ATP6V1G2

ATP6V1G2 Full Name

ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2

ATP6V1G2 Introduction

ATP6V1G2 (ATPase, H+ transporting, lysosomal 13 kDa, V1 subunit G2) encodes the G2 subunit of the vacuolar H+-ATPase (V-ATPase) V1 domain, a critical proton pump complex responsible for maintaining acidic environments within lysosomes, endosomes, and other intracellular compartments. For researchers investigating lysosomal dysfunction, autophagy impairment, and metabolic disorders, ATP6V1G2 represents an important regulatory component because proper organelle acidification is essential for protein degradation, nutrient recycling, and cellular homeostasis. As part of the catalytic V1 sector of V-ATPase, ATP6V1G2 contributes to ATP-dependent proton translocation by supporting the assembly and activity of the enzyme complex, enabling efficient communication between cellular metabolism, autophagic flux, and stress adaptation pathways. Disruption of V-ATPase activity can impair lysosomal function, leading to accumulation of damaged proteins and organelles, which is increasingly recognized as a key mechanism underlying aging-related and neurodegenerative diseases.

Emerging studies have highlighted ATP6V1G2 as a potential link between lysosomal regulation, iron metabolism, and ferroptosis-related pathways. Bioinformatics analyses of Alzheimer's disease (AD)-associated molecular networks have identified ATP6V1G2 as one of the hub genes connecting iron homeostasis and autophagy, suggesting that altered V-ATPase-mediated lysosomal acidification may contribute to impaired clearance mechanisms and neuronal vulnerability. Because lysosomes regulate iron storage, recycling, and degradation of damaged cellular components, ATP6V1G2 dysfunction may influence oxidative stress responses and ferroptotic cell death pathways. Beyond neurological disorders, cross-disease genetic analyses have identified ATP6V1G2 as a pleiotropic susceptibility gene associated with multiple digestive system disorders, including inflammatory bowel disease, irritable bowel syndrome, gastroesophageal reflux disease, and other gastrointestinal conditions. These findings suggest that ATP6V1G2 may participate in broader mechanisms involving energy metabolism, oxidative stress regulation, and tissue-specific inflammatory responses.

In cancer and age-related diseases, ATP6V1G2 has attracted increasing attention as a potential biomarker associated with cellular metabolism, immune regulation, and disease progression. Studies of endometrial cancer have incorporated ATP6V1G2 into ferroptosis-related prognostic models, showing that altered ATP6V1G2 expression is associated with tumor characteristics and patient outcomes, potentially reflecting changes in autophagy, apoptosis, necrosis, and metabolic adaptation within the tumor microenvironment. Proteomic analyses of Down syndrome-associated Alzheimer-like pathology have also identified ATP6V1G2 as a differentially regulated protein involved in energy metabolism and cellular stress responses, supporting its relevance in neurodegenerative progression. Overall, ATP6V1G2 serves as a valuable research target for exploring the intersection of lysosomal biology, autophagy, oxidative stress, ferroptosis, and disease mechanisms, providing potential opportunities for biomarker discovery and therapeutic strategy development in neurodegenerative disorders, inflammatory diseases, and cancer.

Alternate Names for ATP6V1G2

ATP6V1G2; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2; NG38; ATP6G; VMA10; ATP6G2; V-type proton ATPase subunit G 2; V-ATPase 13 kDa subunit 2; vacuolar proton pump G subunit 2; vacuolar ATP synthase subunit G 2

• 1.Zhou B, et al.; Insights into targeted ferroptosis in mechanisms, biology, and role of Alzheimer's disease: an update. Front Aging Neurosci. 2025, 17:1587986.
  2.Jiang Y, et al.; A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders. iScience. 2023, 26(11):108238.