Ppp6r3 is a regulatory subunit of the protein phosphatase 6 (PP6) holoenzyme. PP6 is involved in regulating innate immunity, cell survival, and cellular homeostasis, with PPP6R3 playing a role in the PP6-mediated regulation of pathways like RIPK1-dependent PANoptosis, an innate immune inflammatory lytic cell death pathway [2].

In terms of disease-related findings, the fusion of PPP6R3-USP6 has been identified in cases of nodular fasciitis, some of which showed malignant behavior such as multiple recurrences, metastatic behavior, and aggressive non-regressing growth with local invasion, suggesting an oncogenic role for this fusion in mesenchymal neoplasia [1,3,5]. Also, a deletion of Ppp6r3 in mice was found to decrease bone mineral density (BMD), indicating its potential role in BMD regulation [4].

In conclusion, Ppp6r3, as a regulatory subunit of PP6, is involved in important cellular regulatory pathways. Its role in diseases is demonstrated through its involvement in the PPP6R3-USP6 fusion in nodular fasciitis with malignant transformation and its impact on BMD as shown by gene deletion in mice. Understanding Ppp6r3 contributes to our knowledge of mesenchymal neoplasia and BMD-related pathologies.

References:

1. Guo, Ruifeng, Wang, Xiaoke, Chou, Margaret M, Dong, Jie, Oliveira, Andre M. 2016. PPP6R3-USP6 amplification: Novel oncogenic mechanism in malignant nodular fasciitis. In Genes, chromosomes & cancer, 55, 640-9. doi:10.1002/gcc.22366. https://pubmed.ncbi.nlm.nih.gov/27113271/

2. Bynigeri, Ratnakar R, Malireddi, R K Subbarao, Mall, Raghvendra, Pruett-Miller, Shondra M, Kanneganti, Thirumala-Devi. 2024. The protein phosphatase PP6 promotes RIPK1-dependent PANoptosis. In BMC biology, 22, 122. doi:10.1186/s12915-024-01901-5. https://pubmed.ncbi.nlm.nih.gov/38807188/

3. Teramura, Yasuyo, Yamazaki, Yukari, Tanaka, Miwa, Matsumoto, Seiichi, Nakamura, Takuro. 2019. Case of mesenchymal tumor with the PPP6R3-USP6 fusion, possible nodular fasciitis with malignant transformation. In Pathology international, 69, 706-709. doi:10.1111/pin.12851. https://pubmed.ncbi.nlm.nih.gov/31538390/

4. Al-Barghouthi, Basel Maher, Rosenow, Will T, Du, Kang-Ping, Brautigan, David, Farber, Charles R. 2022. Transcriptome-wide association study and eQTL colocalization identify potentially causal genes responsible for human bone mineral density GWAS associations. In eLife, 11, . doi:10.7554/eLife.77285. https://pubmed.ncbi.nlm.nih.gov/36416764/

5. Saoud, Carla, Agaimy, Abbas, Stoehr, Robert, Charville, Gregory W, Linos, Konstantinos. 2025. Nodular fasciitis: a case series unveiling novel and rare gene fusions, including two cases with aggressive clinical behavior. In Virchows Archiv : an international journal of pathology, , . doi:10.1007/s00428-025-04040-6. https://pubmed.ncbi.nlm.nih.gov/39912885/