3I6W.H | CHEK2

General Structure Information

PDB ID	3i6w
HGNC Gene Label(s)	CHEK2
Structure Name	structure and activation mechanism of the chk2 dna-damage checkpoint kinase
Resolution	3.25Å
Reference	AUTH Z.CAI,N.H.CHEHAB,N.P.PAVLETICHTITL STRUCTURE AND ACTIVATION MECHANISM OF THE CHK2 DNA DAMAGETITL 2 CHECKPOINT KINASE.REF MOL.CELL V. 35 818 2009REFN ISSN 1097-2765PMID 19782031DOI 10.1016/J.MOLCEL.2009.09.007

Variant Set Distributions

ExAC Variants

Number Of Residues	382
Number Of SNVs	119
Number Of Permutations	64748
Optimal Distance Threshold	28.0
K Statistic	0.42
p-value	0.373

ClinVar

Number Of Residues	382
Number Of SNVs	11
Number Of Permutations	9822
Optimal Distance Threshold	13.0
K Statistic	0.2
p-value	0.177

COSMIC

Number Of Residues	382
Number Of SNVs	12
Number Of Permutations	5736
Optimal Distance Threshold	28.0
K Statistic	0.606
p-value	0.096

Ripley’s K Analysis Plots

ExACClinVarCOSMIC

Variant Set Comparisons

ClinVar vs. ExAC

Number Of ExAC SNVs	119
Number Of ClinVar SNVs	7
Optimal Distance Threshold	11.0
K Statistic	0.086
p-value	0.594

Cosmic vs. ExAC

Number Of ExAC SNVs	119
Number Of COSMIC SNVs	10
Optimal Distance Threshold	9.0
K Statistic	0.056
p-value	0.391

Pathogenic Proximity Analysis

ClinVar PathProx Analysis

COSMIC PathProx Analysis

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
22:29130435		P>L	H:92	(-14.37, -76.90, -46.40)
22:29130430		A>S	H:94	(-13.17, -71.55, -49.33)
22:29130415	rs537051622	L>F	H:99	(-9.68, -56.81, -45.33)
22:29130391		E>K	H:107	(-15.63, -71.27, -43.86)
22:29121353		C>S	H:108	(-16.81, -71.71, -48.52)
22:29121337		Y>C	H:113	(-21.69, -69.03, -50.62)
22:29121328		G>A	H:116	(-25.32, -58.24, -50.38)
22:29121326	rs28909982	R>G	H:117	(-27.84, -53.71, -49.96)
22:29121321		D>E	H:118	(-31.10, -58.89, -50.65)
22:29121319	rs373648967	K>R	H:119	(-32.62, -59.51, -45.97)
22:29121313		C>F	H:121	(-27.93, -62.71, -49.64)
22:29121286	rs150677496	L>Q	H:130	(-21.55, -52.48, -43.14)
22:29121280	COSM3424093	R>I	H:132	(-22.94, -46.52, -39.04)
22:29121275	rs372874441 COSM1033071	D>H	H:134	(-20.12, -44.07, -46.59)
22:29121265	rs368570187 CM023899	R>Q	H:137	(-26.48, -46.17, -48.90)
22:29121242	rs137853007	R>W	H:145	(-22.42, -66.00, -58.34)
22:29121239		I>L	H:146	(-18.24, -66.68, -54.82)
22:29121106	COSM478843	G>C	H:151	(-15.28, -79.49, -64.30)
22:29121095	rs564924749	N>K	H:154	(-13.24, -84.99, -61.96)
22:29121087	rs17879961	I>T	H:157	(-13.32, -74.23, -61.30)
22:29121088		I>V	H:157	(-13.32, -74.23, -61.30)
22:29121085		A>T	H:158	(-13.59, -70.82, -58.76)
22:29121082		Y>H	H:159	(-15.90, -69.81, -61.78)
22:29121077	rs575910805	I>M	H:160	(-16.19, -63.85, -59.10)
22:29121072		D>G	H:162	(-20.02, -58.30, -61.23)
22:29121069		H>R	H:163	(-24.33, -59.63, -60.90)
22:29121057	rs144850845	G>E	H:167	(-18.23, -53.08, -58.78)
22:29121058	rs72552322	G>R	H:167	(-18.23, -53.08, -58.78)
22:29121018	rs137853009	R>H	H:180	(-18.52, -66.38, -65.34)
22:29121019	rs77130927	R>C	H:180	(-18.52, -66.38, -65.34)
22:29121015	rs121908701	R>H	H:181	(-12.07, -63.66, -62.84)
22:29121016	rs137853010	R>C	H:181	(-12.07, -63.66, -62.84)
22:29121008		L>F	H:183	(-11.62, -66.73, -57.76)
22:29121002		N>K	H:185	(-5.09, -68.56, -53.91)
22:29121001	rs146198085	N>H	H:186	(-4.11, -64.35, -52.68)
22:29120994		E>G	H:188	(-7.15, -58.57, -52.98)
22:29120992		I>V	H:189	(-12.64, -59.34, -53.31)
22:29120979		L>P	H:193	(-13.60, -48.14, -55.13)
22:29115462		F>L	H:202	(-7.12, -67.62, -49.24)
22:29115452		T>I	H:205	(-8.84, -77.53, -52.93)
22:29115447		D>Y	H:207	(-1.83, -78.45, -50.61)
22:29115437	COSM1033069	S>L	H:210	(-8.53, -85.38, -48.83)
22:29115403	rs200451612	I>M	H:221	(3.89, -84.64, -45.99)
22:29115405	rs199749372	I>V	H:221	(3.89, -84.64, -45.99)
22:29107992		E>K	H:233	(0.73, -86.25, -61.31)
22:29107982		L>P	H:236	(7.54, -83.66, -53.50)
22:29107973		E>G	H:239	(9.75, -90.00, -45.31)
22:29107974	rs121908702	E>K	H:239	(9.75, -90.00, -45.31)
22:29107964		T>I	H:242	(12.76, -88.83, -41.86)
22:29107965		T>A	H:242	(12.76, -88.83, -41.86)
22:29107962	rs141776984	C>R	H:243	(11.90, -85.14, -43.80)
22:29107947		I>V	H:248	(4.78, -89.97, -55.00)
22:29107934		S>N	H:252	(-5.17, -94.05, -63.35)
22:29107935		S>G	H:252	(-5.17, -94.05, -63.35)
22:29106038		L>F	H:268	(-6.30, -106.24, -62.49)
22:29106022		E>A	H:273	(5.22, -104.34, -62.98)
22:29106017	COSM1033067 CM110735	E>Q	H:275	(6.24, -106.37, -55.62)
22:29105996		H>Y	H:282	(22.51, -101.87, -58.57)
22:29099553		P>H	H:283	(23.58, -99.17, -56.43)
22:29099546		I>M	H:285	(18.91, -99.18, -60.19)
22:29099517		E>A	H:295	(-8.63, -93.67, -55.93)
22:29099514		D>G	H:296	(-5.03, -93.07, -58.71)
22:29099495		E>D	H:302	(15.35, -93.14, -54.15)
22:29095924		M>V	H:304	(17.99, -88.55, -56.80)
22:29095919		E>D	H:305	(18.58, -83.64, -54.61)
22:29095917		G>A	H:306	(20.75, -83.89, -59.08)
22:29095918	COSM94077	G>R	H:306	(20.75, -83.89, -59.08)
22:29095903		D>N	H:311	(20.06, -80.96, -66.81)
22:29095897		V>M	H:313	(24.79, -82.45, -71.36)
22:29095894		V>M	H:314	(22.06, -78.78, -71.63)
22:29095885		K>E	H:317	(27.39, -78.25, -71.39)
22:29095882	rs148053495	R>C	H:318	(32.74, -80.96, -73.83)
22:29095878		L>P	H:319	(30.72, -83.96, -68.92)
22:29095872	rs374395284	E>A	H:321	(37.33, -88.21, -70.24)
22:29095867		T>A	H:323	(32.86, -87.44, -64.89)
22:29095860		K>M	H:325	(35.54, -93.28, -66.99)
22:29095854		Y>C	H:327	(28.53, -89.95, -64.14)
22:29095848		Y>C	H:329	(31.76, -98.69, -63.63)
22:29095846		Q>E	H:330	(27.68, -95.80, -62.07)
22:29092971	rs374660293	L>H	H:338	(18.33, -104.33, -65.31)
22:29092969	rs371207635 COSM3800097	H>Y	H:339	(20.23, -106.76, -69.12)
22:29092965		E>G	H:340	(21.86, -110.22, -64.64)
22:29092962		N>T	H:341	(17.34, -109.23, -62.90)
22:29092960		G>S	H:342	(14.95, -109.56, -67.04)
22:29092952	rs202051128	I>M	H:344	(15.32, -105.20, -71.69)
22:29092947	COSM3964171 COSM74137	R>H	H:346	(12.17, -99.88, -75.44)
22:29092948	rs201206424 COSM1415436 COSM444827 COSM726025 CM110730	R>C	H:346	(12.17, -99.88, -75.44)
22:29092945	rs28909980	D>N	H:347	(13.88, -95.46, -73.23)
22:29092931	COSM1033063	E>D	H:351	(16.31, -87.65, -69.91)
22:29092929		N>S	H:352	(16.13, -91.98, -67.98)
22:29092926		V>A	H:353	(20.49, -90.85, -65.96)
22:29092917	rs121908703	S>L	H:356	(22.93, -88.25, -56.14)
22:29092908		E>G	H:359	(29.02, -83.48, -55.33)
22:29092899		C>Y	H:362	(27.90, -88.91, -58.06)
22:29092893		I>T	H:364	(24.43, -92.53, -61.46)
22:29091855		D>N	H:368	(11.75, -94.52, -66.68)
22:29091846	rs531398630 COSM4002125	H>Y	H:371	(9.00, -97.60, -73.02)
22:29091827	rs560973106	E>G	H:377	(5.14, -109.46, -70.19)
22:29091824		T>I	H:378	(5.57, -104.94, -72.31)
22:29091788	rs200928781 COSM1559600	Y>S	H:390	(17.83, -92.32, -77.48)
22:29091782	rs373073383 COSM1415431 COSM1535330	A>V	H:392	(17.83, -99.40, -83.23)
22:29091777	COSM1682176	E>K	H:394	(18.20, -103.57, -85.13)
22:29091753		A>T	H:402	(11.38, -109.40, -82.41)
22:29091742		N>K	H:405	(17.96, -108.42, -77.20)
22:29091743	rs369070738	N>S	H:405	(17.96, -108.42, -77.20)
22:29091740	rs200649225	R>H	H:406	(20.20, -108.40, -72.75)
22:29091741		R>C	H:406	(20.20, -108.40, -72.75)
22:29091731		D>V	H:409	(19.70, -101.22, -73.55)
22:29091732		D>H	H:409	(19.70, -101.22, -73.55)
22:29091713		V>D	H:415	(23.86, -92.59, -77.73)
22:29091220	rs139366548	Y>H	H:424	(28.05, -83.98, -80.90)
22:29091207	rs137853011	S>F	H:428	(20.87, -84.47, -86.67)
22:29091178	rs200050883 CM077522	D>Y	H:438	(18.19, -93.03, -93.31)
22:29091175		Q>E	H:439	(21.89, -90.58, -90.02)
22:29091154	rs121908705	N>D	H:446	(28.07, -86.26, -86.57)
22:29091147	rs17886163	I>S	H:448	(32.79, -82.88, -84.90)
22:29091148		I>V	H:448	(32.79, -82.88, -84.90)
22:29091138	rs139088611	V>D	H:451	(34.93, -82.22, -80.40)
22:29091139	rs548796284	V>I	H:451	(34.93, -82.22, -80.40)
22:29091136		W>R	H:452	(34.81, -87.15, -80.40)
22:29091133		A>P	H:453	(40.45, -83.98, -80.21)
22:29091115		A>P	H:459	(36.49, -93.36, -75.61)
22:29090097	COSM3371880	L>V	H:462	(33.54, -97.89, -75.92)
22:29090089		K>N	H:464	(33.78, -96.62, -82.85)
22:29090075		V>A	H:469	(24.45, -101.39, -87.34)
22:29090060	rs121908706	R>H	H:474	(25.38, -103.71, -80.91)
22:29090061	rs540635787	R>C	H:474	(25.38, -103.71, -80.91)
22:29090058	rs370968992	F>I	H:475	(31.06, -104.29, -77.26)
22:29090054	rs142763740	T>M	H:476	(27.96, -106.78, -74.55)
22:29090052		T>A	H:477	(27.18, -105.00, -70.75)
22:29090043	COSM3972904	A>T	H:480	(32.09, -102.81, -71.97)
22:29090030	rs564605612 CM110733	P>L	H:484	(40.29, -100.63, -72.47)
22:29085183		K>N	H:494	(36.46, -91.74, -57.35)
22:29085176	rs143965148	D>N	H:497	(34.68, -93.77, -51.80)
22:29085164	rs17883172	E>K	H:501	(26.78, -93.17, -48.57)

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
22:29121265	COSM4672127	R>Q	H:137	(-26.48, -46.17, -48.90)
22:29121245	COSM184396	F>L	H:144	(-20.07, -60.57, -54.96)
22:29107949	COSM1682177	A>D	H:247	(8.89, -89.54, -55.31)
22:29107936	COSM1751780	I>M	H:251	(-1.15, -93.50, -62.41)
22:29095854	COSM3719532	Y>C	H:327	(28.53, -89.95, -64.14)
22:29092948	COSM726025	R>G	H:346	(12.17, -99.88, -75.44)
22:29092920	COSM1579032	L>P	H:355	(22.66, -87.05, -60.93)
22:29092897	COSM1190411	L>F	H:363	(25.88, -92.47, -56.87)
22:29091839	COSM1294063	SK>SE	H:373	(10.90, -107.06, -71.92)
22:29091840	COSM42871	K>E	H:373	(10.90, -107.06, -71.92)
22:29091816	COSM1559601	M>V	H:381	(3.46, -98.51, -67.01)
22:29091788	COSM1559600	Y>C	H:390	(17.83, -92.32, -77.48)
22:29091777	COSM1682176	E>K	H:394	(18.20, -103.57, -85.13)
22:29091747	COSM1559598	Y>D	H:404	(11.74, -105.71, -77.45)

3I6W.H | CHEK2.

3I6W.H | CHEK2

General Structure Information

Variant Set Distributions

Ripley’s K Analysis Plots

Variant Set Comparisons

Pathogenic Proximity Analysis

Mapped Variants

[+] ExAC Missense Variants

[+] ClinVar Missense Variants

[+] COSMIC Missense Variants