4GQS.C | CYP2C19

General Structure Information

PDB ID	4gqs
HGNC Gene Label(s)	CYP2C19
Structure Name	structure of human microsomal cytochrome p450 (cyp) 2c19
Resolution	2.87Å
Reference	AUTH R.L.REYNALD,S.SANSEN,C.D.STOUT,E.F.JOHNSONTITL STRUCTURAL CHARACTERIZATION OF HUMAN CYTOCHROME P450 2C19:TITL 2 ACTIVE SITE DIFFERENCES BETWEEN P450S 2C8, 2C9, AND 2C19.REF J.BIOL.CHEM. V. 287 44581 2012REFN ISSN 0021-9258PMID 23118231DOI 10.1074/JBC.M112.424895

Variant Set Distributions

ExAC Variants

Number Of Residues	461
Number Of SNVs	158
Number Of Permutations	28661
Optimal Distance Threshold	12.0
K Statistic	0.071
p-value	0.095

COSMIC

Number Of Residues	461
Number Of SNVs	22
Number Of Permutations	18684
Optimal Distance Threshold	7.0
K Statistic	0.004
p-value	0.559

Ripley’s K Analysis Plots

ExACCOSMIC

Variant Set Comparisons

Cosmic vs. ExAC

Number Of ExAC SNVs	158
Number Of COSMIC SNVs	17
Optimal Distance Threshold	13.0
K Statistic	-0.042
p-value	0.2

Pathogenic Proximity Analysis

COSMIC PathProx Analysis

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
10:96522547		L>F	C:29	(-51.50, 37.65, -21.06)
10:96522551		P>L	C:30	(-52.34, 34.04, -19.73)
10:96522574	COSM3441932	V>M	C:38	(-66.34, 47.60, -16.52)
10:96522599		D>V	C:46	(-70.61, 30.98, -8.77)
10:96534815		L>V	C:57	(-62.41, 28.38, -15.44)
10:96534831		G>A	C:62	(-56.19, 25.37, -17.31)
10:96534836	rs150045105	V>M	C:64	(-52.29, 29.17, -16.35)
10:96534843		T>S	C:66	(-56.52, 35.56, -17.49)
10:96534864	rs201306972	R>H	C:73	(-54.88, 42.07, -16.27)
10:96534869		V>M	C:75	(-52.99, 35.35, -13.30)
10:96534887	rs149072229	E>K	C:81	(-47.27, 20.96, -11.19)
10:96534906		L>Q	C:87	(-45.43, 30.33, -4.50)
10:96534917	rs118203756	G>R	C:91	(-40.89, 33.66, -5.06)
10:96534922	rs17878459	E>D	C:92	(-38.70, 37.22, -4.32)
10:96534926		F>L	C:94	(-44.90, 34.89, -7.98)
10:96534938	rs375159521	G>S	C:98	(-52.36, 41.95, -3.85)
10:96534951	rs372985779	L>P	C:102	(-61.13, 47.06, 2.13)
10:96534968		R>G	C:108	(-52.42, 54.35, 5.37)
10:96534972	rs200347843 COSM3441939	G>A	C:109	(-49.05, 50.09, 4.03)
10:96534975	rs112197069	F>Y	C:110	(-48.39, 51.26, 7.40)
10:96534977		G>R	C:111	(-47.60, 46.06, 8.31)
10:96535150	rs372875966	I>T	C:112	(-47.27, 41.67, 8.06)
10:96535152	rs145119820	V>I	C:113	(-50.87, 41.18, 5.76)
10:96535162	COSM361115	N>S	C:116	(-45.08, 45.30, -0.47)
10:96535173	rs41291556	W>R	C:120	(-42.99, 41.52, 3.31)
10:96535180	rs17885179	E>A	C:122	(-37.35, 45.33, 7.39)
10:96535184		I>M	C:123	(-42.07, 44.35, 9.51)
10:96535186	rs200346442	R>Q	C:124	(-42.23, 38.00, 7.23)
10:96535188	rs200150287	R>C	C:125	(-37.46, 38.10, 8.70)
10:96535189	rs141774245	R>H	C:125	(-37.46, 38.10, 8.70)
10:96535198		L>P	C:128	(-40.70, 35.40, 11.38)
10:96535204	rs150152656	T>M	C:130	(-40.52, 37.92, 17.89)
10:96535207	rs371309036	L>P	C:131	(-43.38, 34.77, 16.59)
10:96535210	rs72552267	R>Q	C:132	(-37.61, 32.69, 17.13)
10:96535224	rs374950950	G>R	C:137	(-37.78, 36.32, 26.28)
10:96535225		G>E	C:137	(-37.78, 36.32, 26.28)
10:96535244		D>E	C:143	(-45.74, 29.14, 28.96)
10:96535245	rs368767518 COSM122460	R>C	C:144	(-47.16, 32.87, 26.43)
10:96535255	rs147453531	E>G	C:147	(-51.71, 29.98, 30.94)
10:96535260		A>T	C:149	(-55.29, 25.59, 27.63)
10:96535263	rs142974781	R>C	C:150	(-53.81, 25.57, 32.11)
10:96535264	rs58973490	R>H	C:150	(-53.81, 25.57, 32.11)
10:96535293	rs375760063	K>E	C:160	(-72.92, 22.14, 34.21)
10:96540258		S>P	C:162	(-74.41, 21.46, 28.70)
10:96540262		P>L	C:163	(-76.30, 22.23, 25.67)
10:96540271	rs149694239	P>L	C:166	(-68.51, 26.23, 20.68)
10:96540295	COSM3441951	P>H	C:174	(-57.33, 31.85, 20.04)
10:96540301	rs57700608	N>S	C:176	(-55.95, 35.60, 25.16)
10:96540311		C>W	C:179	(-52.94, 39.10, 23.59)
10:96540330	rs183701923	R>C	C:186	(-54.91, 35.44, 30.04)
10:96540336	rs370803989 COSM921735	D>N	C:188	(-60.00, 37.54, 32.81)
10:96540340	rs373613403 COSM3738799	Y>F	C:189	(-62.06, 33.87, 28.93)
10:96540367	rs186489608	M>T	C:198	(-64.28, 38.79, 20.90)
10:96540381		E>K	C:203	(-68.40, 43.61, 13.73)
10:96540382		E>G	C:203	(-68.40, 43.61, 13.73)
10:96540388		I>S	C:205	(-64.91, 38.54, 9.94)
10:96540403		T>N	C:210	(-70.23, 39.58, 3.33)
10:96540405		P>T	C:211	(-71.05, 38.51, -0.11)
10:96541582		C>Y	C:216	(-66.76, 46.13, -3.21)
10:96541583	rs576823729	C>W	C:216	(-66.76, 46.13, -3.21)
10:96541591		F>Y	C:219	(-66.75, 46.62, -8.59)
10:96541606		D>V	C:224	(-68.95, 54.96, -2.08)
10:96541615	rs6413438	P>L	C:227	(-71.78, 53.69, 3.24)
10:96541642		N>T	C:236	(-64.19, 49.00, 14.65)
10:96541643		N>K	C:236	(-64.19, 49.00, 14.65)
10:96541647		A>T	C:238	(-59.72, 53.19, 15.16)
10:96541648		A>V	C:238	(-59.72, 53.19, 15.16)
10:96541656	COSM540052	E>K	C:241	(-55.57, 51.06, 15.58)
10:96541661		S>R	C:242	(-56.37, 53.79, 20.03)
10:96541671		E>Q	C:246	(-52.80, 54.26, 24.62)
10:96541688	rs148247410	H>Q	C:251	(-45.40, 48.59, 27.15)
10:96541699		M>T	C:255	(-38.41, 49.24, 28.20)
10:96541704		I>F	C:257	(-33.25, 47.50, 27.19)
10:96541708	rs537050749	N>S	C:258	(-31.65, 44.08, 29.17)
10:96541712		N>K	C:259	(-36.43, 42.26, 30.82)
10:96541716		R>W	C:261	(-42.65, 43.50, 29.49)
10:96541719	rs577255883	D>N	C:262	(-44.06, 42.09, 25.09)
10:96541721		D>E	C:262	(-44.06, 42.09, 25.09)
10:96541726		I>T	C:264	(-44.76, 46.13, 22.47)
10:96541748		M>I	C:271	(-37.54, 51.71, 17.74)
10:96580263	rs146582098	N>I	C:277	(-32.05, 54.70, 10.15)
10:96580272	rs58744432	S>Y	C:280	(-36.35, 52.78, 9.98)
10:96580274		E>K	C:281	(-39.81, 50.90, 7.82)
10:96580281	rs201391010	T>I	C:283	(-42.42, 52.99, 13.21)
10:96580283		I>V	C:284	(-45.12, 53.78, 17.00)
10:96580284		I>T	C:284	(-45.12, 53.78, 17.00)
10:96580295		V>I	C:288	(-50.30, 49.93, 16.08)
10:96580298	rs371913046	I>V	C:289	(-50.75, 48.70, 11.93)
10:96580316		L>V	C:295	(-55.19, 40.63, 16.76)
10:96580320		G>A	C:296	(-56.91, 38.91, 12.68)
10:96580322		A>T	C:297	(-54.61, 36.64, 11.58)
10:96580326		G>A	C:298	(-55.36, 34.39, 14.52)
10:96580328		T>A	C:299	(-58.64, 34.95, 15.95)
10:96580340		S>G	C:303	(-61.60, 29.65, 15.90)
10:96580344		T>R	C:304	(-63.02, 28.40, 12.38)
10:96580346		T>A	C:305	(-59.88, 25.40, 12.47)
10:96580347		T>I	C:305	(-59.88, 25.40, 12.47)
10:96580356		Y>C	C:308	(-65.13, 22.45, 10.49)
10:96580358		A>T	C:309	(-62.69, 19.75, 14.72)
10:96580371		L>P	C:313	(-64.41, 14.97, 16.45)
10:96580374		L>R	C:314	(-69.32, 15.20, 16.91)
10:96580389		V>A	C:319	(-61.06, 9.49, 14.93)
10:96580391		T>A	C:320	(-62.49, 10.78, 18.86)
10:96580392		T>I	C:320	(-62.49, 10.78, 18.86)
10:96580394		A>S	C:321	(-61.09, 7.31, 20.25)
10:96602597		K>I	C:322	(-58.73, 5.98, 16.86)
10:96602623	rs3758581	V>I	C:331	(-49.73, 12.01, 28.52)
10:96602633		N>I	C:334	(-49.76, 12.19, 36.15)
10:96602634	rs563052490	N>K	C:334	(-49.76, 12.19, 36.15)
10:96602635	rs368758960	R>W	C:335	(-48.12, 15.12, 31.40)
10:96602636	rs118203757	R>Q	C:335	(-48.12, 15.12, 31.40)
10:96602639	rs143833145	S>I	C:336	(-50.94, 18.06, 30.59)
10:96602641		P>S	C:337	(-50.86, 17.81, 26.99)
10:96602642	COSM4016875	P>H	C:337	(-50.86, 17.81, 26.99)
10:96602645	rs568429823	C>F	C:338	(-46.58, 18.58, 25.33)
10:96602648	rs146357635	M>R	C:339	(-45.75, 20.46, 21.40)
10:96602660		G>D	C:343	(-43.68, 12.70, 17.94)
10:96602666	rs201132803	M>K	C:345	(-49.19, 11.72, 19.49)
10:96602668		P>S	C:346	(-48.60, 9.39, 15.25)
10:96602669		P>L	C:346	(-48.60, 9.39, 15.25)
10:96602674		T>A	C:348	(-53.14, 13.13, 16.98)
10:96602680	rs201509150	A>T	C:350	(-53.03, 13.30, 11.35)
10:96602690	rs373024844	H>R	C:353	(-51.78, 17.83, 9.38)
10:96602692	COSM348313	E>K	C:354	(-57.43, 15.58, 7.18)
10:96602701		R>G	C:357	(-57.15, 17.91, 3.41)
10:96602704		Y>H	C:358	(-62.71, 18.36, 4.93)
10:96602707		I>V	C:359	(-61.47, 23.00, 6.29)
10:96602708	rs374493781	I>N	C:359	(-61.47, 23.00, 6.29)
10:96602712	COSM3441969	D>E	C:360	(-60.10, 24.91, 2.05)
10:96602719		P>S	C:363	(-59.89, 28.50, -0.55)
10:96602738		A>V	C:369	(-48.03, 39.68, -6.84)
10:96602743		T>A	C:371	(-42.14, 41.59, -8.08)
10:96602752	rs113934938	V>I	C:374	(-43.00, 36.58, -14.89)
10:96602759		F>Y	C:376	(-45.08, 30.68, -14.77)
10:96602780		K>R	C:383	(-44.36, 45.07, -12.28)
10:96609674	rs188851578	G>R	C:384	(-48.42, 43.66, -10.64)
10:96609680		T>A	C:386	(-53.07, 39.95, -9.26)
10:96609683	rs372873637	I>V	C:387	(-51.15, 36.17, -8.67)
10:96609684	rs562912432	I>T	C:387	(-51.15, 36.17, -8.67)
10:96609690	COSM4016876	T>I	C:389	(-52.99, 30.69, -5.32)
10:96609695		L>V	C:391	(-54.59, 26.87, -1.56)
10:96609698		T>S	C:392	(-58.55, 24.01, -2.97)
10:96609705		V>A	C:394	(-53.26, 21.51, -3.43)
10:96609720		K>R	C:399	(-53.24, 12.01, -8.20)
10:96609729		P>L	C:402	(-57.18, 9.42, -1.91)
10:96609737		E>Q	C:405	(-64.30, 15.62, -0.99)
10:96609740	rs144056033	M>V	C:406	(-63.97, 11.43, 2.37)
10:96609742		M>I	C:406	(-63.97, 11.43, 2.37)
10:96609744		F>S	C:407	(-62.09, 13.58, 8.18)
10:96609749		P>S	C:409	(-57.28, 10.37, 8.95)
10:96609752	rs17879685	R>C	C:410	(-57.14, 6.28, 6.26)
10:96609753		R>H	C:410	(-57.14, 6.28, 6.26)
10:96609769	rs527499296	E>D	C:415	(-49.19, 1.05, 5.34)
10:96609776		N>D	C:418	(-46.05, 6.21, 11.40)
10:96609786	rs145599727	K>R	C:421	(-44.37, 14.66, 6.17)
10:96609791		N>H	C:423	(-45.23, 18.08, -0.86)
10:96609795	rs148899014	Y>C	C:424	(-49.78, 17.90, -2.91)
10:96609802		M>I	C:426	(-50.13, 24.31, 0.72)
10:96609812	rs369403039	A>P	C:430	(-46.30, 29.16, 0.30)
10:96609815		G>R	C:431	(-43.33, 30.92, 0.37)
10:96612493	rs146991374	K>I	C:432	(-40.62, 34.13, 0.42)
10:96612495	rs56337013	R>W	C:433	(-46.30, 37.12, 1.70)
10:96612496	COSM215441	R>Q	C:433	(-46.30, 37.12, 1.70)
10:96612516		L>V	C:440	(-48.86, 29.96, 17.07)
10:96612528	rs540369401	E>Q	C:444	(-52.84, 27.30, 18.92)
10:96612531		L>V	C:445	(-54.62, 23.23, 16.27)
10:96612532	COSM74316	L>P	C:445	(-54.62, 23.23, 16.27)
10:96612541		F>S	C:448	(-55.89, 24.90, 22.26)
10:96612542	rs118203759	F>L	C:448	(-55.89, 24.90, 22.26)
10:96612550	rs369665827	F>S	C:451	(-55.15, 20.30, 27.05)
10:96612553		I>T	C:452	(-60.58, 19.37, 24.94)
10:96612563	COSM141302	N>K	C:455	(-60.22, 16.82, 30.23)
10:96612571		L>R	C:458	(-67.11, 15.18, 22.16)
10:96612588	rs58519063	P>S	C:464	(-73.71, 11.21, 14.40)
10:96612595		D>G	C:466	(-77.87, 12.97, 10.69)
10:96612612		V>I	C:472	(-70.96, 27.19, 4.54)
10:96612627		A>T	C:477	(-64.14, 31.82, 3.59)
10:96612633		V>F	C:479	(-67.97, 28.33, 7.73)
10:96612637	COSM3808066	P>L	C:480	(-68.49, 25.55, 10.02)
10:96612663	rs542090374	P>S	C:489	(-66.45, 15.16, 32.03)

4GQS.C | CYP2C19.

4GQS.C | CYP2C19

General Structure Information

Variant Set Distributions

Ripley’s K Analysis Plots

Variant Set Comparisons

Pathogenic Proximity Analysis

Mapped Variants

[+] ExAC Missense Variants

[+] COSMIC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
10:96534839	COSM1349996	F>L	C:65	(-57.02, 30.83, -15.64)
10:96534882	COSM231220	G>E	C:79	(-52.30, 23.30, -9.13)
10:96534922	COSM5019653	E>D	C:92	(-38.70, 37.22, -4.32)
10:96534969	COSM1702799	R>K	C:108	(-52.42, 54.35, 5.37)
10:96534972	COSM3441939	G>E	C:109	(-49.05, 50.09, 4.03)
10:96535179	COSM3441943	E>K	C:122	(-37.35, 45.33, 7.39)
10:96535189	COSM921733	R>H	C:125	(-37.46, 38.10, 8.70)
10:96535209	COSM3967240	R>W	C:132	(-37.61, 32.69, 17.13)
10:96535243	COSM1638698	D>G	C:143	(-45.74, 29.14, 28.96)
10:96535264	COSM3985824	R>H	C:150	(-53.81, 25.57, 32.11)
10:96540267	COSM1702800	D>N	C:165	(-72.09, 27.75, 20.12)
10:96540313	COSM122461	S>F	C:180	(-49.88, 37.03, 25.41)
10:96541593	COSM3441954	P>S	C:220	(-64.05, 50.82, -5.79)
10:96541683	COSM3441957	E>K	C:250	(-48.73, 51.50, 28.98)
10:96602605	COSM3441965	E>K	C:325	(-56.80, 5.24, 22.26)
10:96602618	COSM3967242	R>H	C:329	(-49.92, 5.49, 23.71)
10:96602623	COSM5019812	V>I	C:331	(-49.73, 12.01, 28.52)
10:96602692	COSM348313	E>K	C:354	(-57.43, 15.58, 7.18)
10:96609728	COSM1702803	P>S	C:402	(-57.18, 9.42, -1.91)
10:96609774	COSM232122	G>E	C:417	(-48.90, 4.46, 11.43)
10:96612496	COSM215441	R>Q	C:433	(-46.30, 37.12, 1.70)
10:96612523	COSM198925	R>H	C:442	(-49.23, 22.70, 13.57)