Laboratory of Biochemistry, Molecular Biotechnology, and Molecular Biology, Department of Biology, Ecology and Earth Sciences (DiBEST), University of Calabria, Via P. Bucci 4c, 87036 Arcavacata di Rende, Italy.
Institute of Biomembranes, Bioenergetics and Molecular Biotechnology (IBIOM), National Research Council (CNR), Via Amendola 122/O, 70126 Bari, Italy.
Int J Mol Sci. 2024 Aug 10;25(16):8743. doi: 10.3390/ijms25168743.
OCTN1 and OCTN2 are membrane transport proteins encoded by the and genes, respectively. Even though several transcripts have been predicted by bioinformatics for both genes, only one functional protein isoform has been described for each of them. Both proteins are ubiquitous, and depending on the physiopathological state of the cell, their expression is regulated by well-known transcription factors, although some aspects have been neglected. A plethora of missense variants with uncertain clinical significance are reported both in the dbSNP and the Catalogue of Somatic Mutations in Cancer (COSMIC) databases for both genes. Due to their involvement in human pathologies, such as inflammatory-based diseases (OCTN1/2), systemic primary carnitine deficiency (OCTN2), and drug disposition, it would be interesting to predict the impact of variants on human health from the perspective of precision medicine. Although the lack of a 3D structure for these two transport proteins hampers any speculation on the consequences of the polymorphisms, the already available 3D structures for other members of the SLC22 family may provide powerful tools to perform structure/function studies on WT and mutant proteins.
OCTN1 和 OCTN2 是分别由 和 基因编码的膜转运蛋白。尽管生物信息学预测了这两个基因的多个转录本，但它们每个基因都只描述了一种功能性蛋白同工型。这两种蛋白都是普遍存在的，并且根据细胞的生理病理状态，它们的表达受众所周知的转录因子调节，尽管有些方面被忽视了。在 dbSNP 和癌症体细胞突变目录 (COSMIC) 数据库中，这两个基因都报告了大量具有不确定临床意义的错义变体。由于它们与人类病理学有关，例如炎症相关疾病（OCTN1/2）、全身性原发性肉碱缺乏症（OCTN2）和药物处置，因此从精准医学的角度预测变异对人类健康的影响将是有趣的。尽管这两种转运蛋白缺乏 3D 结构，无法对多态性的后果进行任何推测，但其他 SLC22 家族成员的已有 3D 结构可能为 WT 和突变蛋白的结构/功能研究提供强大的工具。
