General Structure Information
| PDB ID | 4leo |
| HGNC Gene Label(s) | ERBB3 |
| Structure Name | crystal structure of anti-her3 fab rg7116 in complex with the extracellular domains of human her3 (erbb3) |
| Resolution | 2.64Å |
| Reference | AUTH C.MIRSCHBERGER,C.B.SCHILLER,M.SCHRAML,N.DIMOUDIS,T.FRIESS,AUTH 2 C.A.GERDES,U.REIFF,V.LIFKE,G.HOELZLWIMMER,I.KOLM,AUTH 3 K.P.HOPFNER,G.NIEDERFELLNER,B.BOSSENMAIERTITL RG7116, A THERAPEUTIC ANTIBODY THAT BINDS THE INACTIVE HER3TITL 2 RECEPTOR AND IS OPTIMIZED FOR IMMUNE EFFECTOR ACTIVATION.REF CANCER RES. V. 73 5183 2013REFN ISSN 0008-5472PMID 23780344DOI 10.1158/0008-5472.CAN-13-0099 |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 601 |
| Number Of SNVs | 143 |
| Number Of Permutations | 39386 |
| Optimal Distance Threshold | 7.0 |
| K Statistic | 0.011 |
| p-value | 0.558 |
COSMIC
| Number Of Residues | 601 |
| Number Of SNVs | 24 |
| Number Of Permutations | 31542 |
| Optimal Distance Threshold | 18.0 |
| K Statistic | 0.174 |
| p-value | 0.044 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 143 |
| Number Of COSMIC SNVs | 21 |
| Optimal Distance Threshold | 41.0 |
| K Statistic | 0.11 |
| p-value | 0.16 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:56477537 | C>R | C:10 | (27.58, 28.28, -24.34) | |
| 12:56477541 | rs56017157 | P>L | C:11 | (28.76, 24.82, -24.24) |
| 12:56477576 | A>T | C:23 | (28.98, 20.28, -3.84) | |
| 12:56477579 | E>K | C:24 | (31.38, 24.16, -4.24) | |
| 12:56477595 | T>I | C:29 | (31.18, 23.23, -13.28) | |
| 12:56477610 | Y>C | C:34 | (25.99, 27.48, -18.42) | |
| 12:56477612 | E>K | C:35 | (30.22, 32.88, -16.93) | |
| 12:56477615 | R>W | C:36 | (28.48, 37.87, -20.27) | |
| 12:56477624 | V>M | C:39 | (23.51, 30.86, -27.09) | |
| 12:56477627 | V>M | C:40 | (23.08, 27.12, -24.70) | |
| 12:56477633 | G>R | C:42 | (22.43, 22.67, -25.60) | |
| 12:56477646 | I>T | C:46 | (19.89, 23.73, -13.10) | |
| 12:56477655 | rs142735651 | T>M | C:49 | (21.65, 24.15, -6.48) |
| 12:56477667 | rs570614098 | A>D | C:53 | (23.10, 30.54, -5.06) |
| 12:56477669 | rs143770796 | D>N | C:54 | (24.84, 33.77, -7.86) |
| 12:56478791 | V>M | C:64 | (18.30, 26.72, -25.08) | |
| 12:56478798 | G>A | C:66 | (17.70, 22.17, -26.15) | |
| 12:56478809 | rs77228285 | V>M | C:70 | (15.05, 22.48, -13.22) |
| 12:56478830 | rs200856864 | T>A | C:77 | (14.04, 32.17, -7.26) |
| 12:56478848 | L>F | C:83 | (14.69, 32.46, -21.68) | |
| 12:56478851 | rs146486757 | R>C | C:84 | (12.60, 36.04, -26.17) |
| 12:56478852 | COSM191839 | R>H | C:84 | (12.60, 36.04, -26.17) |
| 12:56478861 | R>Q | C:87 | (15.86, 26.03, -31.38) | |
| 12:56478879 | D>G | C:93 | (12.52, 11.02, -21.61) | |
| 12:56478903 | M>T | C:101 | (11.45, 16.94, -10.74) | |
| 12:56478938 | rs569206705 | R>C | C:113 | (8.77, 29.35, -2.83) |
| 12:56478944 | L>F | C:115 | (9.64, 29.44, -12.81) | |
| 12:56478947 | COSM1747133 COSM254681 COSM1747132 |
R>C | C:116 | (10.64, 35.41, -12.17) |
| 12:56478948 | R>H | C:116 | (10.64, 35.41, -12.17) | |
| 12:56478965 | E>K | C:122 | (9.07, 30.27, -29.54) | |
| 12:56480330 | rs374619740 | G>A | C:127 | (7.54, 19.96, -23.87) |
| 12:56480339 | I>T | C:130 | (6.04, 21.52, -14.21) | |
| 12:56480362 | rs141700623 | H>Y | C:138 | (1.90, 31.51, -9.64) |
| 12:56480374 | rs188795493 | I>V | C:142 | (1.12, 29.76, -17.54) |
| 12:56480377 | D>N | C:143 | (-1.35, 29.64, -22.27) | |
| 12:56480384 | rs560422339 | R>K | C:145 | (-0.60, 24.40, -26.11) |
| 12:56480389 | rs374643843 | I>V | C:147 | (4.94, 29.13, -25.14) |
| 12:56480392 | V>L | C:148 | (4.20, 25.04, -27.18) | |
| 12:56480402 | rs200978269 | R>Q | C:151 | (-1.03, 22.28, -32.78) |
| 12:56480407 | A>S | C:153 | (3.30, 18.36, -27.28) | |
| 12:56480417 | V>G | C:156 | (2.53, 17.73, -17.62) | |
| 12:56480431 | G>R | C:161 | (1.32, 24.06, -5.20) | |
| 12:56480435 | rs371016430 | R>K | C:162 | (-1.07, 21.96, -1.93) |
| 12:56481363 | P>T | C:165 | (-0.64, 33.16, -3.90) | |
| 12:56481367 | P>R | C:166 | (-3.76, 35.19, -5.53) | |
| 12:56481369 | C>G | C:167 | (-2.77, 36.33, -9.93) | |
| 12:56481391 | rs561743080 | R>Q | C:174 | (-2.96, 33.45, -17.92) |
| 12:56481412 | E>G | C:181 | (6.69, 44.00, -13.15) | |
| 12:56481424 | rs56107455 | T>I | C:185 | (3.21, 38.38, -22.38) |
| 12:56481585 | K>R | C:188 | (0.23, 32.27, -30.06) | |
| 12:56481630 | N>S | C:203 | (-1.88, 41.78, -43.02) | |
| 12:56481631 | N>K | C:203 | (-1.88, 41.78, -43.02) | |
| 12:56481635 | rs549747369 | N>Y | C:205 | (1.97, 42.25, -46.08) |
| 12:56481640 | Q>H | C:206 | (1.25, 41.73, -41.01) | |
| 12:56481642 | C>Y | C:207 | (4.22, 37.57, -42.51) | |
| 12:56481648 | COSM4043439 COSM4043438 |
H>R | C:209 | (12.15, 36.64, -43.08) |
| 12:56481650 | rs201079200 | D>N | C:210 | (11.19, 33.17, -45.12) |
| 12:56481654 | E>V | C:211 | (15.54, 32.66, -42.30) | |
| 12:56481656 | rs376656358 | C>G | C:212 | (11.77, 32.92, -38.94) |
| 12:56481659 | rs140656187 COSM4043441 COSM4043440 |
A>T | C:213 | (11.61, 29.41, -36.79) |
| 12:56481662 | G>R | C:214 | (8.67, 31.05, -35.89) | |
| 12:56481811 | R>W | C:228 | (13.93, 28.42, -40.30) | |
| 12:56481812 | rs374485725 | R>Q | C:228 | (13.93, 28.42, -40.30) |
| 12:56481821 | N>S | C:231 | (22.52, 35.14, -35.99) | |
| 12:56481833 | rs375740977 | A>D | C:235 | (20.51, 38.56, -38.87) |
| 12:56481844 | COSM941486 | R>C | C:239 | (24.73, 31.64, -47.60) |
| 12:56481859 | rs370272057 | L>F | C:244 | (36.42, 32.61, -51.26) |
| 12:56481862 | V>I | C:245 | (34.89, 36.87, -53.19) | |
| 12:56481863 | COSM4043443 COSM4043442 |
V>A | C:245 | (34.89, 36.87, -53.19) |
| 12:56481901 | H>Y | C:258 | (32.69, 41.20, -44.98) | |
| 12:56481905 | T>I | C:259 | (34.67, 35.90, -43.51) | |
| 12:56481908 | K>R | C:260 | (31.28, 35.74, -40.13) | |
| 12:56481925 | rs149635848 | V>I | C:266 | (26.19, 31.84, -34.47) |
| 12:56481941 | rs143406438 | C>Y | C:271 | (36.72, 30.05, -33.50) |
| 12:56481944 | COSM3463319 COSM3463318 |
P>L | C:272 | (36.37, 29.19, -29.99) |
| 12:56481946 | COSM1128537 COSM1128536 |
H>Y | C:273 | (39.93, 29.79, -26.61) |
| 12:56482344 | COSM48868 | Q>E | C:279 | (34.75, 23.19, -44.77) |
| 12:56482362 | A>S | C:285 | (38.71, 18.32, -34.52) | |
| 12:56482393 | rs137870123 | K>R | C:295 | (46.35, 30.05, -42.78) |
| 12:56482420 | C>F | C:304 | (48.02, 16.63, -45.89) | |
| 12:56482422 | rs375335792 | G>R | C:305 | (49.23, 15.82, -49.37) |
| 12:56482432 | C>S | C:308 | (49.03, 13.20, -42.02) | |
| 12:56482549 | S>P | C:317 | (67.96, 6.15, -25.81) | |
| 12:56482559 | R>H | C:320 | (58.63, 0.40, -23.41) | |
| 12:56482577 | COSM1586602 COSM941492 |
S>L | C:326 | (57.22, -8.57, -33.22) |
| 12:56482592 | G>A | C:331 | (53.50, 1.39, -34.22) | |
| 12:56482604 | C>Y | C:335 | (55.27, 7.26, -38.89) | |
| 12:56482642 | G>S | C:348 | (64.99, -8.42, -33.01) | |
| 12:56482649 | rs200211366 | N>S | C:350 | (66.70, -13.24, -35.42) |
| 12:56486535 | P>A | C:353 | (64.26, -16.50, -26.66) | |
| 12:56486536 | P>R | C:353 | (64.26, -16.50, -26.66) | |
| 12:56486538 | rs371094129 | W>R | C:354 | (66.70, -14.97, -23.94) |
| 12:56486575 | rs12320176 | N>S | C:366 | (57.93, -2.21, -45.81) |
| 12:56486583 | R>W | C:369 | (59.04, 2.21, -47.64) | |
| 12:56486584 | rs570637025 COSM1299649 COSM1299648 |
R>Q | C:369 | (59.04, 2.21, -47.64) |
| 12:56486592 | rs139868331 | R>W | C:372 | (58.80, 12.49, -43.72) |
| 12:56486593 | COSM3671134 COSM3671133 |
R>Q | C:372 | (58.80, 12.49, -43.72) |
| 12:56486794 | rs370847503 | P>L | C:384 | (67.09, -9.00, -43.55) |
| 12:56486802 | M>L | C:387 | (66.31, -7.00, -47.22) | |
| 12:56486810 | N>K | C:389 | (68.58, -2.52, -49.68) | |
| 12:56486811 | F>L | C:390 | (69.37, -0.18, -45.53) | |
| 12:56486815 | S>I | C:391 | (64.69, 0.70, -49.39) | |
| 12:56486857 | Y>C | C:405 | (74.63, 3.34, -29.97) | |
| 12:56487130 | rs375932235 | R>W | C:407 | (83.30, 5.49, -28.25) |
| 12:56487149 | I>T | C:413 | (75.61, 0.52, -40.63) | |
| 12:56487181 | F>I | C:424 | (69.84, 5.65, -46.65) | |
| 12:56487185 | COSM4043453 COSM4043452 |
R>Q | C:425 | (65.71, 7.36, -52.95) |
| 12:56487211 | R>C | C:434 | (81.41, 9.64, -34.52) | |
| 12:56487212 | rs144549266 | R>H | C:434 | (81.41, 9.64, -34.52) |
| 12:56487220 | rs200007116 | I>V | C:437 | (79.75, 2.56, -42.10) |
| 12:56487235 | Q>K | C:442 | (78.91, -7.87, -49.82) | |
| 12:56487270 | K>N | C:453 | (77.36, 17.85, -49.56) | |
| 12:56487278 | rs372171124 | R>Q | C:456 | (74.62, 20.58, -40.27) |
| 12:56487281 | G>E | C:457 | (79.87, 20.22, -39.83) | |
| 12:56487296 | R>P | C:462 | (81.71, 13.93, -37.15) | |
| 12:56487317 | COSM1580860 COSM1580859 |
R>Q | C:469 | (83.14, -5.21, -52.03) |
| 12:56487320 | P>L | C:470 | (86.89, -3.48, -51.57) | |
| 12:56487322 | R>C | C:471 | (86.85, 2.91, -54.24) | |
| 12:56487323 | rs149951770 | R>H | C:471 | (86.85, 2.91, -54.24) |
| 12:56487334 | rs182692782 | V>L | C:475 | (85.00, -0.37, -60.00) |
| 12:56487556 | rs375153329 | G>S | C:478 | (80.21, -1.75, -61.82) |
| 12:56487560 | rs146593760 | K>I | C:479 | (78.75, -2.33, -58.05) |
| 12:56487592 | C>S | C:490 | (75.85, 7.39, -54.57) | |
| 12:56487605 | rs145108143 | G>D | C:494 | (71.14, 5.13, -60.43) |
| 12:56487610 | G>S | C:496 | (67.77, 7.81, -57.88) | |
| 12:56487629 | COSM1586601 COSM941494 |
R>Q | C:502 | (76.43, 16.41, -63.49) |
| 12:56487631 | N>Y | C:503 | (71.64, 18.68, -65.11) | |
| 12:56487634 | Y>H | C:504 | (67.56, 20.04, -64.71) | |
| 12:56487641 | R>Q | C:506 | (61.37, 14.19, -63.75) | |
| 12:56487653 | C>F | C:510 | (68.38, 12.33, -61.94) | |
| 12:56487658 | rs200670489 | T>S | C:512 | (68.81, 15.42, -68.77) |
| 12:56487664 | rs147888915 | C>R | C:514 | (62.52, 19.02, -68.15) |
| 12:56487677 | N>S | C:518 | (58.00, 16.82, -75.96) | |
| 12:56487891 | R>Q | C:522 | (55.05, 20.44, -71.68) | |
| 12:56487911 | E>Q | C:529 | (63.64, 21.05, -58.62) | |
| 12:56487917 | rs569403749 | F>L | C:531 | (58.35, 21.64, -60.27) |
| 12:56487920 | S>A | C:532 | (53.96, 20.50, -63.71) | |
| 12:56487921 | rs201942735 | S>F | C:532 | (53.96, 20.50, -63.71) |
| 12:56487930 | rs370634710 COSM1638331 COSM1638330 |
P>L | C:535 | (46.30, 22.06, -65.60) |
| 12:56487942 | P>L | C:539 | (50.46, 21.91, -75.26) | |
| 12:56487972 | COSM1363003 COSM1363002 |
S>L | C:549 | (53.10, 27.46, -61.18) |
| 12:56488186 | rs368322587 | G>R | C:550 | (49.85, 28.48, -63.10) |
| 12:56488199 | C>Y | C:554 | (50.22, 29.85, -69.50) | |
| 12:56488210 | rs141636701 | A>T | C:558 | (43.20, 24.80, -73.43) |
| 12:56488252 | H>Y | C:572 | (29.03, 28.81, -63.99) | |
| 12:56488255 | G>R | C:573 | (27.84, 32.18, -60.57) | |
| 12:56488274 | G>V | C:579 | (26.71, 39.27, -56.48) | |
| 12:56488283 | Y>C | C:582 | (26.29, 34.63, -64.15) | |
| 12:56488311 | C>W | C:591 | (35.86, 35.21, -70.60) | |
| 12:56488312 | rs373609369 | R>W | C:592 | (35.05, 39.27, -72.60) |
| 12:56488324 | rs143726790 | E>K | C:596 | (23.37, 45.87, -66.89) |
| 12:56488334 | T>I | C:599 | (18.79, 36.81, -64.70) | |
| 12:56489052 | rs151083303 | P>R | C:605 | (26.86, 39.88, -75.56) |
| 12:56489054 | E>K | C:606 | (23.86, 41.45, -76.94) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:56477580 | COSM1578800 | E>G | C:24 | (31.38, 24.16, -4.24) |
| 12:56477630 | COSM1606368 | M>L | C:41 | (25.09, 24.91, -28.54) |
| 12:56477631 | COSM1586593 | M>R | C:41 | (25.09, 24.91, -28.54) |
| 12:56478817 | COSM1299638 | M>I | C:72 | (17.11, 17.76, -7.41) |
| 12:56478847 | COSM1236237 | N>K | C:82 | (17.10, 37.61, -21.17) |
| 12:56478854 | COSM1299641 | V>L | C:85 | (13.97, 30.41, -27.47) |
| 12:56478922 | COSM270926 | N>K | C:107 | (12.09, 18.93, 5.99) |
| 12:56478947 | COSM254681 | R>C | C:116 | (10.64, 35.41, -12.17) |
| 12:56480341 | COSM254675 | E>K | C:131 | (5.09, 16.76, -11.63) |
| 12:56480404 | COSM1705797 | D>N | C:152 | (1.57, 16.83, -31.30) |
| 12:56481612 | COSM212332 | G>A | C:197 | (2.43, 30.34, -38.79) |
| 12:56481648 | COSM4043439 | H>R | C:209 | (12.15, 36.64, -43.08) |
| 12:56481660 | COSM1242239 | A>V | C:213 | (11.61, 29.41, -36.79) |
| 12:56481671 | COSM1299646 | S>P | C:217 | (8.47, 41.23, -33.83) |
| 12:56481806 | COSM941485 | A>V | C:226 | (14.39, 32.22, -33.91) |
| 12:56481845 | COSM266472 | R>H | C:239 | (24.73, 31.64, -47.60) |
| 12:56481898 | COSM1747135 | P>S | C:257 | (36.54, 40.82, -46.01) |
| 12:56481922 | COSM48360 | G>R | C:265 | (23.89, 29.32, -35.18) |
| 12:56482341 | COSM1299647 | D>Y | C:278 | (36.92, 22.23, -41.63) |
| 12:56482369 | COSM4043444 | P>H | C:287 | (39.87, 15.99, -40.18) |
| 12:56482537 | COSM1747136 | E>K | C:313 | (57.65, 7.05, -28.47) |
| 12:56482607 | COSM1476732 | T>I | C:336 | (56.32, 10.87, -40.54) |
| 12:56486587 | COSM4681515 | T>K | C:370 | (56.20, 6.70, -43.88) |
| 12:56487167 | COSM1363000 | V>A | C:419 | (74.08, -4.82, -47.42) |
| 12:56487277 | COSM1363001 | R>W | C:456 | (74.62, 20.58, -40.27) |
| 12:56487317 | COSM1580860 | R>Q | C:469 | (83.14, -5.21, -52.03) |
| 12:56487323 | COSM1645710 | R>H | C:471 | (86.85, 2.91, -54.24) |
| 12:56487560 | COSM1236019 | K>I | C:479 | (78.75, -2.33, -58.05) |
| 12:56488225 | COSM254680 | G>W | C:563 | (42.21, 37.31, -68.08) |