GeneID: 144

Description:
The NPRL3 gene encodes a subunit of the GATOR1 (GTPase-activating proteins toward Rags 1) complex, which regulates the mTORC1 signaling pathway. GATOR1 is localised at the lysosomal membrane where it mediates hydrolysis of GTP and thereby inactivation of the GTPases Rag A and Rag B. Since RagsA/B facilitate the recruitment of the mammalian TORC1 (mTORC1) complex to the lysosomal surface to be activated, GATOR1 serves as an upstream regulator of the mTORC1 pathway. mTORC1 functions as a master regulator of growth in response to various signals, including amino acids, and its deregulation has been seen in cancer and diabetes. The NPRL3 gene is found upstream of the HBA1/HBA2 gene cluster and polymoprhisms in this gene associated with haemolytic anaemia in sickle cell patients. Deletion of the NPRL3 gene resulted in embryonic lethality from multiple cardiovascular defects in a mouse model.

Synonyms: C16orf35 , CGTHBA , HS-40 , MARE , NPR3 , RMD11

Comments:
N/A

Number of entries/variants: 21

1. Kowalczyk MS, Hughes JR, Babbs C, Sanchez-Pulido L, Szumska D, Sharpe JA, Sloane-Stanley JA, Morriss-Kay GM, Smoot LB, Roberts AE, Watkins H, Bhattacharya S, Gibbons RJ, Ponting CP, Wood WG, Higgs DR, Nprl3 is required for normal development of the cardiovascular system., Mamm. Genome , 23(7), 404-15, 2012 PubMed
2. Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM, A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1., Science , 340(6136), 1100-6, 2013 PubMed
3. Milton JN, Rooks H, Drasar E, McCabe EL, Baldwin CT, Melista E, Gordeuk VR, Nouraie M, Kato GR, Kato GJ, Minniti C, Taylor J, Campbell A, Luchtman-Jones L, Rana S, Castro O, Zhang Y, Thein SL, Sebastiani P, Gladwin MT, , Steinberg MH, Genetic determinants of haemolysis in sickle cell anaemia., Br. J. Haematol. , 161(2), 270-8, 2013 PubMed
4. Wei Y, Reveal B, Reich J, Laursen WJ, Senger S, Akbar T, Iida-Jones T, Cai W, Jarnik M, Lilly MA, TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila., Proc. Natl. Acad. Sci. U.S.A. , 111(52), E5670-7, 2014 PubMed