PCMTD1, Protein-L-isoaspartate O-Methyltransferase Domain-Containing Protein 1, contains N -terminal motifs similar to those in PCMT1 that bind l -isoaspartate and AdoMet, and a C -terminal SOCS box for ubiquitin ligase recruitment. It may act as an E3 ubiquitin ligase substrate adaptor protein, providing an alternate pathway for maintaining modified proteins in mammalian cells [3].

In a study of moyamoya disease, a p.N321S variant in PCMTD1 was initially detected in exome analysis of eight index cases but could not be confirmed by the Sanger method, suggesting it may not be a true susceptibility factor for this disease [1]. In an infant, a mesenchymal spindle cell neoplasm harbored a novel PCMTD1-PLAG1 fusion, and since PLAG1 is related to cell proliferation regulation and PCMTD1 has links to carcinoma development, this could potentially define a new group of “plagomas” [2]. Also, in genetic association studies of primary angle-closure disease (including glaucoma), SNPs in the region between PCMTD1 and ST18 (PCMTD1-ST18) have shown associations with the disease in some populations, indicating a possible role of PCMTD1 in the pathogenesis of primary angle-closure disease [4,5,6,7,8,9,10].

In summary, PCMTD1 may be involved in protein modification maintenance pathways and potentially in the development of certain tumors and primary angle-closure disease. Its study in various genetic models can help clarify its functions in normal and disease-related biological processes.

References:

1. Liu, Wanyang, Morito, Daisuke, Takashima, Seiji, Hashimoto, Nobuo, Koizumi, Akio. 2011. Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development. In PloS one, 6, e22542. doi:10.1371/journal.pone.0022542. https://pubmed.ncbi.nlm.nih.gov/21799892/

2. Tomás-Velázquez, Alejandra, Surrey, Lea F, Miele, Evelina, Reyes-Múgica, Miguel, Salgado, Cláudia Maria. . Mesenchymal PLAG1 Tumor With PCMTD1-PLAG1 Fusion in an Infant: A New Type of "Plagoma". In The American Journal of dermatopathology, 44, 54-57. doi:10.1097/DAD.0000000000001978. https://pubmed.ncbi.nlm.nih.gov/34291746/

3. Warmack, Rebeccah A, Pang, Eric Z, Peluso, Esther, Torres, Jorge Z, Clarke, Steven G. 2022. Human Protein-l-isoaspartate O-Methyltransferase Domain-Containing Protein 1 (PCMTD1) Associates with Cullin-RING Ligase Proteins. In Biochemistry, 61, 879-894. doi:10.1021/acs.biochem.2c00130. https://pubmed.ncbi.nlm.nih.gov/35486881/

4. Sakurada, Yoichi, Mabuchi, Fumihiko. 2015. Advances in glaucoma genetics. In Progress in brain research, 220, 107-26. doi:10.1016/bs.pbr.2015.04.006. https://pubmed.ncbi.nlm.nih.gov/26497787/

5. Liang, Yu Jing, Wang, Yu Yao, Rong, Shi Song, Tham, Clement C, Chen, Li Jia. . Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-Analysis. In JAMA ophthalmology, 142, 437-444. doi:10.1001/jamaophthalmol.2024.0363. https://pubmed.ncbi.nlm.nih.gov/38546604/

6. Khor, Chiea Chuen, Do, Tan, Jia, Hongyan, Wang, Ningli, Aung, Tin. 2016. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. In Nature genetics, 48, 556-62. doi:10.1038/ng.3540. https://pubmed.ncbi.nlm.nih.gov/27064256/

7. Rong, Shi Song, Tang, Fang Yao, Chu, Wai Kit, Pang, Chi Pui, Chen, Li Jia. 2016. Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-analysis. In Ophthalmology, 123, 1211-21. doi:10.1016/j.ophtha.2015.12.027. https://pubmed.ncbi.nlm.nih.gov/26854036/

8. Tan, Chang, Huang, Lulin, Yang, Zhenglin. . [Association of PLEKHA7, COL11A1 and PCMTD1-ST18 gene polymorphisms with primary angle closure glaucoma in ethnic Han Chinese from Sichuan]. In Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics, 33, 545-9. doi:10.3760/cma.j.issn.1003-9406.2016.04.027. https://pubmed.ncbi.nlm.nih.gov/27455018/

9. Nongpiur, Monisha E, Cheng, Ching-Yu, Duvesh, Roopam, Aung, Tin, Vithana, Eranga N. 2018. Evaluation of Primary Angle-Closure Glaucoma Susceptibility Loci in Patients with Early Stages of Angle-Closure Disease. In Ophthalmology, 125, 664-670. doi:10.1016/j.ophtha.2017.11.016. https://pubmed.ncbi.nlm.nih.gov/29310965/

10. Suneel, Sangaraju, Kaliaperumal, Subashini, Kodidela, Sunitha, Goud, Alladi Charanraj, Stephen, Mary. . Ocular Biometry and Genomic Association in Primary Angle Closure Disease. A Descriptive study. In Romanian journal of ophthalmology, 68, 415-420. doi:10.22336/rjo.2024.75. https://pubmed.ncbi.nlm.nih.gov/39936063/