General Structure Information
| PDB ID | 2shp |
| HGNC Gene Label(s) | PTPN11 |
| Structure Name | tyrosine phosphatase shp-2 |
| Resolution | 2.0Å |
| Reference | AUTH P.HOF,S.PLUSKEY,S.DHE-PAGANON,M.J.ECK,S.E.SHOELSONTITL CRYSTAL STRUCTURE OF THE TYROSINE PHOSPHATASETITL 2 SHP-2.REF CELL(CAMBRIDGE,MASS.) V. 92 441 1998REFN ISSN 0092-8674PMID 9491886DOI 10.1016/S0092-8674(00)80938-1 |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 491 |
| Number Of SNVs | 73 |
| Number Of Permutations | 47645 |
| Optimal Distance Threshold | 23.0 |
| K Statistic | 0.322 |
| p-value | 0.128 |
ClinVar
| Number Of Residues | 491 |
| Number Of SNVs | 46 |
| Number Of Permutations | 33322 |
| Optimal Distance Threshold | 12.0 |
| K Statistic | 0.247 |
| p-value | 0.0 |
COSMIC
| Number Of Residues | 491 |
| Number Of SNVs | 28 |
| Number Of Permutations | 28220 |
| Optimal Distance Threshold | 13.0 |
| K Statistic | 0.304 |
| p-value | 0.0 |
Ripley’s K Analysis Plots
ExACClinVarCOSMIC
Variant Set Comparisons
ClinVar vs. ExAC
| Number Of ExAC SNVs | 73 |
| Number Of ClinVar SNVs | 44 |
| Optimal Distance Threshold | 13.0 |
| K Statistic | 0.186 |
| p-value | 0.0 |
Cosmic vs. ExAC
| Number Of ExAC SNVs | 73 |
| Number Of COSMIC SNVs | 25 |
| Optimal Distance Threshold | 13.0 |
| K Statistic | 0.304 |
| p-value | 0.0 |
Pathogenic Proximity Analysis
ClinVar PathProx Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:112884090 | rs566068139 | P>A | B:9 | (34.03, 21.78, 12.66) |
| 12:112884091 | rs536503257 | P>Q | B:9 | (34.03, 21.78, 12.66) |
| 12:112884093 | rs368633510 | N>D | B:10 | (37.55, 22.77, 11.15) |
| 12:112884094 | rs200613531 | N>S | B:10 | (37.55, 22.77, 11.15) |
| 12:112884117 | N>D | B:18 | (45.61, 28.22, 21.89) | |
| 12:112884118 | N>S | B:18 | (45.61, 28.22, 21.89) | |
| 12:112884123 | L>V | B:20 | (39.44, 28.50, 25.28) | |
| 12:112884129 | T>A | B:22 | (43.35, 33.53, 23.66) | |
| 12:112884141 | D>N | B:26 | (37.11, 31.33, 33.53) | |
| 12:112888127 | N>S | B:48 | (40.40, 27.58, 37.85) | |
| 12:112888132 | A>T | B:50 | (42.68, 26.30, 32.91) | |
| 12:112888157 | N>S | B:58 | (27.54, 8.49, 19.89) | |
| 12:112888168 | rs121918460 CM021128 CM060446 |
Y>N | B:62 | (23.72, 6.14, 24.37) |
| 12:112888172 | rs121918459 | Y>C | B:63 | (25.40, 12.02, 21.58) |
| 12:112888196 | F>C | B:71 | (22.73, 13.64, 27.15) | |
| 12:112888221 | Q>H | B:79 | (19.51, 23.44, 26.80) | |
| 12:112888273 | rs397507516 | E>Q | B:97 | (31.05, 26.24, 35.69) |
| 12:112888285 | P>A | B:101 | (29.26, 30.19, 24.45) | |
| 12:112891058 | rs397516805 | K>R | B:131 | (12.05, 27.66, -6.14) |
| 12:112891117 | V>L | B:151 | (20.21, 35.95, -4.71) | |
| 12:112891121 | rs397507521 COSM22468 |
R>H | B:152 | (15.28, 31.80, -8.53) |
| 12:112891127 | rs376027245 | G>A | B:154 | (11.05, 36.25, -7.68) |
| 12:112891153 | G>S | B:163 | (8.10, 33.86, -11.14) | |
| 12:112891183 | rs545138829 | R>C | B:173 | (36.39, 44.60, 0.21) |
| 12:112891184 | rs369155025 | R>L | B:173 | (36.39, 44.60, 0.21) |
| 12:112892398 | rs143433437 | R>W | B:186 | (34.69, 45.91, 9.53) |
| 12:112892399 | R>Q | B:186 | (34.69, 45.91, 9.53) | |
| 12:112892414 | rs370763866 | T>R | B:191 | (27.27, 33.22, 9.91) |
| 12:112892427 | E>D | B:195 | (21.60, 35.76, 10.08) | |
| 12:112893762 | N>K | B:217 | (18.06, 21.77, -1.73) | |
| 12:112893763 | T>A | B:218 | (22.71, 20.79, -1.62) | |
| 12:112893770 | R>H | B:220 | (16.03, 18.61, -3.91) | |
| 12:112910748 | T>A | B:253 | (25.62, 20.35, 7.36) | |
| 12:112910770 | K>R | B:260 | (16.26, 25.15, 13.44) | |
| 12:112910773 | L>H | B:261 | (15.07, 20.58, 17.03) | |
| 12:112910776 | rs397507526 | L>H | B:262 | (15.65, 22.60, 21.49) |
| 12:112910779 | Y>C | B:263 | (10.99, 21.33, 19.58) | |
| 12:112910785 | rs376607329 | R>Q | B:265 | (13.11, 17.28, 27.04) |
| 12:112910792 | E>D | B:267 | (5.10, 15.67, 30.96) | |
| 12:112910793 | rs397507527 CM060444 CM060443 |
G>C | B:268 | (9.19, 13.69, 31.18) |
| 12:112910805 | E>K | B:272 | (5.33, 11.49, 38.99) | |
| 12:112910815 | rs397507528 | N>T | B:275 | (10.95, 5.32, 37.54) |
| 12:112910818 | K>R | B:276 | (7.24, 6.40, 34.26) | |
| 12:112910838 | L>M | B:283 | (13.24, 12.87, 27.41) | |
| 12:112915482 | D>G | B:294 | (-5.56, 4.07, 30.24) | |
| 12:112915523 | rs28933386 | N>D | B:308 | (7.53, 10.18, 20.59) |
| 12:112915526 | rs201787206 CM021136 |
I>V | B:309 | (3.76, 9.49, 17.32) |
| 12:112915532 | M>V | B:311 | (3.43, 11.09, 11.26) | |
| 12:112915533 | rs201226824 | M>T | B:311 | (3.43, 11.09, 11.26) |
| 12:112915698 | K>R | B:324 | (-2.05, 5.61, 4.41) | |
| 12:112915710 | rs369430257 | I>T | B:328 | (5.37, 4.12, 17.76) |
| 12:112915712 | A>T | B:329 | (9.12, 5.75, 18.62) | |
| 12:112915755 | rs535800148 | R>Q | B:343 | (-1.62, 1.76, 29.59) |
| 12:112915775 | rs146571700 | S>A | B:350 | (-0.28, -1.18, 17.38) |
| 12:112915779 | rs397507534 | R>Q | B:351 | (-3.13, -5.11, 14.47) |
| 12:112915781 | V>L | B:352 | (3.72, -4.44, 13.90) | |
| 12:112915784 | I>L | B:353 | (6.54, -5.08, 17.21) | |
| 12:112915796 | T>A | B:357 | (18.03, -5.11, 20.71) | |
| 12:112919887 | V>I | B:368 | (12.86, -5.86, 29.57) | |
| 12:112919906 | E>G | B:374 | (7.06, -20.67, 22.19) | |
| 12:112919909 | rs41299183 | Y>C | B:375 | (4.00, -22.69, 22.18) |
| 12:112919935 | COSM935281 | R>C | B:384 | (-5.82, -12.00, 29.27) |
| 12:112919947 | V>I | B:388 | (1.09, -18.10, 19.32) | |
| 12:112919959 | A>T | B:392 | (13.26, -18.94, 13.27) | |
| 12:112919975 | T>M | B:397 | (13.19, -14.05, 15.79) | |
| 12:112924280 | rs201247699 CM070248 |
G>A | B:409 | (-13.74, -10.41, 25.01) |
| 12:112924292 | R>K | B:413 | (-5.92, -6.31, 19.36) | |
| 12:112924339 | P>S | B:429 | (24.53, -3.60, 9.64) | |
| 12:112924381 | H>Y | B:443 | (6.02, -2.99, 3.93) | |
| 12:112924399 | I>V | B:449 | (-2.73, -5.80, 8.62) | |
| 12:112924420 | rs397516796 | V>L | B:456 | (6.05, -0.44, 17.18) |
| 12:112926270 | rs121918457 | T>M | B:468 | (18.42, 4.39, 11.76) |
| 12:112926275 | I>V | B:470 | (12.18, 4.69, 11.24) | |
| 12:112926306 | R>K | B:480 | (8.17, -0.09, -1.02) | |
| 12:112926848 | V>I | B:490 | (18.57, 11.92, 3.21) | |
| 12:112926851 | rs397507539 COSM13033 CM044253 CX097234 |
P>S | B:491 | (19.24, 15.17, 5.04) |
| 12:112926863 | Q>E | B:495 | (16.05, 17.78, 10.73) | |
| 12:112926909 | rs121918470 | Q>R | B:510 | (23.68, 5.08, 12.68) |
| 12:112926926 | M>V | B:516 | (24.74, 2.40, 1.66) |
[+] ClinVar Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:112884189 | rs397507501 | T>A | B:42 | (35.98, 16.66, 22.76) |
| 12:112888139 | rs397507503 | T>I | B:52 | (39.22, 20.76, 30.99) |
| 12:112888156 | rs397507505 | N>Y | B:58 | (27.54, 8.49, 19.89) |
| 12:112888158 | rs397507506 | N>K | B:58 | (27.54, 8.49, 19.89) |
| 12:112888162 | rs397507507 | G>S | B:60 | (24.81, 4.91, 18.63) |
| 12:112888163 | rs397507509 | G>V | B:60 | (24.81, 4.91, 18.63) |
| 12:112888165 | rs397507510 | D>N | B:61 | (22.91, 3.91, 21.17) |
| 12:112888166 | rs121918461 | D>V | B:61 | (22.91, 3.91, 21.17) |
| 12:112888168 | rs121918460 | Y>N | B:62 | (23.72, 6.14, 24.37) |
| 12:112888172 | rs121918459 | Y>C | B:63 | (25.40, 12.02, 21.58) |
| 12:112888189 | rs397507511 | E>Q | B:69 | (24.22, 12.58, 32.88) |
| 12:112888193 | rs397516801 | K>R | B:70 | (24.27, 8.09, 29.41) |
| 12:112888195 | rs397507512 | F>L | B:71 | (22.73, 13.64, 27.15) |
| 12:112888199 | rs121918454 | A>V | B:72 | (20.07, 12.89, 22.77) |
| 12:112888200 | rs397516802 | AT>AL | B:72 | (20.07, 12.89, 22.77) |
| 12:112888201 | rs397507513 | T>P | B:73 | (21.16, 16.10, 21.39) |
| 12:112888202 | rs121918462 | T>I | B:73 | (21.16, 16.10, 21.39) |
| 12:112888210 | rs121918464 | E>K | B:76 | (19.39, 18.00, 24.07) |
| 12:112888211 | rs121918465 | E>V | B:76 | (19.39, 18.00, 24.07) |
| 12:112888212 | rs397507514 | E>D | B:76 | (19.39, 18.00, 24.07) |
| 12:112888219 | rs397516803 | Q>K | B:79 | (19.51, 23.44, 26.80) |
| 12:112888220 | rs121918466 | Q>R | B:79 | (19.51, 23.44, 26.80) |
| 12:112888301 | rs397507517 | D>A | B:106 | (34.07, 28.04, 10.17) |
| 12:112888312 | rs397507518 | E>K | B:110 | (26.40, 27.01, 7.41) |
| 12:112888313 | rs397507519 | E>A | B:110 | (26.40, 27.01, 7.41) |
| 12:112891083 | rs397507520 | E>D | B:139 | (34.71, 30.53, -2.47) |
| 12:112891121 | rs397507521 | R>H | B:152 | (15.28, 31.80, -8.53) |
| 12:112892440 | rs727503381 | N>Y | B:200 | (17.83, 43.75, 8.17) |
| 12:112893772 | rs397516806 | I>L | B:221 | (18.66, 12.91, -4.80) |
| 12:112910758 | rs397507523 | Q>R | B:256 | (25.60, 23.07, 13.03) |
| 12:112910765 | rs397516809 | E>D | B:258 | (20.73, 19.94, 16.57) |
| 12:112910772 | rs397507525 | L>F | B:261 | (15.07, 20.58, 17.03) |
| 12:112910776 | rs397507526 | L>H | B:262 | (15.65, 22.60, 21.49) |
| 12:112910785 | rs376607329 | R>Q | B:265 | (13.11, 17.28, 27.04) |
| 12:112910793 | rs397507527 | G>S | B:268 | (9.19, 13.69, 31.18) |
| 12:112910827 | rs121918456 | Y>S | B:279 | (18.84, 5.75, 29.04) |
| 12:112910835 | rs397507529 | I>V | B:282 | (16.89, 10.38, 26.89) |
| 12:112910837 | rs397507530 | I>M | B:282 | (16.89, 10.38, 26.89) |
| 12:112910844 | rs397507531 | F>L | B:285 | (9.93, 15.92, 21.70) |
| 12:112915523 | rs28933386 | N>D | B:308 | (7.53, 10.18, 20.59) |
| 12:112915524 | rs121918455 | N>T | B:308 | (7.53, 10.18, 20.59) |
| 12:112924280 | rs201247699 | G>A | B:409 | (-13.74, -10.41, 25.01) |
| 12:112924286 | rs121918467 | T>K | B:411 | (-10.46, -7.35, 22.88) |
| 12:112924336 | rs397507536 | V>M | B:428 | (26.34, -0.67, 11.21) |
| 12:112926248 | rs121918468 | A>T | B:461 | (17.17, 4.54, 23.69) |
| 12:112926249 | rs397509344 | A>G | B:461 | (17.17, 4.54, 23.69) |
| 12:112926258 | rs121918469 | G>A | B:464 | (19.12, 5.27, 17.20) |
| 12:112926269 | rs397507537 | T>P | B:468 | (18.42, 4.39, 11.76) |
| 12:112926270 | rs121918457 | T>M | B:468 | (18.42, 4.39, 11.76) |
| 12:112926833 | rs397507538 | D>Y | B:485 | (11.89, 8.19, -11.40) |
| 12:112926840 | rs730880994 | D>G | B:487 | (12.70, 13.43, -5.91) |
| 12:112926851 | rs397507539 | P>T | B:491 | (19.24, 15.17, 5.04) |
| 12:112926852 | rs397507540 | P>H | B:491 | (19.24, 15.17, 5.04) |
| 12:112926872 | rs397507541 | R>W | B:498 | (17.72, 14.54, 13.68) |
| 12:112926873 | rs397507542 | R>L | B:498 | (17.72, 14.54, 13.68) |
| 12:112926882 | rs397507543 | R>K | B:501 | (12.23, 9.78, 20.42) |
| 12:112926884 | rs121918458 | S>T | B:502 | (14.91, 13.72, 20.57) |
| 12:112926885 | rs397507544 | S>L | B:502 | (14.91, 13.72, 20.57) |
| 12:112926887 | rs397507545 | G>R | B:503 | (17.85, 12.44, 17.92) |
| 12:112926888 | rs397507546 | G>E | B:503 | (17.85, 12.44, 17.92) |
| 12:112926890 | rs397507547 | M>V | B:504 | (15.72, 10.30, 15.58) |
| 12:112926897 | rs397507548 | Q>P | B:506 | (22.16, 9.39, 17.47) |
| 12:112926908 | rs397507549 | Q>K | B:510 | (23.68, 5.08, 12.68) |
| 12:112926909 | rs121918470 | Q>P | B:510 | (23.68, 5.08, 12.68) |
| 12:112926910 | rs397507550 | Q>H | B:510 | (23.68, 5.08, 12.68) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:112888139 | COSM13993 | T>S | B:52 | (39.22, 20.76, 30.99) |
| 12:112888145 | COSM1677359 | I>T | B:54 | (35.19, 16.67, 28.68) |
| 12:112888156 | COSM13032 | N>Y | B:58 | (27.54, 8.49, 19.89) |
| 12:112888162 | COSM13010 | G>R | B:60 | (24.81, 4.91, 18.63) |
| 12:112888163 | COSM13037 | G>A | B:60 | (24.81, 4.91, 18.63) |
| 12:112888165 | COSM13011 | D>Y | B:61 | (22.91, 3.91, 21.17) |
| 12:112888166 | COSM13022 | D>V | B:61 | (22.91, 3.91, 21.17) |
| 12:112888172 | COSM1358886 | Y>F | B:63 | (25.40, 12.02, 21.58) |
| 12:112888189 | COSM13013 | E>K | B:69 | (24.22, 12.58, 32.88) |
| 12:112888190 | COSM1358888 | E>G | B:69 | (24.22, 12.58, 32.88) |
| 12:112888195 | COSM13039 | F>L | B:71 | (22.73, 13.64, 27.15) |
| 12:112888198 | COSM1948744 | A>S | B:72 | (20.07, 12.89, 22.77) |
| 12:112888199 | COSM13035 | A>D | B:72 | (20.07, 12.89, 22.77) |
| 12:112888202 | COSM13019 | T>I | B:73 | (21.16, 16.10, 21.39) |
| 12:112888210 | COSM13016 | E>Q | B:76 | (19.39, 18.00, 24.07) |
| 12:112888211 | COSM13026 | E>A | B:76 | (19.39, 18.00, 24.07) |
| 12:112891006 | COSM3456259 | H>Y | B:114 | (27.56, 26.27, -1.51) |
| 12:112891035 | COSM201196 | E>D | B:123 | (23.74, 31.60, -12.45) |
| 12:112891082 | COSM1358892 | E>G | B:139 | (34.71, 30.53, -2.47) |
| 12:112891083 | COSM13018 | E>D | B:139 | (34.71, 30.53, -2.47) |
| 12:112892383 | COSM935276 | V>I | B:181 | (28.25, 44.43, 1.74) |
| 12:112892407 | COSM147613 | S>A | B:189 | (30.78, 36.16, 10.78) |
| 12:112910827 | COSM1731441 | Y>C | B:279 | (18.84, 5.75, 29.04) |
| 12:112910837 | COSM35820 | I>M | B:282 | (16.89, 10.38, 26.89) |
| 12:112915523 | COSM24612 | N>D | B:308 | (7.53, 10.18, 20.59) |
| 12:112915524 | COSM303867 | N>S | B:308 | (7.53, 10.18, 20.59) |
| 12:112915743 | COSM78372 | N>S | B:339 | (2.62, -3.66, 32.36) |
| 12:112924336 | COSM546362 | V>M | B:428 | (26.34, -0.67, 11.21) |
| 12:112926248 | COSM1287456 | A>T | B:461 | (17.17, 4.54, 23.69) |
| 12:112926249 | COSM935282 | A>G | B:461 | (17.17, 4.54, 23.69) |
| 12:112926270 | COSM170715 | T>M | B:468 | (18.42, 4.39, 11.76) |
| 12:112926852 | COSM13034 | P>L | B:491 | (19.24, 15.17, 5.04) |
| 12:112926884 | COSM20901 | S>A | B:502 | (14.91, 13.72, 20.57) |
| 12:112926885 | COSM13023 | S>L | B:502 | (14.91, 13.72, 20.57) |
| 12:112926888 | COSM13027 | G>A | B:503 | (17.85, 12.44, 17.92) |
| 12:112926897 | COSM1658770 | Q>P | B:506 | (22.16, 9.39, 17.47) |
| 12:112926899 | COSM1358900 | T>A | B:507 | (25.77, 7.57, 14.13) |
| 12:112926900 | COSM13036 | T>K | B:507 | (25.77, 7.57, 14.13) |
| 12:112926908 | COSM13031 | Q>K | B:510 | (23.68, 5.08, 12.68) |
| 12:112926909 | COSM1318059 | Q>L | B:510 | (23.68, 5.08, 12.68) |
| 12:112926910 | COSM1948766 | Q>H | B:510 | (23.68, 5.08, 12.68) |