General Structure Information
| PDB ID | 4h8s |
| HGNC Gene Label(s) | APPL2 |
| Structure Name | crystal structure of human appl2barph domain |
| Resolution | 3.5Å |
| Reference | AUTH G.J.KING,J.STOCKLI,S.H.HU,B.WINNEN,W.G.DUPREZ,C.C.MEOLI,AUTH 2 J.R.JUNUTULA,R.J.JARROTT,D.E.JAMES,A.E.WHITTEN,J.L.MARTINTITL MEMBRANE CURVATURE PROTEIN EXHIBITS INTERDOMAIN FLEXIBILITYTITL 2 AND BINDS A SMALL GTPASE.REF J.BIOL.CHEM. V. 287 40996 2012REFN ISSN 0021-9258PMID 23055524DOI 10.1074/JBC.M112.349803 |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 374 |
| Number Of SNVs | 113 |
| Number Of Permutations | 47353 |
| Optimal Distance Threshold | 26.0 |
| K Statistic | 0.217 |
| p-value | 0.195 |
COSMIC
| Number Of Residues | 374 |
| Number Of SNVs | 5 |
| Number Of Permutations | 5890 |
| Optimal Distance Threshold | 29.0 |
| K Statistic | 0.1 |
| p-value | 0.71 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 113 |
| Number Of COSMIC SNVs | 4 |
| Optimal Distance Threshold | 29.0 |
| K Statistic | -0.255 |
| p-value | 0.313 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:105623001 | T>A | C:19 | (-0.81, 26.40, 21.63) | |
| 12:105622998 | R>C | C:20 | (1.54, 30.40, 18.62) | |
| 12:105622989 | rs139323627 | L>M | C:23 | (2.14, 25.25, 16.15) |
| 12:105622985 | S>T | C:24 | (6.84, 25.03, 17.49) | |
| 12:105622983 | rs143353224 | V>M | C:25 | (7.31, 20.68, 18.45) |
| 12:105622979 | F>Y | C:26 | (2.76, 19.34, 15.70) | |
| 12:105622977 | rs374010500 | E>K | C:27 | (6.00, 23.86, 12.59) |
| 12:105622958 | rs139884004 | L>P | C:33 | (7.83, 14.26, 7.19) |
| 12:105622952 | D>G | C:35 | (13.51, 16.87, 4.44) | |
| 12:105622950 | rs200398672 | Y>D | C:36 | (12.36, 10.25, 4.82) |
| 12:105622947 | T>A | C:37 | (9.18, 12.52, 2.09) | |
| 12:105622935 | L>F | C:41 | (10.07, 11.15, -4.38) | |
| 12:105622931 | Q>R | C:42 | (15.20, 11.93, -4.92) | |
| 12:105622926 | rs201895822 | M>V | C:44 | (10.66, 5.61, -4.46) |
| 12:105622922 | rs143947108 | Q>R | C:45 | (11.57, 8.81, -8.88) |
| 12:105622919 | rs149470075 | R>H | C:46 | (19.14, 5.33, -8.39) |
| 12:105622920 | R>C | C:46 | (19.14, 5.33, -8.39) | |
| 12:105622913 | rs150695109 | Y>C | C:48 | (10.12, 4.02, -12.81) |
| 12:105611501 | N>K | C:52 | (12.24, 2.57, -17.61) | |
| 12:105611493 | C>Y | C:55 | (12.13, -1.86, -20.33) | |
| 12:105611488 | A>S | C:57 | (17.96, -2.43, -22.56) | |
| 12:105611468 | K>N | C:63 | (16.09, -3.12, -33.51) | |
| 12:105611463 | L>R | C:65 | (19.04, -10.86, -30.97) | |
| 12:105611448 | rs36126236 | K>R | C:70 | (16.88, -7.86, -41.98) |
| 12:105610914 | F>C | C:73 | (26.71, -12.27, -42.58) | |
| 12:105610881 | S>L | C:84 | (15.71, -20.29, -37.01) | |
| 12:105610879 | rs528912301 | T>A | C:85 | (18.53, -20.38, -33.34) |
| 12:105610872 | H>R | C:87 | (13.90, -15.45, -35.19) | |
| 12:105610869 | rs372091392 | Y>C | C:88 | (12.75, -19.74, -29.18) |
| 12:105610857 | V>A | C:92 | (12.79, -15.48, -24.94) | |
| 12:105605085 | L>P | C:99 | (7.05, -10.03, -17.71) | |
| 12:105605068 | K>E | C:105 | (1.77, 1.29, -16.76) | |
| 12:105605050 | COSM1476069 | M>V | C:111 | (6.44, 2.54, -5.57) |
| 12:105605040 | P>L | C:114 | (1.43, 6.64, -3.99) | |
| 12:105605038 | I>V | C:115 | (5.80, 8.96, -1.88) | |
| 12:105605025 | R>Q | C:119 | (6.43, 17.35, -1.19) | |
| 12:105605017 | D>N | C:122 | (-0.73, 16.23, 1.55) | |
| 12:105605008 | rs201895197 | E>K | C:125 | (-2.77, 21.31, 2.26) |
| 12:105601972 | S>G | C:127 | (3.57, 24.70, 3.70) | |
| 12:105601957 | rs147095029 | L>I | C:132 | (-2.88, 31.26, 4.87) |
| 12:105601954 | F>I | C:133 | (-1.60, 30.78, 11.46) | |
| 12:105601948 | L>F | C:135 | (-0.40, 36.58, 5.97) | |
| 12:105601945 | rs202080524 COSM1358380 |
A>T | C:136 | (-3.60, 35.88, 9.72) |
| 12:105601938 | N>S | C:138 | (1.54, 39.13, 10.88) | |
| 12:105601805 | rs199849659 | H>Y | C:140 | (-4.56, 39.72, 15.49) |
| 12:105601802 | D>N | C:141 | (-0.22, 41.37, 15.77) | |
| 12:105601789 | rs530932657 | A>V | C:145 | (-1.03, 47.58, 17.66) |
| 12:105601776 | R>S | C:149 | (-1.64, 52.81, 18.70) | |
| 12:105601771 | P>R | C:151 | (-8.09, 58.22, 22.43) | |
| 12:105601758 | E>D | C:155 | (-13.19, 57.93, 23.14) | |
| 12:105601752 | E>D | C:157 | (-17.92, 56.76, 20.14) | |
| 12:105600985 | V>M | C:159 | (-12.37, 56.35, 15.57) | |
| 12:105600978 | T>I | C:161 | (-17.03, 51.44, 17.76) | |
| 12:105600976 | rs141732009 | E>K | C:162 | (-14.18, 52.00, 12.78) |
| 12:105600970 | rs148334760 | G>R | C:164 | (-13.09, 47.29, 16.92) |
| 12:105600955 | A>T | C:169 | (-11.67, 41.45, 10.79) | |
| 12:105600948 | COSM3398282 | R>L | C:171 | (-9.76, 38.46, 17.59) |
| 12:105600945 | R>Q | C:172 | (-14.17, 35.23, 11.89) | |
| 12:105600936 | H>L | C:175 | (-10.45, 31.20, 15.26) | |
| 12:105600937 | H>Y | C:175 | (-10.45, 31.20, 15.26) | |
| 12:105600900 | rs140436242 | A>V | C:187 | (-4.81, 14.64, 9.40) |
| 12:105600901 | rs558129964 COSM691477 |
A>T | C:187 | (-4.81, 14.64, 9.40) |
| 12:105600882 | Q>R | C:193 | (1.14, 6.40, 10.13) | |
| 12:105600855 | rs368049760 | G>A | C:202 | (2.56, -1.82, -4.24) |
| 12:105600846 | rs146751866 | H>R | C:205 | (1.23, -6.70, -4.84) |
| 12:105600844 | rs56721530 | G>R | C:206 | (4.50, -5.67, -8.76) |
| 12:105597563 | I>V | C:208 | (4.03, -11.07, -6.16) | |
| 12:105597555 | F>L | C:210 | (8.62, -9.66, -12.71) | |
| 12:105597552 | COSM1358379 | F>L | C:211 | (10.08, -12.33, -9.48) |
| 12:105597542 | A>T | C:215 | (8.77, -18.06, -13.07) | |
| 12:105597529 | S>C | C:219 | (10.02, -22.93, -16.30) | |
| 12:105597523 | R>H | C:221 | (6.69, -25.85, -19.08) | |
| 12:105597524 | R>C | C:221 | (6.69, -25.85, -19.08) | |
| 12:105597521 | M>V | C:222 | (13.29, -22.02, -21.64) | |
| 12:105597518 | D>H | C:223 | (15.64, -26.44, -19.99) | |
| 12:105597489 | COSM691478 | M>I | C:232 | (22.73, -27.01, -32.26) |
| 12:105597490 | M>R | C:232 | (22.73, -27.01, -32.26) | |
| 12:105597491 | rs373794263 COSM4038218 |
M>V | C:232 | (22.73, -27.01, -32.26) |
| 12:105593304 | rs370041244 | Q>R | C:237 | (34.09, -27.08, -30.62) |
| 12:105593292 | E>A | C:241 | (38.31, -29.25, -32.73) | |
| 12:105593287 | E>K | C:243 | (38.09, -28.33, -40.64) | |
| 12:105593274 | M>T | C:247 | (42.94, -26.19, -41.66) | |
| 12:105593271 | rs573855703 | R>Q | C:248 | (48.34, -28.96, -37.73) |
| 12:105593272 | R>W | C:248 | (48.34, -28.96, -37.73) | |
| 12:105593265 | S>F | C:250 | (47.49, -29.20, -45.07) | |
| 12:105593244 | V>A | C:257 | (57.86, -26.96, -51.36) | |
| 12:105593242 | rs200933846 | D>Y | C:258 | (62.45, -27.23, -52.20) |
| 12:105593237 | E>D | C:259 | (64.50, -22.17, -52.55) | |
| 12:105593239 | E>Q | C:259 | (64.50, -22.17, -52.55) | |
| 12:105593235 | COSM1358378 | S>C | C:260 | (63.52, -24.88, -56.58) |
| 12:105593224 | COSM3954094 | P>A | C:264 | (61.72, -16.73, -60.18) |
| 12:105593217 | S>F | C:266 | (63.80, -22.59, -61.55) | |
| 12:105593214 | D>V | C:267 | (62.14, -24.27, -65.11) | |
| 12:105593209 | A>T | C:269 | (67.37, -24.81, -68.88) | |
| 12:105593205 | rs200465844 | A>V | C:270 | (64.68, -27.87, -68.58) |
| 12:105593202 | P>Q | C:271 | (61.61, -25.41, -70.13) | |
| 12:105593188 | N>H | C:276 | (48.12, -26.94, -76.80) | |
| 12:105593169 | rs186184574 | G>A | C:282 | (48.05, -15.30, -63.50) |
| 12:105591723 | G>A | C:291 | (48.92, 10.34, -70.40) | |
| 12:105591705 | W>L | C:297 | (55.90, -1.92, -67.13) | |
| 12:105591702 | rs531059218 | E>G | C:298 | (50.79, -1.89, -62.76) |
| 12:105591679 | G>S | C:306 | (35.08, -15.71, -72.54) | |
| 12:105591676 | G>R | C:307 | (37.73, -15.62, -74.76) | |
| 12:105591663 | C>Y | C:311 | (42.09, -8.04, -64.44) | |
| 12:105591657 | P>R | C:313 | (41.86, -6.08, -59.05) | |
| 12:105591649 | A>P | C:316 | (37.79, -7.53, -56.46) | |
| 12:105591643 | A>T | C:318 | (35.33, -10.66, -60.80) | |
| 12:105591616 | N>D | C:327 | (40.49, -11.64, -83.26) | |
| 12:105591603 | rs201147739 | M>T | C:331 | (54.62, -11.06, -81.50) |
| 12:105591598 | V>M | C:333 | (57.71, -7.32, -77.78) | |
| 12:105591589 | rs192353876 | E>K | C:336 | (61.38, -0.57, -71.52) |
| 12:105591582 | rs370645949 | R>Q | C:338 | (61.05, -4.74, -68.42) |
| 12:105591583 | rs138871502 | R>W | C:338 | (61.05, -4.74, -68.42) |
| 12:105591579 | rs150223880 | R>H | C:339 | (64.46, -11.42, -68.35) |
| 12:105591552 | N>S | C:348 | (41.84, -2.63, -86.25) | |
| 12:105591553 | rs148108135 | N>D | C:348 | (41.84, -2.63, -86.25) |
| 12:105591543 | S>L | C:351 | (47.71, -0.07, -81.15) | |
| 12:105589404 | rs375176995 | G>R | C:352 | (48.53, -2.79, -78.65) |
| 12:105589401 | rs183791204 | I>V | C:353 | (47.69, -4.39, -74.23) |
| 12:105589384 | rs140500827 | E>D | C:358 | (58.04, -14.84, -63.97) |
| 12:105589379 | R>T | C:360 | (62.35, -18.66, -71.73) | |
| 12:105589258 | I>V | C:373 | (41.76, -18.30, -76.26) | |
| 12:105589244 | I>M | C:377 | (36.80, -22.42, -85.38) | |
| 12:105589246 | I>V | C:377 | (36.80, -22.42, -85.38) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:105622917 | COSM1639016 | V>I | C:47 | (14.07, 1.69, -7.86) |
| 12:105601945 | COSM1358380 | A>T | C:136 | (-3.60, 35.88, 9.72) |
| 12:105600919 | COSM3376089 | Y>H | C:181 | (-1.52, 25.29, 10.36) |
| 12:105597508 | COSM97960 | L>S | C:226 | (18.11, -23.32, -23.25) |
| 12:105591583 | COSM1746703 | R>W | C:338 | (61.05, -4.74, -68.42) |