3U7U.C | ERBB4

General Structure Information

PDB ID	3u7u
HGNC Gene Label(s)	ERBB4
Structure Name	crystal structure of extracellular region of human epidermal growth factor receptor 4 in complex with neuregulin-1 beta
Resolution	3.03Å
Reference	AUTH P.LIU,T.E.CLEVELAND,S.BOUYAIN,P.O.BYRNE,P.A.LONGO,D.J.LEAHYTITL A SINGLE LIGAND IS SUFFICIENT TO ACTIVATE EGFR DIMERS.REF PROC.NATL.ACAD.SCI.USA V. 109 10861 2012REFN ISSN 0027-8424PMID 22699492DOI 10.1073/PNAS.1201114109

Variant Set Distributions

ExAC Variants

Number Of Residues	598
Number Of SNVs	125
Number Of Permutations	84725
Optimal Distance Threshold	6.0
K Statistic	0.005
p-value	0.025

COSMIC

Number Of Residues	598
Number Of SNVs	28
Number Of Permutations	55910
Optimal Distance Threshold	7.0
K Statistic	0.005
p-value	0.719

Ripley’s K Analysis Plots

ExACCOSMIC

Variant Set Comparisons

Cosmic vs. ExAC

Number Of ExAC SNVs	125
Number Of COSMIC SNVs	20
Optimal Distance Threshold	30.0
K Statistic	0.069
p-value	0.436

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
2:213403178		Q>R	C:1	(-67.45, 3.09, 14.30)
2:212989571	COSM209869	R>Q	C:22	(-68.09, 27.46, 5.34)
2:212989562	COSM1016002	R>H	C:25	(-67.65, 22.99, 10.98)
2:212989563	rs372631205 COSM2716452 COSM2716453	R>C	C:25	(-67.65, 22.99, 10.98)
2:212989553		Y>C	C:28	(-61.58, 17.29, 9.36)
2:212989538	rs545249326	V>A	C:33	(-61.40, 7.77, 12.06)
2:212989526		N>S	C:37	(-53.76, 14.02, 6.92)
2:212989509		I>V	C:43	(-58.13, 29.04, 11.65)
2:212989502		H>R	C:45	(-59.49, 34.86, 18.21)
2:212989498	rs368312588	N>K	C:46	(-63.78, 34.21, 15.97)
2:212989496		R>P	C:47	(-63.95, 31.31, 13.35)
2:212989493	COSM442268	D>G	C:48	(-66.49, 26.83, 16.98)
2:212989487	COSM1405192	S>F	C:50	(-66.37, 22.09, 19.02)
2:212812334		R>Q	C:56	(-62.68, 9.87, 19.20)
2:212812329		V>I	C:58	(-55.14, 10.55, 12.94)
2:212812320		Y>H	C:61	(-50.05, 14.92, 8.52)
2:212812308	rs201678258 COSM394748	A>S	C:65	(-50.54, 26.07, 11.52)
2:212812298		Q>R	C:68	(-54.86, 33.50, 14.84)
2:212812292		R>H	C:70	(-58.23, 31.02, 24.13)
2:212812293	rs569995088	R>C	C:70	(-58.23, 31.02, 24.13)
2:212812284		P>S	C:73	(-60.54, 21.34, 20.62)
2:212812268	COSM573349 COSM1649742	R>H	C:78	(-56.11, 8.09, 23.24)
2:212812269	rs201152419 COSM719370 COSM1647279	R>C	C:78	(-56.11, 8.09, 23.24)
2:212812245	COSM131763	Y>H	C:86	(-45.24, 18.43, 7.67)
2:212812235	COSM1405190 COSM2716436	R>Q	C:89	(-39.27, 15.78, 9.65)
2:212812220		I>T	C:94	(-47.95, 22.45, 16.91)
2:212812205		R>K	C:99	(-51.80, 38.52, 14.59)
2:212812194	rs150757966	N>D	C:103	(-53.40, 40.78, 19.65)
2:212812190		F>S	C:104	(-55.27, 37.73, 19.18)
2:212812184	rs192066345	L>P	C:106	(-52.42, 28.42, 20.68)
2:212812166	rs566211797	K>R	C:112	(-55.76, 14.66, 29.35)
2:212652875		N>S	C:119	(-44.46, 6.59, 12.75)
2:212652863		Y>C	C:123	(-41.93, 21.45, 14.78)
2:212652833	rs370840578	A>E	C:133	(-46.19, 22.04, 26.02)
2:212652834	rs375361752	A>T	C:133	(-46.19, 22.04, 26.02)
2:212652822		H>Y	C:137	(-42.18, 12.59, 28.59)
2:212652807		V>I	C:142	(-43.33, 8.61, 20.73)
2:212652803	rs200302763	R>Q	C:143	(-45.23, 2.22, 21.20)
2:212652804	rs138433638	R>W	C:143	(-45.23, 2.22, 21.20)
2:212652800		N>S	C:144	(-41.38, 4.16, 16.86)
2:212652755	COSM3838522 COSM3838523	S>L	C:159	(-42.66, 33.41, 28.72)
2:212652752		G>E	C:160	(-45.25, 33.73, 31.35)
2:212615423	rs191386517	R>H	C:163	(-45.00, 26.27, 38.53)
2:212615424		R>C	C:163	(-45.00, 26.27, 38.53)
2:212615417	COSM1494763	H>R	C:165	(-52.00, 21.25, 40.39)
2:212615406		T>A	C:169	(-45.60, 15.57, 38.76)
2:212615399	rs369165560	R>H	C:171	(-44.34, 16.11, 32.95)
2:212615400	COSM3577357 COSM3577358	R>C	C:171	(-44.34, 16.11, 32.95)
2:212615391		G>R	C:174	(-52.69, 22.91, 32.15)
2:212589917	rs552079714	T>S	C:184	(-48.94, 5.21, 29.34)
2:212589910	COSM1530586	T>M	C:186	(-42.26, 5.83, 31.40)
2:212589898	rs148992844	E>A	C:190	(-39.35, -2.69, 34.46)
2:212589888		D>E	C:193	(-43.18, -5.27, 27.08)
2:212589886		G>V	C:194	(-46.10, -1.76, 26.92)
2:212589887		G>S	C:194	(-46.10, -1.76, 26.92)
2:212589875		G>R	C:198	(-50.29, 1.54, 36.19)
2:212589866	rs561236916 COSM1405185	V>I	C:201	(-47.30, -6.44, 36.96)
2:212589820		P>L	C:216	(-55.71, -7.15, 31.12)
2:212589811	COSM1405183 COSM48368	T>I	C:219	(-60.80, -6.87, 24.62)
2:212587258	rs537320227	A>V	C:223	(-56.32, 1.08, 20.37)
2:212587214	COSM3702124 COSM3702125	P>S	C:238	(-57.45, -15.74, 11.54)
2:212587198	COSM209862	Y>C	C:243	(-47.71, -27.34, 11.09)
2:212587118	rs74898139	H>Y	C:270	(-68.39, -8.87, -4.87)
2:212578337		A>V	C:282	(-54.39, -6.18, -6.52)
2:212578313		V>A	C:290	(-60.11, -15.72, -11.11)
2:212578302		G>R	C:294	(-68.21, -14.46, -7.24)
2:212578291		M>I	C:297	(-59.77, -15.62, -6.36)
2:212578274		D>G	C:303	(-48.86, -19.40, -20.06)
2:212578260		A>S	C:308	(-52.01, -4.59, -16.12)
2:212576862		Q>R	C:321	(-51.25, 14.48, -8.51)
2:212576859		T>S	C:322	(-52.33, 13.78, -13.61)
2:212576834		K>N	C:330	(-46.14, 4.86, -18.86)
2:212576829	rs374243191	I>T	C:332	(-49.41, 1.97, -25.04)
2:212576830		I>V	C:332	(-49.41, 1.97, -25.04)
2:212576814	rs528780505	I>N	C:337	(-56.15, 0.62, -15.32)
2:212576777	rs76603692	H>Q	C:349	(-54.59, 22.64, -20.19)
2:212570111		P>R	C:352	(-45.45, 25.16, -16.43)
2:212570105		N>S	C:354	(-42.54, 20.83, -12.80)
2:212570100		I>V	C:356	(-44.91, 19.13, -17.79)
2:212570091	rs138476466	I>V	C:359	(-51.82, 16.24, -23.22)
2:212570085		P>T	C:361	(-55.18, 15.89, -27.79)
2:212570069		V>A	C:366	(-54.01, 5.26, -25.38)
2:212570063		R>Q	C:368	(-60.36, 4.31, -28.28)
2:212570061		T>A	C:369	(-57.31, -0.59, -25.06)
2:212570054	rs368876919	R>K	C:371	(-61.28, -4.73, -21.53)
2:212570049		I>V	C:373	(-60.89, 1.44, -14.24)
2:212568914		L>V	C:377	(-62.75, 7.96, -13.97)
2:212568893		P>A	C:384	(-61.19, 22.08, -25.43)
2:212568872		V>I	C:391	(-61.25, 7.60, -25.58)
2:212568835		L>P	C:403	(-63.36, 5.60, -3.52)
2:212566862		Q>R	C:415	(-68.10, 23.99, -20.21)
2:212566863	rs370646276	Q>E	C:415	(-68.10, 23.99, -20.21)
2:212566824	rs200092686	I>F	C:428	(-70.26, 1.53, -11.49)
2:212566786	rs200755699	N>K	C:440	(-72.82, 22.26, -22.66)
2:212566775	rs201156609	Y>C	C:444	(-77.47, 14.30, -17.79)
2:212566767	rs149168827	I>V	C:447	(-78.70, 7.37, -17.99)
2:212566754		T>I	C:451	(-78.52, -0.46, -14.34)
2:212566755		T>A	C:451	(-78.52, -0.46, -14.34)
2:212566740	rs368860175	I>V	C:456	(-78.96, -0.28, -2.35)
2:212566736		N>S	C:457	(-75.60, 1.85, -0.42)
2:212566718		R>Q	C:463	(-74.47, 19.82, -9.02)
2:212566707		K>E	C:467	(-82.88, 22.23, -17.69)
2:212543907		A>S	C:473	(-85.69, 21.20, -27.26)
2:212543885		H>L	C:480	(-86.27, 4.80, -32.61)
2:212543873	rs376154931	S>N	C:484	(-86.09, 2.99, -20.82)
2:212543852		G>E	C:491	(-77.82, 7.00, -31.50)
2:212543834	COSM4090927 COSM4090928	S>L	C:497	(-80.53, -1.10, -24.11)
2:212543828	rs371593463	R>H	C:499	(-87.07, -0.00, -27.59)
2:212543829		R>C	C:499	(-87.07, -0.00, -27.59)
2:212543825		R>H	C:500	(-87.06, -3.32, -32.95)
2:212543826		R>C	C:500	(-87.06, -3.32, -32.95)
2:212543802		I>V	C:508	(-81.00, -2.81, -35.99)
2:212543797		E>D	C:509	(-85.26, -0.90, -37.46)
2:212537981	rs535202189 COSM131770 COSM3577328	E>K	C:517	(-73.92, -5.33, -49.18)
2:212537978	rs141594820	F>I	C:518	(-72.19, -8.31, -46.59)
2:212537974		R>Q	C:519	(-78.84, -10.75, -47.38)
2:212537964		E>D	C:522	(-82.61, -14.16, -35.64)
2:212537959		G>V	C:524	(-81.94, -14.95, -30.40)
2:212537956		S>F	C:525	(-81.58, -10.04, -31.43)
2:212537936		P>S	C:532	(-68.66, -15.53, -47.35)
2:212537911		G>D	C:540	(-88.12, -14.88, -49.85)
2:212537909		L>F	C:541	(-85.46, -17.34, -50.25)
2:212537906	COSM353100	L>F	C:542	(-83.79, -17.93, -45.86)
2:212537896	rs147639134	H>R	C:545	(-79.82, -22.38, -42.28)
2:212537897		H>Y	C:545	(-79.82, -22.38, -42.28)
2:212537890	COSM3577324 COSM3577325	P>L	C:547	(-73.53, -20.44, -38.27)
2:212530202		G>S	C:548	(-71.28, -21.06, -41.66)
2:212530199	rs200792124 COSM1251440	P>T	C:549	(-70.01, -22.91, -44.41)
2:212530191		N>K	C:551	(-75.72, -23.98, -41.25)
2:212530182	rs377501321	K>N	C:554	(-76.55, -22.43, -53.52)
2:212530173		H>Q	C:557	(-68.42, -20.30, -55.74)
2:212530159		P>R	C:562	(-70.53, -30.04, -45.33)
2:212530157		N>Y	C:563	(-68.43, -27.02, -45.63)
2:212530139	rs373306524 COSM3773947 COSM3773948	P>T	C:569	(-59.22, -29.03, -52.34)
2:212530086		D>E	C:586	(-73.44, -31.57, -59.51)
2:212530084	rs139122290	R>Q	C:587	(-70.90, -26.06, -59.05)
2:212530085	rs561997094	R>W	C:587	(-70.90, -26.06, -59.05)
2:212530051		Q>R	C:598	(-48.93, -33.27, -59.86)
2:212522546	COSM3962341	G>S	C:602	(-61.08, -37.03, -61.76)
2:212522540		T>A	C:604	(-59.93, -42.08, -62.54)

[+] COSMIC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
2:212989563	COSM2716453	R>C	C:25	(-67.65, 22.99, 10.98)
2:212812293	COSM2716442	R>C	C:70	(-58.23, 31.02, 24.13)
2:212812269	COSM719370	R>C	C:78	(-56.11, 8.09, 23.24)
2:212812259	COSM1405191	R>H	C:81	(-52.14, 4.62, 13.78)
2:212812260	COSM1205582	R>C	C:81	(-52.14, 4.62, 13.78)
2:212812235	COSM1405190	R>Q	C:89	(-39.27, 15.78, 9.65)
2:212652823	COSM1669726	I>M	C:136	(-45.48, 17.36, 27.69)
2:212652810	COSM1723973	I>F	C:141	(-46.72, 10.12, 23.42)
2:212652804	COSM232262	R>W	C:143	(-45.23, 2.22, 21.20)
2:212615400	COSM3577358	R>C	C:171	(-44.34, 16.11, 32.95)
2:212615384	COSM4911103	T>K	C:176	(-56.19, 22.44, 36.18)
2:212589893	COSM4090943	C>R	C:192	(-44.55, -3.90, 31.12)
2:212589812	COSM1405184	T>A	C:219	(-60.80, -6.87, 24.62)
2:212587251	COSM1015996	M>I	C:225	(-50.65, -1.67, 17.59)
2:212587208	COSM1614290	T>A	C:240	(-56.87, -20.30, 5.68)
2:212578349	COSM12833	S>Y	C:278	(-56.37, -11.20, 2.29)
2:212578341	COSM1306390	R>C	C:281	(-56.85, -1.79, -3.27)
2:212578294	COSM1159573	K>N	C:296	(-63.25, -10.92, -7.53)
2:212576877	COSM110095	S>L	C:316	(-44.81, 3.39, -11.83)
2:212576857	COSM48365	V>L	C:323	(-52.77, 11.83, -17.07)
2:212576794	COSM2716376	L>I	C:344	(-55.89, 17.22, -12.95)
2:212566857	COSM3709390	I>V	C:417	(-68.61, 17.71, -22.40)
2:212566832	COSM1405178	L>P	C:425	(-70.05, 1.59, -18.85)
2:212566827	COSM131768	E>K	C:427	(-69.85, -3.13, -13.39)
2:212566758	COSM145377	T>P	C:450	(-79.62, 1.78, -10.85)
2:212566719	COSM4090934	R>W	C:463	(-74.47, 19.82, -9.02)
2:212566709	COSM4896803	R>K	C:466	(-77.61, 22.17, -21.59)
2:212543900	COSM442265	G>E	C:475	(-82.85, 17.17, -29.74)
2:212537981	COSM131770	E>K	C:517	(-73.92, -5.33, -49.18)
2:212537918	COSM4991691	E>K	C:538	(-84.22, -12.53, -53.67)
2:212537906	COSM353100	L>F	C:542	(-83.79, -17.93, -45.86)
2:212537891	COSM1691939	P>S	C:547	(-73.53, -20.44, -38.27)
2:212530138	COSM1669722	P>Q	C:569	(-59.22, -29.03, -52.34)
2:212530135	COSM1405173	D>G	C:570	(-54.95, -27.60, -54.87)
2:212530064	COSM1752314	P>A	C:594	(-54.18, -42.22, -54.75)