General Structure Information
| PDB ID | 4ccz |
| HGNC Gene Label(s) | MTR |
| Structure Name | crystal structure of human 5-methyltetrahydrofolate- homocysteine methyltransferase, the homocysteine and folate binding domains |
| Resolution | 2.7Å |
| Reference | AUTH M.VOLLMAR,W.KIYANI,T.KROJER,S.GOUBIN,N.BURGESS-BROWN,AUTH 2 F.VON DELFT,U.OPPERMANN,A.EDWARDS,C.ARROWSMITH,C.BOUNTRA,AUTH 3 W.W.YUETITL CRYSTAL STRUCTURE OF HUMAN 5-TITL 2 METHYLTETRAHYDROFOLATE-HOMOCYSTEINE METHYLTRANSFERASE, THETITL 3 HOMOCYSTEINE AND FOLATE BINDING DOMAINSREF TO BE PUBLISHEDREFN |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 611 |
| Number Of SNVs | 131 |
| Number Of Permutations | 70216 |
| Optimal Distance Threshold | 6.0 |
| K Statistic | 0.007 |
| p-value | 0.465 |
COSMIC
| Number Of Residues | 611 |
| Number Of SNVs | 4 |
| Number Of Permutations | 1742 |
| Optimal Distance Threshold | 27.0 |
| K Statistic | 0.833 |
| p-value | 0.168 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 131 |
| Number Of COSMIC SNVs | 4 |
| Optimal Distance Threshold | 27.0 |
| K Statistic | 0.462 |
| p-value | 0.323 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:236966760 | N>D | A:23 | (-71.29, 23.57, -1.11) | |
| 1:236966761 | N>S | A:23 | (-71.29, 23.57, -1.11) | |
| 1:236966766 | I>F | A:25 | (-73.99, 19.12, -2.20) | |
| 1:236966803 | rs371079306 | M>T | A:37 | (-64.16, 12.22, -24.21) |
| 1:236966820 | R>W | A:43 | (-64.98, 4.70, -30.19) | |
| 1:236966825 | rs373236234 | E>D | A:44 | (-66.65, 6.64, -32.77) |
| 1:236966828 | K>N | A:45 | (-64.83, 6.02, -35.53) | |
| 1:236966835 | COSM4029864 | E>K | A:48 | (-62.58, 10.47, -40.33) |
| 1:236966841 | H>Y | A:50 | (-64.51, 13.89, -43.39) | |
| 1:236966842 | H>R | A:50 | (-64.51, 13.89, -43.39) | |
| 1:236966848 | rs12749581 | R>Q | A:52 | (-63.40, 16.10, -38.04) |
| 1:236966851 | G>V | A:53 | (-67.17, 18.61, -42.13) | |
| 1:236966855 | Q>H | A:54 | (-69.73, 20.67, -43.28) | |
| 1:236966872 | COSM220368 | A>G | A:60 | (-55.93, 23.66, -45.50) |
| 1:236966877 | P>S | A:62 | (-55.33, 18.71, -41.16) | |
| 1:236966878 | rs61736442 | P>L | A:62 | (-55.33, 18.71, -41.16) |
| 1:236966893 | N>S | A:67 | (-61.64, 15.84, -30.31) | |
| 1:236966909 | I>M | A:72 | (-69.10, 23.00, -34.67) | |
| 1:236966911 | T>S | A:73 | (-68.47, 19.28, -37.04) | |
| 1:236969447 | Y>N | A:85 | (-70.11, 10.02, -19.26) | |
| 1:236969448 | Y>F | A:85 | (-70.11, 10.02, -19.26) | |
| 1:236969467 | D>E | A:91 | (-72.98, 14.76, -12.18) | |
| 1:236969471 | I>V | A:93 | (-69.97, 18.20, -17.32) | |
| 1:236969472 | I>T | A:93 | (-69.97, 18.20, -17.32) | |
| 1:236969478 | T>I | A:95 | (-66.48, 21.56, -21.66) | |
| 1:236969495 | T>A | A:101 | (-57.12, 28.00, -27.62) | |
| 1:236969502 | rs367730702 | I>T | A:103 | (-52.51, 28.22, -29.08) |
| 1:236969519 | G>S | A:109 | (-56.31, 27.06, -38.34) | |
| 1:236969525 | E>Q | A:111 | (-55.78, 30.61, -34.87) | |
| 1:236972005 | A>V | A:114 | (-61.91, 30.14, -29.73) | |
| 1:236972019 | rs538707626 | M>V | A:119 | (-70.46, 29.78, -26.99) |
| 1:236972020 | rs151161326 | M>T | A:119 | (-70.46, 29.78, -26.99) |
| 1:236972029 | rs557603489 | A>V | A:122 | (-71.25, 25.10, -23.61) |
| 1:236972052 | E>K | A:130 | (-80.98, 21.52, -19.18) | |
| 1:236972062 | T>S | A:133 | (-82.17, 17.89, -14.79) | |
| 1:236973823 | G>W | A:144 | (-65.08, 24.66, -17.87) | |
| 1:236973826 | A>T | A:145 | (-62.52, 23.28, -19.84) | |
| 1:236973836 | P>L | A:148 | (-52.65, 22.93, -20.89) | |
| 1:236973878 | rs201799064 COSM3485662 COSM3485663 |
P>L | A:162 | (-31.74, 27.66, -20.50) |
| 1:236973884 | Y>C | A:164 | (-36.48, 30.10, -25.70) | |
| 1:236973887 | R>K | A:165 | (-38.85, 30.14, -21.60) | |
| 1:236976043 | D>Y | A:170 | (-49.06, 38.70, -21.01) | |
| 1:236976049 | L>F | A:172 | (-50.93, 32.18, -21.79) | |
| 1:236976070 | Q>E | A:179 | (-61.30, 29.39, -23.20) | |
| 1:236976072 | Q>H | A:179 | (-61.30, 29.39, -23.20) | |
| 1:236976092 | G>D | A:186 | (-72.37, 29.55, -22.23) | |
| 1:236976114 | I>M | A:193 | (-57.85, 25.27, -14.46) | |
| 1:236976121 | I>V | A:196 | (-52.03, 21.94, -14.39) | |
| 1:236976138 | N>K | A:201 | (-49.59, 27.85, -17.75) | |
| 1:236976144 | K>N | A:203 | (-50.08, 31.48, -11.79) | |
| 1:236978908 | A>V | A:205 | (-55.63, 31.35, -16.00) | |
| 1:236978915 | rs148101911 | F>L | A:207 | (-53.98, 37.67, -14.16) |
| 1:236978926 | rs546918671 COSM1296047 |
N>S | A:211 | (-58.77, 40.16, -15.76) |
| 1:236978931 | F>V | A:213 | (-64.41, 37.16, -12.33) | |
| 1:236978949 | P>S | A:219 | (-67.92, 35.40, -9.68) | |
| 1:236978952 | rs533191536 | R>W | A:220 | (-67.48, 31.34, -10.87) |
| 1:236978953 | R>Q | A:220 | (-67.48, 31.34, -10.87) | |
| 1:236978955 | P>A | A:221 | (-67.01, 28.36, -9.25) | |
| 1:236979761 | I>V | A:228 | (-48.40, 14.13, -10.46) | |
| 1:236979764 | rs61736441 | V>I | A:229 | (-45.56, 12.60, -13.71) |
| 1:236979801 | G>V | A:241 | (-48.39, 19.62, -4.32) | |
| 1:236979834 | E>G | A:252 | (-59.70, 31.88, -3.22) | |
| 1:236979837 | P>L | A:253 | (-59.85, 27.48, -5.17) | |
| 1:236979843 | rs1140598 | C>F | A:255 | (-61.89, 22.40, -5.82) |
| 1:236987459 | P>A | A:269 | (-50.21, 9.16, -1.71) | |
| 1:236987475 | rs368380397 | I>T | A:274 | (-53.26, 17.99, -1.65) |
| 1:236987483 | C>G | A:277 | (-52.55, 21.46, 2.76) | |
| 1:236987486 | T>A | A:278 | (-56.65, 22.61, 1.51) | |
| 1:236987490 | T>I | A:279 | (-59.88, 24.86, 3.23) | |
| 1:236987496 | Y>C | A:281 | (-64.82, 21.22, -0.95) | |
| 1:236987499 | V>D | A:282 | (-60.38, 17.25, -2.91) | |
| 1:236987501 | L>F | A:283 | (-60.48, 16.79, -6.69) | |
| 1:236987514 | N>S | A:287 | (-56.52, 7.22, -15.41) | |
| 1:236990141 | rs116252762 | D>N | A:314 | (-60.25, 7.40, 3.53) |
| 1:236990151 | V>D | A:317 | (-62.48, 12.52, -1.72) | |
| 1:236990154 | N>S | A:318 | (-65.06, 15.27, -2.73) | |
| 1:236990157 | I>T | A:319 | (-65.17, 15.65, -6.55) | |
| 1:236990162 | G>R | A:321 | (-63.45, 10.51, -11.63) | |
| 1:236990190 | H>R | A:330 | (-65.39, 2.86, -16.03) | |
| 1:236990193 | rs369312480 | I>T | A:331 | (-69.01, 6.22, -13.81) |
| 1:236992505 | V>M | A:338 | (-69.92, 7.01, -3.66) | |
| 1:236992515 | C>Y | A:341 | (-69.71, 7.63, 0.93) | |
| 1:236992520 | P>A | A:343 | (-68.18, 13.50, 2.68) | |
| 1:236992532 | rs140956566 | P>S | A:347 | (-59.24, 21.67, 6.88) |
| 1:236992542 | A>V | A:350 | (-55.07, 25.22, 7.35) | |
| 1:236992551 | rs144839980 | G>A | A:353 | (-50.44, 31.67, 10.65) |
| 1:236995279 | rs145217819 | F>L | A:363 | (-40.50, 28.25, 3.24) |
| 1:236995283 | I>V | A:365 | (-43.04, 31.48, 7.72) | |
| 1:236995286 | G>R | A:366 | (-44.56, 30.22, 11.43) | |
| 1:236995290 | P>L | A:367 | (-45.46, 31.16, 14.59) | |
| 1:236995311 | I>T | A:374 | (-33.69, 36.11, 2.59) | |
| 1:236995319 | rs138876566 | R>C | A:377 | (-23.50, 36.78, -2.81) |
| 1:236995331 | rs144777709 | A>T | A:381 | (-25.08, 46.36, -5.92) |
| 1:236995371 | rs376183112 | N>S | A:394 | (-21.51, 34.19, -17.08) |
| 1:236995374 | rs138734002 | Y>C | A:395 | (-27.01, 35.47, -16.87) |
| 1:236998905 | N>S | A:416 | (-31.29, 43.01, -7.39) | |
| 1:236998917 | G>V | A:420 | (-27.88, 51.24, -15.64) | |
| 1:236998925 | rs139054026 | D>H | A:423 | (-33.02, 45.45, -19.46) |
| 1:236998934 | rs374396973 | S>G | A:426 | (-34.84, 41.30, -19.41) |
| 1:236998949 | F>V | A:431 | (-31.04, 34.73, -12.78) | |
| 1:236998968 | rs368619885 CM021639 |
S>Y | A:437 | (-33.31, 25.09, -14.73) |
| 1:236998982 | A>T | A:442 | (-36.08, 25.99, -7.72) | |
| 1:237001732 | S>A | A:450 | (-36.86, 46.37, -7.54) | |
| 1:237001733 | S>Y | A:450 | (-36.86, 46.37, -7.54) | |
| 1:237001777 | G>R | A:465 | (-44.09, 30.41, -7.33) | |
| 1:237001780 | K>E | A:466 | (-46.27, 32.61, -3.01) | |
| 1:237001798 | I>V | A:472 | (-44.30, 48.48, -2.03) | |
| 1:237001817 | E>V | A:478 | (-53.03, 56.30, -0.55) | |
| 1:237001835 | K>T | A:484 | (-47.69, 49.41, -6.92) | |
| 1:237001838 | A>V | A:485 | (-50.93, 46.19, -3.91) | |
| 1:237001862 | rs150652021 | A>V | A:493 | (-47.57, 37.70, -3.59) |
| 1:237001867 | COSM325864 | M>V | A:495 | (-45.94, 42.61, 0.00) |
| 1:237001868 | M>K | A:495 | (-45.94, 42.61, 0.00) | |
| 1:237001869 | rs140424701 | M>I | A:495 | (-45.94, 42.61, 0.00) |
| 1:237001878 | M>I | A:498 | (-39.91, 49.72, 2.85) | |
| 1:237013653 | T>A | A:509 | (-39.13, 54.39, 16.48) | |
| 1:237013660 | T>R | A:511 | (-41.26, 57.38, 11.70) | |
| 1:237013670 | rs200479834 | R>S | A:514 | (-45.71, 57.56, 10.38) |
| 1:237013675 | C>Y | A:516 | (-46.17, 50.30, 9.02) | |
| 1:237013677 | T>P | A:517 | (-49.75, 51.56, 11.15) | |
| 1:237013680 | R>W | A:518 | (-50.62, 55.31, 5.89) | |
| 1:237013689 | H>Y | A:521 | (-54.79, 49.90, 7.01) | |
| 1:237013722 | rs140183705 | N>D | A:532 | (-50.15, 36.25, 7.19) |
| 1:237013727 | D>E | A:533 | (-49.12, 37.71, 2.51) | |
| 1:237013736 | F>L | A:536 | (-44.45, 45.82, 7.53) | |
| 1:237013756 | rs200362373 | I>T | A:543 | (-24.42, 51.89, 12.82) |
| 1:237013779 | rs151031178 | N>D | A:551 | (-25.97, 56.87, 17.22) |
| 1:237013785 | Y>H | A:553 | (-30.49, 55.35, 12.58) | |
| 1:237013786 | Y>F | A:553 | (-30.49, 55.35, 12.58) | |
| 1:237013797 | F>I | A:557 | (-35.29, 47.45, 13.15) | |
| 1:237015843 | I>T | A:573 | (-40.52, 42.13, 10.68) | |
| 1:237015867 | S>F | A:581 | (-21.92, 46.73, 8.50) | |
| 1:237015876 | F>S | A:584 | (-16.82, 47.92, 8.89) | |
| 1:237015905 | rs531465813 | M>V | A:594 | (-22.01, 44.02, 14.04) |
| 1:237015937 | K>N | A:604 | (-36.64, 38.92, 20.55) | |
| 1:237016270 | V>A | A:612 | (-28.84, 37.46, 5.28) | |
| 1:237016282 | N>S | A:616 | (-21.37, 34.29, 6.77) | |
| 1:237016290 | rs557853306 | V>L | A:619 | (-23.90, 31.39, 17.27) |
| 1:237016297 | rs61736440 | D>G | A:621 | (-22.92, 31.89, 22.30) |
| 1:237016321 | Q>R | A:629 | (-19.91, 43.66, 24.45) | |
| 1:237016338 | I>L | A:635 | (-26.41, 48.08, 18.57) | |
| 1:237016341 | W>R | A:636 | (-29.35, 48.39, 22.57) | |
| 1:237016378 | R>H | A:648 | (-9.74, 50.96, 20.18) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:236976058 | COSM282921 | A>T | A:175 | (-56.08, 33.02, -24.54) |
| 1:236979789 | COSM3485664 | S>F | A:237 | (-42.59, 22.17, -13.56) |
| 1:236998877 | COSM1748247 | E>K | A:407 | (-25.14, 24.11, -0.56) |
| 1:237001790 | COSM4029868 | V>A | A:469 | (-42.63, 41.52, -3.59) |