General Structure Information
| PDB ID | 1dmw |
| HGNC Gene Label(s) | PAH |
| Structure Name | crystal structure of double truncated human phenylalanine hydroxylase with bound 7,8-dihydro-l-biopterin |
| Resolution | 2.0Å |
| Reference | AUTH H.ERLANDSEN,E.BJORGO,T.FLATMARK,R.C.STEVENSTITL CRYSTAL STRUCTURE AND SITE-SPECIFIC MUTAGENESIS OFTITL 2 PTERIN-BOUND HUMAN PHENYLALANINE HYDROXYLASE.REF BIOCHEMISTRY V. 39 2208 2000REFN ISSN 0006-2960PMID 10694386DOI 10.1021/BI992531+ |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 307 |
| Number Of SNVs | 98 |
| Number Of Permutations | 28731 |
| Optimal Distance Threshold | 12.0 |
| K Statistic | 0.109 |
| p-value | 0.141 |
ClinVar
| Number Of Residues | 307 |
| Number Of SNVs | 61 |
| Number Of Permutations | 20324 |
| Optimal Distance Threshold | 17.0 |
| K Statistic | 0.293 |
| p-value | 0.03 |
COSMIC
| Number Of Residues | 307 |
| Number Of SNVs | 11 |
| Number Of Permutations | 8409 |
| Optimal Distance Threshold | 18.0 |
| K Statistic | 0.164 |
| p-value | 0.499 |
Ripley’s K Analysis Plots
ExACClinVarCOSMIC
Variant Set Comparisons
ClinVar vs. ExAC
| Number Of ExAC SNVs | 98 |
| Number Of ClinVar SNVs | 41 |
| Optimal Distance Threshold | 12.0 |
| K Statistic | -0.013 |
| p-value | 0.874 |
Cosmic vs. ExAC
| Number Of ExAC SNVs | 98 |
| Number Of COSMIC SNVs | 8 |
| Optimal Distance Threshold | 10.0 |
| K Statistic | -0.065 |
| p-value | 0.757 |
Pathogenic Proximity Analysis
ClinVar PathProx Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:103288513 | V>M | A:118 | (-22.59, 33.73, 18.87) | |
| 12:103271326 | rs398123292 CM043044 |
P>S | A:119 | (-20.66, 31.50, 16.69) |
| 12:103271300 | E>D | A:127 | (-14.75, 21.59, 23.87) | |
| 12:103271265 | rs375384973 | G>E | A:139 | (-11.16, 14.63, -0.98) |
| 12:103271247 | rs140175796 | D>V | A:145 | (-6.30, 15.96, -10.70) |
| 12:103260419 | rs199475663 PAH_c.464G>C PAH_c.464G>A CM981433 CM000544 |
R>H | A:155 | (-7.92, 6.01, -2.83) |
| 12:103260420 | rs539743701 | R>C | A:155 | (-7.92, 6.01, -2.83) |
| 12:103260411 | rs75166491 | R>W | A:158 | (-4.63, 9.88, 2.06) |
| 12:103260399 | rs547566250 | A>S | A:162 | (-8.04, 9.21, 8.40) |
| 12:103260393 | rs199475647 PAH_c.490A>G CM992945 |
I>V | A:164 | (-5.22, 7.59, 12.85) |
| 12:103260390 | rs199475626 PAH_c.493G>A PAH_c.493G>C CM971128 CM010956 |
A>P | A:165 | (-7.70, 11.23, 13.03) |
| 12:103260386 | Y>C | A:166 | (-13.26, 9.59, 13.10) | |
| 12:103260377 | rs199475679 PAH_c.506G>A CM992371 |
R>H | A:169 | (-10.61, 11.28, 20.54) |
| 12:103260378 | rs281865440 COSM1706144 |
R>C | A:169 | (-10.61, 11.28, 20.54) |
| 12:103249109 | rs199475613 PAH_c.511G>A CM010958 |
G>W | A:171 | (-4.38, 13.32, 25.20) |
| 12:103249104 | rs192592111 | Q>H | A:172 | (-5.19, 10.07, 22.86) |
| 12:103249099 | rs138809906 | I>N | A:174 | (0.02, 11.08, 18.05) |
| 12:103249087 | rs77958223 | E>G | A:178 | (6.35, 1.36, 9.63) |
| 12:103249081 | M>R | A:180 | (5.90, 2.68, 2.99) | |
| 12:103249075 | rs199475617 PAH_c.545A>G COSM78257 CM950885 |
E>G | A:182 | (8.07, 3.39, -1.34) |
| 12:103249073 | rs199475664 PAH_c.547G>C CM000545 |
E>K | A:183 | (5.92, 6.75, 2.31) |
| 12:103249057 | rs62507260 rs199475689 PAH_c.563delG PAH_c.563G>A CM078134 CD011181 |
G>A | A:188 | (13.93, 12.98, 0.85) |
| 12:103249051 | rs62514919 | V>A | A:190 | (11.18, 17.16, -0.13) |
| 12:103249039 | rs5030844 | L>P | A:194 | (13.50, 22.45, 0.70) |
| 12:103249009 | rs62514927 PAH_c.611A>G CS971842 |
Y>C | A:204 | (17.75, 33.27, 13.94) |
| 12:103248967 | rs62514933 | G>V | A:218 | (14.48, 12.98, 13.04) |
| 12:103248958 | rs62514934 | E>G | A:221 | (18.10, 12.47, 4.25) |
| 12:103248946 | rs62517204 PAH_c.674C>G CM112741 CM990995 |
P>L | A:225 | (9.25, 12.70, 11.43) |
| 12:103248942 | rs62508615 PAH_c.678G>C CM004891 |
Q>H | A:226 | (6.66, 9.67, 14.13) |
| 12:103248932 | rs62516152 | V>I | A:230 | (7.07, 16.82, 16.73) |
| 12:103246726 | rs372723640 | C>R | A:237 | (9.33, 25.08, 22.99) |
| 12:103246713 | rs62508730 | R>H | A:241 | (-0.56, 20.49, 22.27) |
| 12:103246714 | rs76687508 | R>C | A:241 | (-0.56, 20.49, 22.27) |
| 12:103246707 | rs62508588 | R>Q | A:243 | (-5.87, 16.89, 17.18) |
| 12:103246704 | rs118203923 | P>L | A:244 | (-4.12, 14.14, 14.32) |
| 12:103246702 | rs62508694 PAH_c.733G>C PAH_c.733G>A CM961077 |
V>L | A:245 | (-6.02, 16.20, 10.48) |
| 12:103246698 | rs199475666 PAH_c.737C>A PAH_c.737C>T PAH_c.737delC CM010964 CD000606 CM981441 |
A>V | A:246 | (-7.99, 14.05, 7.96) |
| 12:103246695 | rs199475579 PAH_c.740G>T PAH_c.740G>A CM043314 CM920551 |
G>D | A:247 | (-8.56, 17.08, 6.47) |
| 12:103246690 | rs74503222 | L>F | A:249 | (-10.79, 21.64, 9.28) |
| 12:103246683 | rs369646949 | S>F | A:251 | (-11.36, 28.31, 8.71) |
| 12:103246681 | rs5030847 | R>W | A:252 | (-15.31, 29.39, 12.73) |
| 12:103246678 | D>N | A:253 | (-12.91, 24.54, 13.30) | |
| 12:103246659 | rs118203921 | A>V | A:259 | (-6.24, 29.49, 20.87) |
| 12:103246660 | rs62642932 | A>T | A:259 | (-6.24, 29.49, 20.87) |
| 12:103246653 | rs5030849 | R>Q | A:261 | (-0.02, 28.06, 22.28) |
| 12:103246646 | rs62642944 | F>L | A:263 | (-0.99, 22.67, 13.54) |
| 12:103246645 | H>Y | A:264 | (-5.64, 20.83, 13.74) | |
| 12:103246634 | rs199475675 PAH_c.801G>C CM056670 |
Q>H | A:267 | (0.06, 11.26, 9.95) |
| 12:103246635 | Q>L | A:267 | (0.06, 11.26, 9.95) | |
| 12:103246626 | rs62514950 | R>K | A:270 | (3.93, 14.96, -1.16) |
| 12:103246623 | rs199475692 PAH_c.812A>G CM113432 |
H>R | A:271 | (1.80, 9.64, -5.19) |
| 12:103246624 | rs62517164 | H>Y | A:271 | (1.80, 9.64, -5.19) |
| 12:103246617 | rs62514953 | S>F | A:273 | (4.67, 10.60, -8.68) |
| 12:103246615 | rs142934616 | K>E | A:274 | (3.82, 14.24, -8.88) |
| 12:103246608 | rs62508722 PAH_c.827T>A PAH_c.827T>G CM034746 CM034745 |
M>T | A:276 | (8.85, 18.60, -5.83) |
| 12:103246609 | rs62516149 PAH_c.826A>G CM930552 |
M>L | A:276 | (8.85, 18.60, -5.83) |
| 12:103246605 | rs62516155 | Y>C | A:277 | (1.99, 18.83, -6.93) |
| 12:103246606 | rs78655458 | Y>D | A:277 | (1.99, 18.83, -6.93) |
| 12:103246597 | rs62508698 | E>K | A:280 | (-2.81, 18.11, -0.43) |
| 12:103246593 | rs5030851 | P>L | A:281 | (-1.79, 19.77, 2.95) |
| 12:103246594 | rs199475654 PAH_c.841C>T CM043045 CM992948 |
P>S | A:281 | (-1.79, 19.77, 2.95) |
| 12:103245533 | rs199475582 PAH_c.844G>A CM930554 |
D>N | A:282 | (2.10, 16.91, 3.04) |
| 12:103245530 | rs62517168 | I>F | A:283 | (4.11, 15.12, 6.65) |
| 12:103245521 | rs62508739 | E>K | A:286 | (2.40, 20.14, 8.15) |
| 12:103245518 | L>V | A:287 | (7.18, 18.50, 9.68) | |
| 12:103245491 | D>N | A:296 | (9.32, 31.29, 18.19) | |
| 12:103245487 | rs62642939 | R>H | A:297 | (8.25, 33.45, 23.46) |
| 12:103245488 | rs62642945 | R>C | A:297 | (8.25, 33.45, 23.46) |
| 12:103245481 | rs62642933 | F>C | A:299 | (4.83, 32.12, 14.86) |
| 12:103245479 | rs5030853 | A>S | A:300 | (3.23, 31.32, 19.06) |
| 12:103240726 | rs62642934 | I>V | A:306 | (-4.83, 34.56, 14.41) |
| 12:103240716 | rs62642935 | A>V | A:309 | (-9.91, 36.39, 16.85) |
| 12:103240710 | rs62642936 | L>P | A:311 | (-12.89, 32.45, 19.37) |
| 12:103240705 | rs62642912 PAH_c.937G>A CM014737 |
A>S | A:313 | (-16.46, 35.24, 14.72) |
| 12:103240682 | rs199475615 PAH_c.960G>C CM961081 |
K>N | A:320 | (-11.61, 39.58, 6.86) |
| 12:103240677 | rs62514958 | A>G | A:322 | (-7.84, 33.45, 6.58) |
| 12:103240678 | rs62514957 | A>T | A:322 | (-7.84, 33.45, 6.58) |
| 12:103238199 | rs535752872 | F>Y | A:327 | (-1.19, 37.21, 2.58) |
| 12:103238197 | rs199475616 PAH_c.982A>G CM010977 |
T>A | A:328 | (1.18, 35.46, 7.68) |
| 12:103238193 | V>A | A:329 | (1.32, 31.43, 8.76) | |
| 12:103238173 | rs62516061 PAH_c.1006C>T CM930557 |
Q>E | A:336 | (16.36, 39.12, 9.48) |
| 12:103238169 | rs62517206 PAH_c.1010G>T CM010979 |
G>E | A:337 | (17.19, 43.71, 9.78) |
| 12:103238167 | rs62516150 | D>Y | A:338 | (19.17, 45.67, 7.04) |
| 12:103238146 | rs62516062 PAH_c.1033G>A PAH_c.1033G>T CM010983 CM920560 |
A>S | A:345 | (4.88, 27.38, 5.32) |
| 12:103238137 | rs62516092 | L>V | A:348 | (9.56, 27.39, 4.32) |
| 12:103238134 | rs62508646 | S>P | A:349 | (7.22, 23.81, 1.53) |
| 12:103237557 | rs62507320 | Y>H | A:356 | (8.93, 34.30, -6.79) |
| 12:103237549 | rs376480977 | L>F | A:358 | (13.52, 36.42, -1.40) |
| 12:103237539 | rs62507329 PAH_c.1084C>A CM971135 |
P>S | A:362 | (7.85, 39.60, -6.20) |
| 12:103237503 | I>V | A:374 | (-9.45, 42.94, 1.60) | |
| 12:103237500 | rs184148104 | Q>E | A:375 | (-5.52, 41.04, -1.31) |
| 12:103237490 | T>I | A:378 | (-4.60, 32.27, -6.17) | |
| 12:103237487 | V>A | A:379 | (-3.98, 28.24, -4.38) | |
| 12:103237484 | rs62642937 | T>M | A:380 | (-2.65, 27.79, -8.37) |
| 12:103237461 | rs62516101 | V>M | A:388 | (6.72, 42.55, 4.98) |
| 12:103237454 | rs5030856 | E>G | A:390 | (8.32, 45.10, 10.94) |
| 12:103237449 | rs180819807 | F>I | A:392 | (7.05, 37.02, 14.18) |
| 12:103237446 | N>H | A:393 | (6.16, 40.73, 18.71) | |
| 12:103237439 | rs62508736 PAH_c.1184C>G PAH_c.1184C>A CM981456 CM043319 |
A>G | A:395 | (1.91, 41.07, 13.96) |
| 12:103237440 | rs62516103 PAH_c.1183G>C COSM691583 CM930566 |
A>P | A:395 | (1.91, 41.07, 13.96) |
| 12:103237436 | K>R | A:396 | (1.16, 39.79, 18.72) | |
| 12:103234285 | rs5030857 | A>V | A:403 | (-9.80, 41.88, 16.93) |
| 12:103234275 | rs141953705 | I>M | A:406 | (-14.14, 41.38, 15.32) |
| 12:103234277 | I>V | A:406 | (-14.14, 41.38, 15.32) | |
| 12:103234270 | rs5030859 | R>Q | A:408 | (-15.75, 39.14, 19.41) |
| 12:103234271 | rs5030858 | R>W | A:408 | (-15.75, 39.14, 19.41) |
| 12:103234256 | rs62644467 | R>C | A:413 | (-8.15, 34.85, 29.47) |
| 12:103234252 | rs5030860 | Y>C | A:414 | (-5.64, 29.58, 26.82) |
| 12:103234253 | rs281865437 | Y>H | A:414 | (-5.64, 29.58, 26.82) |
| 12:103234250 | rs62644499 | D>N | A:415 | (-5.79, 29.79, 31.59) |
| 12:103234237 | Q>R | A:419 | (-5.72, 23.66, 29.09) | |
| 12:103234234 | COSM1706138 | R>M | A:420 | (-10.52, 26.45, 31.46) |
| 12:103234231 | rs199475696 PAH_c.1262T>C COSM3383976 |
I>T | A:421 | (-11.20, 30.17, 26.62) |
[+] ClinVar Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:103271326 | rs398123292 | P>S | A:119 | (-20.66, 31.50, 16.69) |
| 12:103271313 | rs199475681 | R>I | A:123 | (-16.01, 28.37, 26.26) |
| 12:103271296 | rs199475606 | D>Y | A:129 | (-12.42, 16.26, 20.44) |
| 12:103260377 | rs199475679 | R>H | A:169 | (-10.61, 11.28, 20.54) |
| 12:103260378 | rs281865440 | R>C | A:169 | (-10.61, 11.28, 20.54) |
| 12:103260375 | rs199475655 | H>D | A:170 | (-6.89, 16.31, 24.17) |
| 12:103249093 | rs74486803 | R>L | A:176 | (4.98, 6.34, 16.95) |
| 12:103249071 | rs281865433 | E>L | A:183 | (5.92, 6.75, 2.31) |
| 12:103249052 | rs281865441 | V>M | A:190 | (11.18, 17.16, -0.13) |
| 12:103249029 | rs281865442 | L>F | A:197 | (17.04, 27.00, -0.10) |
| 12:103248988 | rs281865443 | P>L | A:211 | (19.45, 22.08, 14.21) |
| 12:103248982 | rs62516109 | L>P | A:213 | (13.97, 19.56, 14.68) |
| 12:103248958 | rs62514934 | E>G | A:221 | (18.10, 12.47, 4.25) |
| 12:103248938 | rs281865444 | E>K | A:228 | (3.88, 12.12, 20.16) |
| 12:103248932 | rs62516152 | V>I | A:230 | (7.07, 16.82, 16.73) |
| 12:103248929 | rs5030845 | S>P | A:231 | (4.18, 17.37, 19.96) |
| 12:103246714 | rs76687508 | R>C | A:241 | (-0.56, 20.49, 22.27) |
| 12:103246704 | rs118203923 | P>L | A:244 | (-4.12, 14.14, 14.32) |
| 12:103246701 | rs76212747 | V>E | A:245 | (-6.02, 16.20, 10.48) |
| 12:103246699 | rs796052017 | VA>AA | A:246 | (-7.99, 14.05, 7.96) |
| 12:103246695 | rs199475579 | G>V | A:247 | (-8.56, 17.08, 6.47) |
| 12:103246690 | rs74503222 | L>F | A:249 | (-10.79, 21.64, 9.28) |
| 12:103246680 | rs62644503 | R>Q | A:252 | (-15.31, 29.39, 12.73) |
| 12:103246681 | rs5030847 | R>W | A:252 | (-15.31, 29.39, 12.73) |
| 12:103246671 | rs62642930 | L>S | A:255 | (-8.13, 29.64, 12.90) |
| 12:103246659 | rs118203921 | A>V | A:259 | (-6.24, 29.49, 20.87) |
| 12:103246650 | rs281865445 | V>G | A:262 | (-3.76, 23.24, 18.88) |
| 12:103246626 | rs62514950 | R>K | A:270 | (3.93, 14.96, -1.16) |
| 12:103246623 | rs199475692 | H>L | A:271 | (1.80, 9.64, -5.19) |
| 12:103246617 | rs62514953 | S>F | A:273 | (4.67, 10.60, -8.68) |
| 12:103246606 | rs78655458 | Y>D | A:277 | (1.99, 18.83, -6.93) |
| 12:103246599 | rs796064503 | P>L | A:279 | (-2.51, 19.29, -4.02) |
| 12:103246597 | rs62508698 | E>K | A:280 | (-2.81, 18.11, -0.43) |
| 12:103246593 | rs5030851 | P>L | A:281 | (-1.79, 19.77, 2.95) |
| 12:103245530 | rs62517168 | I>F | A:283 | (4.11, 15.12, 6.65) |
| 12:103245508 | rs62642919 | H>L | A:290 | (3.44, 25.13, 9.45) |
| 12:103245490 | rs281865446 | D>G | A:296 | (9.32, 31.29, 18.19) |
| 12:103245487 | rs62642939 | R>H | A:297 | (8.25, 33.45, 23.46) |
| 12:103245481 | rs62642933 | F>C | A:299 | (4.83, 32.12, 14.86) |
| 12:103245482 | rs796064504 | F>L | A:299 | (4.83, 32.12, 14.86) |
| 12:103245479 | rs5030853 | A>S | A:300 | (3.23, 31.32, 19.06) |
| 12:103240726 | rs62642934 | I>V | A:306 | (-4.83, 34.56, 14.41) |
| 12:103240716 | rs62642935 | A>V | A:309 | (-9.91, 36.39, 16.85) |
| 12:103240710 | rs62642936 | L>P | A:311 | (-12.89, 32.45, 19.37) |
| 12:103240677 | rs62514958 | A>G | A:322 | (-7.84, 33.45, 6.58) |
| 12:103238205 | rs62508578 | Y>C | A:325 | (-3.01, 31.31, 8.42) |
| 12:103238182 | rs62516060 | L>F | A:333 | (8.02, 37.81, 3.71) |
| 12:103238175 | rs281865434 | K>T | A:335 | (11.59, 43.62, 8.26) |
| 12:103238154 | rs796064501 | A>E | A:342 | (10.98, 33.35, 5.00) |
| 12:103238146 | rs62516062 | A>S | A:345 | (4.88, 27.38, 5.32) |
| 12:103238137 | rs62516092 | L>V | A:348 | (9.56, 27.39, 4.32) |
| 12:103237493 | rs62642942 | Y>C | A:377 | (-5.76, 34.18, -1.75) |
| 12:103237484 | rs62642937 | T>M | A:380 | (-2.65, 27.79, -8.37) |
| 12:103237466 | rs62516141 | Y>C | A:386 | (4.89, 37.55, -1.38) |
| 12:103237460 | rs281865435 | V>A | A:388 | (6.72, 42.55, 4.98) |
| 12:103237454 | rs5030856 | E>G | A:390 | (8.32, 45.10, 10.94) |
| 12:103237452 | rs281865453 | S>G | A:391 | (7.88, 41.42, 13.95) |
| 12:103237443 | rs62516142 | D>Y | A:394 | (4.19, 44.32, 14.92) |
| 12:103237439 | rs62508736 | A>D | A:395 | (1.91, 41.07, 13.96) |
| 12:103237427 | rs281865436 | V>A | A:399 | (-3.95, 40.63, 15.11) |
| 12:103234285 | rs5030857 | A>V | A:403 | (-9.80, 41.88, 16.93) |
| 12:103234273 | rs62644473 | P>L | A:407 | (-18.22, 41.98, 15.49) |
| 12:103234270 | rs5030859 | R>Q | A:408 | (-15.75, 39.14, 19.41) |
| 12:103234271 | rs5030858 | R>W | A:408 | (-15.75, 39.14, 19.41) |
| 12:103234255 | rs79931499 | R>H | A:413 | (-8.15, 34.85, 29.47) |
| 12:103234252 | rs5030860 | Y>C | A:414 | (-5.64, 29.58, 26.82) |
| 12:103234253 | rs281865437 | Y>H | A:414 | (-5.64, 29.58, 26.82) |
| 12:103234250 | rs62644499 | D>N | A:415 | (-5.79, 29.79, 31.59) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 12:103271292 | COSM2063946 | R>K | A:130 | (-17.80, 19.26, 19.00) |
| 12:103249075 | COSM78257 | E>G | A:182 | (8.07, 3.39, -1.34) |
| 12:103249000 | COSM1605462 | N>S | A:207 | (17.88, 28.43, 10.42) |
| 12:103246653 | COSM1358231 | R>Q | A:261 | (-0.02, 28.06, 22.28) |
| 12:103246597 | COSM2063927 | E>K | A:280 | (-2.81, 18.11, -0.43) |
| 12:103245469 | COSM3455200 | S>F | A:303 | (-0.47, 32.15, 15.87) |
| 12:103240729 | COSM1706141 | E>K | A:305 | (-3.82, 36.97, 19.04) |
| 12:103240696 | COSM3710538 | E>K | A:316 | (-18.33, 38.08, 7.97) |
| 12:103237469 | COSM1605460 | L>H | A:385 | (1.48, 40.40, -3.10) |
| 12:103234265 | COSM1746684 | F>I | A:410 | (-17.39, 37.74, 23.25) |
| 12:103234250 | COSM2063913 | D>N | A:415 | (-5.79, 29.79, 31.59) |