General Structure Information
| PDB ID | 4kro |
| HGNC Gene Label(s) | EGFR |
| Structure Name | nanobody/vhh domain ega1 in complex with the extracellular region of egfr |
| Resolution | 3.05Å |
| Reference | AUTH K.R.SCHMITZ,A.BAGCHI,R.C.ROOVERS,AUTH 2 P.M.VAN BERGEN EN HENEGOUWEN,K.M.FERGUSONTITL STRUCTURAL EVALUATION OF EGFR INHIBITION MECHANISMS FORTITL 2 NANOBODIES/VHH DOMAINS.REF STRUCTURE V. 21 1214 2013REFN ISSN 0969-2126PMID 23791944DOI 10.1016/J.STR.2013.05.008 |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 570 |
| Number Of SNVs | 117 |
| Number Of Permutations | 31948 |
| Optimal Distance Threshold | 8.0 |
| K Statistic | 0.014 |
| p-value | 0.894 |
COSMIC
| Number Of Residues | 570 |
| Number Of SNVs | 23 |
| Number Of Permutations | 12698 |
| Optimal Distance Threshold | 43.0 |
| K Statistic | 0.688 |
| p-value | 0.018 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 117 |
| Number Of COSMIC SNVs | 19 |
| Optimal Distance Threshold | 26.0 |
| K Statistic | 0.103 |
| p-value | 0.079 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 7:55087052 | K>E | A:4 | (47.21, -21.90, 86.19) | |
| 7:55087056 | K>T | A:5 | (44.06, -20.63, 86.28) | |
| 7:55209985 | Q>R | A:8 | (40.26, -13.40, 79.70) | |
| 7:55209987 | G>S | A:9 | (40.31, -10.24, 80.83) | |
| 7:55209991 | rs144158123 | T>R | A:10 | (38.65, -6.27, 80.64) |
| 7:55210006 | rs375919121 | T>M | A:15 | (33.26, 2.17, 80.40) |
| 7:55210048 | R>K | A:29 | (32.62, -13.23, 86.94) | |
| 7:55210057 | N>S | A:32 | (35.58, -16.18, 90.29) | |
| 7:55210065 | E>K | A:35 | (45.73, -18.14, 88.97) | |
| 7:55210066 | E>A | A:35 | (45.73, -18.14, 88.97) | |
| 7:55210102 | rs369580836 | Q>R | A:47 | (31.68, -0.47, 95.89) |
| 7:55210116 | L>I | A:52 | (37.08, -8.11, 96.94) | |
| 7:55210998 | rs374986786 | T>A | A:57 | (43.25, -15.87, 93.16) |
| 7:55211025 | L>F | A:66 | (43.64, -0.72, 85.78) | |
| 7:55211026 | rs142061256 | L>H | A:66 | (43.64, -0.72, 85.78) |
| 7:55211032 | A>V | A:68 | (39.93, 3.56, 88.50) | |
| 7:55211046 | E>Q | A:73 | (38.64, -0.03, 101.11) | |
| 7:55211073 | I>V | A:82 | (54.78, -10.79, 86.28) | |
| 7:55211083 | rs145113601 | G>A | A:85 | (52.74, -5.01, 79.83) |
| 7:55211089 | M>T | A:87 | (49.55, -3.48, 76.69) | |
| 7:55211102 | N>K | A:91 | (50.23, 6.37, 76.77) | |
| 7:55211157 | E>K | A:110 | (44.25, -0.53, 100.76) | |
| 7:55211166 | M>V | A:113 | (50.25, -4.63, 94.83) | |
| 7:55211180 | Q>H | A:117 | (58.44, -7.79, 91.83) | |
| 7:55214308 | rs150234987 | H>R | A:121 | (57.09, -3.32, 80.61) |
| 7:55214313 | rs532655845 | A>T | A:123 | (55.56, 3.23, 83.38) |
| 7:55214319 | COSM3412168 COSM3412169 |
R>W | A:125 | (50.75, 5.80, 87.62) |
| 7:55214320 | R>Q | A:125 | (50.75, 5.80, 87.62) | |
| 7:55214329 | rs551591429 | N>S | A:128 | (44.30, 11.36, 92.84) |
| 7:55214367 | COSM252488 COSM252489 |
R>W | A:141 | (63.39, 1.00, 91.11) |
| 7:55214368 | COSM1205052 COSM1205053 |
R>Q | A:141 | (63.39, 1.00, 91.11) |
| 7:55214374 | I>T | A:143 | (58.74, -2.91, 90.93) | |
| 7:55214376 | rs530692924 | V>L | A:144 | (59.62, -0.06, 86.80) |
| 7:55214404 | S>L | A:153 | (53.44, 9.70, 86.84) | |
| 7:55219001 | P>T | A:168 | (60.63, -1.78, 112.20) | |
| 7:55219014 | N>S | A:172 | (64.19, 1.81, 104.10) | |
| 7:55219037 | COSM94179 COSM94180 |
E>K | A:180 | (56.16, -7.51, 108.27) |
| 7:55220340 | rs554981236 | R>W | A:220 | (68.14, -22.18, 87.64) |
| 7:55220341 | rs200664836 | R>Q | A:220 | (68.14, -22.18, 87.64) |
| 7:55220356 | L>P | A:225 | (57.86, -18.01, 90.32) | |
| 7:55221710 | COSM1451547 COSM35752 COSM1559807 COSM1451548 |
R>G | A:228 | (60.50, -14.42, 81.58) |
| 7:55221711 | COSM3412178 COSM1176673 COSM1176674 COSM3412179 |
R>H | A:228 | (60.50, -14.42, 81.58) |
| 7:55221714 | rs374084791 | K>R | A:229 | (60.13, -14.88, 78.18) |
| 7:55221720 | rs372202099 | R>Q | A:231 | (55.30, -21.62, 82.02) |
| 7:55221725 | rs138847501 | E>K | A:233 | (57.06, -27.27, 82.08) |
| 7:55221732 | T>M | A:235 | (61.97, -25.22, 81.64) | |
| 7:55221750 | P>H | A:241 | (60.05, -25.43, 71.41) | |
| 7:55221783 | Q>R | A:252 | (65.93, -28.34, 53.96) | |
| 7:55221800 | rs199796955 COSM453243 COSM453244 |
E>K | A:258 | (59.92, -31.24, 69.72) |
| 7:55221809 | Y>H | A:261 | (51.60, -24.69, 68.61) | |
| 7:55221831 | V>A | A:268 | (51.72, -25.47, 74.07) | |
| 7:55221845 | R>C | A:273 | (37.44, -25.84, 71.85) | |
| 7:55223534 | V>L | A:277 | (47.91, -21.67, 65.13) | |
| 7:55223555 | V>I | A:284 | (45.10, -15.91, 68.67) | |
| 7:55223568 | G>A | A:288 | (42.83, -11.78, 62.10) | |
| 7:55223571 | rs149321481 | A>V | A:289 | (41.32, -8.36, 60.28) |
| 7:55223577 | S>N | A:291 | (43.92, -13.11, 58.14) | |
| 7:55223587 | M>I | A:294 | (42.17, -22.60, 57.90) | |
| 7:55223597 | G>S | A:298 | (43.39, -30.76, 62.56) | |
| 7:55223600 | COSM145360 COSM145361 |
V>I | A:299 | (44.83, -27.91, 63.36) |
| 7:55223601 | rs367680488 | V>A | A:299 | (44.83, -27.91, 63.36) |
| 7:55223604 | COSM21688 COSM3881812 COSM1736054 COSM3881813 |
R>H | A:300 | (43.17, -24.61, 63.18) |
| 7:55223606 | K>Q | A:301 | (45.00, -22.20, 61.02) | |
| 7:55223615 | rs144460286 | K>Q | A:304 | (46.84, -14.75, 54.86) |
| 7:55223618 | C>R | A:305 | (43.89, -12.65, 52.92) | |
| 7:55223621 | rs139429793 | E>K | A:306 | (44.47, -13.32, 49.04) |
| 7:55223634 | R>H | A:310 | (34.18, -14.54, 50.68) | |
| 7:55224247 | G>V | A:319 | (16.96, -7.82, 54.15) | |
| 7:55224270 | COSM3881814 COSM3881815 |
I>V | A:327 | (23.60, 1.10, 44.99) |
| 7:55224321 | D>H | A:344 | (20.32, -8.44, 42.95) | |
| 7:55224322 | D>V | A:344 | (20.32, -8.44, 42.95) | |
| 7:55224324 | L>I | A:345 | (24.39, -4.58, 42.69) | |
| 7:55224465 | H>N | A:359 | (14.51, 11.02, 51.96) | |
| 7:55224510 | V>I | A:374 | (32.11, -6.45, 44.38) | |
| 7:55225358 | F>I | A:380 | (19.72, -8.99, 38.90) | |
| 7:55225386 | N>S | A:389 | (32.01, 12.19, 34.07) | |
| 7:55225396 | D>E | A:392 | (34.28, 2.36, 31.83) | |
| 7:55225409 | E>K | A:397 | (38.01, -2.97, 37.61) | |
| 7:55225431 | G>D | A:404 | (22.10, -15.11, 37.95) | |
| 7:55225437 | COSM3881818 COSM3881819 |
T>N | A:406 | (17.76, -13.36, 41.21) |
| 7:55225446 | H>R | A:409 | (11.72, -7.97, 34.38) | |
| 7:55227858 | S>N | A:418 | (20.72, 4.34, 28.11) | |
| 7:55227885 | R>H | A:427 | (39.58, -4.88, 32.90) | |
| 7:55227911 | D>N | A:436 | (19.48, -13.37, 29.22) | |
| 7:55227960 | N>S | A:452 | (32.49, -15.42, 22.22) | |
| 7:55227970 | K>N | A:455 | (32.34, -18.29, 26.60) | |
| 7:55227986 | G>S | A:461 | (19.88, -20.93, 26.25) | |
| 7:55228017 | G>D | A:471 | (28.44, 1.63, 15.34) | |
| 7:55229200 | COSM3881820 COSM3881821 |
G>S | A:479 | (40.34, 3.37, 16.26) |
| 7:55229225 | rs371114444 | S>Y | A:487 | (42.94, -12.95, 21.20) |
| 7:55229227 | COSM3639737 COSM3639738 |
P>S | A:488 | (40.94, -13.77, 17.87) |
| 7:55229245 | rs368484180 | P>S | A:494 | (40.66, 0.54, 24.58) |
| 7:55229246 | rs564398642 | P>L | A:494 | (40.66, 0.54, 24.58) |
| 7:55229249 | E>G | A:495 | (43.47, -1.40, 26.27) | |
| 7:55229250 | rs116057045 | E>D | A:495 | (43.47, -1.40, 26.27) |
| 7:55229255 | rs2227983 | R>K | A:497 | (43.97, -2.63, 31.72) |
| 7:55229263 | V>I | A:500 | (38.72, -12.11, 26.15) | |
| 7:55229272 | R>W | A:503 | (49.17, -11.52, 19.51) | |
| 7:55229273 | rs150477666 | R>Q | A:503 | (49.17, -11.52, 19.51) |
| 7:55229275 | N>D | A:504 | (52.01, -13.68, 21.89) | |
| 7:55229299 | COSM382935 COSM382936 |
V>M | A:512 | (52.73, -8.89, 26.75) |
| 7:55229300 | V>A | A:512 | (52.73, -8.89, 26.75) | |
| 7:55229323 | G>S | A:520 | (64.17, -6.93, 30.42) | |
| 7:55231427 | E>K | A:521 | (63.74, -5.58, 33.81) | |
| 7:55231455 | E>G | A:530 | (50.92, -16.64, 32.47) | |
| 7:55231462 | I>M | A:532 | (55.54, -16.65, 36.11) | |
| 7:55231472 | P>T | A:536 | (63.77, -11.94, 43.98) | |
| 7:55231475 | E>Q | A:537 | (67.50, -13.69, 44.36) | |
| 7:55231493 | M>V | A:543 | (73.41, -12.93, 25.10) | |
| 7:55231503 | T>S | A:546 | (67.43, -15.49, 34.61) | |
| 7:55231509 | T>R | A:548 | (64.29, -22.78, 35.29) | |
| 7:55231514 | R>W | A:550 | (56.60, -20.59, 39.81) | |
| 7:55231515 | rs370810719 COSM374570 COSM374571 |
R>Q | A:550 | (56.60, -20.59, 39.81) |
| 7:55232983 | rs556794990 | N>S | A:554 | (64.48, -23.20, 39.71) |
| 7:55232989 | I>T | A:556 | (71.66, -20.03, 35.31) | |
| 7:55232991 | Q>K | A:557 | (73.20, -17.42, 39.02) | |
| 7:55233007 | rs542237406 | I>T | A:562 | (74.71, -19.34, 48.28) |
| 7:55233016 | COSM747427 COSM747428 |
P>H | A:565 | (70.11, -25.86, 46.56) |
| 7:55233024 | rs144943614 | V>I | A:568 | (70.44, -17.04, 50.47) |
| 7:55233031 | T>N | A:570 | (71.63, -13.86, 53.17) | |
| 7:55233039 | COSM48318 COSM35822 COSM1559816 |
A>S | A:573 | (73.47, -16.14, 60.73) |
| 7:55233043 | rs139236063 | G>V | A:574 | (71.44, -18.09, 63.85) |
| 7:55233049 | rs149375515 | M>T | A:576 | (67.81, -22.83, 64.73) |
| 7:55233066 | rs143152775 | L>V | A:582 | (72.58, -22.14, 67.03) |
| 7:55233081 | rs201061916 | A>T | A:587 | (80.78, -15.32, 53.81) |
| 7:55233087 | A>T | A:589 | (85.60, -14.88, 48.10) | |
| 7:55233090 | G>S | A:590 | (82.73, -16.69, 46.13) | |
| 7:55233091 | COSM3412198 COSM3412199 |
G>D | A:590 | (82.73, -16.69, 46.13) |
| 7:55233097 | V>A | A:592 | (79.71, -20.20, 48.50) | |
| 7:55233117 | N>Y | A:599 | (82.44, -23.26, 68.54) | |
| 7:55233129 | G>R | A:603 | (79.04, -16.62, 64.37) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 7:55210075 | COSM1451527 | L>P | A:38 | (45.34, -14.65, 78.71) |
| 7:55210077 | COSM1451531 | G>R | A:39 | (44.60, -9.61, 79.13) |
| 7:55211079 | COSM1451536 | R>G | A:84 | (54.03, -7.69, 81.57) |
| 7:55211080 | COSM4970170 | R>K | A:84 | (54.03, -7.69, 81.57) |
| 7:55211097 | COSM174733 | E>K | A:90 | (47.54, 5.10, 78.61) |
| 7:55214352 | COSM3412170 | E>K | A:136 | (54.29, 6.27, 98.64) |
| 7:55214368 | COSM1205052 | R>Q | A:141 | (63.39, 1.00, 91.11) |
| 7:55219034 | COSM4767521 | G>R | A:179 | (53.10, -5.48, 108.88) |
| 7:55221710 | COSM1559807 | R>C | A:228 | (60.50, -14.42, 81.58) |
| 7:55221711 | COSM3412178 | R>P | A:228 | (60.50, -14.42, 81.58) |
| 7:55221723 | COSM1559808 | D>A | A:232 | (58.01, -24.92, 78.87) |
| 7:55221743 | COSM1451553 | T>A | A:239 | (61.29, -18.72, 71.85) |
| 7:55221796 | COSM4943273 | N>K | A:256 | (60.33, -30.13, 64.94) |
| 7:55221821 | COSM21686 | A>T | A:265 | (53.27, -16.47, 78.52) |
| 7:55221822 | COSM21685 | A>D | A:265 | (53.27, -16.47, 78.52) |
| 7:55223543 | COSM2149971 | H>Y | A:280 | (53.45, -15.41, 64.83) |
| 7:55223567 | COSM3929117 | G>W | A:288 | (42.83, -11.78, 62.10) |
| 7:55223600 | COSM145361 | V>I | A:299 | (44.83, -27.91, 63.36) |
| 7:55223604 | COSM3881812 | R>H | A:300 | (43.17, -24.61, 63.18) |
| 7:55223624 | COSM2151462 | G>R | A:307 | (43.79, -10.01, 48.81) |
| 7:55224307 | COSM2155594 | T>I | A:339 | (34.35, -9.42, 48.49) |
| 7:55225427 | COSM1205051 | R>C | A:403 | (27.23, -17.31, 41.03) |
| 7:55228009 | COSM236670 | S>R | A:468 | (20.91, 0.54, 19.84) |
| 7:55229255 | COSM3721609 | R>K | A:497 | (43.97, -2.63, 31.72) |
| 7:55233016 | COSM747427 | P>L | A:565 | (70.11, -25.86, 46.56) |
| 7:55233036 | COSM3412195 | P>S | A:572 | (72.09, -19.25, 56.97) |
| 7:55233037 | COSM191988 | P>L | A:572 | (72.09, -19.25, 56.97) |
| 7:55233043 | COSM21690 | G>V | A:574 | (71.44, -18.09, 63.85) |
| 7:55233060 | COSM1698694 | N>D | A:580 | (68.11, -26.08, 70.77) |
| 7:55233109 | COSM35825 | C>Y | A:596 | (80.82, -21.83, 61.26) |
| 7:55233130 | COSM1755314 | G>E | A:603 | (79.04, -16.62, 64.37) |
| 7:55238870 | COSM2157152 | C>F | A:604 | (82.15, -16.69, 61.67) |