GNB3 explained

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 is a protein that in humans is encoded by the GNB3 gene.^{[1] [2]}

Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. A single-nucleotide polymorphism (C825T) in this gene is associated with essential hypertension and obesity. This polymorphism is also associated with the occurrence of the splice variant GNB3-s, which appears to have increased activity. GNB3-s is an example of alternative splicing caused by a nucleotide change outside of the splice donor and acceptor sites. Additional splice variants may exist for this gene, but they have not been fully described.^[3]

Further reading

• Wedegaertner PB, Wilson PT, Bourne HR . Lipid modifications of trimeric G proteins. . J. Biol. Chem. . 270 . 2 . 503–6 . 1995 . 7822269 . 10.1074/jbc.270.2.503 . free .
• Downes GB, Gautam N . The G protein subunit gene families. . Genomics . 62 . 3 . 544–52 . 2000 . 10644457 . 10.1006/geno.1999.5992 .
• Sartori M, Parotto E, Ceolotto G . [C825T polymorphism of the GNB3 gene codifying the G-protein beta3-subunit and cardiovascular risk] . Ann. Ital. Med. Int. . 19 . 4 . 240–8 . 2005 . 15678704 . etal.
• Zhu H, Wang X, Lu Y . Update on G-protein polymorphisms in hypertension. . Curr. Hypertens. Rep. . 8 . 1 . 23–9 . 2006 . 16600156 . 10.1007/s11906-006-0037-4 . 26945864 . etal.
• Weder AB . Genetics and hypertension. . Journal of Clinical Hypertension (Greenwich, Conn.) . 9 . 3 . 217–23 . 2007 . 17341998 . 10.1111/j.1524-6175.2007.06587.x . 8109857 . 2027.42/75304 . 10559655 . free .
• Levine MA, Modi WS, O'Brien SJ . Chromosomal localization of the genes encoding two forms of the G protein beta polypeptide, beta 1 and beta 3, in man. . Genomics . 8 . 2 . 380–6 . 1991 . 1979057 . 10.1016/0888-7543(90)90296-7 . free .
• Levine MA, Smallwood PM, Moen PT . Molecular cloning of beta 3 subunit, a third form of the G protein beta-subunit polypeptide. . Proc. Natl. Acad. Sci. U.S.A. . 87 . 6 . 2329–33 . 1990 . 2107550 . 10.1073/pnas.87.6.2329 . 53680 . 1990PNAS...87.2329L . etal. free .
• Garcia-Higuera I, Thomas TC, Yi F, Neer EJ . Intersubunit surfaces in G protein alpha beta gamma heterotrimers. Analysis by cross-linking and mutagenesis of beta gamma. . J. Biol. Chem. . 271 . 1 . 528–35 . 1996 . 8550614 . 10.1074/jbc.271.1.528. free .
• Yan K, Kalyanaraman V, Gautam N . Differential ability to form the G protein betagamma complex among members of the beta and gamma subunit families. . J. Biol. Chem. . 271 . 12 . 7141–6 . 1996 . 8636150 . 10.1074/jbc.271.12.7141 . free .
• Ansari-Lari MA, Muzny DM, Lu J . A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13. . Genome Res. . 6 . 4 . 314–26 . 1996 . 8723724 . 10.1101/gr.6.4.314 . etal. free .
• Ansari-Lari MA, Shen Y, Muzny DM . Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination. . Genome Res. . 7 . 3 . 268–80 . 1997 . 9074930 . 10.1101/gr.7.3.268 . etal. free .
• Siffert W, Rosskopf D, Siffert G . Association of a human G-protein beta3 subunit variant with hypertension. . Nat. Genet. . 18 . 1 . 45–8 . 1998 . 9425898 . 10.1038/ng0198-45 . 10239855 . etal.
• Kageyama K, Murakami T, Iizuka K . Translocation of G-protein beta3 subunit from the cytosol pool to the membrane pool by beta1-adrenergic receptor stimulation in perfused rat hearts. . Biochem. Pharmacol. . 58 . 9 . 1497–500 . 1999 . 10513993 . 10.1016/S0006-2952(99)00230-0 . etal.
• Rosskopf D, Busch S, Manthey I, Siffert W . G protein beta 3 gene: structure, promoter, and additional polymorphisms. . Hypertension . 36 . 1 . 33–41 . 2000 . 10904009 . 10.1161/01.hyp.36.1.33. free .
• Obineche EN, Frossard PM, Bokhari AM . An association study of five genetic loci and left ventricular hypertrophy amongst Gulf Arabs. . Hypertens. Res. . 24 . 6 . 635–9 . 2002 . 11768721 . 10.1291/hypres.24.635 . free .
• Tabara Y, Kohara K, Miki T . Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin-angiotensin system as risk factors for orthostatic hypotension. . J. Hypertens. . 20 . 4 . 651–6 . 2002 . 11910300 . 10.1097/00004872-200204000-00022 . 22407752 .
• Serretti A, Lorenzi C, Lilli R . Pharmacogenetics of lithium prophylaxis in mood disorders: analysis of COMT, MAO-A, and Gbeta3 variants. . Am. J. Med. Genet. . 114 . 4 . 370–9 . 2002 . 11992559 . 10.1002/ajmg.10357 . etal.
• Shlyakhto EV, Shwartz EI, Nefedova YB . Lack of association of G-protein subunit gene C825T polymorphism with left ventricular hypertrophy in essential hypertension. . Med. Sci. Monit. . 8 . 5 . CR337–40 . 2002 . 12011775 . etal.

Notes and References

1. Siffert W . Molecular genetics of G proteins and atherosclerosis risk . Basic Res Cardiol . 96 . 6 . 606–11 . Dec 2001 . 11770079 . 10.1007/s003950170012 . 21235423 .
2. Weinstein LS, Chen M, Xie T, Liu J . Genetic diseases associated with heterotrimeric G proteins . Trends Pharmacol Sci . 27 . 5 . 260–6 . May 2006 . 16600389 . 10.1016/j.tips.2006.03.005 .
3. Web site: Entrez Gene: GNB3 guanine nucleotide binding protein (G protein), beta polypeptide 3.