4NCS.A | NEU2 – ASTRID

4NCS.A | NEU2

General Structure Information

PDB ID	4ncs
HGNC Gene Label(s)	NEU2
Structure Name	human sialidase 2 in complex with 2,3-difluorosialic acid (covalent intermediate)
Resolution	2.2Å
Reference	AUTH S.BUCHINI,F.X.GALLAT,I.R.GREIG,J.H.KIM,S.WAKATSUKI,AUTH 2 L.M.CHAVAS,S.G.WITHERSTITL TUNING MECHANISM-BASED INACTIVATORS OF NEURAMINIDASES:TITL 2 MECHANISTIC AND STRUCTURAL INSIGHTS.REF ANGEW.CHEM.INT.ED.ENGL. V. 53 3382 2014REFN ISSN 1433-7851PMID 24591206DOI 10.1002/ANIE.201309675

Variant Set Distributions

ExAC Variants

Number Of Residues	350
Number Of SNVs	112
Number Of Permutations	46407
Optimal Distance Threshold	6.0
K Statistic	0.014
p-value	0.671

COSMIC

Number Of Residues	350
Number Of SNVs	9
Number Of Permutations	4399
Optimal Distance Threshold	14.0
K Statistic	0.306
p-value	0.111

Ripley’s K Analysis Plots

ExACCOSMIC

Variant Set Comparisons

Cosmic vs. ExAC

Number Of ExAC SNVs	112
Number Of COSMIC SNVs	8
Optimal Distance Threshold	6.0
K Statistic	0.057
p-value	0.987

Pathogenic Proximity Analysis

COSMIC PathProx Analysis

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
2:233897386	rs371812904	A>V	A:2	(23.23, 9.25, -44.34)
2:233897397		V>I	A:6	(31.11, 7.76, -36.16)
2:233897414	rs2233384	S>R	A:11	(24.11, 0.10, -26.85)
2:233897423	rs368601498	Q>H	A:14	(19.30, -3.00, -23.68)
2:233897443		R>K	A:21	(14.11, 7.97, -20.48)
2:233897472		Q>E	A:31	(41.24, 9.08, -15.27)
2:233897473		Q>P	A:31	(41.24, 9.08, -15.27)
2:233897481		L>V	A:34	(33.34, 8.34, -20.15)
2:233897488		A>V	A:36	(27.26, 6.63, -17.88)
2:233897491		F>C	A:37	(25.55, 8.64, -14.80)
2:233897493	COSM3407676	A>T	A:38	(20.69, 6.44, -15.99)
2:233897499		Q>E	A:40	(16.91, 1.27, -13.09)
2:233897502	rs201184759 COSM1017942	R>W	A:41	(12.29, 4.79, -15.73)
2:233897503	rs2233385	R>Q	A:41	(12.29, 4.79, -15.73)
2:233897526	rs374542515	A>T	A:49	(11.20, 5.89, -11.36)
2:233897542		L>P	A:54	(27.31, 3.90, -13.20)
2:233897544	rs367572353	R>C	A:55	(28.11, 1.03, -18.37)
2:233897545	rs150159734	R>H	A:55	(28.11, 1.03, -18.37)
2:233897551		G>E	A:57	(34.67, 4.10, -19.53)
2:233897559	rs370749556	D>N	A:60	(42.20, 3.19, -26.53)
2:233897562	rs181881229	A>T	A:61	(42.76, 6.16, -29.14)
2:233898850		Q>E	A:76	(24.39, 5.82, -1.37)
2:233898853	rs569529469	A>T	A:77	(21.24, 7.82, -5.11)
2:233898856		R>W	A:78	(18.06, 5.58, -1.88)
2:233898857	rs146336403	R>Q	A:78	(18.06, 5.58, -1.88)
2:233898871	rs141846686	R>W	A:83	(10.08, 6.72, -7.40)
2:233898872	rs144970536	R>Q	A:83	(10.08, 6.72, -7.40)
2:233898878		M>T	A:85	(14.25, 11.54, -10.85)
2:233898889		P>S	A:89	(26.82, 14.91, -13.72)
2:233898890		P>R	A:89	(26.82, 14.91, -13.72)
2:233898902	rs140090973	A>V	A:93	(39.10, 20.27, -10.85)
2:233898908	rs201616110	T>M	A:95	(38.54, 18.85, -5.40)
2:233898928		F>V	A:102	(19.70, 12.99, -6.68)
2:233898935		A>V	A:104	(13.58, 13.01, -4.79)
2:233898983		N>S	A:120	(6.72, 20.83, -3.53)
2:233898986		V>A	A:121	(6.90, 16.50, -2.55)
2:233898989	rs575487240	T>M	A:122	(10.44, 17.65, -5.02)
2:233898992	rs140403218	R>Q	A:123	(13.27, 16.65, -0.85)
2:233899002		Q>H	A:126	(24.96, 16.33, -3.08)
2:233899004		V>G	A:127	(26.00, 12.06, -4.08)
2:233899007		T>S	A:128	(30.12, 12.82, -3.17)
2:233899028		T>I	A:135	(32.56, 4.86, -3.87)
2:233899034		S>N	A:137	(28.21, 9.71, -0.38)
2:233899043		R>K	A:140	(24.65, 17.05, 1.12)
2:233899054		D>N	A:144	(15.18, 23.42, 3.01)
2:233899057	rs2233390	A>T	A:145	(19.09, 25.74, 1.84)
2:233899058		A>V	A:145	(19.09, 25.74, 1.84)
2:233899061		A>V	A:146	(18.70, 25.93, -1.77)
2:233899066		G>S	A:148	(13.36, 28.11, 0.36)
2:233899069	rs557690761	P>S	A:149	(11.09, 30.60, 0.81)
2:233899072	rs369918752	A>P	A:150	(10.17, 29.30, -2.93)
2:233899078		R>W	A:152	(5.68, 25.04, 0.03)
2:233899079	rs113887175	R>Q	A:152	(5.68, 25.04, 0.03)
2:233899085		W>L	A:154	(9.30, 26.29, -6.74)
2:233899090		T>A	A:156	(7.82, 20.66, -9.21)
2:233899105		P>S	A:161	(18.76, 16.43, -17.46)
2:233899126	rs2233391	H>N	A:168	(37.14, 30.07, -15.13)
2:233899129		D>N	A:169	(35.30, 31.56, -10.97)
2:233899136		A>V	A:171	(35.63, 30.07, -6.79)
2:233899139		R>Q	A:172	(37.53, 26.29, -9.97)
2:233899145		L>P	A:174	(29.68, 24.49, -8.57)
2:233899147	rs150676202	V>M	A:175	(26.52, 25.85, -12.37)
2:233899148	rs145457252	V>A	A:175	(26.52, 25.85, -12.37)
2:233899162	rs552601468	A>T	A:180	(10.47, 25.60, -11.88)
2:233899165		Y>H	A:181	(6.54, 23.42, -13.53)
2:233899168	rs144556397	R>W	A:182	(7.12, 30.39, -11.47)
2:233899169	rs2233393	R>Q	A:182	(7.12, 30.39, -11.47)
2:233899177		H>Y	A:185	(-1.27, 33.58, -12.25)
2:233899193	rs369079778	P>L	A:190	(1.65, 25.40, -13.23)
2:233899195		I>V	A:191	(4.32, 28.79, -15.62)
2:233899205		A>V	A:194	(14.79, 28.36, -15.94)
2:233899219		S>C	A:199	(28.36, 26.95, -5.37)
2:233899221		S>R	A:199	(28.36, 26.95, -5.37)
2:233899232	rs140984516	G>E	A:203	(29.06, 22.42, -2.30)
2:233899234	rs138984578	R>C	A:204	(29.36, 22.23, 2.39)
2:233899235		R>H	A:204	(29.36, 22.23, 2.39)
2:233899238	rs138530805	T>M	A:205	(26.79, 26.49, 0.21)
2:233899253		H>R	A:210	(17.48, 35.46, -10.24)
2:233899280		C>Y	A:219	(18.50, 23.31, -18.96)
2:233899284		Q>H	A:220	(22.29, 21.70, -20.50)
2:233899291	COSM3579188	E>K	A:223	(32.30, 29.32, -19.52)
2:233899297		E>K	A:225	(35.12, 34.42, -23.57)
2:233899324		L>V	A:234	(20.66, 28.78, -20.61)
2:233899331	rs562872555	A>V	A:236	(16.07, 25.69, -23.28)
2:233899334		R>K	A:237	(11.86, 21.26, -23.16)
2:233899335	rs531621654	R>S	A:237	(11.86, 21.26, -23.16)
2:233899336	rs548820173	S>G	A:238	(10.23, 25.31, -25.24)
2:233899338		S>R	A:238	(10.23, 25.31, -25.24)
2:233899339		H>Y	A:239	(5.76, 24.84, -24.09)
2:233899346	rs373000499	R>Q	A:241	(7.33, 25.40, -33.92)
2:233899352	rs141183314	R>T	A:243	(15.68, 25.08, -27.64)
2:233899355	rs201679476	V>G	A:244	(15.03, 29.37, -25.23)
2:233899360		A>T	A:246	(20.20, 32.64, -22.21)
2:233899367		S>N	A:248	(25.04, 35.28, -17.73)
2:233899378		G>R	A:252	(23.86, 32.75, -13.10)
2:233899382		L>P	A:253	(22.59, 35.52, -10.18)
2:233899418	rs538708272	V>E	A:265	(13.66, 22.64, -33.93)
2:233899427		P>L	A:268	(5.64, 18.01, -31.33)
2:233899443		Q>H	A:273	(16.86, 17.26, -23.60)
2:233899448		S>N	A:275	(23.01, 19.14, -25.10)
2:233899450	rs145543414	V>I	A:276	(25.14, 22.64, -24.54)
2:233899454		I>T	A:277	(29.31, 21.38, -25.09)
2:233899469		P>L	A:282	(39.98, 25.79, -33.84)
2:233899471		R>C	A:283	(39.00, 30.12, -35.86)
2:233899508		Y>S	A:295	(21.98, 21.77, -29.65)
2:233899510	rs376870710	T>A	A:296	(22.60, 17.61, -29.29)
2:233899519	rs568801613	T>A	A:299	(16.22, 17.45, -36.49)
2:233899535		R>T	A:304	(10.95, 13.19, -29.15)
2:233899561		P>T	A:313	(31.07, 29.54, -34.64)
2:233899562	rs376559802 COSM1406335	P>L	A:313	(31.07, 29.54, -34.64)
2:233899576		P>A	A:318	(21.51, 33.48, -32.05)
2:233899583	rs200637515	A>D	A:320	(25.50, 31.36, -35.51)
2:233899595		P>L	A:324	(21.60, 20.52, -38.84)
2:233899633	COSM3972101	L>F	A:337	(27.19, 16.49, -25.26)
2:233899651		G>S	A:343	(41.48, 13.42, -31.50)
2:233899660		G>R	A:346	(43.19, 16.41, -34.09)
2:233899661		G>V	A:346	(43.19, 16.41, -34.09)
2:233899664		S>F	A:347	(39.87, 17.15, -33.93)
2:233899676		G>V	A:351	(30.49, 12.72, -26.60)
2:233899679		C>Y	A:352	(26.78, 11.40, -27.34)
2:233899688	COSM1669861	E>G	A:355	(16.79, 8.70, -25.12)
2:233899694		N>S	A:357	(14.26, 2.37, -30.64)
2:233899702	COSM335168	E>K	A:360	(13.86, -0.16, -26.98)
2:233899712		V>A	A:363	(23.25, 5.18, -27.88)
2:233899735	rs553987242	Q>E	A:371	(34.02, 12.85, -38.06)
2:233899745	rs373144878	P>Q	A:374	(34.07, 19.15, -42.50)
2:233899751		E>A	A:376	(33.73, 24.46, -40.15)
2:233899753		Y>H	A:377	(39.73, 23.68, -39.60)

4NCS.A | NEU2.

4NCS.A | NEU2

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