2FY5.A | CHAT – ASTRID

2FY5.A | CHAT

General Structure Information

PDB ID	2fy5
HGNC Gene Label(s)	CHAT
Structure Name	structures of ligand bound human choline acetyltransferase provide insight into regulation of acetylcholine synthesis
Resolution	2.6Å
Reference	AUTH A.R.KIM,R.J.RYLETT,B.H.SHILTONTITL SUBSTRATE BINDING AND CATALYTIC MECHANISM OF HUMANTITL 2 CHOLINE ACETYLTRANSFERASE.REF BIOCHEMISTRY V. 45 14621 2006REFN ISSN 0006-2960PMID 17144655DOI 10.1021/BI061536L

Variant Set Distributions

ExAC Variants

Number Of Residues	577
Number Of SNVs	160
Number Of Permutations	36365
Optimal Distance Threshold	23.0
K Statistic	0.253
p-value	0.229

ClinVar

Number Of Residues	577
Number Of SNVs	9
Number Of Permutations	2044
Optimal Distance Threshold	14.0
K Statistic	0.417
p-value	0.0

COSMIC

Number Of Residues	577
Number Of SNVs	14
Number Of Permutations	5226
Optimal Distance Threshold	34.0
K Statistic	0.396
p-value	0.13

Ripley’s K Analysis Plots

ExACClinVarCOSMIC

Variant Set Comparisons

ClinVar vs. ExAC

Number Of ExAC SNVs	160
Number Of ClinVar SNVs	9
Optimal Distance Threshold	14.0
K Statistic	0.34
p-value	0.0

Cosmic vs. ExAC

Number Of ExAC SNVs	160
Number Of COSMIC SNVs	13
Optimal Distance Threshold	38.0
K Statistic	-0.153
p-value	0.145

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
10:50824646		S>T	A:11	(7.02, -22.54, 60.70)
10:50827771		G>W	A:12	(10.14, -23.50, 62.53)
10:50827789	rs201479289 COSM1157860 COSM2145613	V>M	A:18	(1.80, -17.62, 77.01)
10:50827825	rs555796797	Q>K	A:30	(7.31, -3.43, 90.53)
10:50827835	rs202059535 COSM3438402 COSM3438403	R>Q	A:33	(4.86, 0.71, 94.11)
10:50827877	rs148155075	I>T	A:47	(-8.05, -4.10, 90.99)
10:50827889		F>S	A:51	(-7.88, -10.26, 86.83)
10:50827892	rs370097299	G>E	A:52	(-5.86, -13.14, 89.99)
10:50827897		P>S	A:54	(-7.82, -18.16, 92.76)
10:50827903	COSM1702352 COSM1702353	G>S	A:56	(-11.01, -16.18, 88.28)
10:50827906		L>F	A:57	(-11.82, -12.99, 85.10)
10:50827907		L>P	A:57	(-11.82, -12.99, 85.10)
10:50827909	rs374586812	G>S	A:58	(-8.05, -14.40, 84.72)
10:50827912	rs115032198	E>K	A:59	(-7.16, -18.23, 86.38)
10:50827915		T>S	A:60	(-11.01, -17.60, 82.58)
10:50827923	rs200143133	Q>H	A:62	(-4.24, -17.36, 80.67)
10:50827930		L>I	A:65	(-4.46, -16.73, 75.63)
10:50827937		E>V	A:67	(-7.91, -22.18, 74.19)
10:50827939	rs141111059	R>W	A:68	(-6.21, -16.69, 70.14)
10:50828555		W>C	A:80	(0.81, -5.05, 67.29)
10:50828563		D>G	A:83	(-3.84, -1.46, 69.81)
10:50828566	rs376808313	M>R	A:84	(0.02, 0.12, 67.73)
10:50828579		N>K	A:88	(-4.77, 5.42, 65.27)
10:50828580		R>C	A:89	(-8.86, 6.76, 63.65)
10:50828590	rs121912820	L>P	A:92	(-0.70, 8.21, 58.83)
10:50828613		V>M	A:100	(14.22, 6.44, 55.90)
10:50828640		G>S	A:109	(20.07, 17.94, 36.63)
10:50828643		T>S	A:110	(16.28, 16.96, 35.80)
10:50828646		D>N	A:111	(18.62, 14.27, 33.46)
10:50828649		D>H	A:112	(21.32, 13.97, 37.44)
10:50830151		A>V	A:118	(15.79, 4.72, 37.64)
10:50830155	rs78925077	S>R	A:119	(18.50, 3.00, 39.70)
10:50830156	rs375606885	L>V	A:120	(15.61, 3.43, 43.31)
10:50830171	rs8178990	L>F	A:125	(12.16, -4.29, 40.05)
10:50830181		K>R	A:128	(9.50, -7.83, 43.90)
10:50830184	rs561562136	A>V	A:129	(12.85, -10.96, 42.76)
10:50830189	rs115510708	L>V	A:131	(10.82, -11.19, 47.88)
10:50833520	rs376994468	H>Y	A:134	(11.00, -17.30, 48.77)
10:50833533		T>I	A:138	(17.14, -16.32, 56.79)
10:50833560		G>E	A:147	(21.66, -17.13, 66.05)
10:50833572		C>F	A:151	(10.45, -13.70, 60.96)
10:50833578		K>R	A:153	(5.18, -12.23, 57.60)
10:50833586		Y>D	A:156	(7.80, -11.71, 51.72)
10:50833607		R>W	A:163	(-3.67, 1.92, 56.64)
10:50833616	rs146236256	G>S	A:166	(-12.18, 3.73, 58.20)
10:50833632	rs139352363	T>M	A:171	(-8.22, -2.60, 56.35)
10:50833661	rs540899575	P>S	A:181	(-0.75, -7.60, 39.50)
10:50833662	rs868749	P>L	A:181	(-0.75, -7.60, 39.50)
10:50833676	rs116362950	V>I	A:186	(5.38, 2.11, 39.68)
10:50833682	rs551219437	V>I	A:188	(5.31, 8.44, 39.35)
10:50833685		A>T	A:189	(4.58, 11.59, 41.88)
10:50833686		A>V	A:189	(4.58, 11.59, 41.88)
10:50835670		V>A	A:199	(8.07, -1.99, 35.76)
10:50835684	rs147815999	R>C	A:204	(10.43, -8.69, 28.70)
10:50835687	COSM1348106	R>C	A:205	(13.88, -5.89, 35.34)
10:50835694		S>T	A:207	(15.61, -0.57, 31.11)
10:50835700	rs546158744	G>E	A:209	(16.84, 3.42, 30.35)
10:50835715		Q>R	A:214	(8.98, 6.13, 30.37)
10:50835726		I>L	A:218	(6.16, 11.43, 33.88)
10:50835727	rs121912823	I>T	A:218	(6.16, 11.43, 33.88)
10:50835736	rs375439849	M>T	A:221	(3.03, 14.42, 31.04)
10:50835745		N>S	A:224	(0.02, 20.33, 30.72)
10:50835747		E>K	A:225	(-1.95, 23.29, 32.53)
10:50835753	rs200776329 COSM3807289 COSM3807290	E>K	A:227	(-4.07, 18.57, 32.60)
10:50835756	rs182935725	R>C	A:228	(-2.15, 20.97, 37.80)
10:50835757		R>H	A:228	(-2.15, 20.97, 37.80)
10:50835765		P>A	A:231	(-4.64, 17.79, 44.99)
10:50835781	COSM684119 COSM3375480 COSM3375481 COSM1646328 CM055128	T>M	A:236	(-4.02, 10.50, 52.12)
10:50835789	rs61731735	G>R	A:239	(-7.78, 11.48, 59.06)
10:50835798		E>K	A:242	(-11.57, 12.46, 58.48)
10:50835807	rs75262191	E>K	A:245	(-16.32, 11.05, 54.85)
10:50835811		A>V	A:246	(-13.72, 11.29, 51.20)
10:50854563	rs201616704	R>Q	A:257	(-15.06, 3.18, 40.90)
10:50854574	rs115212829	D>H	A:261	(-7.43, -0.28, 41.59)
10:50854578		M>T	A:262	(-4.10, 1.42, 39.38)
10:50854581	rs372758559	I>T	A:263	(-2.99, 3.88, 43.85)
10:50854586	COSM310071 COSM310073	R>C	A:265	(-3.63, -3.07, 41.49)
10:50854587	COSM3382907 COSM3382908	R>H	A:265	(-3.63, -3.07, 41.49)
10:50854601		V>L	A:270	(8.42, 7.30, 42.77)
10:50854613	rs115877658	A>T	A:274	(10.18, 19.97, 44.54)
10:50854614	rs114932900	A>V	A:274	(10.18, 19.97, 44.54)
10:50854616	rs201553605	P>S	A:275	(12.61, 22.31, 44.70)
10:50854625	rs536359684	V>M	A:278	(14.90, 25.26, 53.35)
10:50854637	rs8178991	D>N	A:282	(20.21, 16.07, 58.40)
10:50854641	rs539884711	T>N	A:283	(16.38, 18.57, 60.35)
10:50854650	rs192592698	A>V	A:286	(13.32, 14.93, 57.52)
10:50854673		G>S	A:294	(3.04, 20.91, 52.92)
10:50854692	rs376230019 COSM190859	A>V	A:300	(0.55, 16.41, 47.89)
10:50854706		D>N	A:305	(-2.89, 4.68, 52.31)
10:50856554		F>S	A:310	(10.92, 4.84, 47.59)
10:50856559		V>M	A:312	(13.61, 11.40, 44.13)
10:50856566	rs377494035	R>Q	A:314	(16.00, 18.97, 40.81)
10:50856571	rs115964813	G>S	A:316	(18.55, 15.62, 46.79)
10:50856580	rs562560467	G>S	A:319	(13.89, 8.51, 50.58)
10:50856590		C>Y	A:322	(7.09, 4.28, 55.82)
10:50856592	rs121912816	E>K	A:323	(2.17, 2.24, 56.62)
10:50856601		P>A	A:326	(3.19, -3.35, 57.30)
10:50856616		V>I	A:331	(12.80, -5.06, 57.68)
10:50856622		V>L	A:333	(17.00, -0.47, 57.01)
10:50856631		T>A	A:336	(16.91, 0.67, 52.23)
10:50856643	rs76014951	L>F	A:340	(21.15, 2.45, 48.32)
10:50856646		K>E	A:341	(25.18, -2.53, 48.12)
10:50856652	rs4838544	V>M	A:343	(22.23, 2.40, 43.34)
10:50857597	COSM3867362 COSM3867363	E>K	A:357	(7.91, -1.09, 21.88)
10:50857613	rs202125860	R>Q	A:363	(-1.23, 4.34, 32.24)
10:50857622		R>Q	A:366	(-9.10, 9.66, 33.61)
10:50857630	rs375424189	C>S	A:369	(-13.78, 16.45, 40.91)
10:50857631	rs201293521	C>F	A:369	(-13.78, 16.45, 40.91)
10:50857637		P>L	A:371	(-18.44, 20.34, 44.63)
10:50857641		E>D	A:372	(-18.66, 16.62, 47.73)
10:50857646		Q>P	A:374	(-12.66, 21.55, 46.18)
10:50857661	rs141878259	S>F	A:379	(-10.03, 20.33, 55.26)
10:50857664	rs121912821	S>L	A:380	(-6.94, 18.16, 54.19)
10:50857666		A>T	A:381	(-4.99, 21.48, 53.82)
10:50857682	rs200335347 COSM3721235 COSM3721236	R>Q	A:386	(-4.05, 22.23, 62.15)
10:50859953		I>T	A:394	(16.26, 17.84, 66.32)
10:50859959	rs144918120	Y>C	A:396	(22.47, 15.37, 69.25)
10:50859982		T>A	A:404	(33.67, 1.38, 71.78)
10:50859985		F>L	A:405	(33.19, 4.53, 76.71)
10:50860023		I>M	A:417	(21.38, 4.75, 75.03)
10:50863149	rs141881680	R>Q	A:430	(11.15, 19.10, 88.18)
10:50863152		R>I	A:431	(7.27, 13.40, 85.02)
10:50863160	rs147079245	P>S	A:434	(5.18, 6.06, 81.15)
10:50863163		T>P	A:435	(8.83, 4.58, 78.61)
10:50863167		Y>C	A:436	(7.32, 1.57, 73.35)
10:50863169		E>K	A:437	(12.57, 0.02, 74.06)
10:50863175	rs372760913 CM095703	A>T	A:439	(11.11, -5.21, 71.28)
10:50863176	COSM190863	A>V	A:439	(11.11, -5.21, 71.28)
10:50863181	rs202040717	I>V	A:441	(9.06, -10.54, 69.04)
10:50863184		R>C	A:442	(12.26, -10.70, 63.44)
10:50863185	rs121912819	R>H	A:442	(12.26, -10.70, 63.44)
10:50863188	rs80097077	R>Q	A:443	(13.84, -14.56, 69.13)
10:50863202	rs368957556 COSM538846 COSM1648708	R>C	A:448	(5.61, -6.74, 63.97)
10:50863205		V>M	A:449	(7.05, -5.60, 68.65)
10:50863221		S>W	A:454	(12.80, 1.89, 80.45)
10:50863241		A>T	A:461	(17.40, 6.04, 91.91)
10:50863251		R>T	A:464	(14.82, 10.38, 92.83)
10:50863256	rs547073881	V>M	A:466	(22.29, 12.75, 89.45)
10:50863274	rs376947247	A>S	A:472	(24.97, 14.75, 98.40)
10:50863277	rs201485243	V>M	A:473	(24.81, 11.41, 96.31)
10:50863439	rs190968891	E>V	A:477	(26.21, 5.36, 95.41)
10:50863457		K>T	A:483	(26.63, 0.14, 86.38)
10:50863460		D>G	A:484	(21.37, -1.30, 89.39)
10:50863469	rs199926163	R>H	A:487	(20.63, -4.87, 86.76)
10:50863478		T>N	A:490	(19.67, -5.70, 80.34)
10:50863483		Y>N	A:492	(11.66, -5.34, 80.94)
10:50863489		V>L	A:494	(16.33, -10.42, 78.16)
10:50870694		I>V	A:497	(13.82, -10.32, 73.43)
10:50870704		M>T	A:500	(8.42, -13.65, 79.38)
10:50870731		L>P	A:509	(-5.89, -10.93, 78.82)
10:50870734	rs114545628	R>Q	A:510	(-7.63, -5.09, 76.30)
10:50870743		A>V	A:513	(-12.87, -9.84, 77.72)
10:50870745	rs141127966	R>W	A:514	(-13.44, -5.65, 74.53)
10:50870746		R>Q	A:514	(-13.44, -5.65, 74.53)
10:50870749		A>V	A:515	(-15.54, -10.90, 73.72)
10:50870753		M>I	A:516	(-16.67, -12.35, 77.68)
10:50870758		K>R	A:518	(-18.21, -4.59, 76.40)
10:50870760	COSM3438435 COSM3438436	E>K	A:519	(-17.65, -4.46, 79.86)
10:50870769		E>K	A:522	(-11.90, -2.65, 88.18)
10:50870781	COSM1702358 COSM1702359	D>H	A:526	(-7.25, 0.98, 86.65)
10:50870785	rs375665108	E>G	A:527	(-6.30, 5.80, 85.51)
10:50870786		E>D	A:527	(-6.30, 5.80, 85.51)
10:50870790		Y>H	A:529	(-4.07, -0.93, 81.40)
10:50870805		R>W	A:534	(-1.87, 7.57, 78.86)
10:50870806	rs116628504	R>Q	A:534	(-1.87, 7.57, 78.86)
10:50870824	rs138105397	S>N	A:540	(13.57, 3.17, 68.88)
10:50870826		Q>K	A:541	(17.96, 0.57, 68.14)
10:50872848		C>Y	A:550	(14.86, 6.67, 61.36)
10:50872895	rs550322570	P>S	A:566	(23.91, 2.96, 67.81)
10:50872911		I>N	A:571	(25.01, 8.18, 69.56)
10:50872928		S>G	A:577	(7.94, 17.23, 69.93)
10:50872929		S>T	A:577	(7.94, 17.23, 69.93)
10:50872972	rs145995632	K>N	A:591	(21.76, 20.05, 75.93)
10:50873015	COSM169646 COSM1248190	L>M	A:606	(35.53, 7.95, 88.83)
10:50873016		L>R	A:606	(35.53, 7.95, 88.83)

2FY5.A | CHAT.

2FY5.A | CHAT

General Structure Information

Variant Set Distributions

Ripley’s K Analysis Plots

Variant Set Comparisons

Mapped Variants

[+] ExAC Missense Variants

[+] ClinVar Missense Variants

[+] COSMIC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
10:50827789	COSM2145613	V>M	A:18	(1.80, -17.62, 77.01)
10:50830171	COSM4986490	L>F	A:125	(12.16, -4.29, 40.05)
10:50833529	COSM3438408	P>S	A:137	(19.07, -14.21, 52.96)
10:50833673	COSM2145632	H>Y	A:185	(1.82, -0.68, 38.52)
10:50835688	COSM35809	R>H	A:205	(13.88, -5.89, 35.34)
10:50835781	COSM1646328	T>K	A:236	(-4.02, 10.50, 52.12)
10:50854688	COSM3709866	G>W	A:299	(2.46, 17.26, 50.64)
10:50856632	COSM3699911	T>I	A:336	(16.91, 0.67, 52.23)
10:50857639	COSM4527494	E>K	A:372	(-18.66, 16.62, 47.73)
10:50857682	COSM3721235	R>Q	A:386	(-4.05, 22.23, 62.15)
10:50863205	COSM2145720	V>M	A:449	(7.05, -5.60, 68.65)
10:50863468	COSM3686957	R>C	A:487	(20.63, -4.87, 86.76)
10:50870760	COSM3438435	E>K	A:519	(-17.65, -4.46, 79.86)
10:50873009	COSM2152067	C>R	A:604	(32.43, 5.46, 84.19)
10:50873015	COSM1248190	L>M	A:606	(35.53, 7.95, 88.83)