General Structure Information
| PDB ID | 3gcw |
| HGNC Gene Label(s) | PCSK9 |
| Structure Name | pcsk9:egfa(h306y) |
| Resolution | 2.7Å |
| Reference | AUTH M.C.MCNUTT,H.J.KWON,C.CHEN,J.R.CHEN,J.D.HORTON,T.A.LAGACETITL ANTAGONISM OF SECRETED PCSK9 INCREASES LOW DENSITYTITL 2 LIPOPROTEIN RECEPTOR EXPRESSION IN HEPG2 CELLS.REF J.BIOL.CHEM. V. 284 10561 2009REFN ISSN 0021-9258PMID 19224862DOI 10.1074/JBC.M808802200 |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 434 |
| Number Of SNVs | 130 |
| Number Of Permutations | 24264 |
| Optimal Distance Threshold | 12.0 |
| K Statistic | 0.065 |
| p-value | 0.057 |
ClinVar
| Number Of Residues | 434 |
| Number Of SNVs | 4 |
| Number Of Permutations | 466 |
| Optimal Distance Threshold | 12.0 |
| K Statistic | 0.167 |
| p-value | 1.0 |
COSMIC
| Number Of Residues | 434 |
| Number Of SNVs | 13 |
| Number Of Permutations | 12106 |
| Optimal Distance Threshold | 18.0 |
| K Statistic | 0.295 |
| p-value | 0.753 |
Ripley’s K Analysis Plots
ExACClinVarCOSMIC
Variant Set Comparisons
ClinVar vs. ExAC
| Number Of ExAC SNVs | 130 |
| Number Of ClinVar SNVs | 4 |
| Optimal Distance Threshold | 12.0 |
| K Statistic | 0.101 |
| p-value | 0.884 |
Cosmic vs. ExAC
| Number Of ExAC SNVs | 130 |
| Number Of COSMIC SNVs | 12 |
| Optimal Distance Threshold | 6.0 |
| K Statistic | 0.021 |
| p-value | 0.894 |
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:55512260 | P>L | A:155 | (20.59, -26.55, -13.26) | |
| 1:55512266 | rs372600893 | N>S | A:157 | (21.28, -21.51, -12.97) |
| 1:55512267 | rs143117125 | N>K | A:157 | (21.28, -21.51, -12.97) |
| 1:55512272 | E>G | A:159 | (21.17, -22.81, -19.18) | |
| 1:55512275 | rs367620267 | R>Q | A:160 | (19.94, -18.66, -18.56) |
| 1:55512286 | rs138876953 | P>S | A:164 | (26.15, -20.55, -27.36) |
| 1:55512289 | rs141593516 | R>W | A:165 | (31.15, -20.59, -29.22) |
| 1:55512295 | rs137878146 | R>W | A:167 | (35.62, -24.82, -26.31) |
| 1:55512296 | COSM72119 | R>Q | A:167 | (35.62, -24.82, -26.31) |
| 1:55512299 | A>V | A:168 | (34.83, -26.79, -21.27) | |
| 1:55517956 | G>S | A:177 | (50.69, -23.70, -9.27) | |
| 1:55517957 | rs368899514 | G>D | A:177 | (50.69, -23.70, -9.27) |
| 1:55517960 | S>T | A:178 | (48.16, -20.90, -9.88) | |
| 1:55517980 | L>V | A:185 | (32.81, -12.31, 3.80) | |
| 1:55518007 | rs200027662 | R>W | A:194 | (27.94, -34.55, -2.09) |
| 1:55518008 | R>Q | A:194 | (27.94, -34.55, -2.09) | |
| 1:55518016 | E>K | A:197 | (34.13, -32.66, 1.55) | |
| 1:55518019 | G>S | A:198 | (38.00, -30.01, 0.91) | |
| 1:55518043 | COSM4009015 | E>K | A:206 | (36.61, -13.29, 19.41) |
| 1:55518049 | V>M | A:208 | (29.85, -11.99, 15.23) | |
| 1:55518323 | A>T | A:220 | (22.95, -25.99, 13.07) | |
| 1:55518339 | S>N | A:225 | (21.74, -21.69, 5.28) | |
| 1:55518342 | H>L | A:226 | (23.07, -17.24, 3.15) | |
| 1:55518362 | rs150169598 | V>L | A:233 | (26.46, -21.30, -6.08) |
| 1:55518371 | rs149489325 | G>S | A:236 | (29.87, -26.96, -6.67) |
| 1:55518374 | rs148195424 | R>W | A:237 | (30.58, -32.79, -6.85) |
| 1:55518375 | COSM3491048 | R>Q | A:237 | (30.58, -32.79, -6.85) |
| 1:55518383 | G>S | A:240 | (28.19, -25.09, -9.61) | |
| 1:55518386 | rs147478188 | V>M | A:241 | (29.73, -21.95, -11.47) |
| 1:55518390 | rs374014696 | A>V | A:242 | (33.37, -23.13, -10.02) |
| 1:55518405 | M>T | A:247 | (35.96, -21.34, -1.11) | |
| 1:55518407 | R>C | A:248 | (40.38, -19.00, 2.17) | |
| 1:55518408 | R>H | A:248 | (40.38, -19.00, 2.17) | |
| 1:55518412 | S>R | A:249 | (34.90, -18.99, 5.16) | |
| 1:55518416 | COSM302887 | R>C | A:251 | (30.59, -16.32, 11.36) |
| 1:55518417 | rs376945520 | R>H | A:251 | (30.59, -16.32, 11.36) |
| 1:55518422 | rs72646508 | L>F | A:253 | (26.83, -12.75, 8.72) |
| 1:55518437 | K>E | A:258 | (22.48, -9.01, 12.12) | |
| 1:55518452 | rs200146448 CM102604 |
G>S | A:263 | (33.24, -6.93, 10.92) |
| 1:55521678 | I>T | A:271 | (41.49, -10.87, 2.75) | |
| 1:55521680 | R>W | A:272 | (46.32, -6.85, 2.01) | |
| 1:55521695 | rs562011178 | V>L | A:277 | (51.67, -13.99, 4.31) |
| 1:55521701 | rs72646509 | P>T | A:279 | (50.92, -15.27, -2.13) |
| 1:55521713 | rs72646510 | L>M | A:283 | (42.17, -13.25, -4.35) |
| 1:55521729 | rs370748390 | P>L | A:288 | (26.99, -11.89, 0.30) |
| 1:55521737 | G>S | A:291 | (23.89, -1.78, 3.64) | |
| 1:55521747 | S>N | A:294 | (29.74, 3.02, 4.19) | |
| 1:55521749 | R>S | A:295 | (34.14, 7.69, 4.10) | |
| 1:55521750 | R>H | A:295 | (34.14, 7.69, 4.10) | |
| 1:55521752 | V>I | A:296 | (34.71, 2.60, 6.00) | |
| 1:55521758 | rs575003139 | N>D | A:298 | (32.90, 1.87, 0.03) |
| 1:55521771 | Q>R | A:302 | (39.36, 1.89, -3.20) | |
| 1:55521821 | COSM1126980 | R>W | A:319 | (11.50, -3.07, -6.61) |
| 1:55521827 | COSM3491049 | D>N | A:321 | (19.60, 3.20, -6.01) |
| 1:55521843 | S>F | A:326 | (27.32, -0.72, 1.21) | |
| 1:55523004 | V>I | A:333 | (32.86, -3.40, -6.59) | |
| 1:55523011 | T>I | A:335 | (27.34, -4.69, -8.28) | |
| 1:55523023 | T>I | A:339 | (17.69, -12.30, -13.02) | |
| 1:55523026 | N>S | A:340 | (13.82, -14.53, -13.48) | |
| 1:55523041 | P>L | A:345 | (13.63, -8.41, -12.62) | |
| 1:55523049 | L>M | A:348 | (12.24, -10.75, -3.17) | |
| 1:55523061 | G>R | A:352 | (13.75, -6.74, -4.75) | |
| 1:55523076 | rs148562777 | R>C | A:357 | (25.14, 5.03, -10.84) |
| 1:55523080 | C>Y | A:358 | (25.84, 1.17, -8.91) | |
| 1:55523109 | I>L | A:368 | (19.21, -20.93, -7.24) | |
| 1:55523125 | S>I | A:373 | (22.83, -27.20, 6.03) | |
| 1:55523127 | rs137852912 | D>N | A:374 | (19.52, -29.60, 6.60) |
| 1:55523136 | T>P | A:377 | (23.58, -35.22, 0.58) | |
| 1:55523137 | T>S | A:377 | (23.58, -35.22, 0.58) | |
| 1:55523140 | C>Y | A:378 | (21.05, -31.93, 1.21) | |
| 1:55523178 | rs146471967 | H>N | A:391 | (25.82, -17.44, -10.26) |
| 1:55523187 | rs368257906 | G>S | A:394 | (32.46, -18.02, -10.51) |
| 1:55523720 | M>V | A:398 | (36.05, -20.38, -14.42) | |
| 1:55523732 | rs533612423 | A>S | A:402 | (42.70, -19.26, -17.51) |
| 1:55523739 | rs140072072 | P>L | A:404 | (46.07, -15.73, -13.88) |
| 1:55523744 | L>V | A:406 | (42.68, -11.12, -15.88) | |
| 1:55523747 | T>P | A:407 | (43.01, -6.85, -14.51) | |
| 1:55523763 | R>K | A:412 | (34.75, -4.13, -14.45) | |
| 1:55523778 | H>R | A:417 | (31.73, -8.49, -24.75) | |
| 1:55523779 | rs143275858 | H>Q | A:417 | (31.73, -8.49, -24.75) |
| 1:55523784 | S>F | A:419 | (26.61, -10.39, -21.15) | |
| 1:55523793 | D>V | A:422 | (18.71, -5.90, -24.56) | |
| 1:55523796 | rs555751342 | V>A | A:423 | (17.02, -9.97, -21.90) |
| 1:55523798 | I>V | A:424 | (15.99, -7.10, -18.67) | |
| 1:55523802 | rs28362261 | N>S | A:425 | (11.02, -5.50, -19.56) |
| 1:55523815 | rs111427099 | F>L | A:429 | (14.03, -1.51, -13.84) |
| 1:55523822 | rs72646515 | D>N | A:432 | (14.66, 7.85, -12.90) |
| 1:55523828 | R>W | A:434 | (13.28, 2.50, -17.32) | |
| 1:55523831 | V>L | A:435 | (18.96, 4.92, -18.66) | |
| 1:55523838 | rs142055711 | T>N | A:437 | (19.91, -0.11, -15.16) |
| 1:55523855 | rs28362263 | A>T | A:443 | (27.98, -15.13, -19.15) |
| 1:55523862 | COSM1287033 | P>L | A:445 | (33.33, -16.64, -21.66) |
| 1:55523864 | P>S | A:446 | (32.84, -18.63, -25.34) | |
| 1:55524195 | V>I | A:460 | (30.39, 5.35, -16.95) | |
| 1:55524201 | S>P | A:462 | (27.08, 10.23, -13.60) | |
| 1:55524211 | S>W | A:465 | (23.70, 17.09, -10.87) | |
| 1:55524216 | P>A | A:467 | (18.40, 20.21, -9.00) | |
| 1:55524222 | rs141502002 | R>W | A:469 | (21.96, 28.15, -12.01) |
| 1:55524225 | M>L | A:470 | (25.30, 25.86, -13.32) | |
| 1:55524237 | rs562556 | V>I | A:474 | (32.06, 14.22, -12.55) |
| 1:55524240 | COSM681703 | A>T | A:475 | (32.60, 10.80, -15.33) |
| 1:55524243 | R>C | A:476 | (35.55, 9.93, -12.21) | |
| 1:55524244 | rs376388695 COSM329519 |
R>H | A:476 | (35.55, 9.93, -12.21) |
| 1:55524249 | rs375582388 COSM1219888 |
A>T | A:478 | (39.22, 3.06, -14.30) |
| 1:55524262 | rs141995194 | E>G | A:482 | (42.19, 5.26, -21.89) |
| 1:55524292 | rs537114569 | S>T | A:492 | (14.83, 18.78, -20.03) |
| 1:55524300 | COSM1579736 | R>W | A:495 | (22.52, 19.16, -22.66) |
| 1:55524303 | rs374603772 CM066163 |
R>W | A:496 | (26.48, 24.40, -21.59) |
| 1:55524304 | rs139669564 | R>Q | A:496 | (26.48, 24.40, -21.59) |
| 1:55524309 | rs145468572 | E>K | A:498 | (29.54, 17.85, -23.34) |
| 1:55524312 | rs201395805 | R>C | A:499 | (34.05, 20.17, -19.87) |
| 1:55525165 | rs374455190 | G>W | A:504 | (45.28, 14.85, -12.59) |
| 1:55525219 | A>T | A:522 | (27.94, 12.52, -17.19) | |
| 1:55527180 | G>A | A:605 | (46.38, -0.78, -33.17) | |
| 1:55527201 | E>G | A:612 | (26.54, 9.47, -39.92) | |
| 1:55527209 | I>V | A:615 | (15.49, 10.08, -38.66) | |
| 1:55527216 | COSM88103 | A>D | A:617 | (10.87, 13.03, -38.94) |
| 1:55527222 | rs28362277 | Q>P | A:619 | (10.90, 9.49, -33.98) |
| 1:55529045 | T>A | A:623 | (19.92, 4.24, -33.56) | |
| 1:55529048 | V>M | A:624 | (24.09, 3.97, -35.29) | |
| 1:55529055 | C>Y | A:626 | (29.01, -0.94, -35.01) | |
| 1:55529057 | E>K | A:627 | (30.14, -3.40, -38.96) | |
| 1:55529060 | COSM1687731 | E>K | A:628 | (30.72, -8.85, -36.74) |
| 1:55529090 | L>F | A:638 | (24.16, 16.34, -35.34) | |
| 1:55529093 | P>A | A:639 | (22.06, 19.65, -34.29) | |
| 1:55529100 | T>I | A:641 | (15.08, 21.48, -36.21) | |
| 1:55529105 | H>D | A:643 | (15.53, 19.88, -27.27) | |
| 1:55529108 | rs143291739 | V>I | A:644 | (19.05, 16.68, -28.03) |
| 1:55529117 | rs141438059 | A>S | A:647 | (24.05, 10.70, -26.10) |
| 1:55529123 | rs371744393 | A>T | A:649 | (26.50, 3.84, -25.43) |
| 1:55529126 | V>I | A:650 | (23.97, 0.65, -25.64) | |
| 1:55529127 | V>G | A:650 | (23.97, 0.65, -25.64) | |
| 1:55529129 | D>Y | A:651 | (27.05, -2.78, -26.87) | |
| 1:55529132 | rs201280059 | N>D | A:652 | (28.52, -1.77, -30.09) |
| 1:55529136 | T>K | A:653 | (24.14, 0.92, -30.31) | |
| 1:55529138 | C>R | A:654 | (24.66, 5.21, -30.88) | |
| 1:55529141 | V>I | A:655 | (21.49, 5.96, -28.34) | |
| 1:55529144 | V>I | A:656 | (20.13, 9.89, -29.99) | |
| 1:55529147 | R>G | A:657 | (16.40, 9.88, -25.62) | |
| 1:55529154 | R>L | A:659 | (9.67, 15.91, -27.84) | |
| 1:55529201 | V>I | A:675 | (27.52, 10.50, -34.71) | |
| 1:55529216 | rs533555352 COSM681702 |
R>W | A:680 | (38.93, -3.08, -36.86) |
| 1:55529222 | R>W | A:682 | (45.14, -1.32, -38.13) | |
| 1:55529223 | R>Q | A:682 | (45.14, -1.32, -38.13) |
[+] ClinVar Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:55518037 | rs793888521 | D>N | A:204 | (36.05, -18.27, 13.01) |
| 1:55523127 | rs137852912 | D>N | A:374 | (19.52, -29.60, 6.60) |
| 1:55524222 | rs141502002 | R>W | A:469 | (21.96, 28.15, -12.01) |
| 1:55524303 | rs374603772 | R>W | A:496 | (26.48, 24.40, -21.59) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:55512301 | COSM3491043 | D>N | A:169 | (38.38, -27.82, -22.94) |
| 1:55518028 | COSM1602565 | M>L | A:201 | (40.14, -23.43, 4.13) |
| 1:55518416 | COSM302887 | R>C | A:251 | (30.59, -16.32, 11.36) |
| 1:55518420 | COSM2194313 | V>A | A:252 | (30.77, -11.55, 8.89) |
| 1:55521827 | COSM3491049 | D>N | A:321 | (19.60, 3.20, -6.01) |
| 1:55523739 | COSM1343562 | P>L | A:404 | (46.07, -15.73, -13.88) |
| 1:55524200 | COSM217080 | W>C | A:461 | (24.87, 6.95, -17.43) |
| 1:55524222 | COSM910985 | R>W | A:469 | (21.96, 28.15, -12.01) |
| 1:55524237 | COSM3722998 | V>I | A:474 | (32.06, 14.22, -12.55) |
| 1:55524301 | COSM4988890 | R>Q | A:495 | (22.52, 19.16, -22.66) |
| 1:55525216 | COSM3705937 | Y>H | A:521 | (22.51, 11.94, -15.65) |
| 1:55529042 | COSM1667567 | V>M | A:622 | (18.10, 8.16, -33.54) |
| 1:55529123 | COSM3737487 | A>S | A:649 | (26.50, 3.84, -25.43) |