DMD#26047; "A bioinformatics approach for the phenotype prediction of non-synonymous single nucleotide polymorphisms in human cytochrome P450s", by Wang LL, Li Y, and Zhou SF.

Supplementary Table 2.

nsSNPs of human CYP genes and corresponding phenotypical effect based on in vitro and in vivo experiments.

Gene Symbol / Residue 1 / Position / Residue 2 / SNP ID / Phenotypical effect / Experiment / Site-Directed Mutagenesis / Reference
CYP1A2 / Pro / 41 / Arg / swiss:var_025182 / Decreased enzyme activity / in vitro / yes / (Saito et al., 2005)
Phe / 185 / Leu / swiss:var_020850 / Dramastic reduction in O-deethylation of phenacetin and 7-ethoxyresorufin / in vitro / yes / (Murayama et al., 2004)
Asp / 347 / Asn / swiss:var_020793 / Decreased expression / in vivo / yes / (Zhou et al., 2004)
Arg / 376 / Gln / swiss:var_025188 / Dcreased enzyme activity / in vitro / yes / (Saito et al., 2005)
Ile / 385 / Phe / swiss:var_020794 / Decreased expression / in vivo / yes / (Zhou et al., 2004)
Arg / 430 / Trp / swiss:var_020796 / Decreased expression / in vivo / yes / (Chevalier et al., 2001; Zhou et al., 2004)
Arg / 455 / His / swiss:var_025189 / Decreased activity / in vitro / yes / (Saito et al., 2005)
CYP1B1 / Met / 1 / Thr / OMIM0009 / Peters anomaly / in vivo / no / (Vincent et al., 2001)
Trp / 57 / Cys / swiss:var_008350 / Peters anomaly / in vivo / no / (Vincent et al., 2001)
Gly / 61 / Glu / rs28936700 / GLC3A / in vivo / no / (Bejjani et al., 1998)
Tyr / 81 / Asn / rs9282671 / Glaucoma, primary open angle, adult-onset / in vivo / no / (Melki et al., 2004)
Gly / 232 / Arg / OMIM0013 / GLC3A / in vivo / no / (Melki et al., 2004)
Gly / 365 / Trp / swiss:var_001245 / GLC3A / in vivo / no / (Stoilov et al., 1998)
Arg / 368 / His / rs28936414 / GLC3A / in vivo / no / (Vincent et al., 2002)
Asp / 374 / Asn / rs28936413 / GLC3A / in vivo / no / (Bejjani et al., 1998)
Glu / 387 / Lys / swiss:var_008352 / GLC3A / in vivo / no / (Stoilov et al., 1998)
Asn / 423 / Tyr / OMIM0016 / Glaucoma, primary open angle, juvenile-onset / in vivo / no / (Melki et al., 2004)
Arg / 469 / Trp / rs28936701 / GLC3A / in vivo / no / (Bejjani et al., 1998)
CYP2A6 / Val / 110 / Leu / Decrease of enzyme function / in vivo / no / (Mwenifumbo et al., 2008)
Phe / 118 / Leu / rs28399440 / Decrease of enzyme function / In vivo/in vitro / no / (Mwenifumbo et al., 2008)
Arg / 128 / Leu / Decrease of enzyme function / In vivo/in vitro / no / (Mwenifumbo et al., 2008)
Arg / 128 / Gln / rs4986891 / Loss of activity / in vitro / yes / (Kitagawa et al., 2001)
Ser / 131 / Ala / Decrease of enzyme function / In vivo/in vitro / no / (Mwenifumbo et al., 2008)
Leu / 160 / His / rs1801272 / Poor nicotine metabolism / in vivo / no / (Hadidi et al., 1997)
Arg / 203 / Ser / swiss:var_018333 / Decreased activity / in vivo/in vitro / no / (Ho et al., 2008)
Ser / 224 / Pro / rs28399447 / Poor tegafur metabolism / in vivo/in vitro / yes / (Daigo et al., 2002)
Val / 365 / Met / rs28399454 / Decreased activity / in vivo/in vitro / yes / (Fukami et al., 2004)
Phe / 392 / Tyr / rs1809810 / Decreased activity / in vivo/in vitro / yes / (Fukami et al., 2005)
Ile / 471 / Thr / rs5031016 / Decreased activity / in vivo/in vitro / yes / (Ariyoshi et al., 2001)(Yoshida et al., 2002)
Lys / 476 / Arg / rs6413474 / Decreased activity. / in vivo / no / (Haberl et al., 2005)
Gly / 479 / Val / rs5031017 / Loss of activity / in vivo/in vitro / yes / (Oscarson et al., 1999)
Arg / 485 / Leu / rs28399468 / Decreased activity / in vivo / no / (Yoshida et al., 2002)
CYP2B6 / Met / 46 / Val / swiss:var_023564 / Decreased expression. / in vitro / yes / (Lang et al., 2004)
Gly / 99 / Glu / swiss:var_023565 / Decreased expression. / in vitro / yes / (Lang et al., 2004)
Lys / 139 / Glu / rs12721655 / Decreased expression. / in vitro / yes / (Lang et al., 2004)
Arg / 140 / Gln / swiss:var_023566 / Decreased activity / in vitro / yes / (Lang et al., 2004)
Pro / 166 / Ala / dbsnp:rs3826711 / Decreased activity / in vivo / no / (Gatanaga et al., 2007)
Thr / 168 / Ile / Decreased expression. / in vitro / yes / (Klein et al., 2005)
Gln / 172 / His / rs3745274 / Decreased activity / in vivo/in vitro / yes / (Tsuchiya et al., 2004; Hofmann et al., 2008)
Met / 198 / Thr / Decreased activity / in vitro / no / (Rotger et al., 2007)
Lys / 262 / Arg / rs2279343 / Decreased /increased activity / in vivo/in vitro / yes / (Kirchheiner et al., 2003; Klein et al., 2005)
Arg / 336 / Cys / Decreased expression. / in vitro / yes / (Klein et al., 2005)
Ile / 328 / Thr / rs28399499 / Decreased expression. / In vivo/in vitro / yes / (Wang et al., 2006)
Ile / 391 / Asn / swiss:var_023567 / Decreased expression. / in vitro / yes / (Lang et al., 2004)
Pro / 428 / Thr / Decreased expression. / in vitro / yes / (Klein et al., 2005)
CYP2C8 / Arg / 139 / Lys / rs11572080 / Decreased paclitaxelturnover / in vivo/in vitro / yes / (Dai et al., 2001b)
Arg / 186 / Gly / Decreased activity / in vivo/in vitro / yes / (Hichiya et al., 2005)
Ile / 269 / Phe / rs11572103 / Increased Km forpaclitaxel 6-hydroxylation / in vivo/in vitro / yes / (Dai et al., 2001b)
Lys / 399 / Arg / rs10509681 / Decreased paclitaxelturnover / in vivo/in vitro / yes / (Dai et al., 2001b)
CYP2C9 / Leu / 90 / Pro / Decreased activity / in vivo/in vitro / yes / (Guo et al., 2005)
Arg / 125 / His / Decreased activity / in vitro / yes / (DeLozier et al., 2005)
Thr / 130 / Arg / Decreased activity / in vivo/in vitro / yes / (Maekawa et al., 2006)
Arg / 144 / Cys / rs1799853 / Altered warfarin sensitivity / in vitro / no / (King et al., 2004)
Arg / 150 / His / rs7900194 / Decreased activity / in vivo/in vitro / yes / (Blaisdell et al., 2004)
Leu / 208 / Val / OMIM0003 / warfarin sensitivity / in vivo / no / (Leung et al., 2001)
Gln / 214 / Leu / Decreased activity / in vivo/in vitro / yes / (Maekawa et al., 2006)
Thr / 299 / Ala / Decreased activity / in vitro / yes / (DeLozier et al., 2005)
Arg / 335 / Trp / rs28371685 / Decreased activity / in vivo/in vitro / yes / (Higashi et al., 2002; Blaisdell et al., 2004)
Ile / 359 / Leu / rs1057910 / Tolbutamide poor metabolizer / in vivo/in vitro / yes / (Shintani et al., 2001)
Asp / 360 / Glu / rs28371686 / Decreased activity / in vivo/in vitro / yes / (Dickmann et al., 2001; Allabi et al., 2004)
Asp / 397 / Ala / Decreased activity / in vitro / yes / (DeLozier et al., 2005)
Ala / 477 / Thr / Decreased activity / in vivo/in vitro / yes / (Maekawa et al., 2006)
Pro / 489 / Ser / rs9332239 / Decreased activity / in vivo/in vitro / yes / (Blaisdell et al., 2004)
CYP2C19 / Met / 1 / Val / rs28399504 / Poor mephenytoin metabolism / in vivo/in vitro / yes / (Ferguson et al., 1998)
Trp / 120 / Arg / swiss:var_008357 / 2C19*8; loss of activity / in vivo/in vitro / yes / (Ibeanu et al., 1999)
Arg / 132 / Gln / swiss:var_008358 / 2C19*6; loss of activity / in vivo/in vitro / yes / (Ibeanu et al., 1998b)
Trp / 212 / Ter / OMIM0003 / Poor mephenytoin metabolism / In vivo / no / (De Morais et al., 1994)
Pro / 227 / Leu / rs6413438 / Decreased activity / in vivo/in vitro / yes / (Blaisdell et al., 2002)
Ile / 331 / Val / Decreased activity / in vivo/in vitro / yes / (Blaisdell et al., 2002)
Arg / 433 / Trp / swiss:var_008359 / 2C19*5A2C19*5B; loss of activity / in vivo / no / (Ibeanu et al., 1998a)
Arg / 442 / Cys / swiss:var_021275 / 2C19*16; lowered catalytic activity / in vivo / no / (Morita et al., 2004)
CYP2D6 / Pro / 34 / Ser / rs1065852 / 2D6*102D6*14; poor debrisquone metabolism / in vivo/in vitro / yes / (Yokota et al., 1993; Johansson et al., 1994)
Gly / 42 / Arg / rs5030862 / 2D6*12; impaired metabolism of sparteine / in vivo / no / (Marez et al., 1996)
Thr / 107 / Ile / rs28371706 / 2D6*17; poor debrisquone metabolism / in vivo/in vitro / yes / (Masimirembwa et al., 1996; Oscarson et al., 1997)
Val / 136 / Met / Decreased activity / in vivo / no / (Wennerholm et al., 2002)
Gly / 169 / Arg / rs5030865 / 2D6*14; poor debrisquone metabolism / in vivo/in vitro / yes / (Wang et al., 1999)
Gly / 169 / Ter / OMIM0004 / poor debrisquine metabolism / In vivo / no / (Broly et al., 1995)
Arg / 296 / Cys / rs16947 / Decreased activity / in vivo/in vitro / yes / (Johansson et al., 1993; Oscarson et al., 1997)
Val / 338 / Met / Decreased activity / in vivo / no / (Wennerholm et al., 2002)
Ser / 486 / Thr / swiss:var_008341 / Decreased activity / in vivo/in vitro / yes / (Johansson et al., 1993; Johansson et al., 1994)
CYP2E1 / Arg / 76 / His / swiss:var_008360 / 2E1*2; reduced activity / in vivo/in vitro / yes / (Hu et al., 1997)
CYP2J2 / Thr / 143 / Ala / swiss:var_014317 / 2J2*2; significantly reduced metabolism of both arachidonic acid and linoleic acid / in vivo/in vitro / yes / (King et al., 2002)
Arg / 158 / Cys / swiss:var_014318 / 2J2*3; significantly reduced metabolism of both arachidonic acid and linoleic acid / in vivo/in vitro / yes / (King et al., 2002)
Ile / 192 / Asn / swiss:var_014319 / 2J2*4; significantly reduced metabolism of arachidonic acid only / in vivo/in vitro / yes / (King et al., 2002)
Asn / 404 / Tyr / swiss:var_014321 / 2J2*6; significantly reduced metabolism of both arachidonic acid and linoleic acid / in vivo/in vitro / yes / (King et al., 2002)
CYP2R1 / Leu / 99 / Pro / swiss:var_021534 / 25-hydroxyvitamin D3 deficiency; complete loss of activity / in vivo/in vitro / yes / (Cheng et al., 2004)
CYP3A4 / Arg / 129 / Gln / swiss:var_011600 / Decreased activity / in vitro / yes / (Eiselt et al., 2001)
Thr / 185 / Ser / rs12721627 / Decreased activity / in vitro / yes / (Murayama et al., 2002)
Phe / 189 / Ser / rs4987161 / 3A4*17; lowered turnover for testosterone and chlorpyrifos / in vivo/in vitro / yes / (Dai et al., 2001a)
Ser / 221 / Pro / swiss:var_008363 / 3A4*2; lowered intrinsic clearance towards nifedipine / in vivo/in vitro / yes / (Sata et al., 2000)
Leu / 293 / Pro / rs28371759 / 3A4*18; increased turnover for testosterone, chlorpyrifos and estrone (in vitro); low metabolic turnover for midazolam (in vivo) / in vivo/in vitro / yes / (Dai et al., 2001a; Kang et al., 2008)
Thr / 362 / Met / swiss:var_011606 / Decreased activity / in vitro / yes / (Murayama et al., 2002)
Leu / 373 / Phe / rs12721629 / 3A4*12; altered testosterone hydroxylase activity / in vitro / yes / (Eiselt et al., 2001)
Pro / 416 / Leu / rs4986909 / Decreased activity / in vitro / yes / (Eiselt et al., 2001)
CYP3A5 / Arg / 28 / Cys / swiss:var_024731 / Decreased activity. / in vivo/in vitro / yes / (Lee et al., 2003)
His / 30 / Tyr / rs28383468 / Severely decreased activity. / in vivo / no / (Hustert et al., 2001)
Tyr / 53 / Cys / Decreased activity. / in vitro / yes / (Lee et al., 2007b)
Leu / 82 / Arg / Decreased activity. / in vivo/in vitro / yes / (Lee et al., 2003)
Ala / 337 / Thr / rs28383479 / Decreased activity. / in vivo/in vitro / yes / (Lee et al., 2003)
Phe / 446 / Ser / swiss:var_024733 / Decreased activity. / in vivo/in vitro / yes / (Lee et al., 2003)
Ile / 456 / Val / Severely decreased activity. / in vivo / no / (Saeki et al., 2003)
Ile / 488 / Thr / rs28365085 / Severely decreased activity. / in vivo / no / (Saeki et al., 2003)
CYP3A7 / Thr / 409 / Arg / Increased activity. / in vitro / yes / (Rodriguez-Antona et al., 2005)
CYP4A11 / Phe / 434 / Ser / rs4233507 / essential, susceptibility to hypertension, reduced by more than half the 20-HETE synthase activity of CYP4A11 / in vivo / no / (Gainer et al., 2005)
CYP4F2 / Val / 433 / Met / rs2108622 / Association with increased warfarin dosage / in vivo/in vitro / yes / (Stec et al., 2007; Caldwell et al., 2008)
CYP4V2 / Trp / 44 / Arg / swiss:var_023084 / BCD / in vivo / no / (Li et al., 2004)
Gly / 61 / Ser / swiss:var_023085 / BCD / in vivo / no / (Li et al., 2004)
Glu / 79 / Asp / swiss:var_023086 / BCD / in vivo / no / (Li et al., 2004)
Ile / 111 / Thr / swiss:var_023087 / BCD / in vivo / no / (Li et al., 2004)
Met / 123 / Val / swiss:var_023088 / BCD / in vivo / no / (Li et al., 2004)
His / 331 / Pro / swiss:var_023089 / BCD / in vivo / no / (Li et al., 2004)
Ser / 341 / Pro / swiss:var_023090 / BCD / in vivo / no / (Li et al., 2004)
Arg / 508 / His / swiss:var_023091 / BCD / in vivo / no / (Li et al., 2004)
CYP11A1 / Ala / 189 / Val / OMIM0003 / Congenital adrenal insufficiency, decreased activity / in vivo/in vitro / yes / (Katsumata et al., 2002)
Ala / 359 / Val / OMIM0005 / Congenital adrenal insufficiency, with 46,XY sex reversal, decreased activity / in vivo/in vitro / yes / (al Kandari et al., 2006)
Arg / 353 / Trp / swiss:var_016951 / Congenital adrenal insufficiency, loss of activity / in vivo/in vitro / yes / (Katsumata et al., 2002)
CYP11B1 / Pro / 42 / Ser / swiss:var_001260 / Steroid 11--hydroxylase deficiency / in vivo / no / (Joehrer et al., 1997)
Pro / 94 / Leu / OMIM0016 / Steroid 11--hydroxylase deficiency, reduced activity / in vivo/in vitro / yes / (Krone et al., 2006)
Trp / 116 / Ter / OMIM0006 / Steroid 11--hydroxylase deficiency, decreased activity / in vivo/in vitro / yes / (Naiki et al., 1993)
Asn / 133 / His / swiss:var_001261 / Steroid 11--hydroxylase deficiency / in vivo / no / (Joehrer et al., 1997)
Thr / 318 / Met / swiss:var_001262 / Steroid 11--hydroxylase deficiency / in vivo / no / (Pascoe et al., 1992a)
Thr / 319 / Met / swiss:var_001263 / Steroid 11--hydroxylase deficiency / in vivo / no / (Joehrer et al., 1997)
Ala / 368 / Asp / OMIM0017 / Steroid 11--hydroxylase deficiency, reduced activity / in vivo/in vitro / yes / (Krone et al., 2006)
Arg / 374 / Gln / swiss:var_001264 / Steroid 11--hydroxylase deficiency / in vivo / no / (Pascoe et al., 1992a)
Tyr / 423 / Ter / OMIM0015 / Steroid 11--hydroxylase deficiency / in vivo / no / (Joehrer et al., 1997)
Arg / 448 / His / swiss:var_001265 / Steroid 11--hydroxylase deficiency / in vivo / no / (White et al., 1991)
CYP11B2 / Arg / 181 / Trp / rs28931609 / CMO-II; reduces 18- hydroxylase and abolishes 18-oxidase activities; leaves 11 -hydroxylase activity intact / in vivo/in vitro / yes / (Pascoe et al., 1992b)
Thr / 185 / Ile / swiss:var_018471 / CMO-II / in vivo / no / (Peter et al., 1998)
Glu / 198 / Asp / swiss:var_001268 / CMO-I, reduced activity / in vivo/in vitro / yes / (Portrat-Doyen et al., 1998)
Glu / 225 / Ter / OMIM0006 / CMO-I / in vivo / no / (Peter et al., 1997)
Glu / 272 / Ter / OMIM0013 / CMO-II / in vivo / no / (Williams et al., 2004)
Val / 385 / Ala / rs28930074 / CMO-I;CMO-II;reduced activity / in vivo/in vitro / yes / (Pascoe et al., 1992b)(Portrat-Doyen et al., 1998)
Leu / 461 / Pro / swiss:var_018472 / CMO-I; abolishes the 18-hydroxylase activity required for conversion of 11-deoxycorticosterone to aldosterone / in vivo/in vitro / yes / (Nomoto et al., 1997)
Thr / 498 / Ala / swiss:var_018473 / CMO-II / in vivo/in vitro / yes / (Dunlop et al., 2003)
CYP17A1 / Trp / 17 / Ter / OMIM0016 / AH5 / In vivo / no / (Suzuki et al., 1998)
Tyr / 27 / Ter / OMIM0028 / AH5 / In vivo / no / (Mussig et al., 2005)
Pro / 35 / Leu / swiss:var_022745 / AH5; 38% 17-hydroxylase activity and 33% 17,20-lyase activity / in vivo/in vitro / yes / (Biason-Lauber et al., 2000)
Tyr / 64 / Ser / swiss:var_001271 / AH5 / in vivo/in vitro / yes / (Imai et al., 1993)
Phe / 93 / Cys / swiss:var_013147 / AH5 / in vivo/in vitro / yes / (Di Cerbo et al., 2002)
Arg / 96 / Trp / swiss:var_022746 / AH5; 25% of both 17- hydroxylase and 17,20-lyase activities / in vivo/in vitro / yes / (Laflamme et al., 1996)
Arg / 96 / Gln / OMIM0029 / AH5 / In vivo / no / (Brooke et al., 2006)
Ser / 106 / Pro / swiss:var_001272 / AH5 / in vivo/in vitro / yes / (Lin et al., 1991)
Phe / 114 / Val / swiss:var_022747 / AH5 / in vivo/in vitro / yes / (Van Den Akker et al., 2002)
Asp / 116 / Val / swiss:var_022748 / AH5 / in vivo/in vitro / yes / (Van Den Akker et al., 2002)
Arg / 125 / Gln / OMIM0030 / AH5 / in vivo / no / (Ergun-Longmire et al., 2006)
Asn / 177 / Asp / swiss:var_022749 / AH5; 10% 17-hydroxylase and 17,20-lyase activities / in vivo/in vitro / yes / (Biason-Lauber et al., 2000)
Tyr / 201 / Asn / OMIM0027 / AH5 / in vivo/in vitro / yes / (Taniyama et al., 2005)
Arg / 239 / Ter / OMIM0006 / AH5 / in vivo / no / (Ahlgren et al., 1992)
Tyr / 329 / Asp / swiss:var_022750 / AH5 / in vivo / no / (Martin et al., 2003)
Pro / 342 / Thr / swiss:var_001274 / AH5; reduced activity / in vivo/in vitro / yes / (Ahlgren et al., 1992)
Arg / 347 / Cys / swiss:var_022752 / AH5 / in vivo/in vitro / yes / (Van Den Akker et al., 2002)
Arg / 347 / His / swiss:var_001275 / AH5; selectively ablates 17,20-lyase activity, while preserving most 17-hydroxylase activity / in vivo/in vitro / yes / (Gupta et al., 2001; Van Den Akker et al., 2002)
Arg / 358 / Gln / swiss:var_001276 / AH5; selectively ablates 17,20-lyase activity, while preserving most 17-hydroxylase activity / in vivo/in vitro / yes / (Geller et al., 1997; Gupta et al., 2001)
Arg / 362 / Cys / swiss:var_022753 / AH5 / in vivo / no / (Martin et al., 2003)
His / 373 / Leu / swiss:var_001277 / AH5 / in vivo/in vitro / yes / (Monno et al., 1993)
Trp / 406 / Arg / swiss:var_022754 / AH5 / in vivo / no / (Martin et al., 2003)
Arg / 416 / His / OMIM0031 / AH5 / in vivo / no / (Ergun-Longmire et al., 2006)
Phe / 417 / Cys / swiss:var_022755 / AH5; ablates both 17,20-lyase activity and 17-hydroxylase activity; loss of heme-binding and loss of phosphorylation / in vivo/in vitro / yes / (Biason-Lauber et al., 2000; Gupta et al., 2001)
Pro / 428 / Leu / swiss:var_022756 / AH5 / in vivo / no / (Martin et al., 2003)
Arg / 440 / His / swiss:var_001278 / AH5 / in vivo/in vitro / yes / (Fardella et al., 1994)
Phe / 453 / Ser / OMIM0033 / AH5 / In vivo / no / (Yang et al., 2006)
Arg / 496 / Cys / swiss:var_001280 / AH5 / in vivo/in vitro / yes / (Yanase et al., 1992)
Arg / 496 / His / swiss:var_022757 / AH5; 30% 17-hydroxylase activity and 29% 17,20-lyase activity / in vivo/in vitro / yes / (Biason-Lauber et al., 2000)
CYP19A1 / Glu / 210 / Lys / OMIM0012 / Aromatase deficiency / In vivo / no / (Maffei et al., 2004)
Arg / 264 / Cys / rs700519 / Decreased activity / in vivo/in vitro / yes / (Ma et al., 2005)
Met / 364 / Thr / Decreased activity / in vivo/in vitro / yes / (Ma et al., 2005)
Arg / 365 / Gln / swiss:var_016962 / Aromatase deficiency (0.4% of wild-type activity) / in vivo/in vitro / yes / (Carani et al., 1997)
Arg / 375 / Cys / swiss:var_016963 / Aromatase deficiency / in vivo/in vitro / yes / (Morishima et al., 1995)
Arg / 435 / Cys / swiss:var_016964 / Aromatase deficiency (1.1% of wild-type activity) / in vivo/in vitro / yes / (Ito et al., 1993)
Cys / 437 / Tyr / swiss:var_016965 / Aromatase deficiency (complete loss of activity) / in vivo/in vitro / yes / (Ito et al., 1993)
CYP21A2 / Pro / 30 / Gln / swiss:var_026060 / CAH; does not affect membrane binding; enzyme function abolished / in vivo/in vitro / yes / (White et al., 1994; Lajic et al., 1999)
Pro / 30 / Leu / swiss:var_001281 / CAH; non-classic form; 50% activity; 10% of non-classic CAH Texan patients / in vivo/in vitro / yes / (Tusie-Luna et al., 1991)
His / 62 / Leu / swiss:var_018364 / CAH / in vivo / no / (Pinto et al., 2003)
Gly / 64 / Glu / swiss:var_007923 / CAH; no activity / in vivo/in vitro / yes / (Ohlsson et al., 1999)
Ile / 77 / Thr / CAH / in vivo/in vitro / yes / (Krone et al., 2005)
Gly / 90 / Val / swiss:var_026061 / CAH / in vivo/in vitro / yes / (Nunez et al., 1999)
Tyr / 102 / Arg / OMIM0014 / CAH; hydroxylase polymorphism / in vivo / no / (Rodrigues et al., 1987)
Pro / 105 / Leu / swiss:var_001284 / CAH / in vivo/in vitro / yes / (White et al., 1994; Nikoshkov et al., 1997)
Arg / 124 / His / swiss:var_026062 / CAH / in vivo / no / (White et al., 1994; Usui et al., 2004)
Leu / 166 / Pro / CAH / in vivo/in vitro / yes / (Robins et al., 2007)
Cys / 169 / Tyr / swiss:var_001285 / CAH / in vivo/in vitro / yes / (Grischuk et al., 2006)
Cys / 169 / Arg / CAH / in vivo/in vitro / yes / (Grischuk et al., 2006)
Ile / 171 / Asn / CAH / in vivo/in vitro / yes / (Barbaro et al., 2006)
Ile / 173 / Asn / rs6475 / CAH; simple virilizing form; 1-2% activity / in vivo/in vitro / yes / (Tusie-Luna et al., 1990)
Gly / 178 / Ala / swiss:var_026063 / CAH / in vivo/in vitro / yes / (Grischuk et al., 2006)
Gly / 178 / Arg / CAH / in vivo/in vitro / yes / (Grischuk et al., 2006)
Val / 211 / Leu / swiss:var_026064 / CAH; non-classic form; pathogenicity uncertain / in vivo / no / (Speiser et al., 1988)
Ile / 236 / Asn / swiss:var_001288 / CAH; salt wasting form / in vivo/in vitro / yes / (Kapelari et al., 1999; Robins et al., 2005)
Val / 238 / Glu / rs12530380 / CAH; salt wasting form / in vivo/in vitro / yes / (Tusie-Luna et al., 1990)
Met / 239 / Lys / swiss:var_001290 / CAH; salt wasting form / in vivo/in vitro / yes / (Kapelari et al., 1999; Robins et al., 2005)
Leu / 261 / Pro / swiss:var_026065 / CAH / in vivo / no / (Loke et al., 2001)
Ser / 268 / Thr / OMIM0005 / CAH; hydroxylase polymorphism / in vivo / no / (Wu and Chung, 1991)
Val / 281 / Leu / OMIM0002 / CAH / in vivo / no / (Speiser et al., 1988)
Val / 281 / Gly / CAH; salt wasting form / in vivo/in vitro / yes / (Lajic et al., 2001)
Met / 283 / Leu / swiss:var_026067 / CAH / in vivo / no / (Ezquieta et al., 2002)
Gly / 291 / Ser / swiss:var_001293 / CAH; salt wasting form; less then 1% activity / in vivo/in vitro / yes / (Nikoshkov et al., 1998; Ohlsson et al., 1999)
Gly / 291 / Cys / swiss:var_026068 / CAH / in vivo/in vitro / yes / (Nunez et al., 1999)
Gly / 291 / Arg / swiss:var_018365 / CAH / in vivo / no / (Stikkelbroeck et al., 2003)
Leu / 300 / Phe / swiss:var_026069 / CAH; salt wasting form / in vivo/in vitro / yes / (Lajic et al., 2001)
Ser / 301 / Tyr / swiss:var_018366 / CAH / in vivo / no / (Stikkelbroeck et al., 2003)
Trp / 302 / Arg / CAH / in vivo/in vitro / yes / (Grischuk et al., 2006)
Val / 304 / Met / swiss:var_026070 / Hyperandrogenism (due to 21- hydroxylase deficiency; non-classic type; residual activity of 46% for conversion of 17-hydroxyprogesterone and 26% for conversion of progesterone compared with the normal enzyme) / in vivo/in vitro / yes / (Lajic et al., 2002)
Leu / 317 / Met / swiss:var_026071 / CAH / in vivo / no / (Deneux et al., 2001)
Gln / 319 / Ter / rs7755898 / CAH (due to 21-hydroxylase deficiency, salt-wasting type) / in vivo/in vitro / yes / (Globerman et al., 1988)
Arg / 339 / His / swiss:var_001294 / CAH (non-classic form; 50% activity) / in vivo/in vitro / yes / (Helmberg et al., 1992)
Arg / 341 / Pro / swiss:var_018367 / CAH / in vivo/in vitro / no / (Barbaro et al., 2006)
Arg / 341 / Trp / swiss:var_001295 / CAH (non-classic form; mild) / in vivo / no / (White et al., 1994)
Glu / 351 / Lys / CAH / in vivo/in vitro / yes / (Krone et al., 2005)
Arg / 354 / His / swiss:var_026073 / CAH / in vivo/in vitro / yes / (Nunez et al., 1999)
Arg / 354 / Cys / swiss:var_026072 / CAH (salt wasting form) / in vivo / no / (Krone et al., 2000)
Arg / 356 / Pro / swiss:var_001296 / CAH (salt wasting form; 0.15% activity) / in vivo/in vitro / yes / (Lajic et al., 1997)
Arg / 356 / Gln / swiss:var_001297 / CAH (simple virilizing form; mild; 0.65% activity) / in vivo/in vitro / yes / (Lajic et al., 1997)
Arg / 357 / Trp / rs7769409 / CAH (due to 21-hydroxylase deficiency) / in vivo/in vitro / yes / (Chiou et al., 1990)
Ala / 362 / Val / swiss:var_007924 / CAH (no activity) / in vivo/in vitro / yes / (Ohlsson et al., 1999)
Leu / 363 / Trp / swiss:var_026074 / CAH / in vivo / no / (Levo and Partanen, 2001)
His / 365 / Tyr / swiss:var_026075 / CAH / in vivo / no / (Zeng et al., 2004)
Gly / 375 / Ser / swiss:var_026076 / Hyperandrogenism (due to 21- hydroxylase deficiency; almost completely abolished enzyme activity) / in vivo/in vitro / yes / (Lajic et al., 2002)
Glu / 380 / Asp / swiss:var_001299 / in CAH; salt wasting form / in vivo / no / (Kirby-Keyser et al., 1997)
Ala / 391 / Thr / CAH / in vivo/in vitro / yes / (Robins et al., 2007)
Trp / 406 / Ter / OMIM0022 / in CAH; salt wasting form / in vivo / no / (Wedell and Luthman, 1993)
Arg / 408 / Cys / swiss:var_026077 / in CAH; should lead to complete impairment of enzymatic activity / in vivo / no / (Billerbeck et al., 2002)
Gly / 424 / Ser / swiss:var_026078 / CAH / in vivo / no / (Billerbeck et al., 1999)
Arg / 426 / Cys / swiss:var_026079 / in CAH; exhibit only low enzyme activity toward 17-hydroxyprogesterone / in vivo/in vitro / yes / (Grischuk et al., 2006)
Ala / 434 / Val / CAH / in vivo/in vitro / yes / (Krone et al., 2005)
Arg / 435 / Cys / swiss:var_026080 / CAH / in vivo / no / (Deneux et al., 2001)
Leu / 446 / Pro / CAH / in vivo/in vitro / yes / (Barbaro et al., 2006)
Pro / 454 / Ser / rs6445 / CAH, due to 21-hydroxylase deficiency, nonclassic type / in vivo/in vitro / yes / (Nikoshkov et al., 1997)
Arg / 479 / Leu / swiss:var_026081 / CAH / in vivo/in vitro / yes / (Robins et al., 2007)
Pro / 482 / Ser / swiss:var_026082 / in CAH; rediced enzyme activity to 70% of normal / in vivo/in vitro / yes / (Barbaro et al., 2004)
Arg / 483 / Pro / swiss:var_001301 / in CAH; moderate; 1-2% of activity / in vivo/in vitro / yes / (Nikoshkov et al., 1998)
Arg / 483 / Trp / swiss:var_026083 / CAH (salt wasting form) / in vivo / no / (Kharrat et al., 2004)
Arg / 483 / Gln / swiss:var_018368 / CAH / in vivo/in vitro / yes / (Robins et al., 2007)
CYP26A1 / Phe / 186 / Leu / CAH / in vivo/in vitro / yes / (Lee et al., 2007a)
Cys / 358 / Arg / CAH / in vivo/in vitro / yes / (Lee et al., 2007a)
CYP27A1 / Gly / 112 / Glu / OMIM0011 / CTX / in vivo / no / (Lamon-Fava et al., 2002)
Gly / 145 / Glu / swiss:var_016966 / CTX / in vivo / no / (Lamon-Fava et al., 2002)
Thr / 339 / Met / OMIM0013 / CTX / in vivo / no / (Guyant-Marechal et al., 2005)
Arg / 362 / Cys / OMIM0002 / CTX / in vivo/in vitro / yes / (Cali et al., 1991)
Arg / 362 / Ser / OMIM0008 / CTX / in vivo/in vitro / yes / (Chen et al., 1998)
Arg / 372 / Gln / OMIM0007 / CTX / in vivo/in vitro / yes / (Chen et al., 1997)
Arg / 395 / Cys / swiss:var_001303 / CTX / in vivo/in vitro / yes / (Cali et al., 1991)
Arg / 395 / Ser / swiss:var_012285 / CTX / in vivo/in vitro / yes / (Chen et al., 1998)
Arg / 405 / Gln / swiss:var_012286 / CTX / in vivo/in vitro / yes / (Chen et al., 1997)
Arg / 441 / Gln / OMIM0005 / CTX / in vivo/in vitro / no / (Kim et al., 1994)
Arg / 441 / Trp / OMIM0006 / CTX / in vivo/in vitro / no / (Kim et al., 1994)
Arg / 446 / Cys / OMIM0001 / CTX / in vivo/in vitro / yes / (Cali et al., 1991)
Arg / 474 / Gln / swiss:var_012287 / CTX / in vivo/in vitro / no / (Kim et al., 1994)
Arg / 474 / Trp / swiss:var_012288 / CTX / in vivo/in vitro / no / (Kim et al., 1994)
Arg / 479 / Cys / swiss:var_001304 / CTX / in vivo/in vitro / yes / (Cali et al., 1991)
Arg / 479 / Gly / OMIM0014 / CTX / in vivo / no / (Guyant-Marechal et al., 2005)
CYP27B1 / Gln / 65 / His / swiss:var_016969 / VDDR-I / in vivo/in vitro / yes / (Wang et al., 1998)
Arg / 107 / His / swiss:var_016952 / VDDR I (complete loss of activity) / in vivo/in vitro / yes / (Kitanaka et al., 1998)
Gly / 125 / Glu / rs28934605 / VDDR I (complete loss of activity) / in vivo/in vitro / yes / (Kitanaka et al., 1998)
Glu / 189 / Lys / swiss:var_016967 / VDDR I (11% of wild-type activity) / in vivo/in vitro / yes / (Wang et al., 1998)
Glu / 189 / Gly / swiss:var_016954 / VDDR I (22% of wild-type activity) / in vivo/in vitro / yes / (Wang et al., 2002)
Thr / 321 / Arg / swiss:var_016955 / VDDR I (complete loss of activity) / in vivo/in vitro / yes / (Kitanaka et al., 1999)
Ser / 323 / Tyr / swiss:var_016970 / VDDR-I / in vivo/in vitro / no / (Smith et al., 1999)
Arg / 335 / Pro / rs28934606 / VDDR I (complete loss of activity) / in vivo/in vitro / yes / (Kitanaka et al., 1998)
Leu / 343 / Phe / swiss:var_016957 / VDDR I (2.3% of wild-type activity) / in vivo/in vitro / yes / (Wang et al., 2002)
Pro / 382 / Ser / rs28934607 / VDDR I (complete loss of activity) / in vivo/in vitro / yes / (Kitanaka et al., 1998)
Arg / 389 / His / swiss:var_016959 / VDDR I (complete loss of activity) / in vivo/in vitro / yes / (Wang et al., 1998)(Wang et al., 2002)
Arg / 389 / Gly / swiss:var_016960 / VDDR I (complete loss of activity) / in vivo/in vitro / yes / (Wang et al., 2002)
Arg / 389 / Cys / swiss:var_016968 / VDDR I (complete loss of activity) / in vivo/in vitro / yes / (Kitanaka et al., 1999)
Thr / 409 / Ile / swiss:var_016961 / VDDR I / in vivo/in vitro / yes / (Wang et al., 1998)(Wang et al., 2002)
Arg / 429 / Pro / swiss:var_016971 / VDDR I / in vivo/in vitro / yes / (Wang et al., 1998)
Arg / 453 / Cys / swiss:var_016972 / VDDR I / in vivo/in vitro / yes / (Wang et al., 1998)
Val / 478 / Gly / swiss:var_016973 / VDDR I / in vivo/in vitro / no / (Smith et al., 1999)
Pro / 497 / Arg / swiss:var_016974 / VDDR I / in vivo/in vitro / yes / (Wang et al., 1998)

AH5 = Adrenal hyperplasia type 5; BCD = Bietti crystalline corneoretinal dystrophy; CTX = Cerebrotendinous xanthomatosis; CAH = Congenital adrenal hyperplasia;