Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Biomolecules. 2023 Jan 30;13(2):257. doi: 10.3390/biom13020257.
Insulin is amongst the human genome's most well-studied genes/proteins due to its connection to metabolic health. Within this article, we review literature and data to build a knowledge base of Insulin () genetics that influence transcription, transcript processing, translation, hormone maturation, secretion, receptor binding, and metabolism while highlighting the future needs of insulin research. The gene region has 2076 unique variants from population genetics. Several variants are found near the transcriptional start site, enhancers, and following the transcripts that might influence the readthrough fusion transcript . This transcript splice site was confirmed within hundreds of pancreatic RNAseq samples, lacks drift based on human genome sequencing, and has possible elevated expression due to viral regulation within the liver. Moreover, a rare, poorly characterized African population-enriched variant of INS-IGF2 results in a loss of the stop codon. transcript UTR variants rs689 and rs3842753, associated with type 1 diabetes, are found in many pancreatic RNAseq datasets with an elevation of the 3'UTR alternatively spliced transcript. Finally, by combining literature, evolutionary profiling, and structural biology, we map rare missense variants that influence preproinsulin translation, proinsulin processing, dimer/hexamer secretory storage, receptor activation, and C-peptide detection for quasi-insulin blood measurements.
胰岛素是人类基因组中研究最充分的基因/蛋白质之一，因为它与代谢健康有关。在本文中，我们综述了文献和数据，构建了一个影响转录、转录加工、翻译、激素成熟、分泌、受体结合和代谢的胰岛素遗传学知识库，同时强调了胰岛素研究的未来需求。 基因区域具有 2076 个来自群体遗传学的独特变体。一些变体位于转录起始位点、增强子附近，以及紧随其后的 转录本中，可能影响通读融合转录本 。该 转录本剪接位点在数百个胰腺 RNAseq 样本中得到了证实，在基于人类基因组测序的漂移中不存在，并且由于肝脏内的病毒调节，可能存在升高的表达。此外，一种罕见的、特征不明显的非洲人群富集的 INS-IGF2 变体导致终止密码子丢失。与 1 型糖尿病相关的 rs689 和 rs3842753 转录本 UTR 变体在许多胰腺 RNAseq 数据集中都有发现，其 3'UTR 选择性剪接的 转录本升高。最后，通过结合文献、进化分析和结构生物学，我们绘制了影响前胰岛素翻译、胰岛素原加工、二聚体/六聚体分泌储存、受体激活和 C-肽检测的罕见错义变体，用于准胰岛素的血液测量。
