Somatic mutations of GNA 11 and GNAQ in CTNNB 1-mutant aldosterone-producing 13 adenomas presenting in puberty , pregnancy or menopause 14 15

3D-structures for GNAQ and 600 GNAS Somatic or mosaic mutation of p.Gln inhibits GTPase activity 601 and constitutively activates downstream signalling. We find that p.Gln mutation of GNA11/Q 602 stimulates aldosterone production, and, in the adrenal, always co-exists with somatic mutation in 603 exon 3 of CTNNB1 . This prevents inactivation by phosphorylation (e.g. of p.Ser33, in purple, in the 604 partial 3D sequence). Double-mutation of GNA11/Q and CTNNB1 induces high expression of multiple 605 genes, including LHCGR, the G α s/cyclic AMP coupled receptor of luteinizing and pregnancy 606 hormones. The 3D structures of CTNNB1, GNAS, GNAQ, AT1-receptor, renin, ACE were downloaded from models 6M93, 3C14, 4QJ3, 6YV1, 2V0Z, 1O8A, respectively, at www.rcsb.org/.