Bochicchio Silvana, Mazzetti Aurora, Graziani Lorenzo, Tartaglia Gian Gaetano, Gustincich Stefano, Sanges Remo
Neuroscience Area, International School for Advanced Studies (SISSA), Trieste, Italy.
Centre for Human Technologies (CHT), RNA System Biology Lab, Istituto Italiano di Tecnologia (IIT), Genova, Italy.
Hum Genet. 2025 Aug 22. doi: 10.1007/s00439-025-02765-7.
Despite two decades since the completion of the human genome, many genes remain poorly understood, with their functions largely unknown. Among these, AHDC1 stands out as a top-ranking gene in the SFARI database due to its role in the rare and likely underestimated neurodevelopmental disorder, Xia-Gibbs syndrome (XIGIS). First identified in 2014 by Prof. Richard A. Gibbs and his team at Baylor College of Medicine, AHDC1 has historically been understudied. Until July 2023, it was classified as a Tdark gene in the Pharos database, reflecting minimal knowledge of its biological function and the lack of molecular tools for its investigation. However, interest in AHDC1 has grown significantly recently as researchers have strived to uncover the mechanisms underlying XIGIS-associated phenotypes. Recognizing these advances, the Pharos database reclassified AHDC1 as a Tbio gene in 2023, acknowledging its rising significance and the expanding body of research surrounding it. This review consolidates the latest findings on AHDC1, providing an in-depth examination of its genetic structure, regulatory mechanisms, and protein functions while exploring its potential roles in nervous system development and beyond. By compiling existing literature and integrating publicly available data, this review aims to illuminate the broader biological relevance of AHDC1 and its implications for human health and disease.
尽管人类基因组测序工作已完成二十年,但仍有许多基因未被充分了解,其功能大多未知。其中,AHDC1在SFARI数据库中脱颖而出,成为排名靠前的基因,因为它在罕见且可能被低估的神经发育障碍——夏-吉布斯综合征(XIGIS)中发挥作用。AHDC1于2014年由贝勒医学院的理查德·A·吉布斯教授及其团队首次发现,此前一直未得到充分研究。直到2023年7月,它在Pharos数据库中被归类为Tdark基因,这反映出对其生物学功能的了解极少,且缺乏用于研究的分子工具。然而,随着研究人员努力揭示与XIGIS相关表型的潜在机制,最近对AHDC1的兴趣显著增加。认识到这些进展,Pharos数据库在2023年将AHDC1重新归类为Tbio基因,承认其日益重要的地位以及围绕它的研究不断增多。本综述整合了关于AHDC1的最新发现,深入研究了其遗传结构、调控机制和蛋白质功能,同时探讨了它在神经系统发育及其他方面的潜在作用。通过汇编现有文献并整合公开可用数据,本综述旨在阐明AHDC1更广泛的生物学相关性及其对人类健康和疾病的影响。