Gtf2h2, the general transcription factor II subunit H2, functions in nucleotide excision repair (NER) and basal transcription. It is associated with the estrogen pathway and is potentially involved in maintaining genomic stability [7].

In hepatocellular carcinoma (HCC), Gtf2h2-enriched exosomes from Huh7 cells can inhibit the viability, migration, tube formation, and permeability of human umbilical vein endothelial cells, suggesting potential as a novel anti-HCC drug and anti-angiogenesis target [1]. In lung cancer, TEP linc-GTF2H2-1, a related lncRNA, is downregulated and may serve as a biomarker for diagnosis and progression prediction [2]. Regarding spinal muscular atrophy (SMA), studies on patients show a significant difference in the Gtf2h2 gene between healthy and SMA subjects, and pediatric patients with Gtf2h2 deletions demonstrate higher motor functions. Also, some severe type I SMA patients possess large-scale deletions including Gtf2h2, and it acts as a negative modifier of the disease [3,5,8]. In addition, Gtf2h2 is one of the genes significantly differentially expressed in neuropathic pain patients, potentially being a therapeutic target [6]. The N-terminal region of the transcription factor E2F1 recruits Gtf2h2 to mediate the activation of tumor suppressor genes [4].

In summary, Gtf2h2 plays diverse roles in multiple biological processes and diseases. Its functions in angiogenesis, cancer development, and SMA-related motor function have been revealed through studies on patient samples. Understanding Gtf2h2 provides insights into the mechanisms of these diseases, potentially leading to new therapeutic strategies.

References:

1. Li, Zhenkun, Li, Yanmeng, Ouyang, Qin, Li, Xiaojin, Huang, Jian. 2022. Exosome-derived GTF2H2 from Huh7 cells can inhibit endothelial cell viability, migration, tube formation, and permeability. In Tissue & cell, 79, 101922. doi:10.1016/j.tice.2022.101922. https://pubmed.ncbi.nlm.nih.gov/36116407/

2. Li, Xinyi, Liu, Lele, Song, Xingguo, Xie, Li, Song, Xianrang. 2021. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction. In Journal of cancer research and clinical oncology, 147, 1609-1622. doi:10.1007/s00432-020-03502-5. https://pubmed.ncbi.nlm.nih.gov/33792796/

3. Karasu, Nilgun, Acer, Hamit, Akalin, Hilal, Canpolat, Mehmet, Dundar, Munis. 2024. Molecular analysis of SMN2, NAIP, and GTF2H2 gene deletions and relationships with clinical subtypes of spinal muscular atrophy. In Journal of neurogenetics, 38, 102-111. doi:10.1080/01677063.2024.2407332. https://pubmed.ncbi.nlm.nih.gov/39321203/

4. Zhao, Lin, Nakajima, Rinka, Zhou, Yaxuan, Araki, Keigo, Ohtani, Kiyoshi. 2024. The N-Terminal Region of the Transcription Factor E2F1 Contains a Novel Transactivation Domain and Recruits General Transcription Factor GTF2H2. In Biomolecules, 14, . doi:10.3390/biom14111357. https://pubmed.ncbi.nlm.nih.gov/39595534/

5. He, Jin, Zhang, Qi-Jie, Lin, Qi-Fang, Wang, Ning, Chen, Wan-Jin. 2013. Molecular analysis of SMN1, SMN2, NAIP, GTF2H2, and H4F5 genes in 157 Chinese patients with spinal muscular atrophy. In Gene, 518, 325-9. doi:10.1016/j.gene.2012.12.109. https://pubmed.ncbi.nlm.nih.gov/23352792/

6. Hu, Ling, Yin, Wei, Ma, Yao, Zhang, Qiushi, Xu, Qingbang. 2023. Gene expression signature of human neuropathic pain identified through transcriptome analysis. In Frontiers in genetics, 14, 1127167. doi:10.3389/fgene.2023.1127167. https://pubmed.ncbi.nlm.nih.gov/36816032/

7. Li, Yanmeng, Ouyang, Qin, Chen, Zhibin, Jia, Jidong, Huang, Jian. 2025. Novel role of general transcript factor IIH subunit 2 (GTF2H2) in the development and sex disparity of hepatocellular carcinoma. In Oncogene, 44, 1323-1335. doi:10.1038/s41388-025-03301-7. https://pubmed.ncbi.nlm.nih.gov/39972070/

8. Theodorou, L, Nicolaou, P, Koutsou, P, Zamba-Papanicolaou, E, Christodoulou, K. 2015. Genetic findings of Cypriot spinal muscular atrophy patients. In Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 36, 1829-34. doi:10.1007/s10072-015-2263-5. https://pubmed.ncbi.nlm.nih.gov/26017350/