Loss-of-function diseases or abnormalities caused by particular GPCR misfolding The approximate number of total mutations reported, number of sites involved in the mutations and number of traffic-defective mutant receptors, and pharmacological chaperones used in in vitro studies are indicated. Information condensed as follows: rhodopsin (Stojanovic and Hwa, 2002; Mendes et al., 2005; Tao, 2006); V2R (Bernier et al., 2004a,b; Fujiwara and Bichet, 2005; Bichet, 2006; Boson et al., 2006; Robben and Deen, 2007; Robben et al., 2006); GnRHR (Beranova et al., 2001; Janovick et al., 2003a; Ulloa-Aguirre et al., 2004a,b); CaR (Brown, 2007; Huang and Breitwieser, 2007); LHR (Gromoll et al., 2002; Martens et al., 2002; Huhtaniemi and Themmen, 2005; Piersma et al., 2007); FSHR (Rannikko et al., 2002; Meduri et al., 2003; Huhtaniemi and Themmen, 2005); TSHR (Biebermann et al., 1997; Costagliola et al., 1999; Tonacchera et al., 2000, 2004; Calebiro et al., 2005; Davies et al., 2005); E-BR (Tanaka et al., 1998; Fuchs et al., 2001; Chen et al., 2006; Tao, 2006); MC1R–4R (Beaumont et al., 2005; Clark et al., 2005; Govaerts et al., 2005; Tao, 2005, 2006; Farooqi and O'Rahilly, 2006; Hinney et al., 2006; Lubrano-Berthelier et al., 2006; Alharbi et al., 2007; Lin et al., 2007); and CCR5 receptor (Lederman et al., 2006; Tao, 2006; Reiche et al., 2007).

GPCR Disease or Abnormality Total No. of Mutations or Allelic Variants Reported No. of Sites in the Receptor Compromised by Mutations No. of Reported Traffic-Defective or PM Expression-Deficient Mutant Receptors Pharmacoperones
Rhodopsin Retinitis pigmentosa 150 69 29 9-cis-retinal, 11-cis-retinal, 11-cis-7-ring retinal
V2R Nephrogenic diabetes insipidus 188 91 70 SR121463 (satavaptan), SR49059 (relcovaptan), VPA-985, YM087, OPC41061 (tolvaptan), OPC31260
GnRHR Hypogonadotropic hypogonadism 21 19 17 Indoles, quinolones, erythromycin-derived macrolides
CaR Familial hypocalciuric hypercalcemia 61 50 9 NPS R-568
LHR Male pseudohermaphroditism; hypergonadotropic hypogonadism 25 20 9
FSHR Ovarian dysgenesis 9 9 7
TSHR Congenital hypothyroidism 32 28 8
E-BR Hirschsprung's disease 22 22 2
MC1R Red head color and fair skin (RHC) phenotype and propensity to skin cancer 61a 54 5
MC2R (ACTHR) Familial glucocorticoid deficiency 36 31 Not tested
MC3R Obesity 7b 4 1
MC4R Obesity 79 58 29
CCR5 Resistance to HIV-1 infection 19 19 4
  • SR121463, satavaptan; SR49059, relcovaptan; VPA-985, 5-fluoro-2-methyl-N-[5H-pyrrolo[2,1-c]-[1,4]benzodi azepin-10(11H)-ylcarbonyl)-3-chlorophenyl]benzamide; YM087, 4′-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)-ca rbonyl]-2-phenylbenzanilide monohydrochloride; OPC41061, tolvaptan; OPC31260, (±)-5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4,5-tetr ahydro-1H-benzazepine monohydrochloride; CaR, calcium-sensing receptor; NPS R-568, N-(3-[2-chlorophenyl]propyl)-(R)-α-methyl-3-methoxybenzyl amine; LHR, lutropin (luteinizing hormone) receptor; FSHR, follitropin (follicle-stimulating hormone) receptor; TSHR, thyrotropin receptor; E-BR, endothelin-B receptor; MC1R, melanocortin-1 receptor; MC2R, melanocortin-2 receptor [or adrenocorticotropin receptor(ACTHR)]; MC3R: melanocortin-3 receptor; MC4R, melanocortin-4 receptor; CCR5, chemokine receptor-5; HIV, human immunodeficiency virus

  • a Allelic variants plus mutations

  • b Allelic variants