General Structure Information
| PDB ID | 3otq |
| HGNC Gene Label(s) | EPHX2 |
| Structure Name | soluble epoxide hydrolase in complex with pyrazole antagonist |
| Resolution | 3.0Å |
| Reference | AUTH H.Y.LO,C.C.MAN,R.W.FLECK,N.A.FARROW,R.H.INGRAHAM,A.KUKULKA,AUTH 2 J.R.PROUDFOOT,R.BETAGERI,T.KIRRANE,U.PATEL,R.SHARMA,AUTH 3 M.A.HOERMANN,A.KABCENELL,S.D.LOMBAERTTITL SUBSTITUTED PYRAZOLES AS NOVEL SEH ANTAGONIST: INVESTIGATIONTITL 2 OF KEY BINDING INTERACTIONS WITHIN THE CATALYTIC DOMAIN.REF BIOORG.MED.CHEM.LETT. V. 20 6379 2010REFN ISSN 0960-894XPMID 20934334DOI 10.1016/J.BMCL.2010.09.095 |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 545 |
| Number Of SNVs | 164 |
| Number Of Permutations | 46658 |
| Optimal Distance Threshold | 32.0 |
| K Statistic | 0.428 |
| p-value | 0.066 |
COSMIC
| Number Of Residues | 545 |
| Number Of SNVs | 7 |
| Number Of Permutations | 2487 |
| Optimal Distance Threshold | 27.0 |
| K Statistic | 0.095 |
| p-value | 0.148 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 164 |
| Number Of COSMIC SNVs | 7 |
| Optimal Distance Threshold | 27.0 |
| K Statistic | -0.227 |
| p-value | 0.589 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 8:27348739 | A>E | A:5 | (40.97, -6.18, 96.07) | |
| 8:27348744 | V>F | A:7 | (38.00, -0.33, 93.76) | |
| 8:27348745 | V>G | A:7 | (38.00, -0.33, 93.76) | |
| 8:27348749 | F>L | A:8 | (41.28, 2.43, 92.45) | |
| 8:27348756 | D>N | A:11 | (37.04, 12.01, 89.24) | |
| 8:27348787 | rs72473930 | G>A | A:21 | (35.51, 21.20, 91.36) |
| 8:27348792 | L>F | A:23 | (31.15, 23.36, 89.81) | |
| 8:27348802 | T>M | A:26 | (33.97, 28.36, 87.64) | |
| 8:27358448 | rs377050303 | L>P | A:36 | (25.31, 28.32, 92.16) |
| 8:27358456 | rs561926285 | D>H | A:39 | (23.14, 23.49, 93.81) |
| 8:27358457 | D>G | A:39 | (23.14, 23.49, 93.81) | |
| 8:27358490 | T>I | A:50 | (23.08, 14.55, 86.88) | |
| 8:27358496 | rs72475803 | R>Q | A:52 | (17.88, 10.94, 83.31) |
| 8:27358502 | M>K | A:54 | (25.39, 9.10, 86.02) | |
| 8:27358505 | rs41507953 | K>R | A:55 | (21.15, 5.81, 85.95) |
| 8:27358510 | E>K | A:57 | (18.55, 7.65, 81.58) | |
| 8:27358511 | E>A | A:57 | (18.55, 7.65, 81.58) | |
| 8:27358517 | rs188742114 | T>K | A:59 | (23.39, 12.16, 76.09) |
| 8:27361121 | W>R | A:63 | (23.77, 17.51, 82.16) | |
| 8:27361126 | I>M | A:64 | (24.76, 20.39, 78.80) | |
| 8:27361135 | M>I | A:67 | (23.28, 22.41, 84.33) | |
| 8:27361148 | rs536862077 | R>G | A:72 | (18.57, 29.41, 83.40) |
| 8:27361149 | R>M | A:72 | (18.57, 29.41, 83.40) | |
| 8:27361154 | C>R | A:74 | (20.28, 28.13, 91.26) | |
| 8:27361160 | rs374746559 | E>K | A:76 | (15.88, 32.95, 89.61) |
| 8:27361162 | E>D | A:76 | (15.88, 32.95, 89.61) | |
| 8:27361166 | rs372597795 | A>T | A:78 | (19.65, 33.74, 95.21) |
| 8:27361178 | rs376705396 | L>V | A:82 | (23.93, 34.70, 84.52) |
| 8:27361179 | rs369978603 | L>H | A:82 | (23.93, 34.70, 84.52) |
| 8:27361182 | P>L | A:83 | (27.12, 35.81, 82.56) | |
| 8:27361192 | F>L | A:86 | (27.19, 30.19, 82.22) | |
| 8:27361194 | rs573493340 | S>F | A:87 | (29.62, 27.81, 78.82) |
| 8:27361200 | rs146918355 | K>R | A:89 | (30.47, 23.49, 76.17) |
| 8:27361203 | E>A | A:90 | (34.00, 26.74, 77.68) | |
| 8:27361218 | COSM1098746 | A>V | A:95 | (37.87, 20.15, 82.88) |
| 8:27361221 | I>N | A:96 | (37.21, 17.01, 80.45) | |
| 8:27361241 | rs17057255 | R>C | A:103 | (50.66, 8.61, 85.78) |
| 8:27361244 | P>S | A:104 | (51.10, 7.89, 91.59) | |
| 8:27361267 | M>I | A:111 | (52.17, -3.61, 92.57) | |
| 8:27361276 | K>N | A:114 | (53.35, -6.81, 90.07) | |
| 8:27361279 | rs372389894 | K>N | A:115 | (52.56, -8.09, 94.51) |
| 8:27362508 | D>Y | A:128 | (31.16, 11.77, 76.00) | |
| 8:27362511 | D>N | A:129 | (27.52, 13.11, 72.87) | |
| 8:27362514 | rs146853169 | R>C | A:130 | (31.95, 15.91, 74.55) |
| 8:27362521 | rs376426011 | E>V | A:132 | (34.95, 17.78, 72.62) |
| 8:27362522 | E>D | A:132 | (34.95, 17.78, 72.62) | |
| 8:27362526 | D>H | A:134 | (38.59, 11.40, 71.32) | |
| 8:27362547 | rs369553898 | C>R | A:141 | (42.12, 3.66, 76.83) |
| 8:27362560 | M>R | A:145 | (45.45, -1.03, 79.42) | |
| 8:27362577 | rs149400070 | I>L | A:151 | (32.14, -0.74, 86.81) |
| 8:27362578 | rs372428836 | I>T | A:151 | (32.14, -0.74, 86.81) |
| 8:27362584 | COSM1098748 | S>L | A:153 | (27.28, 4.34, 85.60) |
| 8:27362587 | rs57699806 | C>Y | A:154 | (26.45, 4.81, 81.97) |
| 8:27362595 | rs144205298 | G>R | A:157 | (22.18, 1.67, 85.57) |
| 8:27362607 | P>S | A:161 | (25.44, 6.01, 95.61) | |
| 8:27362611 | E>A | A:162 | (22.50, 3.14, 93.68) | |
| 8:27362613 | rs190054509 | P>S | A:163 | (23.51, 0.05, 97.45) |
| 8:27362623 | rs146049019 | Y>C | A:166 | (28.34, -0.20, 96.06) |
| 8:27362626 | rs140021176 | K>R | A:167 | (26.05, -6.73, 95.95) |
| 8:27362638 | D>V | A:171 | (28.89, -10.17, 91.56) | |
| 8:27362646 | K>Q | A:174 | (34.28, -13.69, 91.20) | |
| 8:27362649 | rs375747773 | A>T | A:175 | (34.20, -11.01, 96.24) |
| 8:27362652 | S>R | A:176 | (34.14, -10.67, 99.96) | |
| 8:27362653 | S>I | A:176 | (34.14, -10.67, 99.96) | |
| 8:27364389 | rs201277862 | V>I | A:180 | (37.88, -5.41, 99.05) |
| 8:27364410 | G>R | A:187 | (31.80, 9.59, 101.22) | |
| 8:27364416 | rs376158103 | N>D | A:189 | (30.11, 7.49, 97.30) |
| 8:27364428 | A>T | A:193 | (31.49, -0.27, 101.57) | |
| 8:27364429 | A>G | A:193 | (31.49, -0.27, 101.57) | |
| 8:27364431 | rs369213590 | R>C | A:194 | (32.42, 1.97, 105.64) |
| 8:27364432 | rs151005275 | R>H | A:194 | (32.42, 1.97, 105.64) |
| 8:27364434 | D>N | A:195 | (27.82, 0.28, 105.72) | |
| 8:27364462 | rs200323916 | Q>R | A:204 | (41.66, 14.31, 101.46) |
| 8:27364486 | E>G | A:212 | (45.51, 4.97, 104.30) | |
| 8:27364488 | rs147798306 | L>V | A:213 | (46.79, 1.20, 100.21) |
| 8:27364503 | rs368915541 | G>R | A:218 | (51.55, -4.99, 102.97) |
| 8:27369357 | L>P | A:222 | (54.50, 5.55, 98.50) | |
| 8:27369363 | T>I | A:224 | (58.25, 2.63, 94.64) | |
| 8:27369366 | rs72475821 | P>L | A:225 | (60.87, 1.63, 92.68) |
| 8:27369396 | rs537787758 | S>T | A:235 | (47.35, -12.74, 73.65) |
| 8:27369413 | rs554529874 | Y>H | A:241 | (49.39, -12.45, 59.54) |
| 8:27369414 | Y>C | A:241 | (49.39, -12.45, 59.54) | |
| 8:27369416 | rs574326427 COSM1331045 |
V>M | A:242 | (51.30, -9.56, 54.43) |
| 8:27369422 | V>L | A:244 | (55.18, -10.30, 50.04) | |
| 8:27373236 | P>H | A:246 | (54.87, -16.44, 46.33) | |
| 8:27373241 | V>F | A:248 | (57.01, -14.85, 51.55) | |
| 8:27373244 | R>C | A:249 | (53.03, -15.53, 56.25) | |
| 8:27373245 | rs137956640 | R>H | A:249 | (53.03, -15.53, 56.25) |
| 8:27373269 | S>Y | A:257 | (46.74, 5.58, 65.87) | |
| 8:27373271 | rs546857733 | G>S | A:258 | (48.72, 7.09, 62.95) |
| 8:27373274 | rs143412145 | P>S | A:259 | (51.71, 8.24, 62.42) |
| 8:27373277 | A>S | A:260 | (53.54, 4.68, 60.55) | |
| 8:27373295 | rs201904403 | G>R | A:266 | (66.98, -8.56, 65.39) |
| 8:27373299 | F>S | A:267 | (70.64, -12.64, 65.18) | |
| 8:27373304 | COSM3834509 | E>K | A:269 | (65.61, -10.50, 68.53) |
| 8:27373307 | S>C | A:270 | (61.00, -10.90, 67.92) | |
| 8:27373308 | S>N | A:270 | (61.00, -10.90, 67.92) | |
| 8:27373312 | W>C | A:271 | (56.22, -9.28, 68.57) | |
| 8:27373858 | G>S | A:285 | (50.81, 8.73, 68.36) | |
| 8:27373865 | rs751141 | R>Q | A:287 | (49.55, 2.45, 62.14) |
| 8:27373867 | V>L | A:288 | (53.21, 0.26, 66.10) | |
| 8:27373876 | M>V | A:291 | (57.91, -6.39, 61.60) | |
| 8:27373877 | M>R | A:291 | (57.91, -6.39, 61.60) | |
| 8:27373879 | D>N | A:292 | (58.11, -11.09, 62.70) | |
| 8:27373882 | M>L | A:293 | (61.94, -9.44, 60.40) | |
| 8:27373892 | Y>C | A:296 | (63.66, -14.05, 62.60) | |
| 8:27373897 | rs558835876 | E>K | A:298 | (54.16, -16.06, 63.01) |
| 8:27373906 | A>P | A:301 | (61.39, -19.57, 56.42) | |
| 8:27373915 | E>K | A:304 | (66.47, -20.18, 49.84) | |
| 8:27378418 | rs139709260 | D>N | A:322 | (52.69, -1.48, 48.51) |
| 8:27379943 | L>V | A:326 | (51.23, 2.34, 53.86) | |
| 8:27379952 | A>T | A:329 | (57.02, 4.73, 56.98) | |
| 8:27379971 | D>G | A:335 | (71.06, -5.83, 64.92) | |
| 8:27379972 | rs541480501 | D>E | A:335 | (71.06, -5.83, 64.92) |
| 8:27379977 | G>V | A:337 | (67.31, -3.74, 61.42) | |
| 8:27379988 | V>M | A:341 | (66.56, 0.88, 58.06) | |
| 8:27379991 | W>R | A:342 | (70.79, 3.40, 58.30) | |
| 8:27380001 | A>V | A:345 | (66.87, 5.32, 53.12) | |
| 8:27380003 | L>V | A:346 | (70.32, 4.42, 50.82) | |
| 8:27380010 | Y>C | A:348 | (63.32, 1.87, 48.20) | |
| 8:27380015 | E>K | A:350 | (60.48, 7.81, 48.03) | |
| 8:27382880 | A>T | A:354 | (61.95, 8.20, 59.16) | |
| 8:27382881 | rs76549048 | A>V | A:354 | (61.95, 8.20, 59.16) |
| 8:27382896 | N>S | A:359 | (73.23, -0.24, 68.37) | |
| 8:27382901 | rs201276018 | P>S | A:361 | (76.36, 1.49, 62.17) |
| 8:27382907 | rs183718541 | I>V | A:363 | (79.16, 1.66, 57.65) |
| 8:27382910 | P>T | A:364 | (80.28, 3.02, 54.10) | |
| 8:27382925 | rs72475894 | M>V | A:369 | (88.95, -4.13, 50.34) |
| 8:27382946 | K>E | A:376 | (89.03, -12.06, 57.88) | |
| 8:27382949 | rs148677997 | A>T | A:377 | (89.65, -6.84, 59.98) |
| 8:27382974 | rs144419553 | L>P | A:385 | (83.91, -16.58, 60.36) |
| 8:27394329 | rs200503145 | N>S | A:400 | (68.91, -25.86, 74.31) |
| 8:27394330 | rs186308307 | N>K | A:400 | (68.91, -25.86, 74.31) |
| 8:27394337 | R>W | A:403 | (72.68, -23.47, 76.45) | |
| 8:27394338 | R>Q | A:403 | (72.68, -23.47, 76.45) | |
| 8:27394367 | rs145160595 | D>N | A:413 | (77.54, -7.47, 83.42) |
| 8:27396177 | S>T | A:415 | (78.51, -12.52, 80.05) | |
| 8:27396185 | S>A | A:418 | (83.73, -14.96, 74.22) | |
| 8:27396186 | COSM1098754 COSM3647818 |
S>Y | A:418 | (83.73, -14.96, 74.22) |
| 8:27396192 | H>R | A:420 | (86.95, -13.43, 71.98) | |
| 8:27396198 | rs147584733 | V>A | A:422 | (84.39, -18.94, 68.13) |
| 8:27396207 | rs368358038 | A>V | A:425 | (86.45, -22.80, 69.77) |
| 8:27398073 | G>R | A:427 | (81.86, -22.49, 69.20) | |
| 8:27398080 | rs369819456 | F>S | A:429 | (76.86, -21.79, 73.21) |
| 8:27398085 | N>D | A:431 | (83.83, -22.52, 77.15) | |
| 8:27398092 | rs148997097 | P>L | A:433 | (76.79, -22.60, 80.96) |
| 8:27398094 | rs541962479 | E>K | A:434 | (74.89, -27.29, 79.01) |
| 8:27398109 | S>R | A:439 | (69.04, -12.38, 82.86) | |
| 8:27398118 | rs562224130 | V>L | A:442 | (64.77, -11.51, 81.03) |
| 8:27398128 | E>G | A:445 | (57.86, -16.67, 81.46) | |
| 8:27398143 | rs527892120 COSM3699037 |
Y>C | A:450 | (62.32, -14.61, 72.44) |
| 8:27398994 | P>A | A:462 | (68.00, -16.37, 61.14) | |
| 8:27399010 | rs201410558 | R>Q | A:467 | (74.66, -17.54, 55.83) |
| 8:27399012 | N>H | A:468 | (74.08, -12.41, 51.89) | |
| 8:27399015 | M>V | A:469 | (78.85, -10.60, 53.27) | |
| 8:27399016 | M>T | A:469 | (78.85, -10.60, 53.27) | |
| 8:27399019 | rs68053459 | E>G | A:470 | (80.33, -10.41, 48.19) |
| 8:27399031 | rs202158116 | K>T | A:474 | (78.22, -6.47, 44.64) |
| 8:27399037 | A>G | A:476 | (76.20, -0.99, 48.51) | |
| 8:27399040 | C>Y | A:477 | (78.52, 0.13, 45.87) | |
| 8:27399046 | S>T | A:479 | (75.09, 3.72, 47.46) | |
| 8:27401266 | I>V | A:484 | (70.75, 9.75, 54.21) | |
| 8:27401284 | COSM3768762 | M>L | A:490 | (72.51, 6.66, 65.50) |
| 8:27401291 | T>M | A:492 | (74.83, 4.79, 70.59) | |
| 8:27401293 | rs542880196 | A>S | A:493 | (75.54, 1.68, 73.25) |
| 8:27401308 | V>M | A:498 | (79.67, -6.01, 68.44) | |
| 8:27401314 | rs200277522 | V>I | A:500 | (80.87, 0.02, 69.31) |
| 8:27401325 | rs572922758 | M>I | A:503 | (81.44, 1.43, 64.07) |
| 8:27401327 | S>F | A:504 | (78.95, 5.82, 64.36) | |
| 8:27401332 | rs375528474 | H>N | A:506 | (83.20, 8.82, 60.30) |
| 8:27401333 | H>R | A:506 | (83.20, 8.82, 60.30) | |
| 8:27401339 | E>A | A:508 | (77.84, 12.91, 60.41) | |
| 8:27401344 | W>G | A:510 | (78.13, 8.95, 53.37) | |
| 8:27401704 | I>T | A:511 | (73.70, 11.13, 57.58) | |
| 8:27401706 | COSM3929526 | P>T | A:512 | (74.20, 15.59, 56.86) |
| 8:27401709 | H>Y | A:513 | (71.00, 17.27, 58.56) | |
| 8:27401710 | rs150813461 | H>R | A:513 | (71.00, 17.27, 58.56) |
| 8:27401719 | rs139248331 | R>M | A:516 | (74.65, 10.79, 66.94) |
| 8:27401721 | G>R | A:517 | (72.03, 8.88, 70.64) | |
| 8:27401736 | C>R | A:522 | (73.65, -0.09, 77.31) | |
| 8:27401737 | C>Y | A:522 | (73.65, -0.09, 77.31) | |
| 8:27401755 | M>T | A:528 | (65.39, -5.99, 76.62) | |
| 8:27401968 | rs377238003 | E>K | A:533 | (66.13, 5.27, 78.48) |
| 8:27401976 | N>K | A:535 | (60.63, 4.81, 75.03) | |
| 8:27401979 | Q>H | A:536 | (62.75, 10.05, 76.33) | |
| 8:27402007 | rs147425478 | A>P | A:546 | (58.54, 12.81, 61.73) |
| 8:27402010 | R>W | A:547 | (53.51, 13.53, 63.73) | |
| 8:27402011 | rs552123183 COSM3358253 |
R>Q | A:547 | (53.51, 13.53, 63.73) |
| 8:27402013 | rs189341740 | N>D | A:548 | (56.29, 17.69, 60.42) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 8:27358505 | COSM3763287 | K>R | A:55 | (21.15, 5.81, 85.95) |
| 8:27362584 | COSM1098748 | S>L | A:153 | (27.28, 4.34, 85.60) |
| 8:27364474 | COSM1098751 | T>M | A:208 | (47.76, 9.59, 102.92) |
| 8:27373865 | COSM3763288 | R>Q | A:287 | (49.55, 2.45, 62.14) |
| 8:27382881 | COSM310910 | A>V | A:354 | (61.95, 8.20, 59.16) |
| 8:27382971 | COSM1623883 | Q>L | A:384 | (80.56, -12.23, 61.53) |
| 8:27398124 | COSM422165 | E>K | A:444 | (61.90, -18.34, 82.45) |