2WK3.B | IDE – ASTRID

2WK3.B | IDE

General Structure Information

PDB ID	2wk3
HGNC Gene Label(s)	IDE
Structure Name	crystal structure of human insulin-degrading enzyme in complex with amyloid-beta (1-42)
Resolution	2.59Å
Reference	AUTH Q.GUO,M.MANOLOPOULOU,Y.BIAN,A.B.SCHILLING,W.J.TANGTITL MOLECULAR BASIS FOR THE RECOGNITION AND CLEAVAGESTITL 2 OF IGF-II, TGF-ALPHA, AND AMYLIN BY HUMAN INSULINTITL 3 DEGRADING ENZYME.REF J.MOL.BIOL. V. 395 430 2010REFN ISSN 0022-2836PMID 19896952DOI 10.1016/J.JMB.2009.10.072

Variant Set Distributions

ExAC Variants

Number Of Residues	956
Number Of SNVs	200
Number Of Permutations	29385
Optimal Distance Threshold	26.0
K Statistic	0.192
p-value	0.002

COSMIC

Number Of Residues	956
Number Of SNVs	8
Number Of Permutations	2354
Optimal Distance Threshold	30.0
K Statistic	0.179
p-value	0.885

Ripley’s K Analysis Plots

ExACCOSMIC

Variant Set Comparisons

Cosmic vs. ExAC

Number Of ExAC SNVs	200
Number Of COSMIC SNVs	7
Optimal Distance Threshold	20.0
K Statistic	0.131
p-value	0.637

Pathogenic Proximity Analysis

COSMIC PathProx Analysis

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
10:94297263	rs151208561	K>R	B:48	(-74.31, 64.55, 55.31)
10:94297260		R>K	B:49	(-73.69, 64.96, 50.18)
10:94297257		I>T	B:50	(-70.38, 61.23, 48.11)
10:94297249		H>Y	B:53	(-68.18, 64.35, 37.46)
10:94297246	COSM325526	I>F	B:54	(-66.66, 67.45, 40.08)
10:94297243	rs374132274	T>A	B:55	(-67.68, 69.94, 36.09)
10:94297224		K>M	B:61	(-54.99, 65.26, 32.90)
10:94297212	rs142209574	R>Q	B:65	(-64.31, 62.07, 45.67)
10:94297198		A>T	B:70	(-71.72, 65.10, 59.19)
10:94297195	rs142309020	N>D	B:71	(-69.42, 68.20, 60.53)
10:94297192		G>S	B:72	(-70.91, 70.30, 57.33)
10:94297189	COSM466091	I>F	B:73	(-67.14, 70.19, 56.63)
10:94297173		I>T	B:78	(-57.56, 67.64, 44.42)
10:94297158		T>M	B:83	(-47.83, 66.78, 42.91)
10:94297140		A>V	B:89	(-57.40, 74.66, 52.62)
10:94297141		A>S	B:89	(-57.40, 74.66, 52.62)
10:94297138		L>F	B:90	(-60.10, 75.75, 56.18)
10:94297133	rs377092920	D>E	B:91	(-62.88, 79.21, 54.21)
10:94294533		S>W	B:98	(-68.23, 89.37, 63.03)
10:94294520		N>K	B:102	(-65.67, 95.95, 72.17)
10:94294522		N>D	B:102	(-65.67, 95.95, 72.17)
10:94294483		F>L	B:115	(-50.39, 80.29, 62.27)
10:94294443	rs528804574	S>N	B:128	(-43.60, 76.65, 60.70)
10:94294392		E>G	B:145	(-68.06, 87.45, 54.67)
10:94294356		H>R	B:157	(-44.18, 64.69, 54.46)
10:94294357		H>Y	B:157	(-44.18, 64.69, 54.46)
10:94291652		P>A	B:172	(-56.58, 76.64, 69.82)
10:94291632	rs539131694	C>W	B:178	(-48.07, 84.85, 72.48)
10:94291620		E>D	B:182	(-48.29, 88.19, 67.13)
10:94291607	rs201014275	D>N	B:187	(-49.54, 97.54, 65.64)
10:94291601		E>K	B:189	(-50.37, 94.49, 59.44)
10:94291579		N>S	B:196	(-51.44, 103.01, 51.68)
10:94291530	rs116003953	K>N	B:212	(-74.36, 101.18, 62.68)
10:94291525		P>L	B:214	(-71.24, 96.24, 60.24)
10:94291518		S>R	B:216	(-67.97, 100.65, 60.02)
10:94291519		S>N	B:216	(-67.97, 100.65, 60.02)
10:94274793	rs371393455	K>R	B:223	(-50.69, 97.73, 70.96)
10:94274766	rs139878071	Q>R	B:232	(-59.23, 101.39, 79.84)
10:94274760		G>D	B:234	(-61.70, 94.62, 81.60)
10:94274757		I>T	B:235	(-61.77, 93.10, 78.12)
10:94274752		V>I	B:237	(-58.21, 89.34, 74.94)
10:94274742		E>A	B:240	(-63.14, 87.73, 74.11)
10:94274736		L>R	B:242	(-61.05, 81.05, 73.46)
10:94274706		N>S	B:252	(-71.81, 75.21, 59.86)
10:94274700	rs200118524	M>T	B:254	(-65.78, 74.97, 58.20)
10:94274683	rs192563243	G>S	B:260	(-52.59, 64.93, 46.22)
10:94274679		R>Q	B:261	(-48.24, 62.16, 44.31)
10:94269913		L>S	B:264	(-60.16, 60.34, 45.39)
10:94269879		F>L	B:275	(-60.77, 68.02, 59.30)
10:94269869		E>Q	B:279	(-67.81, 70.99, 67.92)
10:94269866		N>D	B:280	(-72.05, 71.70, 64.29)
10:94269854		P>A	B:284	(-76.13, 81.46, 62.10)
10:94269847		P>L	B:286	(-73.57, 86.04, 58.76)
10:94269839		P>A	B:289	(-79.81, 93.05, 54.48)
10:94269820		E>G	B:295	(-81.25, 108.77, 51.01)
10:94269821		E>K	B:295	(-81.25, 108.77, 51.01)
10:94269813		H>Q	B:297	(-75.23, 107.74, 53.62)
10:94268629		P>S	B:306	(-53.51, 112.63, 49.07)
10:94268624		I>M	B:307	(-49.91, 110.65, 51.22)
10:94268612		R>S	B:311	(-54.11, 114.11, 39.62)
10:94268593	rs201437960	P>A	B:318	(-75.63, 101.77, 45.72)
10:94268590		I>V	B:319	(-75.68, 97.35, 44.14)
10:94268586		P>L	B:320	(-78.33, 94.93, 45.03)
10:94268568		Y>C	B:326	(-74.33, 81.91, 39.82)
10:94268565		K>R	B:327	(-76.78, 81.04, 36.59)
10:94268527	COSM1675431	H>Y	B:340	(-64.45, 98.28, 26.40)
10:94268518	rs373243794	P>S	B:343	(-63.16, 101.78, 19.92)
10:94268511		S>N	B:345	(-65.12, 103.92, 24.96)
10:94267953	rs77824934	N>S	B:357	(-55.00, 108.37, 31.66)
10:94267950		T>S	B:358	(-56.84, 104.99, 33.78)
10:94267880	rs200246238	E>D	B:381	(-53.14, 119.10, 35.22)
10:94267421		H>Y	B:386	(-63.24, 119.83, 33.22)
10:94267409		I>V	B:390	(-65.73, 113.31, 33.88)
10:94267387		Y>C	B:397	(-71.38, 104.36, 27.89)
10:94267385		I>L	B:398	(-75.09, 104.86, 31.60)
10:94267372		R>H	B:402	(-80.60, 103.47, 30.36)
10:94267373	rs533637479	R>C	B:402	(-80.60, 103.47, 30.36)
10:94267369		A>V	B:403	(-81.18, 103.20, 24.45)
10:94267354	rs577941336	E>G	B:408	(-77.96, 87.88, 23.29)
10:94266277		D>E	B:416	(-68.21, 81.83, 23.58)
10:94266239		R>K	B:429	(-48.35, 77.61, 41.35)
10:94266227	rs200912671	Y>C	B:433	(-56.90, 75.01, 42.48)
10:94266225		T>A	B:434	(-56.45, 74.93, 47.81)
10:94264653	rs372615598	Y>C	B:443	(-70.28, 81.67, 47.89)
10:94264650		Y>C	B:444	(-70.80, 78.44, 43.76)
10:94264632		L>P	B:450	(-64.04, 73.66, 39.17)
10:94264633		L>F	B:450	(-64.04, 73.66, 39.17)
10:94264629		T>I	B:451	(-67.61, 75.79, 36.52)
10:94264626	rs34708742	A>V	B:452	(-68.71, 79.03, 38.66)
10:94264627	rs141915194	A>T	B:452	(-68.71, 79.03, 38.66)
10:94264608		E>G	B:458	(-78.43, 82.97, 30.94)
10:94264589		I>M	B:464	(-79.07, 93.77, 32.47)
10:94264587	rs143289472	E>A	B:465	(-83.33, 96.36, 32.24)
10:94264588		E>K	B:465	(-83.33, 96.36, 32.24)
10:94264581		V>G	B:467	(-78.29, 96.77, 37.60)
10:94264576		D>N	B:469	(-82.64, 101.51, 37.15)
10:94264551		R>Q	B:477	(-71.02, 107.80, 47.65)
10:94264552		R>W	B:477	(-71.02, 107.80, 47.65)
10:94250351	rs530609089	V>F	B:478	(-68.50, 111.65, 44.37)
10:94250348		A>T	B:479	(-64.68, 110.85, 45.24)
10:94250332	rs117251230	S>C	B:484	(-55.89, 120.62, 45.86)
10:94250333	rs149596491	S>A	B:484	(-55.89, 120.62, 45.86)
10:94250311	rs140884087	R>H	B:491	(-65.24, 115.93, 58.39)
10:94250301	rs375432951	E>D	B:494	(-61.45, 107.38, 64.20)
10:94250298		W>C	B:495	(-59.40, 103.65, 63.40)
10:94250273	COSM360734	A>P	B:504	(-73.81, 118.13, 49.09)
10:94250270		I>V	B:505	(-74.07, 116.76, 45.17)
10:94250266	rs150132183	P>L	B:506	(-75.62, 120.44, 44.09)
10:94250260		E>A	B:508	(-78.24, 121.35, 39.69)
10:94250258		V>I	B:509	(-75.30, 118.82, 39.61)
10:94250252	rs147628298	K>E	B:511	(-80.30, 117.54, 37.21)
10:94247068		Q>L	B:514	(-81.20, 113.39, 36.38)
10:94247063		A>T	B:516	(-78.26, 112.83, 29.88)
10:94247053		N>S	B:519	(-72.21, 111.59, 22.98)
10:94247040		K>N	B:523	(-69.49, 103.98, 19.45)
10:94247026		N>S	B:528	(-63.37, 90.60, 19.59)
10:94246993	rs147012131	P>L	B:539	(-47.31, 67.74, 15.78)
10:94246978	rs375936259 COSM311914	A>V	B:544	(-37.57, 68.13, 19.67)
10:94246969	rs142102179	Y>C	B:547	(-33.63, 71.54, 28.43)
10:94246954		K>T	B:552	(-31.05, 82.81, 14.28)
10:94246955	rs369716492	K>E	B:552	(-31.05, 82.81, 14.28)
10:94243084		M>R	B:556	(-29.66, 91.53, 14.28)
10:94243085		M>V	B:556	(-29.66, 91.53, 14.28)
10:94243080		S>R	B:557	(-30.42, 87.41, 16.16)
10:94243081		S>N	B:557	(-30.42, 87.41, 16.16)
10:94243063		Q>R	B:563	(-42.27, 72.14, 20.25)
10:94243042	rs371515558	P>L	B:570	(-53.60, 76.51, 22.53)
10:94243039	rs374640603	K>M	B:571	(-51.47, 78.82, 25.28)
10:94243023		F>L	B:576	(-38.79, 89.29, 21.63)
10:94243019		F>L	B:578	(-35.47, 94.47, 21.61)
10:94239173		F>Y	B:582	(-28.27, 104.88, 22.58)
10:94239137		Y>C	B:594	(-41.13, 105.17, 31.02)
10:94239102		E>K	B:606	(-58.32, 101.87, 21.34)
10:94239089	rs374338329	A>V	B:610	(-59.34, 93.06, 22.35)
10:94239084		E>Q	B:612	(-56.01, 91.54, 27.44)
10:94239072		L>V	B:616	(-53.42, 87.91, 22.84)
10:94239065	rs370339786	Y>C	B:618	(-48.53, 94.20, 24.99)
10:94239037		M>I	B:627	(-36.64, 97.60, 24.57)
10:94239035		Y>C	B:628	(-39.58, 92.36, 28.08)
10:94235718		I>V	B:640	(-51.73, 89.60, 13.83)
10:94235703		I>V	B:645	(-46.21, 95.81, 18.63)
10:94235675		I>T	B:654	(-45.33, 111.35, 19.23)
10:94235660		F>S	B:659	(-44.83, 114.45, 25.65)
10:94235653	rs139706336	I>M	B:661	(-50.75, 113.89, 29.88)
10:94235650		I>M	B:662	(-47.58, 110.47, 29.83)
10:94234713		M>I	B:667	(-42.42, 114.28, 37.43)
10:94234714		M>T	B:667	(-42.42, 114.28, 37.43)
10:94234679		H>Y	B:679	(-39.55, 97.54, 52.92)
10:94234665	rs375351375	M>I	B:683	(-34.80, 96.81, 48.56)
10:94234667	rs146391334	M>V	B:683	(-34.80, 96.81, 48.56)
10:94234654		R>H	B:687	(-29.29, 98.60, 44.11)
10:94234655	rs142295768	R>C	B:687	(-29.29, 98.60, 44.11)
10:94230090		P>R	B:710	(-38.37, 117.74, 19.78)
10:94230087	rs368677026	R>H	B:711	(-33.44, 115.54, 22.72)
10:94230088	COSM1254582	R>C	B:711	(-33.44, 115.54, 22.72)
10:94230078		A>G	B:714	(-34.82, 112.11, 17.72)
10:94230079		A>T	B:714	(-34.82, 112.11, 17.72)
10:94230071	rs190422480	I>M	B:716	(-37.48, 106.83, 18.56)
10:94230073	rs374236596	I>V	B:716	(-37.48, 106.83, 18.56)
10:94230055	rs76587725	R>W	B:722	(-28.83, 99.85, 16.72)
10:94230037	rs202130657	L>I	B:728	(-37.63, 82.34, 24.39)
10:94230012		Q>R	B:736	(-40.22, 77.21, 11.04)
10:94228744	rs200555551	A>P	B:738	(-39.79, 80.66, 14.80)
10:94228731	rs114285269	M>T	B:742	(-37.12, 86.68, 14.54)
10:94228725		M>T	B:744	(-41.79, 89.32, 11.15)
10:94228713		T>I	B:748	(-40.37, 95.18, 10.45)
10:94228701		H>L	B:752	(-40.63, 100.46, 8.64)
10:94228688		K>N	B:756	(-28.09, 98.28, 10.37)
10:94228686		P>L	B:757	(-26.12, 95.07, 13.35)
10:94228663		R>W	B:765	(-23.04, 93.80, 31.13)
10:94225597		G>E	B:775	(-16.15, 95.10, 55.58)
10:94225580		Q>E	B:781	(-31.62, 108.31, 53.68)
10:94225573		N>S	B:783	(-39.23, 107.59, 55.00)
10:94225568		V>I	B:785	(-44.06, 109.34, 54.93)
10:94225561	rs531759698	N>S	B:787	(-42.93, 106.73, 62.18)
10:94225555	rs371158499	C>Y	B:789	(-37.63, 101.60, 60.25)
10:94225526		M>L	B:799	(-18.81, 84.58, 41.14)
10:94225481		I>L	B:814	(-30.68, 75.96, 57.74)
10:94225474		S>L	B:816	(-35.69, 80.60, 56.99)
10:94225453		L>P	B:823	(-36.07, 88.43, 64.12)
10:94225450	COSM1210231	R>H	B:824	(-43.00, 88.27, 63.17)
10:94223755		I>V	B:832	(-41.77, 93.22, 57.32)
10:94223752		V>I	B:833	(-39.00, 89.57, 58.87)
10:94223739		P>L	B:837	(-31.05, 84.48, 48.85)
10:94223725		G>S	B:842	(-23.52, 87.21, 39.35)
10:94223679	rs547079065	H>P	B:857	(-28.85, 101.13, 66.47)
10:94223680		H>N	B:857	(-28.85, 101.13, 66.47)
10:94223656		A>T	B:865	(-27.49, 87.56, 67.64)
10:94223640		M>T	B:870	(-28.51, 79.78, 63.59)
10:94223628		I>T	B:874	(-25.83, 74.45, 62.57)
10:94223617	rs145451690	T>A	B:878	(-29.39, 65.98, 63.94)
10:94223608		A>S	B:881	(-32.05, 67.47, 60.36)
10:94223603	rs150078715	F>L	B:882	(-27.86, 68.76, 57.10)
10:94223604		F>C	B:882	(-27.86, 68.76, 57.10)
10:94223581		A>S	B:890	(-34.48, 69.61, 46.69)
10:94223578	COSM3935208	I>V	B:891	(-38.41, 69.09, 46.71)
10:94223571		R>Q	B:893	(-33.74, 74.37, 42.95)
10:94223535		A>G	B:905	(-39.14, 81.98, 33.41)
10:94223515		I>V	B:912	(-31.81, 87.74, 31.20)
10:94221003	rs140729995	T>I	B:923	(-26.32, 70.10, 38.40)
10:94221000		E>V	B:924	(-27.45, 73.44, 41.42)
10:94220995	rs150947060	A>T	B:926	(-26.46, 66.75, 43.01)
10:94220992		Y>H	B:927	(-22.57, 70.31, 45.01)
10:94220966		D>E	B:935	(-19.02, 71.65, 54.24)
10:94220964	rs145220987	I>T	B:936	(-22.57, 74.68, 55.86)
10:94220965		I>V	B:936	(-22.57, 74.68, 55.86)
10:94220962		I>V	B:937	(-19.94, 75.14, 59.88)
10:94220958	COSM3383087	K>R	B:938	(-16.82, 76.51, 56.98)
10:94220955		F>S	B:939	(-20.16, 79.34, 53.74)
10:94220950		K>E	B:941	(-16.40, 79.60, 60.67)
10:94216163		R>K	B:950	(-13.95, 85.74, 52.06)
10:94216152		V>L	B:954	(-23.62, 96.52, 52.98)
10:94216146	rs375559999	V>I	B:956	(-29.38, 100.18, 54.00)
10:94216131		R>W	B:961	(-42.32, 110.69, 60.20)
10:94216121		D>G	B:964	(-32.52, 110.49, 65.57)
10:94215356		S>P	B:981	(-29.69, 86.95, 72.65)
10:94214272		E>K	B:997	(-17.38, 109.39, 46.65)
10:94214262		R>H	B:1000	(-15.94, 106.38, 40.82)
10:94214259	COSM921461	G>V	B:1001	(-13.41, 102.90, 45.64)
10:94214260		G>S	B:1001	(-13.41, 102.90, 45.64)
10:94214257		L>V	B:1002	(-14.79, 99.74, 45.62)
10:94214254	COSM257144	P>S	B:1003	(-13.41, 96.90, 43.39)
10:94214235		K>R	B:1009	(-19.41, 82.45, 32.48)
10:94214229		H>R	B:1011	(-23.04, 76.22, 30.15)

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
10:94269887	COSM77879	K>Q	B:273	(-58.16, 60.57, 60.50)
10:94268527	COSM1675431	H>Y	B:340	(-64.45, 98.28, 26.40)
10:94267958	COSM2152918	W>C	B:355	(-61.56, 115.77, 30.63)
10:94267388	COSM1675430	Y>H	B:397	(-71.38, 104.36, 27.89)
10:94234621	COSM1349814	D>G	B:698	(-33.40, 112.52, 42.59)
10:94225488	COSM1745970	F>L	B:811	(-26.97, 79.47, 56.02)
10:94225450	COSM1210231	R>H	B:824	(-43.00, 88.27, 63.17)
10:94216166	COSM3665954	P>R	B:949	(-11.95, 85.95, 56.92)

2WK3.B | IDE.

2WK3.B | IDE

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