2C0O.B | HCK – ASTRID

2C0O.B | HCK

General Structure Information

PDB ID	2c0o
HGNC Gene Label(s)	HCK
Structure Name	src family kinase hck with bound inhibitor a-770041
Resolution	2.85Å
Reference	AUTH A.BURCHAT,D.W.BORHANI,D.J.CALDERWOOD,G.C.HIRST,B.LI,AUTH 2 R.F.STACHLEWITZTITL DISCOVERY OF A-770041, A SRC-FAMILY SELECTIVE ORALLY ACTIVETITL 2 LCK INHIBITOR THAT PREVENTS ORGAN ALLOGRAFT REJECTION.REF BIOORG.MED.CHEM.LETT. V. 16 118 2006REFN ISSN 0960-894XPMID 16216497DOI 10.1016/J.BMCL.2005.09.039

Variant Set Distributions

ExAC Variants

Number Of Residues	432
Number Of SNVs	101
Number Of Permutations	16297
Optimal Distance Threshold	13.0
K Statistic	0.067
p-value	0.208

COSMIC

Number Of Residues	432
Number Of SNVs	11
Number Of Permutations	3300
Optimal Distance Threshold	11.0
K Statistic	0.109
p-value	0.606

Ripley’s K Analysis Plots

ExACCOSMIC

Variant Set Comparisons

Cosmic vs. ExAC

Number Of ExAC SNVs	101
Number Of COSMIC SNVs	10
Optimal Distance Threshold	36.0
K Statistic	-0.178
p-value	0.25

Pathogenic Proximity Analysis

COSMIC PathProx Analysis

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
20:30661566	rs373209595	I>V	B:71	(19.29, 53.77, 86.30)
20:30661575		E>K	B:74	(12.74, 45.92, 88.38)
20:30661596		G>R	B:81	(28.25, 40.34, 74.76)
20:30662448	rs146372860	R>G	B:97	(16.99, 34.47, 82.16)
20:30662449	rs200519132	R>Q	B:97	(16.99, 34.47, 82.16)
20:30662452		S>F	B:98	(21.76, 36.96, 82.27)
20:30662463	COSM403769 COSM403768	R>W	B:102	(21.03, 32.62, 85.22)
20:30662464	rs182852728	R>Q	B:102	(21.03, 32.62, 85.22)
20:30662485		S>N	B:109	(15.09, 47.22, 73.19)
20:30662499	rs375313782	R>C	B:114	(16.96, 38.39, 67.52)
20:30662502	COSM175567 COSM2888971	V>I	B:115	(22.48, 36.04, 68.07)
20:30662503		V>A	B:115	(22.48, 36.04, 68.07)
20:30662511	rs529087706	L>V	B:118	(23.53, 41.89, 60.05)
20:30662514	rs199725229	E>Q	B:119	(21.56, 44.70, 64.44)
20:30662524		E>A	B:122	(31.09, 46.49, 65.10)
20:30667582	rs199815006 COSM1176414 COSM1176413	F>C	B:124	(24.38, 46.71, 59.65)
20:30667599	rs546660596	R>W	B:130	(21.77, 59.25, 50.95)
20:30667605	COSM577197 COSM577196	D>N	B:132	(21.42, 59.95, 58.63)
20:30667609		A>G	B:133	(25.28, 58.27, 56.87)
20:30667611		E>K	B:134	(26.25, 62.35, 54.57)
20:30667615	COSM1751378 COSM1751377	R>H	B:135	(23.99, 64.07, 58.81)
20:30667630		P>L	B:140	(33.66, 63.73, 65.30)
20:30667632	rs528935522	G>S	B:141	(36.12, 59.84, 64.78)
20:30667668		E>K	B:153	(16.51, 55.20, 51.59)
20:30671701		S>R	B:158	(18.80, 45.85, 49.83)
20:30671706	COSM3545168 COSM3545167	S>F	B:160	(24.31, 50.24, 51.12)
20:30671714		V>M	B:163	(32.89, 55.31, 52.07)
20:30671718		R>Q	B:164	(35.23, 60.02, 55.61)
20:30671724	rs199854883	Y>C	B:166	(40.01, 64.99, 50.56)
20:30671729		P>T	B:168	(41.27, 68.22, 46.52)
20:30671733		R>Q	B:169	(38.81, 70.66, 43.06)
20:30671747	COSM1743471 COSM1743470	V>M	B:174	(30.33, 60.37, 51.73)
20:30671766		R>Q	B:180	(23.74, 45.51, 43.27)
20:30671772		L>P	B:182	(18.98, 38.02, 42.21)
20:30671780	rs200896933	G>R	B:185	(22.89, 35.36, 48.13)
20:30671786		F>V	B:187	(25.98, 39.88, 49.25)
20:30671802	rs202001086	R>Q	B:192	(35.08, 41.81, 38.70)
20:30671808		T>I	B:194	(31.59, 37.82, 44.17)
20:30671820		L>P	B:198	(28.01, 41.42, 53.82)
20:30671824		Q>H	B:199	(32.60, 40.26, 57.12)
20:30671828	COSM1580987 COSM1580986	L>M	B:201	(32.16, 42.90, 50.93)
20:30671843		K>E	B:206	(39.41, 46.27, 55.23)
20:30671844		K>R	B:206	(39.41, 46.27, 55.23)
20:30671845	rs570713481	K>N	B:206	(39.41, 46.27, 55.23)
20:30671846		K>Q	B:207	(43.22, 43.22, 51.92)
20:30672197		G>E	B:208	(42.12, 47.41, 49.29)
20:30672200		N>T	B:209	(40.90, 50.09, 46.34)
20:30672202		D>N	B:210	(38.66, 46.88, 44.14)
20:30672205	rs199531584	G>R	B:211	(36.95, 50.81, 42.47)
20:30672229		P>A	B:219	(34.16, 50.71, 61.47)
20:30672235	rs563800077	M>V	B:221	(32.84, 55.70, 65.40)
20:30672236		M>T	B:221	(32.84, 55.70, 65.40)
20:30672255		K>N	B:227	(19.29, 55.32, 78.72)
20:30672256		P>A	B:228	(14.96, 54.39, 77.34)
20:30672286	rs189947820	R>W	B:238	(5.19, 67.81, 91.25)
20:30672287		R>Q	B:238	(5.19, 67.81, 91.25)
20:30672292		S>T	B:240	(10.55, 62.70, 90.58)
20:30672300	rs546287799	K>N	B:242	(15.52, 67.15, 92.44)
20:30672307	rs370473046	K>Q	B:245	(19.56, 76.53, 86.81)
20:30674449		T>I	B:264	(17.86, 61.01, 84.37)
20:30674467	rs200178250 COSM1580991 COSM1580990	T>M	B:270	(6.45, 75.12, 84.14)
20:30674484		M>L	B:276	(-6.05, 75.92, 80.59)
20:30674490		V>M	B:278	(-6.96, 70.12, 83.28)
20:30674495		E>D	B:279	(-9.37, 67.78, 81.02)
20:30674517	COSM4136811 COSM4136810	V>M	B:287	(-1.98, 63.14, 70.82)
20:30674527		T>S	B:290	(1.62, 59.35, 69.56)
20:30674534		Q>H	B:292	(7.37, 59.14, 69.03)
20:30674552		K>N	B:298	(11.32, 62.08, 73.15)
20:30674553		L>F	B:299	(6.96, 64.30, 75.27)
20:30674576		E>D	B:306	(-2.86, 72.70, 88.39)
20:30674577		P>S	B:307	(1.31, 73.49, 88.56)
20:30674593		T>M	B:312	(11.63, 67.07, 77.66)
20:30674603		M>I	B:315	(18.65, 69.36, 73.82)
20:30676389		L>P	B:324	(23.47, 80.31, 65.67)
20:30676404		G>A	B:329	(27.95, 79.45, 66.16)
20:30676408		S>R	B:330	(30.33, 81.75, 64.88)
20:30676424		K>Q	B:336	(26.92, 72.22, 59.46)
20:30676431	rs151054795	I>T	B:338	(22.31, 74.03, 54.66)
20:30681681	rs114505022	A>T	B:349	(7.66, 66.80, 56.76)
20:30681712		R>Q	B:359	(-0.52, 77.78, 65.25)
20:30681723	rs181577847	A>S	B:363	(15.01, 79.41, 66.32)
20:30681731		N>K	B:365	(10.80, 77.05, 69.20)
20:30681741		S>A	B:369	(22.27, 68.20, 70.45)
20:30681753		V>M	B:373	(20.75, 67.08, 66.45)
20:30681757		C>Y	B:374	(18.16, 69.77, 65.13)
20:30681783	rs145632103	R>W	B:383	(-2.88, 74.47, 70.22)
20:30686846		I>T	B:408	(-1.16, 88.39, 60.35)
20:30686858	rs202169601	S>F	B:412	(-5.49, 81.65, 58.05)
20:30686878	rs555782474	V>I	B:419	(6.38, 77.10, 54.55)
20:30686911	rs557160696	V>I	B:430	(21.96, 82.48, 57.05)
20:30686920		G>S	B:433	(19.99, 85.26, 64.52)
20:30686923	rs137871205	R>W	B:434	(19.32, 89.23, 61.47)
20:30686924	rs374360915	R>Q	B:434	(19.32, 89.23, 61.47)
20:30689132		P>L	B:443	(3.94, 97.80, 62.61)
20:30689147		A>D	B:448	(5.97, 96.03, 53.57)
20:30689155	COSM1734179 COSM1734178	R>C	B:451	(4.37, 98.54, 50.72)
20:30689156	rs369369487	R>H	B:451	(4.37, 98.54, 50.72)
20:30689158		G>R	B:452	(6.00, 93.25, 48.56)
20:30689159		G>A	B:452	(6.00, 93.25, 48.56)
20:30689164	COSM1723572 COSM1723571	R>W	B:454	(9.33, 89.87, 50.42)
20:30689165	COSM4097494 COSM4097493	R>L	B:454	(9.33, 89.87, 50.42)
20:30689167		M>L	B:455	(14.33, 89.81, 53.92)
20:30689173		R>C	B:457	(21.85, 87.78, 48.61)
20:30689174	COSM1025679 COSM1025677	R>H	B:457	(21.85, 87.78, 48.61)
20:30689200	rs200005064	Y>H	B:466	(17.11, 85.05, 48.35)
20:30689206		I>V	B:468	(14.31, 78.11, 48.90)
20:30689210		M>T	B:469	(14.40, 82.11, 51.40)
20:30689216	COSM443621 COSM443620	R>H	B:471	(9.80, 78.38, 45.77)
20:30689230		R>C	B:476	(-1.19, 83.45, 44.70)
20:30689233		P>S	B:477	(-0.51, 80.19, 49.96)
20:30689254		E>K	B:484	(8.33, 65.68, 50.46)
20:30689256		E>D	B:484	(8.33, 65.68, 50.46)
20:30689267		S>I	B:488	(14.82, 67.30, 48.88)
20:30689284		Y>N	B:494	(26.31, 71.62, 48.81)

2C0O.B | HCK.

2C0O.B | HCK

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

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
20:30662502	COSM2888971	V>I	B:115	(22.48, 36.04, 68.07)
20:30667615	COSM1751377	R>H	B:135	(23.99, 64.07, 58.81)
20:30671711	COSM1411010	S>P	B:162	(28.79, 54.37, 53.19)
20:30671747	COSM1743470	V>M	B:174	(30.33, 60.37, 51.73)
20:30671834	COSM477994	D>N	B:203	(37.27, 41.53, 55.15)
20:30672286	COSM1025662	R>W	B:238	(5.19, 67.81, 91.25)
20:30674488	COSM1411019	S>L	B:277	(-8.88, 72.71, 80.90)
20:30674574	COSM3911077	E>K	B:306	(-2.86, 72.70, 88.39)
20:30674595	COSM3545181	E>K	B:313	(15.01, 65.40, 75.01)
20:30681769	COSM1411028	D>G	B:378	(7.05, 74.34, 71.49)
20:30686836	COSM48418	P>S	B:405	(0.19, 87.04, 55.54)
20:30689164	COSM1723572	R>W	B:454	(9.33, 89.87, 50.42)
20:30689234	COSM1411040	P>L	B:477	(-0.51, 80.19, 49.96)