General Structure Information
| PDB ID | 1as4 |
| HGNC Gene Label(s) | SERPINA3 |
| Structure Name | cleaved antichymotrypsin a349r |
| Resolution | 2.1Å |
| Reference | AUTH C.M.LUKACS,H.RUBIN,D.W.CHRISTIANSONTITL ENGINEERING AN ANION-BINDING CAVITY INTITL 2 ANTICHYMOTRYPSIN MODULATES THE SPRING-LOADEDTITL 3 SERPIN-PROTEASE INTERACTION.REF BIOCHEMISTRY V. 37 3297 1998REFN ISSN 0006-2960PMID 9521649DOI 10.1021/BI972359E |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 334 |
| Number Of SNVs | 116 |
| Number Of Permutations | 51150 |
| Optimal Distance Threshold | 13.0 |
| K Statistic | 0.094 |
| p-value | 0.857 |
COSMIC
| Number Of Residues | 334 |
| Number Of SNVs | 7 |
| Number Of Permutations | 1861 |
| Optimal Distance Threshold | 18.0 |
| K Statistic | 0.048 |
| p-value | 0.188 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 116 |
| Number Of COSMIC SNVs | 9 |
| Optimal Distance Threshold | 28.0 |
| K Statistic | -0.254 |
| p-value | 0.023 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 14:95080920 | COSM287684 COSM4053270 |
G>R | A:25 | (-2.93, 23.07, 24.78) |
| 14:95080926 | A>T | A:27 | (-0.61, 20.03, 27.34) | |
| 14:95080932 | rs188602956 | A>T | A:29 | (0.07, 17.96, 22.77) |
| 14:95080936 | COSM248738 | N>S | A:30 | (3.24, 17.06, 25.78) |
| 14:95080938 | V>M | A:31 | (0.08, 14.04, 26.75) | |
| 14:95080943 | D>E | A:32 | (-0.71, 12.91, 22.04) | |
| 14:95080946 | F>L | A:33 | (5.19, 13.99, 21.47) | |
| 14:95080947 | A>T | A:34 | (4.43, 11.34, 25.04) | |
| 14:95080951 | F>S | A:35 | (1.44, 8.64, 26.16) | |
| 14:95080953 | rs200348449 | S>G | A:36 | (3.31, 8.67, 20.64) |
| 14:95080995 | V>F | A:50 | (11.89, 3.86, 28.88) | |
| 14:95080999 | I>N | A:51 | (14.56, 7.08, 30.56) | |
| 14:95081014 | S>N | A:56 | (13.27, 18.28, 25.92) | |
| 14:95081016 | I>V | A:57 | (12.01, 16.07, 22.71) | |
| 14:95081025 | rs199923400 COSM2253565 COSM2253564 |
A>T | A:60 | (13.92, 21.37, 20.44) |
| 14:95081026 | A>V | A:60 | (13.92, 21.37, 20.44) | |
| 14:95081041 | S>Y | A:65 | (10.06, 25.31, 13.99) | |
| 14:95081049 | A>P | A:68 | (10.88, 26.30, 9.28) | |
| 14:95081050 | A>V | A:68 | (10.88, 26.30, 9.28) | |
| 14:95081055 | rs542942614 | N>D | A:70 | (6.84, 25.31, 3.52) |
| 14:95081061 | T>P | A:72 | (9.86, 21.21, 7.03) | |
| 14:95081062 | rs138782301 | T>I | A:72 | (9.86, 21.21, 7.03) |
| 14:95081074 | I>N | A:76 | (7.98, 19.77, 12.91) | |
| 14:95081079 | K>E | A:78 | (1.28, 17.40, 11.61) | |
| 14:95081101 | rs375245228 COSM167999 COSM3499428 |
T>M | A:85 | (-7.34, 23.33, 12.40) |
| 14:95081107 | T>I | A:87 | (-3.34, 25.79, 16.76) | |
| 14:95081116 | rs372323053 | A>V | A:90 | (1.87, 31.74, 17.00) |
| 14:95081125 | H>R | A:93 | (6.36, 29.35, 18.69) | |
| 14:95081131 | S>N | A:95 | (2.86, 28.23, 24.64) | |
| 14:95081139 | rs571405902 | H>Y | A:98 | (3.95, 31.95, 28.34) |
| 14:95081149 | R>H | A:101 | (7.89, 33.85, 32.61) | |
| 14:95081152 | T>N | A:102 | (6.48, 28.88, 34.44) | |
| 14:95081154 | L>F | A:103 | (9.23, 25.41, 34.14) | |
| 14:95081158 | rs145819878 | N>S | A:104 | (12.95, 28.43, 35.12) |
| 14:95081161 | rs373891589 | Q>L | A:105 | (10.47, 27.50, 40.59) |
| 14:95081162 | Q>H | A:105 | (10.47, 27.50, 40.59) | |
| 14:95081169 | rs193129853 | D>N | A:108 | (10.46, 26.79, 46.75) |
| 14:95081186 | S>R | A:113 | (15.95, 23.91, 35.27) | |
| 14:95081187 | M>L | A:114 | (14.32, 24.33, 30.63) | |
| 14:95081213 | COSM1728011 COSM1728010 |
E>D | A:122 | (33.24, 30.92, 13.98) |
| 14:95081214 | rs569265798 | Q>K | A:123 | (32.35, 33.74, 9.96) |
| 14:95081217 | rs536239718 | L>V | A:124 | (26.69, 31.18, 9.76) |
| 14:95081232 | R>G | A:129 | (11.86, 36.51, 12.25) | |
| 14:95081239 | T>M | A:131 | (18.36, 35.57, 16.60) | |
| 14:95081260 | rs566778767 | Y>C | A:138 | (11.93, 28.95, 22.12) |
| 14:95081266 | S>F | A:140 | (18.35, 31.11, 23.08) | |
| 14:95081287 | rs370400377 COSM959234 |
F>S | A:147 | (31.07, 23.28, 14.67) |
| 14:95081288 | F>L | A:147 | (31.07, 23.28, 14.67) | |
| 14:95081292 | D>N | A:149 | (38.33, 21.96, 16.78) | |
| 14:95081298 | A>T | A:151 | (37.17, 18.55, 20.14) | |
| 14:95081299 | A>V | A:151 | (37.17, 18.55, 20.14) | |
| 14:95081304 | A>T | A:153 | (32.89, 21.70, 20.00) | |
| 14:95081305 | A>V | A:153 | (32.89, 21.70, 20.00) | |
| 14:95081316 | rs201696762 | I>F | A:157 | (27.98, 21.41, 23.38) |
| 14:95081317 | rs538754919 | I>N | A:157 | (27.98, 21.41, 23.38) |
| 14:95081318 | I>M | A:157 | (27.98, 21.41, 23.38) | |
| 14:95081322 | rs556765561 | D>N | A:159 | (31.14, 21.60, 29.44) |
| 14:95081324 | D>E | A:159 | (31.14, 21.60, 29.44) | |
| 14:95081328 | rs542255755 COSM1678223 |
V>M | A:161 | (24.82, 20.05, 29.17) |
| 14:95081343 | rs146703583 | R>G | A:166 | (22.74, 21.45, 38.43) |
| 14:95081369 | rs561175087 | K>N | A:174 | (28.81, 10.67, 21.93) |
| 14:95081370 | D>N | A:175 | (29.68, 12.20, 17.01) | |
| 14:95081376 | D>N | A:177 | (29.42, 15.75, 11.16) | |
| 14:95081390 | M>I | A:181 | (26.95, 24.53, 10.11) | |
| 14:95081400 | rs368397050 | V>M | A:185 | (20.79, 22.43, 23.12) |
| 14:95081409 | rs184704051 | I>L | A:188 | (15.24, 19.46, 31.67) |
| 14:95085542 | E>D | A:195 | (4.98, 15.39, 51.08) | |
| 14:95085547 | P>L | A:197 | (10.35, 10.98, 53.41) | |
| 14:95085554 | rs373313640 | D>E | A:199 | (14.05, 5.54, 57.09) |
| 14:95085556 | P>L | A:200 | (17.25, 5.00, 55.25) | |
| 14:95085561 | rs567715410 | D>H | A:202 | (13.12, 1.01, 56.66) |
| 14:95085567 | H>Y | A:204 | (15.93, -3.70, 54.01) | |
| 14:95085571 | rs143453310 | Q>R | A:205 | (18.83, -5.83, 49.27) |
| 14:95085572 | rs185981965 | Q>H | A:205 | (18.83, -5.83, 49.27) |
| 14:95085587 | rs370200741 | L>F | A:210 | (13.18, -9.18, 35.57) |
| 14:95085588 | S>R | A:211 | (10.41, -12.64, 35.16) | |
| 14:95085598 | rs76970295 | K>R | A:214 | (14.68, -13.61, 35.61) |
| 14:95085604 | V>A | A:216 | (17.18, -8.59, 40.45) | |
| 14:95085608 | M>I | A:217 | (18.59, -8.65, 44.84) | |
| 14:95085612 | rs140884476 | P>S | A:219 | (17.71, -1.51, 46.94) |
| 14:95085615 | M>V | A:220 | (12.96, -2.45, 48.25) | |
| 14:95085619 | M>T | A:221 | (12.68, 2.28, 49.31) | |
| 14:95085630 | H>Y | A:225 | (0.98, 2.58, 58.80) | |
| 14:95085651 | rs139055497 | R>W | A:231 | (-6.73, -2.16, 40.89) |
| 14:95085652 | rs536399107 | R>Q | A:231 | (-6.73, -2.16, 40.89) |
| 14:95085657 | rs374902447 COSM229564 COSM2253596 |
E>K | A:233 | (-9.81, -4.38, 38.36) |
| 14:95085675 | rs146977492 | V>M | A:239 | (-2.52, 4.06, 40.28) |
| 14:95085696 | G>S | A:246 | (5.49, 21.10, 45.55) | |
| 14:95085703 | A>G | A:248 | (5.11, 17.86, 41.92) | |
| 14:95085708 | rs144237088 | A>T | A:250 | (4.78, 10.77, 41.21) |
| 14:95085717 | I>F | A:253 | (1.51, 2.85, 36.69) | |
| 14:95085721 | L>P | A:254 | (2.02, -1.85, 39.44) | |
| 14:95085730 | Q>P | A:257 | (3.03, -10.61, 36.60) | |
| 14:95085731 | Q>H | A:257 | (3.03, -10.61, 36.60) | |
| 14:95085750 | E>K | A:264 | (2.56, -0.41, 27.17) | |
| 14:95085756 | M>L | A:266 | (-4.69, 1.44, 26.52) | |
| 14:95085758 | rs148556633 | M>I | A:266 | (-4.69, 1.44, 26.52) |
| 14:95085779 | K>N | A:273 | (-8.51, 12.63, 32.39) | |
| 14:95085781 | rs139747783 | R>Q | A:274 | (-9.55, 6.28, 33.74) |
| 14:95085790 | D>V | A:277 | (-10.03, 12.19, 37.49) | |
| 14:95085805 | R>T | A:281 | (-7.07, 3.08, 49.90) | |
| 14:95088681 | rs553980476 | E>D | A:282 | (-5.17, 4.06, 55.43) |
| 14:95088682 | I>V | A:283 | (-1.29, 2.26, 52.15) | |
| 14:95088683 | rs142398813 | I>T | A:283 | (-1.29, 2.26, 52.15) |
| 14:95088686 | G>D | A:284 | (0.41, -0.17, 55.01) | |
| 14:95088707 | COSM3499458 COSM3499457 |
F>S | A:291 | (15.86, 3.53, 40.69) |
| 14:95088716 | COSM174004 COSM2253623 |
S>L | A:294 | (20.68, 5.66, 32.06) |
| 14:95088721 | D>N | A:296 | (21.86, 7.04, 24.97) | |
| 14:95088734 | rs539470184 | N>T | A:300 | (16.80, 9.88, 13.57) |
| 14:95088736 | COSM959238 | D>N | A:301 | (14.51, 5.79, 13.76) |
| 14:95088739 | I>L | A:302 | (11.49, 7.66, 16.77) | |
| 14:95088745 | rs199725647 | L>F | A:304 | (11.29, 9.46, 10.39) |
| 14:95088757 | rs200519805 | I>L | A:308 | (9.42, 14.47, 11.67) |
| 14:95088758 | rs371483383 | I>T | A:308 | (9.42, 14.47, 11.67) |
| 14:95088766 | A>T | A:311 | (14.29, 17.82, 7.92) | |
| 14:95088767 | A>G | A:311 | (14.29, 17.82, 7.92) | |
| 14:95088773 | T>I | A:313 | (15.69, 15.40, 3.42) | |
| 14:95088786 | D>E | A:317 | (12.60, 24.56, 4.00) | |
| 14:95088794 | G>E | A:320 | (14.65, 30.73, 8.43) | |
| 14:95088814 | L>I | A:327 | (20.67, 24.17, 6.81) | |
| 14:95088820 | V>I | A:329 | (18.52, 17.58, 10.42) | |
| 14:95088821 | V>A | A:329 | (18.52, 17.58, 10.42) | |
| 14:95088827 | rs527354355 | Q>P | A:331 | (21.73, 12.95, 14.82) |
| 14:95089956 | rs149892304 | H>Q | A:334 | (17.06, 12.40, 24.83) |
| 14:95089972 | V>I | A:340 | (14.85, 7.01, 42.90) | |
| 14:95089975 | rs368789568 | F>V | A:341 | (16.88, 9.55, 46.24) |
| 14:95089976 | F>Y | A:341 | (16.88, 9.55, 46.24) | |
| 14:95089983 | E>D | A:343 | (16.14, 11.56, 50.55) | |
| 14:95089985 | G>A | A:344 | (14.04, 11.65, 46.33) | |
| 14:95090002 | rs373895665 | A>P | A:350 | (19.07, 16.27, 27.00) |
| 14:95090006 | T>I | A:351 | (17.72, 17.34, 23.41) | |
| 14:95090008 | rs376451584 | A>S | A:352 | (20.38, 17.46, 20.40) |
| 14:95090009 | rs370632161 COSM396425 |
A>V | A:352 | (20.38, 17.46, 20.40) |
| 14:95090011 | V>I | A:353 | (19.38, 19.32, 16.88) | |
| 14:95090015 | K>R | A:354 | (23.55, 16.77, 15.38) | |
| 14:95090021 | rs549484493 | T>S | A:356 | (24.37, 19.70, 8.34) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 14:95080920 | COSM287684 | G>R | A:25 | (-2.93, 23.07, 24.78) |
| 14:95081101 | COSM3499428 | T>M | A:85 | (-7.34, 23.33, 12.40) |
| 14:95081211 | COSM249638 | E>K | A:122 | (33.24, 30.92, 13.98) |
| 14:95081252 | COSM4821329 | K>N | A:135 | (17.10, 36.06, 22.61) |
| 14:95081328 | COSM1678223 | V>M | A:161 | (24.82, 20.05, 29.17) |
| 14:95085657 | COSM229564 | E>K | A:233 | (-9.81, -4.38, 38.36) |
| 14:95085658 | COSM2151436 | E>V | A:233 | (-9.81, -4.38, 38.36) |
| 14:95085740 | COSM1707832 | M>I | A:260 | (3.45, -3.60, 31.02) |
| 14:95088688 | COSM554137 | E>K | A:285 | (3.31, -2.39, 53.90) |
| 14:95088716 | COSM2253623 | S>L | A:294 | (20.68, 5.66, 32.06) |
| 14:95088736 | COSM4394497 | D>N | A:301 | (14.51, 5.79, 13.76) |