General Structure Information
| PDB ID | 3ua5 |
| HGNC Gene Label(s) | CYP2B6 |
| Structure Name | crystal structure of p450 2b6 (y226h/k262r) in complex with two molecules of amlodipine |
| Resolution | 2.8Å |
| Reference | AUTH M.B.SHAH,P.R.WILDERMAN,J.PASCUAL,Q.ZHANG,C.D.STOUT,AUTH 2 J.R.HALPERTTITL CONFORMATIONAL ADAPTATION OF HUMAN CYTOCHROME P450 2B6 ANDTITL 2 RABBIT CYTOCHROME P450 2B4 REVEALED UPON BINDING MULTIPLETITL 3 AMLODIPINE MOLECULES.REF BIOCHEMISTRY V. 51 7225 2012REFN ISSN 0006-2960PMID 22909231DOI 10.1021/BI300894Z |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 461 |
| Number Of SNVs | 148 |
| Number Of Permutations | 54064 |
| Optimal Distance Threshold | 6.0 |
| K Statistic | 0.011 |
| p-value | 0.243 |
COSMIC
| Number Of Residues | 461 |
| Number Of SNVs | 13 |
| Number Of Permutations | 4399 |
| Optimal Distance Threshold | 20.0 |
| K Statistic | 0.167 |
| p-value | 0.589 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 148 |
| Number Of COSMIC SNVs | 11 |
| Optimal Distance Threshold | 21.0 |
| K Statistic | -0.086 |
| p-value | 0.759 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 19:41497295 | R>C | B:29 | (4.46, -9.25, -33.61) | |
| 19:41497298 | L>F | B:30 | (1.61, -7.98, -30.75) | |
| 19:41497313 | COSM339684 | R>C | B:35 | (-10.84, -2.91, -36.52) |
| 19:41497314 | COSM1393921 | R>H | B:35 | (-10.84, -2.91, -36.52) |
| 19:41497319 | L>M | B:37 | (-9.50, 2.98, -35.57) | |
| 19:41497325 | L>F | B:39 | (-5.53, 8.42, -33.14) | |
| 19:41497332 | G>E | B:41 | (-8.26, 2.56, -31.56) | |
| 19:41497335 | N>I | B:42 | (-9.72, -0.65, -29.99) | |
| 19:41497346 | rs35303484 | M>V | B:46 | (-14.34, -0.11, -25.30) |
| 19:41497349 | rs142373781 | D>N | B:47 | (-18.68, -1.42, -22.49) |
| 19:41497353 | R>K | B:48 | (-19.09, 3.13, -23.44) | |
| 19:41497365 | rs151274228 | L>P | B:52 | (-12.82, -4.68, -16.46) |
| 19:41497367 | rs140474673 | K>Q | B:53 | (-17.31, -6.26, -18.30) |
| 19:41497379 | R>W | B:57 | (-17.36, -8.18, -24.84) | |
| 19:41509934 | rs138264188 | T>M | B:67 | (-3.68, -6.43, -28.13) |
| 19:41509949 | P>L | B:72 | (-2.40, 5.93, -29.64) | |
| 19:41509957 | COSM4078398 | V>M | B:75 | (-1.95, -2.25, -24.01) |
| 19:41509976 | rs138912615 | V>A | B:81 | (-2.98, -17.46, -12.56) |
| 19:41509988 | rs572134005 COSM566302 |
R>Q | B:85 | (2.38, -17.84, -11.98) |
| 19:41509996 | L>F | B:88 | (5.29, -11.06, -13.24) | |
| 19:41510007 | K>N | B:91 | (9.20, -14.34, -18.53) | |
| 19:41510021 | rs144760726 | S>C | B:96 | (9.54, -5.82, -13.93) |
| 19:41510026 | rs183427203 | R>W | B:98 | (5.49, 0.38, -13.00) |
| 19:41510027 | rs372295360 | R>Q | B:98 | (5.49, 0.38, -13.00) |
| 19:41510030 | rs36060847 | G>E | B:99 | (4.32, 2.48, -16.15) |
| 19:41510051 | P>Q | B:106 | (4.67, 15.32, -14.64) | |
| 19:41510059 | rs142421637 | R>W | B:109 | (10.66, 14.23, -13.70) |
| 19:41510060 | rs145946484 | R>Q | B:109 | (10.66, 14.23, -13.70) |
| 19:41510062 | G>R | B:110 | (10.69, 8.72, -11.51) | |
| 19:41510063 | rs186335453 | G>V | B:110 | (10.69, 8.72, -11.51) |
| 19:41510066 | Y>C | B:111 | (12.73, 10.49, -8.68) | |
| 19:41510208 | rs139801276 | I>T | B:114 | (4.88, 3.04, -7.45) |
| 19:41510217 | rs376236759 | N>S | B:117 | (11.81, 1.97, -13.76) |
| 19:41510225 | COSM996879 | R>C | B:120 | (15.69, 6.08, -10.12) |
| 19:41510226 | rs553968231 | R>H | B:120 | (15.69, 6.08, -10.12) |
| 19:41510234 | V>M | B:123 | (18.66, 1.06, -5.12) | |
| 19:41510240 | R>W | B:125 | (11.30, -2.91, -3.63) | |
| 19:41510241 | COSM3357135 | R>Q | B:125 | (11.30, -2.91, -3.63) |
| 19:41510244 | R>Q | B:126 | (17.31, -4.40, -0.55) | |
| 19:41510250 | S>F | B:128 | (12.39, 0.20, 1.56) | |
| 19:41510258 | T>A | B:131 | (13.90, -0.06, 6.41) | |
| 19:41510273 | COSM4078399 | G>R | B:136 | (11.54, -1.99, 15.36) |
| 19:41510278 | M>I | B:137 | (14.41, -3.06, 15.98) | |
| 19:41510282 | rs12721655 | K>E | B:139 | (12.46, 1.79, 15.78) |
| 19:41510284 | K>N | B:139 | (12.46, 1.79, 15.78) | |
| 19:41510285 | rs535039125 | R>W | B:140 | (6.66, 2.57, 18.45) |
| 19:41510300 | rs375508968 | R>W | B:145 | (3.92, 2.69, 15.40) |
| 19:41510301 | rs139173201 | R>Q | B:145 | (3.92, 2.69, 15.40) |
| 19:41510312 | E>K | B:149 | (-4.62, 4.50, 15.29) | |
| 19:41510315 | A>P | B:150 | (-6.80, 1.08, 17.28) | |
| 19:41510316 | rs368809408 | A>D | B:150 | (-6.80, 1.08, 17.28) |
| 19:41510321 | C>S | B:152 | (-7.39, 5.89, 18.99) | |
| 19:41510328 | I>T | B:154 | (-11.88, 2.22, 19.98) | |
| 19:41510333 | E>K | B:156 | (-13.65, 8.74, 17.56) | |
| 19:41510339 | rs183040778 | R>W | B:158 | (-16.58, 4.05, 22.84) |
| 19:41510340 | rs141666881 | R>Q | B:158 | (-16.58, 4.05, 22.84) |
| 19:41512820 | rs376694380 COSM1712323 |
M>I | B:165 | (-21.01, 6.75, 10.94) |
| 19:41512824 | rs3826711 | P>A | B:167 | (-16.98, 5.29, 7.60) |
| 19:41512828 | rs36056539 | T>I | B:168 | (-14.94, 7.07, 4.38) |
| 19:41512843 | rs148377536 | S>C | B:173 | (-7.69, 8.65, 8.83) |
| 19:41512845 | I>F | B:174 | (-6.93, 4.67, 10.35) | |
| 19:41512854 | N>Y | B:177 | (-2.24, 8.15, 11.20) | |
| 19:41512872 | rs58871670 | V>I | B:183 | (7.41, 8.56, 7.78) |
| 19:41512875 | F>L | B:184 | (5.96, 12.26, 9.25) | |
| 19:41512879 | G>E | B:185 | (6.85, 9.57, 14.03) | |
| 19:41512885 | rs141530852 | R>Q | B:187 | (-1.63, 9.92, 15.91) |
| 19:41512896 | Q>K | B:191 | (-10.70, 16.27, 14.90) | |
| 19:41512901 | D>E | B:192 | (-5.51, 18.29, 12.86) | |
| 19:41512910 | F>L | B:195 | (-4.62, 14.80, 9.17) | |
| 19:41512912 | rs369101463 | L>P | B:196 | (-8.79, 16.77, 7.76) |
| 19:41512918 | rs36079186 | M>T | B:198 | (-2.70, 17.49, 3.83) |
| 19:41512932 | rs140578107 | Y>H | B:203 | (-10.94, 12.00, -2.32) |
| 19:41512942 | F>S | B:206 | (-6.06, 9.34, -5.74) | |
| 19:41512944 | rs558163100 | S>P | B:207 | (-10.81, 12.03, -7.99) |
| 19:41512953 | S>G | B:210 | (-10.77, 8.77, -11.24) | |
| 19:41512962 | rs371424910 | F>L | B:213 | (-9.30, 15.53, -18.59) |
| 19:41512963 | F>S | B:213 | (-9.30, 15.53, -18.59) | |
| 19:41512966 | G>V | B:214 | (-7.79, 11.62, -16.90) | |
| 19:41515160 | P>S | B:228 | (-5.89, 23.85, -19.40) | |
| 19:41515203 | N>S | B:242 | (6.21, 18.20, -1.44) | |
| 19:41515212 | I>T | B:245 | (7.30, 16.20, 3.02) | |
| 19:41515236 | rs373086625 COSM996884 |
R>H | B:253 | (18.15, 17.49, 7.65) |
| 19:41515247 | rs34646544 | D>N | B:257 | (20.47, 10.76, 17.51) |
| 19:41515263 | rs2279343 | K>R | B:262 | (13.07, 10.41, 15.46) |
| 19:41515274 | COSM4078401 | D>N | B:266 | (15.48, 9.96, 11.06) |
| 19:41515278 | T>N | B:267 | (16.48, 5.83, 8.40) | |
| 19:41515284 | L>R | B:269 | (18.39, 11.73, 6.68) | |
| 19:41515286 | rs145691111 | L>I | B:270 | (21.15, 8.25, 8.85) |
| 19:41515296 | E>A | B:273 | (25.28, 11.19, 6.46) | |
| 19:41515933 | rs146617126 | Q>R | B:286 | (17.04, 9.31, -5.07) |
| 19:41515941 | N>H | B:289 | (10.70, 15.21, -0.59) | |
| 19:41515943 | rs34277950 | N>K | B:289 | (10.70, 15.21, -0.59) |
| 19:41515953 | L>F | B:293 | (4.77, 12.14, -1.68) | |
| 19:41515995 | L>F | B:307 | (-11.49, -1.46, 6.07) | |
| 19:41516001 | Y>H | B:309 | (-16.36, -3.27, -0.47) | |
| 19:41516002 | Y>C | B:309 | (-16.36, -3.27, -0.47) | |
| 19:41516029 | P>L | B:318 | (-24.83, -10.72, 9.80) | |
| 19:41518205 | rs201282330 | R>G | B:323 | (-18.25, -18.12, 12.25) |
| 19:41518206 | R>T | B:323 | (-18.25, -18.12, 12.25) | |
| 19:41518208 | V>I | B:324 | (-15.44, -13.25, 13.66) | |
| 19:41518221 | rs28399499 | I>T | B:328 | (-12.37, -12.52, 18.79) |
| 19:41518223 | rs370251507 | E>K | B:329 | (-15.27, -13.95, 23.09) |
| 19:41518233 | I>T | B:332 | (-8.45, -12.32, 22.02) | |
| 19:41518235 | G>S | B:333 | (-11.24, -11.62, 24.27) | |
| 19:41518244 | rs34826503 | R>C | B:336 | (-5.73, -9.43, 24.45) |
| 19:41518248 | rs550123822 COSM375674 |
P>L | B:337 | (-5.09, -5.84, 22.89) |
| 19:41518254 | rs140552426 | E>A | B:339 | (-1.45, -9.87, 19.41) |
| 19:41518259 | rs138030127 | H>D | B:341 | (0.86, -14.87, 18.04) |
| 19:41518260 | rs553658831 | H>R | B:341 | (0.86, -14.87, 18.04) |
| 19:41518261 | rs200407252 | H>Q | B:341 | (0.86, -14.87, 18.04) |
| 19:41518264 | D>E | B:342 | (-3.99, -13.77, 17.92) | |
| 19:41518266 | rs565980641 COSM3534267 |
R>Q | B:343 | (-2.35, -13.37, 11.84) |
| 19:41518277 | P>S | B:347 | (-8.70, -19.62, 11.17) | |
| 19:41518284 | T>R | B:349 | (-10.75, -14.08, 10.88) | |
| 19:41518287 | COSM439567 | E>G | B:350 | (-6.50, -15.37, 8.48) |
| 19:41518299 | Y>C | B:354 | (-7.07, -14.05, 2.94) | |
| 19:41518301 | E>K | B:355 | (-13.60, -13.58, 0.33) | |
| 19:41518313 | F>L | B:359 | (-16.23, -9.27, -3.32) | |
| 19:41518316 | S>A | B:360 | (-12.94, -5.97, -3.14) | |
| 19:41518319 | rs375020909 | D>N | B:361 | (-10.93, -6.34, -7.34) |
| 19:41518323 | rs368366665 | L>H | B:362 | (-8.63, -2.34, -4.68) |
| 19:41518328 | COSM996889 | P>T | B:364 | (-9.10, -4.45, -11.30) |
| 19:41518335 | G>D | B:366 | (-3.29, -3.09, -11.50) | |
| 19:41518337 | rs143979776 | V>L | B:367 | (-0.06, -1.17, -11.77) |
| 19:41518341 | P>L | B:368 | (0.70, -0.15, -15.09) | |
| 19:41518343 | H>Y | B:369 | (3.74, -3.78, -15.32) | |
| 19:41518352 | T>A | B:372 | (12.54, -4.15, -20.01) | |
| 19:41518358 | H>N | B:374 | (12.79, -6.65, -27.27) | |
| 19:41518364 | rs202144306 | S>G | B:376 | (8.78, -14.81, -25.90) |
| 19:41518371 | rs200458614 COSM566298 COSM1393925 |
R>Q | B:378 | (1.29, -17.92, -23.83) |
| 19:41518376 | rs201500445 | Y>H | B:380 | (1.96, -14.13, -29.18) |
| 19:41518379 | I>L | B:381 | (7.49, -11.10, -30.48) | |
| 19:41518383 | rs200238771 | I>N | B:382 | (6.20, -8.36, -26.54) |
| 19:41518580 | D>G | B:385 | (9.19, 0.24, -24.05) | |
| 19:41518594 | rs530338921 | L>I | B:390 | (-1.34, -7.79, -14.90) |
| 19:41518598 | rs35979566 | I>N | B:391 | (-6.21, -8.42, -15.66) |
| 19:41518609 | rs569717498 | A>T | B:395 | (-7.64, -14.42, -10.64) |
| 19:41518662 | H>Q | B:412 | (-14.21, -19.17, -1.37) | |
| 19:41518663 | F>L | B:413 | (-10.02, -18.27, 1.41) | |
| 19:41518676 | N>S | B:417 | (-10.93, -29.46, 8.57) | |
| 19:41518679 | G>E | B:418 | (-11.54, -25.13, 8.96) | |
| 19:41518700 | A>D | B:425 | (-5.22, -17.18, -6.94) | |
| 19:41518707 | COSM3534272 | I>M | B:427 | (-2.68, -12.47, -6.84) |
| 19:41518708 | rs35010098 | P>T | B:428 | (-4.30, -9.23, -4.43) |
| 19:41518718 | L>S | B:431 | (2.81, -11.98, -8.48) | |
| 19:41522557 | R>Q | B:434 | (7.22, -3.53, -9.62) | |
| 19:41522569 | rs148856816 | G>V | B:438 | (2.58, -3.24, 1.72) |
| 19:41522575 | G>V | B:440 | (2.49, -6.30, 5.45) | |
| 19:41522578 | rs559298344 | I>T | B:441 | (2.03, -2.72, 6.42) |
| 19:41522581 | A>V | B:442 | (-1.87, -4.36, 4.95) | |
| 19:41522584 | rs374099483 COSM996893 |
R>H | B:443 | (-1.69, -9.56, 5.82) |
| 19:41522587 | rs368451099 COSM4078403 COSM566297 |
A>V | B:444 | (-1.65, -5.71, 9.57) |
| 19:41522589 | COSM3226493 | E>Q | B:445 | (-3.50, -1.85, 8.41) |
| 19:41522605 | F>C | B:450 | (-12.14, -6.82, 10.99) | |
| 19:41522611 | T>I | B:452 | (-9.90, -4.03, 17.51) | |
| 19:41522631 | rs3211369 | M>V | B:459 | (-21.92, -4.02, 13.20) |
| 19:41522632 | rs201028567 | M>T | B:459 | (-21.92, -4.02, 13.20) |
| 19:41522634 | A>T | B:460 | (-25.78, -1.37, 12.32) | |
| 19:41522643 | rs373442191 | V>M | B:463 | (-30.29, -1.22, 5.38) |
| 19:41522646 | rs117872433 | A>T | B:464 | (-31.47, -4.73, 4.97) |
| 19:41522670 | rs147410578 | P>S | B:472 | (-18.87, -2.10, -7.55) |
| 19:41522671 | P>L | B:472 | (-18.87, -2.10, -7.55) | |
| 19:41522683 | rs564083989 | G>D | B:476 | (-12.00, 3.37, -13.06) |
| 19:41522698 | COSM3534275 | P>L | B:481 | (-17.20, 1.04, -2.09) |
| 19:41522716 | rs149386398 | R>H | B:487 | (-25.86, 2.88, 14.08) |
| 19:41522727 | R>C | B:491 | (-20.16, -6.19, 22.06) | |
| 19:41522728 | rs148520554 | R>H | B:491 | (-20.16, -6.19, 22.06) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 19:41497314 | COSM1393921 | R>H | B:35 | (-10.84, -2.91, -36.52) |
| 19:41510225 | COSM996879 | R>C | B:120 | (15.69, 6.08, -10.12) |
| 19:41512841 | COSM3756813 | Q>H | B:172 | (-9.54, 7.78, 4.31) |
| 19:41512931 | COSM712821 | F>L | B:202 | (-3.28, 12.49, -0.92) |
| 19:41515236 | COSM996884 | R>H | B:253 | (18.15, 17.49, 7.65) |
| 19:41515256 | COSM566299 | A>T | B:260 | (18.25, 7.41, 17.63) |
| 19:41515263 | COSM4131883 | K>R | B:262 | (13.07, 10.41, 15.46) |
| 19:41515901 | COSM996885 | E>D | B:275 | (25.57, 6.43, 0.35) |
| 19:41515926 | COSM2151063 | S>C | B:284 | (22.24, 10.52, -3.18) |
| 19:41516031 | COSM1612289 | H>D | B:319 | (-25.37, -14.60, 10.53) |
| 19:41518600 | COSM996890 | L>M | B:392 | (-5.43, -8.92, -10.70) |
| 19:41518615 | COSM1721780 | H>Y | B:397 | (-13.31, -13.15, -9.95) |
| 19:41518645 | COSM1304625 | A>S | B:407 | (-19.99, -14.44, -4.05) |
| 19:41522715 | COSM4986109 | R>C | B:487 | (-25.86, 2.88, 14.08) |