General Structure Information
| PDB ID | 1r1j |
| HGNC Gene Label(s) | MME |
| Structure Name | structural analysis of neprilysin with various specific and potent inhibitors |
| Resolution | 2.35Å |
| Reference | AUTH C.OEFNER,B.P.ROQUES,M.C.FOURNIE-ZALUSKI,G.E.DALETITL STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC ANDTITL 2 POTENT INHIBITORS.REF ACTA CRYSTALLOGR.,SECT.D V. 60 392 2004REFN ISSN 0907-4449PMID 14747736DOI 10.1107/S0907444903027410 |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 696 |
| Number Of SNVs | 179 |
| Number Of Permutations | 70263 |
| Optimal Distance Threshold | 6.0 |
| K Statistic | 0.007 |
| p-value | 0.883 |
COSMIC
| Number Of Residues | 696 |
| Number Of SNVs | 22 |
| Number Of Permutations | 21465 |
| Optimal Distance Threshold | 11.0 |
| K Statistic | 0.017 |
| p-value | 0.541 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 179 |
| Number Of COSMIC SNVs | 23 |
| Optimal Distance Threshold | 10.0 |
| K Statistic | -0.023 |
| p-value | 0.557 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 3:154832789 | rs199791655 | R>Q | A:67 | (34.76, 53.46, 49.68) |
| 3:154832803 | rs149683309 | M>V | A:72 | (42.64, 50.04, 51.99) |
| 3:154832818 | rs369006679 | E>K | A:77 | (53.39, 46.71, 48.14) |
| 3:154832825 | C>Y | A:79 | (53.43, 46.25, 43.71) | |
| 3:154832837 | F>S | A:83 | (42.24, 41.66, 45.82) | |
| 3:154832839 | K>E | A:84 | (45.70, 41.28, 49.85) | |
| 3:154832851 | G>R | A:88 | (41.49, 43.52, 52.75) | |
| 3:154832866 | rs184108383 | R>G | A:93 | (36.31, 45.04, 58.26) |
| 3:154832867 | rs201870091 | R>H | A:93 | (36.31, 45.04, 58.26) |
| 3:154832885 | T>I | A:99 | (21.86, 33.52, 51.02) | |
| 3:154832887 | S>G | A:100 | (25.36, 34.27, 49.15) | |
| 3:154832888 | S>I | A:100 | (25.36, 34.27, 49.15) | |
| 3:154832893 | R>C | A:102 | (29.12, 36.87, 43.91) | |
| 3:154832894 | rs574482291 COSM71659 COSM1420143 |
R>H | A:102 | (29.12, 36.87, 43.91) |
| 3:154832899 | G>S | A:104 | (30.34, 42.25, 47.50) | |
| 3:154832907 | rs200172402 | F>L | A:106 | (28.06, 44.61, 41.35) |
| 3:154832910 | rs370203542 | D>E | A:107 | (26.77, 41.31, 45.15) |
| 3:154832911 | I>V | A:108 | (26.48, 45.06, 48.69) | |
| 3:154832932 | COSM1670660 | V>I | A:115 | (15.61, 47.73, 49.84) |
| 3:154832935 | rs201338166 | V>I | A:116 | (14.22, 50.52, 46.84) |
| 3:154834287 | K>N | A:125 | (0.59, 54.65, 46.24) | |
| 3:154834298 | rs200313798 | I>T | A:129 | (-0.82, 53.47, 36.98) |
| 3:154834307 | V>G | A:132 | (2.00, 49.99, 39.53) | |
| 3:154834333 | S>A | A:141 | (1.47, 36.86, 44.83) | |
| 3:154834348 | S>A | A:146 | (-0.15, 30.92, 53.28) | |
| 3:154834458 | rs200157166 | I>V | A:148 | (2.02, 29.28, 48.05) |
| 3:154834459 | I>T | A:148 | (2.02, 29.28, 48.05) | |
| 3:154834465 | rs199930825 | S>N | A:150 | (-2.38, 25.79, 50.99) |
| 3:154834470 | G>S | A:152 | (1.01, 22.53, 47.26) | |
| 3:154834476 | E>K | A:154 | (-2.77, 21.78, 42.59) | |
| 3:154834488 | K>E | A:158 | (-3.83, 20.18, 36.79) | |
| 3:154834489 | rs144486590 | K>R | A:158 | (-3.83, 20.18, 36.79) |
| 3:154834491 | L>V | A:159 | (0.88, 22.04, 34.33) | |
| 3:154834503 | I>V | A:163 | (3.80, 18.69, 29.63) | |
| 3:154834505 | rs148441836 | I>M | A:163 | (3.80, 18.69, 29.63) |
| 3:154834506 | Y>H | A:164 | (2.45, 15.38, 25.84) | |
| 3:154834509 | G>R | A:165 | (3.93, 14.36, 31.45) | |
| 3:154834527 | rs200164975 COSM3588996 |
E>Q | A:171 | (-0.89, 6.07, 36.54) |
| 3:154834529 | rs201333758 | E>D | A:171 | (-0.89, 6.07, 36.54) |
| 3:154834680 | A>S | A:186 | (6.60, 17.63, 23.12) | |
| 3:154834692 | rs202191484 | L>V | A:190 | (7.76, 22.22, 26.75) |
| 3:154834693 | rs575160886 | L>R | A:190 | (7.76, 22.22, 26.75) |
| 3:154834710 | COSM1040248 | K>E | A:196 | (11.83, 24.90, 29.09) |
| 3:154834722 | I>F | A:200 | (15.84, 20.66, 19.65) | |
| 3:154834723 | rs374541166 | I>T | A:200 | (15.84, 20.66, 19.65) |
| 3:154834768 | rs371845470 | V>E | A:215 | (15.42, 34.62, 12.10) |
| 3:154834774 | rs142506311 | H>R | A:217 | (17.60, 31.30, 15.39) |
| 3:154836537 | rs200489145 | I>M | A:218 | (18.01, 25.63, 15.53) |
| 3:154836545 | P>L | A:221 | (20.29, 22.29, 24.41) | |
| 3:154836554 | rs147564881 | G>A | A:224 | (20.86, 21.23, 34.40) |
| 3:154836557 | L>P | A:225 | (23.96, 20.36, 35.48) | |
| 3:154836575 | rs189540914 | Y>C | A:231 | (26.57, 16.45, 32.98) |
| 3:154836583 | rs199894624 | T>A | A:234 | (34.27, 13.22, 38.50) |
| 3:154836593 | rs202126163 | Y>C | A:237 | (32.48, 18.53, 38.43) |
| 3:154855940 | rs199818584 | R>H | A:256 | (4.17, 8.32, 42.32) |
| 3:154855943 | Q>R | A:257 | (3.88, 10.86, 48.36) | |
| 3:154855949 | rs200279069 | E>G | A:259 | (-1.51, 12.00, 42.69) |
| 3:154855963 | D>N | A:264 | (9.67, 1.33, 43.66) | |
| 3:154855970 | N>T | A:266 | (14.76, 0.33, 42.78) | |
| 3:154855975 | L>V | A:268 | (12.13, 6.34, 41.30) | |
| 3:154855987 | rs554131206 | M>V | A:272 | (15.48, 9.52, 37.22) |
| 3:154855989 | COSM3774663 | M>I | A:272 | (15.48, 9.52, 37.22) |
| 3:154856024 | rs200961860 CM106682 |
N>S | A:284 | (29.62, 14.73, 24.95) |
| 3:154857984 | rs202094946 | T>M | A:286 | (27.25, 19.90, 23.54) |
| 3:154858005 | rs201002280 | N>S | A:293 | (34.36, 31.89, 19.84) |
| 3:154858011 | P>L | A:295 | (30.43, 34.83, 14.98) | |
| 3:154858020 | rs377067895 | L>P | A:298 | (27.84, 29.89, 15.14) |
| 3:154858029 | K>T | A:301 | (20.89, 31.39, 6.52) | |
| 3:154858035 | rs1042290 | T>I | A:303 | (16.43, 25.72, 3.91) |
| 3:154858044 | Q>R | A:306 | (18.96, 23.08, 3.49) | |
| 3:154858054 | rs535222266 COSM445838 |
N>K | A:309 | (17.90, 16.64, 3.45) |
| 3:154858058 | COSM1617093 COSM3365056 |
F>V | A:311 | (20.89, 18.28, 10.21) |
| 3:154858064 | L>V | A:313 | (16.42, 13.14, 13.95) | |
| 3:154858065 | L>P | A:313 | (16.42, 13.14, 13.95) | |
| 3:154858068 | E>G | A:314 | (14.40, 7.60, 14.20) | |
| 3:154858069 | E>D | A:314 | (14.40, 7.60, 14.20) | |
| 3:154858073 | N>D | A:316 | (9.46, 6.64, 19.46) | |
| 3:154858074 | rs191787277 | N>S | A:316 | (9.46, 6.64, 19.46) |
| 3:154859819 | COSM3945018 | T>S | A:332 | (0.88, 29.40, 18.85) |
| 3:154859822 | COSM728621 | V>M | A:333 | (1.59, 33.14, 16.38) |
| 3:154859823 | rs201930789 | V>A | A:333 | (1.59, 33.14, 16.38) |
| 3:154859838 | T>I | A:338 | (6.89, 26.51, 4.15) | |
| 3:154859849 | D>Y | A:342 | (15.52, 31.13, 5.71) | |
| 3:154859855 | rs61758194 | V>I | A:344 | (20.06, 30.40, 11.93) |
| 3:154859858 | V>F | A:345 | (21.86, 26.31, 12.25) | |
| 3:154859859 | rs145615985 | V>D | A:345 | (21.86, 26.31, 12.25) |
| 3:154859862 | rs138218277 | Y>C | A:346 | (23.62, 29.60, 16.15) |
| 3:154859880 | rs200567355 | T>N | A:352 | (24.81, 15.29, 13.36) |
| 3:154859884 | K>N | A:353 | (26.91, 14.80, 17.35) | |
| 3:154859892 | COSM1693635 | P>L | A:356 | (22.96, 8.48, 17.19) |
| 3:154859915 | R>G | A:364 | (8.83, 6.28, 30.42) | |
| 3:154860028 | D>G | A:365 | (13.47, 7.51, 28.54) | |
| 3:154860030 | COSM171626 | L>I | A:366 | (13.03, 11.37, 25.62) |
| 3:154860039 | L>V | A:369 | (14.92, 14.95, 30.35) | |
| 3:154860043 | rs200216802 | M>T | A:370 | (11.53, 16.40, 28.02) |
| 3:154860064 | rs201810771 | D>V | A:377 | (12.50, 25.68, 36.79) |
| 3:154860079 | L>R | A:382 | (5.28, 24.84, 44.77) | |
| 3:154860082 | S>N | A:383 | (5.13, 23.86, 48.88) | |
| 3:154860085 | rs200791566 COSM207009 |
R>Q | A:384 | (9.14, 25.39, 52.17) |
| 3:154860108 | A>P | A:392 | (21.40, 19.92, 47.87) | |
| 3:154860114 | rs201459271 | R>C | A:394 | (20.65, 25.55, 47.28) |
| 3:154860115 | rs199804325 COSM240703 |
R>H | A:394 | (20.65, 25.55, 47.28) |
| 3:154861239 | Y>C | A:398 | (24.36, 28.08, 43.23) | |
| 3:154861271 | rs369531733 COSM4114666 |
R>C | A:409 | (12.64, 34.79, 46.51) |
| 3:154861272 | rs201238171 | R>H | A:409 | (12.64, 34.79, 46.51) |
| 3:154861292 | G>R | A:416 | (11.87, 40.82, 35.25) | |
| 3:154861293 | rs199910677 COSM136382 |
G>E | A:416 | (11.87, 40.82, 35.25) |
| 3:154861299 | rs200191547 | M>T | A:418 | (6.79, 44.31, 35.39) |
| 3:154861302 | E>G | A:419 | (11.97, 45.58, 32.64) | |
| 3:154861308 | A>D | A:421 | (7.24, 49.28, 35.87) | |
| 3:154861335 | A>G | A:430 | (16.52, 56.56, 43.52) | |
| 3:154861350 | S>N | A:435 | (22.86, 61.82, 36.56) | |
| 3:154861356 | H>R | A:437 | (22.05, 65.54, 31.75) | |
| 3:154862151 | E>K | A:440 | (24.85, 62.25, 28.36) | |
| 3:154862154 | D>H | A:441 | (30.01, 64.58, 28.85) | |
| 3:154862161 | rs150782596 | I>T | A:443 | (29.48, 58.47, 27.19) |
| 3:154862163 | A>S | A:444 | (31.57, 61.58, 24.86) | |
| 3:154862178 | rs147133542 | V>F | A:449 | (39.62, 58.39, 23.97) |
| 3:154862220 | rs200864897 COSM358007 COSM3846566 |
E>K | A:463 | (42.21, 50.17, 5.60) |
| 3:154864934 | rs375302479 | A>G | A:472 | (32.10, 54.44, 17.40) |
| 3:154864957 | rs201180963 | G>S | A:480 | (19.05, 55.10, 32.96) |
| 3:154864961 | rs201936237 | Y>S | A:481 | (15.07, 57.16, 32.92) |
| 3:154864963 | COSM3589004 COSM728616 |
P>S | A:482 | (13.32, 54.97, 29.51) |
| 3:154864966 | D>H | A:483 | (11.92, 59.79, 29.58) | |
| 3:154864967 | D>V | A:483 | (11.92, 59.79, 29.58) | |
| 3:154864972 | I>V | A:485 | (9.07, 54.53, 32.04) | |
| 3:154864985 | D>G | A:489 | (0.96, 56.54, 31.83) | |
| 3:154864987 | N>D | A:490 | (-1.46, 55.07, 27.79) | |
| 3:154864991 | K>I | A:491 | (4.17, 52.92, 26.12) | |
| 3:154865005 | rs200308207 | Y>H | A:496 | (2.79, 45.51, 31.62) |
| 3:154865011 | rs201292663 | E>K | A:498 | (-2.73, 40.80, 26.90) |
| 3:154866341 | L>F | A:499 | (-0.81, 40.38, 31.89) | |
| 3:154866346 | Y>C | A:501 | (-0.72, 39.36, 37.35) | |
| 3:154866352 | rs201239248 | E>V | A:503 | (-3.54, 39.19, 45.22) |
| 3:154866361 | rs367899772 | Y>C | A:506 | (3.73, 33.19, 42.25) |
| 3:154866366 | rs200715594 | E>K | A:508 | (-1.59, 30.24, 38.55) |
| 3:154866367 | E>G | A:508 | (-1.59, 30.24, 38.55) | |
| 3:154866372 | I>V | A:510 | (4.38, 31.95, 37.33) | |
| 3:154866376 | rs372080418 | I>N | A:511 | (2.40, 29.82, 34.11) |
| 3:154866396 | Q>E | A:518 | (7.53, 32.20, 24.18) | |
| 3:154866400 | S>T | A:519 | (3.58, 34.56, 22.45) | |
| 3:154866421 | rs202008298 | R>Q | A:526 | (7.57, 36.91, 9.32) |
| 3:154866430 | rs144240445 | V>G | A:529 | (13.95, 45.04, 15.31) |
| 3:154866438 | D>N | A:532 | (13.26, 52.73, 20.34) | |
| 3:154866439 | D>G | A:532 | (13.26, 52.73, 20.34) | |
| 3:154878187 | S>N | A:536 | (18.13, 47.04, 30.61) | |
| 3:154878190 | G>A | A:537 | (16.46, 47.81, 32.82) | |
| 3:154878201 | V>I | A:541 | (23.53, 46.76, 39.33) | |
| 3:154878217 | rs200973878 COSM728613 |
S>F | A:546 | (24.19, 45.06, 21.68) |
| 3:154884730 | rs202024179 COSM207012 |
A>D | A:566 | (28.44, 64.60, 40.98) |
| 3:154884735 | Q>K | A:568 | (32.60, 61.08, 43.51) | |
| 3:154884744 | rs113051376 | S>A | A:571 | (39.22, 60.13, 40.46) |
| 3:154884751 | N>S | A:573 | (33.56, 59.23, 38.65) | |
| 3:154884757 | G>E | A:575 | (37.42, 54.53, 37.64) | |
| 3:154884760 | rs371862411 | G>D | A:576 | (34.45, 53.74, 37.37) |
| 3:154884765 | G>S | A:578 | (34.42, 55.08, 33.05) | |
| 3:154884769 | M>T | A:579 | (35.81, 51.07, 33.66) | |
| 3:154884770 | M>I | A:579 | (35.81, 51.07, 33.66) | |
| 3:154884777 | G>R | A:582 | (34.71, 51.17, 27.95) | |
| 3:154884783 | COSM245723 | E>K | A:584 | (30.12, 48.10, 27.90) |
| 3:154884790 | rs201628363 | T>I | A:586 | (35.70, 47.64, 24.10) |
| 3:154884808 | rs200657784 | N>S | A:592 | (31.54, 38.90, 19.21) |
| 3:154886299 | rs560995914 | D>G | A:599 | (24.30, 49.03, 11.14) |
| 3:154886310 | rs200308077 | V>I | A:603 | (29.96, 42.28, 8.11) |
| 3:154886334 | rs373479159 | A>T | A:611 | (42.42, 40.08, 11.97) |
| 3:154886340 | N>Y | A:613 | (47.29, 41.49, 13.92) | |
| 3:154886341 | N>S | A:613 | (47.29, 41.49, 13.92) | |
| 3:154886349 | rs376371123 | E>K | A:616 | (49.09, 37.95, 17.13) |
| 3:154886364 | rs201459318 | M>V | A:621 | (44.65, 38.94, 27.11) |
| 3:154886366 | M>I | A:621 | (44.65, 38.94, 27.11) | |
| 3:154886367 | V>M | A:622 | (44.25, 33.75, 26.28) | |
| 3:154886383 | rs181745819 | N>S | A:627 | (48.47, 30.97, 33.21) |
| 3:154886398 | rs201331064 | L>P | A:632 | (38.14, 29.60, 45.96) |
| 3:154886403 | G>C | A:634 | (41.21, 24.10, 43.22) | |
| 3:154886404 | rs151302020 | G>D | A:634 | (41.21, 24.10, 43.22) |
| 3:154886521 | L>F | A:638 | (40.92, 31.19, 34.69) | |
| 3:154886530 | I>L | A:641 | (39.15, 31.19, 25.24) | |
| 3:154886531 | I>N | A:641 | (39.15, 31.19, 25.24) | |
| 3:154886536 | rs201171603 | T>A | A:643 | (37.35, 35.21, 29.80) |
| 3:154886539 | rs202245924 | L>M | A:644 | (38.99, 37.11, 25.46) |
| 3:154886567 | G>A | A:653 | (38.66, 50.65, 29.62) | |
| 3:154886581 | Y>H | A:658 | (44.83, 57.08, 33.27) | |
| 3:154889906 | A>T | A:660 | (39.98, 60.84, 30.12) | |
| 3:154889921 | I>V | A:665 | (43.96, 66.77, 34.78) | |
| 3:154889934 | rs562989515 | G>D | A:669 | (42.79, 70.36, 36.76) |
| 3:154889936 | rs551727774 | E>K | A:670 | (44.49, 67.63, 39.97) |
| 3:154889961 | D>G | A:678 | (48.62, 59.31, 52.39) | |
| 3:154889962 | D>E | A:678 | (48.62, 59.31, 52.39) | |
| 3:154889969 | H>Y | A:681 | (43.22, 62.09, 42.74) | |
| 3:154889975 | rs200678412 | Q>E | A:683 | (47.57, 56.67, 43.85) |
| 3:154889992 | rs146536523 | N>K | A:688 | (37.40, 53.18, 42.86) |
| 3:154890000 | Q>R | A:691 | (37.57, 49.34, 46.21) | |
| 3:154890343 | rs141200910 | R>G | A:698 | (30.13, 30.14, 49.29) |
| 3:154890350 | COSM124465 | E>G | A:700 | (30.66, 25.24, 46.27) |
| 3:154890356 | rs200313650 | A>V | A:702 | (33.93, 28.81, 41.79) |
| 3:154890358 | COSM402378 | V>I | A:703 | (33.45, 25.12, 40.46) |
| 3:154890365 | S>F | A:705 | (32.16, 30.62, 37.53) | |
| 3:154890367 | I>V | A:706 | (35.89, 28.68, 36.25) | |
| 3:154890374 | T>R | A:708 | (29.44, 29.51, 33.78) | |
| 3:154898151 | I>S | A:718 | (42.13, 43.76, 39.78) | |
| 3:154898190 | A>G | A:731 | (51.39, 55.43, 40.35) | |
| 3:154898201 | R>C | A:735 | (61.64, 46.98, 41.96) | |
| 3:154898218 | M>I | A:740 | (51.15, 44.03, 39.81) | |
| 3:154898220 | N>S | A:741 | (55.50, 45.62, 36.59) | |
| 3:154898228 | rs148040689 | K>E | A:744 | (54.65, 40.12, 28.09) |
| 3:154898237 | rs141665432 | R>W | A:747 | (47.27, 47.76, 24.25) |
| 3:154898238 | rs200966070 COSM1420157 |
R>Q | A:747 | (47.27, 47.76, 24.25) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 3:154832866 | COSM347255 | R>C | A:93 | (36.31, 45.04, 58.26) |
| 3:154832894 | COSM71659 | R>L | A:102 | (29.12, 36.87, 43.91) |
| 3:154832932 | COSM1670660 | V>F | A:115 | (15.61, 47.73, 49.84) |
| 3:154834271 | COSM3714391 | V>A | A:120 | (8.38, 50.64, 45.53) |
| 3:154834311 | COSM1752977 | Q>H | A:133 | (-2.37, 48.81, 40.10) |
| 3:154834336 | COSM3004583 | C>R | A:142 | (5.27, 36.11, 45.70) |
| 3:154834710 | COSM1040248 | K>E | A:196 | (11.83, 24.90, 29.09) |
| 3:154834744 | COSM3660278 | D>G | A:207 | (19.47, 37.90, 11.32) |
| 3:154855909 | COSM4423753 | D>Y | A:246 | (19.03, 12.53, 44.88) |
| 3:154855939 | COSM1040250 | R>C | A:256 | (4.17, 8.32, 42.32) |
| 3:154855984 | COSM3589000 | E>K | A:271 | (12.72, 5.98, 35.43) |
| 3:154856008 | COSM3427253 | E>K | A:279 | (21.43, 15.50, 30.36) |
| 3:154857980 | COSM1040251 | A>T | A:285 | (27.07, 16.62, 22.06) |
| 3:154858002 | COSM173419 | R>Q | A:292 | (28.98, 28.14, 20.53) |
| 3:154858032 | COSM1617092 | M>T | A:302 | (20.04, 26.18, 6.62) |
| 3:154858058 | COSM3365056 | F>L | A:311 | (20.89, 18.28, 10.21) |
| 3:154859807 | COSM3589001 | E>K | A:328 | (3.21, 21.85, 16.45) |
| 3:154860085 | COSM207009 | R>Q | A:384 | (9.14, 25.39, 52.17) |
| 3:154860115 | COSM240703 | R>H | A:394 | (20.65, 25.55, 47.28) |
| 3:154861271 | COSM4114666 | R>C | A:409 | (12.64, 34.79, 46.51) |
| 3:154861319 | COSM3589002 | L>F | A:425 | (8.49, 52.66, 40.81) |
| 3:154861355 | COSM1617094 | H>Y | A:437 | (22.05, 65.54, 31.75) |
| 3:154862220 | COSM358007 | E>K | A:463 | (42.21, 50.17, 5.60) |
| 3:154884783 | COSM245723 | E>K | A:584 | (30.12, 48.10, 27.90) |
| 3:154884801 | COSM1536931 | D>Y | A:590 | (35.09, 41.75, 21.39) |