General Structure Information
| PDB ID | 4ip7 |
| HGNC Gene Label(s) | PKLR |
| Structure Name | structure of the s12d variant of human liver pyruvate kinase in complex with citrate and fbp. |
| Resolution | 1.8Å |
| Reference | AUTH T.HOLYOAK,B.ZHANG,J.DENG,Q.TANG,C.B.PRASANNAN,A.W.FENTONTITL ENERGETIC COUPLING BETWEEN AN OXIDIZABLE CYSTEINE AND THETITL 2 PHOSPHORYLATABLE N-TERMINUS OF HUMAN LIVER PYRUVATE KINASE.REF BIOCHEMISTRY V. 52 466 2013REFN ISSN 0006-2960PMID 23270483DOI 10.1021/BI301341R |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 507 |
| Number Of SNVs | 128 |
| Number Of Permutations | 33498 |
| Optimal Distance Threshold | 6.0 |
| K Statistic | 0.008 |
| p-value | 0.875 |
ClinVar
| Number Of Residues | 507 |
| Number Of SNVs | 7 |
| Number Of Permutations | 1501 |
| Optimal Distance Threshold | 14.0 |
| K Statistic | 0.19 |
| p-value | 0.435 |
COSMIC
| Number Of Residues | 507 |
| Number Of SNVs | 9 |
| Number Of Permutations | 2528 |
| Optimal Distance Threshold | 16.0 |
| K Statistic | 0.056 |
| p-value | 0.551 |
Ripley’s K Analysis Plots
ExACClinVarCOSMIC
Variant Set Comparisons
ClinVar vs. ExAC
| Number Of ExAC SNVs | 128 |
| Number Of ClinVar SNVs | 7 |
| Optimal Distance Threshold | 14.0 |
| K Statistic | 0.098 |
| p-value | 0.483 |
Cosmic vs. ExAC
| Number Of ExAC SNVs | 128 |
| Number Of COSMIC SNVs | 7 |
| Optimal Distance Threshold | 10.0 |
| K Statistic | -0.038 |
| p-value | 0.816 |
Pathogenic Proximity Analysis
ClinVar PathProx Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:155270017 | G>D | D:21 | (18.37, 19.42, 22.10) | |
| 1:155270018 | G>C | D:21 | (18.37, 19.42, 22.10) | |
| 1:155269979 | M>V | D:34 | (24.07, 9.38, 12.64) | |
| 1:155269955 | L>F | D:42 | (18.99, 7.29, 0.88) | |
| 1:155269931 | rs139707114 | E>K | D:50 | (12.98, 21.74, 8.03) |
| 1:155269928 | rs151005140 | P>A | D:51 | (16.54, 23.30, 6.61) |
| 1:155269925 | rs368492204 | V>M | D:52 | (19.39, 24.93, 10.15) |
| 1:155269915 | rs375471342 CM981550 |
R>H | D:55 | (22.70, 29.28, 0.02) |
| 1:155269916 | R>G | D:55 | (22.70, 29.28, 0.02) | |
| 1:155269913 | S>C | D:56 | (26.49, 26.59, 0.70) | |
| 1:155269900 | I>T | D:60 | (26.08, 31.83, -11.10) | |
| 1:155265535 | rs534895384 | R>H | D:68 | (21.14, 45.78, -17.48) |
| 1:155265536 | rs148636159 | R>C | D:68 | (21.14, 45.78, -17.48) |
| 1:155265533 | S>T | D:69 | (17.77, 46.83, -12.90) | |
| 1:155265530 | rs143984223 | V>L | D:70 | (19.77, 48.74, -9.75) |
| 1:155265497 | M>V | D:81 | (23.02, 37.03, -6.83) | |
| 1:155265490 | I>T | D:83 | (28.36, 34.96, -8.90) | |
| 1:155265484 | R>L | D:85 | (26.92, 34.66, -17.19) | |
| 1:155265481 | L>R | D:86 | (29.10, 39.32, -17.70) | |
| 1:155265457 | E>A | D:94 | (28.72, 50.52, -23.03) | |
| 1:155265458 | E>Q | D:94 | (28.72, 50.52, -23.03) | |
| 1:155265350 | E>K | D:98 | (25.79, 49.77, -19.05) | |
| 1:155265336 | COSM896875 | N>K | D:102 | (23.90, 48.47, -12.81) |
| 1:155265337 | N>I | D:102 | (23.90, 48.47, -12.81) | |
| 1:155265334 | V>D | D:103 | (26.20, 44.96, -10.06) | |
| 1:155265320 | E>K | D:108 | (28.04, 49.57, -2.57) | |
| 1:155265280 | A>G | D:121 | (30.94, 38.34, -8.12) | |
| 1:155265275 | A>T | D:123 | (31.81, 36.87, -14.22) | |
| 1:155265266 | T>P | D:126 | (34.21, 33.82, -23.12) | |
| 1:155265077 | V>A | D:144 | (13.14, 27.57, -43.08) | |
| 1:155265078 | rs370513342 | V>M | D:144 | (13.14, 27.57, -43.08) |
| 1:155265069 | V>M | D:147 | (12.87, 18.15, -44.72) | |
| 1:155265041 | V>A | D:156 | (31.66, 29.27, -46.67) | |
| 1:155265039 | D>Y | D:157 | (29.88, 32.28, -50.54) | |
| 1:155265036 | rs577247981 | P>A | D:158 | (30.86, 35.28, -49.22) |
| 1:155265020 | rs552916457 | R>L | D:163 | (20.22, 32.78, -50.71) |
| 1:155265013 | N>K | D:165 | (17.08, 28.33, -48.37) | |
| 1:155265011 | A>V | D:166 | (15.35, 24.96, -47.24) | |
| 1:155265007 | N>K | D:167 | (17.93, 23.20, -49.58) | |
| 1:155264984 | N>S | D:175 | (38.33, 25.71, -42.41) | |
| 1:155264975 | rs200480300 | R>Q | D:178 | (40.01, 23.14, -45.68) |
| 1:155264970 | V>L | D:180 | (33.43, 17.78, -41.78) | |
| 1:155264966 | P>L | D:181 | (34.36, 14.36, -43.14) | |
| 1:155264967 | P>S | D:181 | (34.36, 14.36, -43.14) | |
| 1:155264963 | V>A | D:182 | (32.55, 11.56, -45.57) | |
| 1:155264952 | I>L | D:186 | (26.70, 19.34, -39.17) | |
| 1:155264945 | I>T | D:188 | (22.03, 23.46, -36.74) | |
| 1:155264946 | I>F | D:188 | (22.03, 23.46, -36.74) | |
| 1:155264927 | S>F | D:194 | (21.26, 17.18, -38.11) | |
| 1:155264921 | V>E | D:196 | (25.22, 13.74, -42.72) | |
| 1:155264919 | V>I | D:197 | (28.65, 15.07, -45.11) | |
| 1:155264915 | Q>R | D:198 | (26.64, 13.39, -48.79) | |
| 1:155264516 | E>V | D:210 | (20.34, 12.88, -39.24) | |
| 1:155264511 | G>S | D:212 | (14.69, 18.11, -38.56) | |
| 1:155264507 | G>D | D:213 | (13.35, 21.65, -38.72) | |
| 1:155264505 | rs555712170 | V>I | D:214 | (12.12, 25.27, -37.75) |
| 1:155264492 | rs368830326 | R>Q | D:218 | (23.65, 34.46, -37.57) |
| 1:155264493 | R>W | D:218 | (23.65, 34.46, -37.57) | |
| 1:155264439 | Q>K | D:236 | (36.18, 39.62, -29.66) | |
| 1:155264432 | V>A | D:238 | (41.88, 39.00, -26.45) | |
| 1:155264433 | rs200695047 COSM2154835 |
V>F | D:238 | (41.88, 39.00, -26.45) |
| 1:155264424 | rs147659527 | L>V | D:241 | (39.86, 38.75, -21.56) |
| 1:155264420 | rs141393570 | R>H | D:242 | (43.34, 43.28, -21.34) |
| 1:155264421 | R>C | D:242 | (43.34, 43.28, -21.34) | |
| 1:155264412 | V>M | D:245 | (41.38, 43.74, -16.80) | |
| 1:155264409 | rs147689373 | E>K | D:246 | (39.07, 48.52, -18.25) |
| 1:155264402 | G>E | D:248 | (37.54, 44.29, -12.49) | |
| 1:155264372 | COSM72194 COSM1334622 |
R>Q | D:258 | (40.98, 22.70, -26.79) |
| 1:155264358 | V>L | D:263 | (44.52, 28.02, -19.57) | |
| 1:155264354 | A>V | D:264 | (47.79, 29.99, -21.12) | |
| 1:155264355 | A>T | D:264 | (47.79, 29.99, -21.12) | |
| 1:155264342 | A>D | D:268 | (48.29, 35.96, -21.43) | |
| 1:155264330 | P>L | D:272 | (50.30, 41.66, -15.95) | |
| 1:155264331 | rs201979697 | P>A | D:272 | (50.30, 41.66, -15.95) |
| 1:155264318 | G>V | D:276 | (43.96, 37.74, -9.81) | |
| 1:155264301 | K>Q | D:282 | (33.75, 26.87, -20.27) | |
| 1:155264285 | E>G | D:287 | (40.13, 17.58, -26.43) | |
| 1:155264282 | G>D | D:288 | (38.10, 18.17, -22.34) | |
| 1:155264280 | rs549295725 CM074438 CM051965 |
V>L | D:289 | (36.35, 15.25, -21.00) |
| 1:155264171 | D>G | D:293 | (43.38, 15.50, -15.22) | |
| 1:155264162 | L>Q | D:296 | (41.99, 20.81, -12.82) | |
| 1:155264163 | L>V | D:296 | (41.99, 20.81, -12.82) | |
| 1:155264151 | D>N | D:300 | (41.65, 28.56, -10.59) | |
| 1:155264148 | G>S | D:301 | (38.48, 25.75, -12.29) | |
| 1:155264093 | F>Y | D:319 | (25.15, 10.99, -16.53) | |
| 1:155264075 | M>T | D:325 | (34.10, 16.88, -14.36) | |
| 1:155264072 | I>T | D:326 | (31.83, 17.39, -9.72) | |
| 1:155264067 | rs138871700 | R>C | D:328 | (38.51, 13.87, -11.80) |
| 1:155264063 | C>S | D:329 | (37.11, 19.04, -8.54) | |
| 1:155264061 | N>D | D:330 | (35.37, 17.56, -4.95) | |
| 1:155264054 | A>E | D:332 | (41.45, 18.90, -5.89) | |
| 1:155264043 | V>F | D:336 | (32.77, 22.77, -9.68) | |
| 1:155263356 | P>L | D:350 | (5.99, 30.34, -12.16) | |
| 1:155263329 | D>G | D:359 | (19.45, 19.04, -12.12) | |
| 1:155263326 | V>A | D:360 | (19.40, 21.69, -8.60) | |
| 1:155263320 | N>S | D:362 | (21.16, 15.49, -8.01) | |
| 1:155263289 | rs368784290 CM051968 |
M>I | D:372 | (24.51, 28.80, -13.80) |
| 1:155263290 | M>T | D:372 | (24.51, 28.80, -13.80) | |
| 1:155263281 | G>E | D:375 | (17.71, 32.65, -18.99) | |
| 1:155263263 | N>T | D:381 | (8.97, 36.52, -17.31) | |
| 1:155263248 | COSM1287177 | A>V | D:386 | (14.91, 31.40, -10.03) |
| 1:155263246 | V>M | D:387 | (17.39, 32.95, -7.40) | |
| 1:155263130 | A>D | D:394 | (20.33, 23.95, -2.15) | |
| 1:155263131 | A>T | D:394 | (20.33, 23.95, -2.15) | |
| 1:155263127 | R>Q | D:395 | (18.75, 25.68, 3.14) | |
| 1:155263113 | A>T | D:400 | (21.38, 15.53, 2.34) | |
| 1:155263101 | rs142238268 | R>W | D:404 | (29.26, 8.93, 8.89) |
| 1:155263079 | rs370554398 | R>H | D:411 | (39.71, 11.25, 6.03) |
| 1:155263080 | R>C | D:411 | (39.71, 11.25, 6.03) | |
| 1:155263076 | R>Q | D:412 | (40.47, 5.91, 3.07) | |
| 1:155263070 | COSM2210434 | A>V | D:414 | (44.11, 12.86, 0.38) |
| 1:155263058 | rs149932430 | R>H | D:418 | (55.45, 18.36, 5.89) |
| 1:155263059 | rs189360283 | R>C | D:418 | (55.45, 18.36, 5.89) |
| 1:155263046 | E>A | D:422 | (46.16, 21.58, 3.78) | |
| 1:155263041 | T>A | D:424 | (44.82, 23.56, 10.39) | |
| 1:155263031 | G>D | D:427 | (41.16, 19.66, 12.15) | |
| 1:155263025 | rs149946271 | V>A | D:429 | (36.57, 20.10, 9.60) |
| 1:155263026 | V>M | D:429 | (36.57, 20.10, 9.60) | |
| 1:155263001 | A>G | D:437 | (29.83, 23.72, 14.83) | |
| 1:155262996 | A>S | D:439 | (31.20, 27.91, 12.68) | |
| 1:155262975 | T>A | D:446 | (44.05, 34.90, -0.63) | |
| 1:155262968 | rs118204085 | R>H | D:448 | (45.39, 28.56, 0.55) |
| 1:155262969 | R>C | D:448 | (45.39, 28.56, 0.55) | |
| 1:155261723 | A>V | D:450 | (38.81, 28.95, 3.13) | |
| 1:155261708 | COSM3965867 CM061899 |
R>Q | D:455 | (39.43, 20.14, 0.23) |
| 1:155261709 | rs116100695 | R>W | D:455 | (39.43, 20.14, 0.23) |
| 1:155261702 | rs369183199 CM981576 |
R>Q | D:457 | (32.45, 20.19, 0.94) |
| 1:155261697 | R>W | D:459 | (27.06, 19.85, 8.86) | |
| 1:155261687 | V>D | D:462 | (33.36, 28.84, 6.27) | |
| 1:155261681 | rs141560532 | A>V | D:464 | (35.65, 34.57, 5.78) |
| 1:155261657 | A>V | D:472 | (35.37, 38.33, -1.03) | |
| 1:155261654 | rs185753709 | R>L | D:473 | (34.59, 40.41, -5.01) |
| 1:155261649 | rs8177988 | V>I | D:475 | (35.45, 33.11, -1.72) |
| 1:155261646 | H>N | D:476 | (30.95, 33.87, -3.14) | |
| 1:155261636 | rs113403872 | R>Q | D:479 | (29.73, 23.58, -1.18) |
| 1:155261612 | R>H | D:487 | (34.97, 47.98, 5.20) | |
| 1:155261613 | rs139002629 | R>C | D:487 | (34.97, 47.98, 5.20) |
| 1:155261607 | P>T | D:489 | (42.46, 50.37, 10.01) | |
| 1:155261604 | P>S | D:490 | (45.61, 48.11, 11.09) | |
| 1:155261586 | D>N | D:496 | (44.85, 43.30, 19.50) | |
| 1:155261570 | R>Q | D:501 | (40.70, 40.41, 11.74) | |
| 1:155261571 | R>W | D:501 | (40.70, 40.41, 11.74) | |
| 1:155261551 | E>D | D:507 | (29.05, 40.35, 16.38) | |
| 1:155260460 | R>H | D:512 | (24.91, 37.83, 8.25) | |
| 1:155260448 | rs375525211 | R>H | D:516 | (21.84, 31.10, 17.83) |
| 1:155260449 | R>C | D:516 | (21.84, 31.10, 17.83) | |
| 1:155260443 | rs190966689 | G>R | D:518 | (26.35, 28.71, 22.87) |
| 1:155260433 | V>A | D:521 | (33.09, 28.55, 17.04) | |
| 1:155260425 | V>L | D:524 | (41.28, 29.32, 11.65) | |
| 1:155260389 | I>F | D:536 | (46.19, 28.47, 14.98) | |
| 1:155260384 | M>I | D:537 | (42.18, 24.94, 15.90) | |
| 1:155260385 | M>T | D:537 | (42.18, 24.94, 15.90) | |
| 1:155260382 | rs61755431 | R>Q | D:538 | (41.08, 29.65, 18.75) |
[+] ClinVar Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:155265346 | rs118204089 | S>Y | D:99 | (25.91, 45.42, -16.37) |
| 1:155265248 | rs118204083 | R>C | D:132 | (26.14, 31.72, -34.61) |
| 1:155263347 | rs74315362 | T>M | D:353 | (10.06, 20.90, -13.87) |
| 1:155263237 | rs118204084 | Q>K | D:390 | (18.93, 27.60, -7.72) |
| 1:155262968 | rs118204085 | R>H | D:448 | (45.39, 28.56, 0.55) |
| 1:155261709 | rs116100695 | R>W | D:455 | (39.43, 20.14, 0.23) |
| 1:155261636 | rs113403872 | R>Q | D:479 | (29.73, 23.58, -1.18) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:155265256 | COSM4023001 | P>L | D:129 | (34.64, 28.90, -30.37) |
| 1:155265064 | COSM2210468 | K>N | D:148 | (14.37, 13.25, -42.04) |
| 1:155264487 | COSM36782 | G>S | D:220 | (24.33, 27.29, -33.74) |
| 1:155264433 | COSM2154835 | V>I | D:238 | (41.88, 39.00, -26.45) |
| 1:155264397 | COSM1720029 | D>N | D:250 | (36.30, 39.07, -9.82) |
| 1:155264373 | COSM1334623 | R>W | D:258 | (40.98, 22.70, -26.79) |
| 1:155264349 | COSM4714797 | V>F | D:266 | (43.40, 33.15, -20.83) |
| 1:155264286 | COSM3474935 | E>K | D:287 | (40.13, 17.58, -26.43) |
| 1:155263347 | COSM675768 | T>M | D:353 | (10.06, 20.90, -13.87) |
| 1:155263101 | COSM1716443 | R>W | D:404 | (29.26, 8.93, 8.89) |
| 1:155261669 | COSM225970 | S>F | D:468 | (40.28, 41.42, -0.02) |