Prps1, or phosphoribosylpyrophosphate synthetase 1, codes for PRS-I enzyme which catalyzes the first step of nucleotide synthesis, being crucial for the de novo purine nucleotide synthesis pathway [1,2,4]. It is essential for cell development, pluripotent stem cell survival and stemness [2,4].

Mutations in PRPS1 are associated with a range of human diseases. Gain-of-function mutations lead to PRS-I superactivity and purine overproduction, causing symptoms like uric acid overproduction, hypotonia, ataxia, neurodevelopment abnormalities, and postlingual hearing impairment. Loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness (DFNX-2), Charcot-Marie-Tooth disease-5 (CMTX5), and Arts syndrome depending on the residual activity of PRS-I [1,3]. For instance, mild PRS-I deficiency (DFNX-2) leads to non-syndromic progressive hearing loss, while moderate (CMTX5) and severe (Arts syndrome) deficiencies present with peripheral or optic neuropathy, prelingual progressive sensorineural hearing loss, and central nervous system impairment [1]. In addition, PRPS1 has been linked to melanoma progression where NRF2-directed upregulation promotes melanoma proliferation, migration, invasion and inhibits apoptosis [2].

In conclusion, Prps1 is vital for nucleotide synthesis and cell development. Research on Prps1-related mutations, through functional studies in the context of associated diseases, has revealed its role in various pathological conditions such as hearing loss, neurological disorders, and cancer. Understanding Prps1 function may offer new therapeutic strategies for these diseases.

References:

1. Mittal, Rahul, Patel, Kunal, Mittal, Jeenu, Grati, M'hamed, Liu, Xue Zhong. 2015. Association of PRPS1 Mutations with Disease Phenotypes. In Disease markers, 2015, 127013. doi:10.1155/2015/127013. https://pubmed.ncbi.nlm.nih.gov/26089585/

2. Xiong, Guohang, Feng, Yu, Yi, Xiaojia, Kuang, Yingmin, Zhu, Yuechun. 2022. NRF2-directed PRPS1 upregulation to promote the progression and metastasis of melanoma. In Frontiers in immunology, 13, 989263. doi:10.3389/fimmu.2022.989263. https://pubmed.ncbi.nlm.nih.gov/36203561/

3. Liu, Xue Zhong, Xie, Dinghua, Yuan, Hui Jun, Christodoulou, John, Yan, Denise. 2012. Hearing loss and PRPS1 mutations: Wide spectrum of phenotypes and potential therapy. In International journal of audiology, 52, 23-8. doi:10.3109/14992027.2012.736032. https://pubmed.ncbi.nlm.nih.gov/23190330/

4. Yang, Yi, Song, Lili, Huang, Xia, Feng, Haizhong, Li, Yanxin. 2021. PRPS1-mediated purine biosynthesis is critical for pluripotent stem cell survival and stemness. In Aging, 13, 4063-4078. doi:10.18632/aging.202372. https://pubmed.ncbi.nlm.nih.gov/33493137/