Ncoa7, known as nuclear receptor coactivator 7, is associated with multiple biological functions. It interacts with the vacuolar (V)-ATPase, influencing its assembly and activity, which is crucial for lysosomal function, endolysosomal homeostasis, and related processes [3,4,7]. It is also involved in regulating the MAPK/ERK signaling pathway and epithelial-mesenchymal transformation (EMT), and plays a role in anti-oxidation [1,5].

Gene knockout (KO) mouse models have been instrumental in understanding Ncoa7's function. In Ncoa7 KO mice, incomplete distal renal tubular acidosis (dRTA) occurs, likely due to reduced abundance of V-ATPase subunits and other key acid-base regulators in the renal medulla, suggesting Ncoa7 is important for urine acidification [6]. In endothelial-specific Ncoa7-deficient mice, lysosomal dysregulation leads to an oxysterol and bile acid signature, promoting endothelial pathophenotypes and worsening pulmonary arterial hypertension (PAH) [2]. Also, Ncoa7 deletion in mice results in abnormal neuronal patterning, reduced lysosomal markers, and behavioral defects like anxiety and social deficits [3].

In summary, Ncoa7 is essential for maintaining normal physiological functions, especially in the nervous system, kidneys, and endothelial cells. KO mouse models have revealed its role in diseases such as dRTA, PAH, and potentially neurodevelopmental disorders, highlighting its significance as a potential therapeutic target and prognostic marker in these disease areas.

References:

1. Guo, Jiayu, Ke, Shuai, Chen, Qi, Guo, Jia, Qiu, Tao. 2023. NCOA7 Regulates Growth and Metastasis of Clear Cell Renal Cell Carcinoma via MAPK/ERK Signaling Pathway. In International journal of molecular sciences, 24, . doi:10.3390/ijms241411584. https://pubmed.ncbi.nlm.nih.gov/37511343/

2. Harvey, Lloyd D, Alotaibi, Mona, Tai, Yi-Yin, Jain, Mohit, Chan, Stephen Y. 2025. Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension. In Science (New York, N.Y.), 387, eadn7277. doi:10.1126/science.adn7277. https://pubmed.ncbi.nlm.nih.gov/39847635/

3. Castroflorio, Enrico, den Hoed, Joery, Svistunova, Daria, Davies, Benjamin, Oliver, Peter L. 2020. The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour. In Cellular and molecular life sciences : CMLS, 78, 3503-3524. doi:10.1007/s00018-020-03721-6. https://pubmed.ncbi.nlm.nih.gov/33340069/

4. Arnaud-Arnould, Mary, Tauziet, Marine, Moncorgé, Olivier, Goujon, Caroline, Blaise, Mickaël. 2021. Crystal structure of the TLDc domain of human NCOA7-AS. In Acta crystallographica. Section F, Structural biology communications, 77, 230-237. doi:10.1107/S2053230X21006853. https://pubmed.ncbi.nlm.nih.gov/34341188/

5. Wang, Lincui, Wei, Zhixiao, Wu, Yumeng, Yang, Wannian, Lin, Qiong. 2024. Nuclear receptor coactivator 7 (NCOA7) protects cancer cells from oxidative damage through its ERbd domain. In Cellular signalling, 124, 111382. doi:10.1016/j.cellsig.2024.111382. https://pubmed.ncbi.nlm.nih.gov/39243920/

6. Merkulova, Maria, Păunescu, Teodor G, Nair, Anil V, Breton, Sylvie, Brown, Dennis. 2018. Targeted deletion of the Ncoa7 gene results in incomplete distal renal tubular acidosis in mice. In American journal of physiology. Renal physiology, 315, F173-F185. doi:10.1152/ajprenal.00407.2017. https://pubmed.ncbi.nlm.nih.gov/29384414/

7. Doyle, Tomas, Moncorgé, Olivier, Bonaventure, Boris, Goujon, Caroline, Malim, Michael H. 2018. The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry. In Nature microbiology, 3, 1369-1376. doi:10.1038/s41564-018-0273-9. https://pubmed.ncbi.nlm.nih.gov/30478388/