Molecular features of AHDC1: insights into an overlooked gene with broad functional potential

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.