing cytoskeletal and morphologic changes in the cell [3]. SNPs in TMEM132D have been linked to various psychiatric disorders, suggesting its importance in neural-related biological processes [1,2,4,5,6].

In human studies, TMEM132D polymorphisms are associated with panic disorder, anxiety symptoms, and depressive symptoms. Risk genotypes for panic disorder are related to higher TMEM132D mRNA expression levels in the frontal cortex [1]. In a mouse model of trait anxiety, anxiety-related behavior was positively correlated with Tmem132d mRNA expression in the anterior cingulate cortex. Polymorphisms in Tmem132d promoter region can regulate its expression and anxiety-related behavior through binding of RNA polymerase II complex [2]. In C. elegans, loss-of-function mutants of the sole TMEM132 ortholog show abnormal morphologic phenotypes in dopaminergic PDE neurons [3].

In conclusion, TMEM132D plays a role in neural-related biological processes, especially in anxiety-related behaviors. Studies on TMEM132D using genetic models like mouse models and C. elegans mutants have revealed its importance in psychiatric disorders, providing insights into the molecular mechanisms underlying these disorders.

References:

1. Erhardt, A, Czibere, L, Roeske, D, Holsboer, F, Binder, E B. 2010. TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies. In Molecular psychiatry, 16, 647-63. doi:10.1038/mp.2010.41. https://pubmed.ncbi.nlm.nih.gov/20368705/

2. Naik, Roshan R, Sotnikov, Sergey V, Diepold, Rebekka P, Landgraf, Rainer, Czibere, Ludwig. 2018. Polymorphism in Tmem132d regulates expression and anxiety-related behavior through binding of RNA polymerase II complex. In Translational psychiatry, 8, 1. doi:10.1038/s41398-017-0025-2. https://pubmed.ncbi.nlm.nih.gov/29317594/

3. Wang, Xin, Jiang, Wei, Luo, Shuo, Shen, Yin, Ma, Dengke K. 2021. The C. elegans homolog of human panic-disorder risk gene TMEM132D orchestrates neuronal morphogenesis through the WAVE-regulatory complex. In Molecular brain, 14, 54. doi:10.1186/s13041-021-00767-w. https://pubmed.ncbi.nlm.nih.gov/33726789/

4. Chen, Shumin, Cui, Kaiwen, Zhang, Dongfeng. 2025. Association between TMEM132D gene polymorphisms and depressive symptoms in Qingdao Chinese elderly. In Nucleosides, nucleotides & nucleic acids, , 1-14. doi:10.1080/15257770.2025.2474587. https://pubmed.ncbi.nlm.nih.gov/40045749/

5. Inoue, Ayako, Akiyoshi, Jotaro, Muronaga, Masaaki, Hanada, Hiroaki, Kawano, Yoshihisa. 2015. Association of TMEM132D, COMT, and GABRA6 genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic and major depressive disorder. In International journal of psychiatry in clinical practice, 19, 192-200. doi:10.3109/13651501.2015.1043133. https://pubmed.ncbi.nlm.nih.gov/25974322/

6. Shimada-Sugimoto, Mihoko, Otowa, Takeshi, Miyagawa, Taku, Tokunaga, Katsushi, Sasaki, Tsukasa. 2016. Polymorphisms in the TMEM132D region are associated with panic disorder in HLA-DRB1*13:02-negative individuals of a Japanese population. In Human genome variation, 3, 16001. doi:10.1038/hgv.2016.1. https://pubmed.ncbi.nlm.nih.gov/27081567/