1SIQ.A | GCDH – ASTRID

1SIQ.A | GCDH

General Structure Information

PDB ID	1siq
HGNC Gene Label(s)	GCDH
Structure Name	the crystal structure and mechanism of human glutaryl-coa dehydrogenase
Resolution	2.1Å
Reference	AUTH Z.FU,M.WANG,R.PASCHKE,K.S.RAO,F.E.FRERMAN,J.J.KIMTITL CRYSTAL STRUCTURES OF HUMAN GLUTARYL-COA DEHYDROGENASE WITHTITL 2 AND WITHOUT AN ALTERNATE SUBSTRATE: STRUCTURAL BASES OFTITL 3 DEHYDROGENATION AND DECARBOXYLATION REACTIONSREF BIOCHEMISTRY V. 43 9674 2004REFN ISSN 0006-2960PMID 15274622DOI 10.1021/BI049290C

Variant Set Distributions

ExAC Variants

Number Of Residues	390
Number Of SNVs	112
Number Of Permutations	69399
Optimal Distance Threshold	9.0
K Statistic	0.033
p-value	0.653

ClinVar

Number Of Residues	390
Number Of SNVs	22
Number Of Permutations	19759
Optimal Distance Threshold	15.0
K Statistic	0.242
p-value	0.016

COSMIC

Number Of Residues	390
Number Of SNVs	4
Number Of Permutations	1635
Optimal Distance Threshold	53.0
K Statistic	0.833
p-value	0.533

Ripley’s K Analysis Plots

ExACClinVarCOSMIC

Variant Set Comparisons

ClinVar vs. ExAC

Number Of ExAC SNVs	112
Number Of ClinVar SNVs	22
Optimal Distance Threshold	15.0
K Statistic	0.098
p-value	0.034

Cosmic vs. ExAC

Number Of ExAC SNVs	112
Number Of COSMIC SNVs	7
Optimal Distance Threshold	16.0
K Statistic	-0.167
p-value	0.761

Pathogenic Proximity Analysis

ClinVar PathProx Analysis

COSMIC PathProx Analysis

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
19:13002665		W>G	A:6	(-13.12, 39.13, -5.90)
19:13002674		P>S	A:9	(-15.72, 33.51, -10.38)
19:13002686		E>K	A:13	(-6.19, 28.93, -12.65)
19:13002698		T>S	A:17	(-1.66, 24.85, -18.92)
19:13002701		T>A	A:18	(1.45, 24.26, -16.10)
19:13002704		D>N	A:19	(3.16, 25.76, -19.48)
19:13002713		L>F	A:22	(4.85, 29.65, -15.61)
19:13002726		T>N	A:26	(6.62, 35.39, -15.49)
19:13002728	rs371766365	F>L	A:27	(4.41, 39.49, -18.91)
19:13002732		R>H	A:28	(0.81, 39.10, -13.32)
19:13002735		T>I	A:29	(6.36, 40.03, -12.30)
19:13002740		C>G	A:31	(4.11, 44.21, -15.94)
19:13002751		R>S	A:34	(10.54, 47.44, -15.43)
19:13002759		P>R	A:37	(6.44, 52.05, -12.63)
19:13002779	rs142967670	R>C	A:44	(0.74, 63.30, -16.37)
19:13002939	rs566417795 CM980850	R>Q	A:50	(12.52, 51.01, -28.78)
19:13002941		E>Q	A:51	(13.22, 51.24, -23.80)
19:13002944		I>V	A:52	(8.90, 48.74, -23.45)
19:13002947		I>V	A:53	(9.72, 46.60, -27.60)
19:13002958		M>I	A:56	(8.53, 42.88, -24.38)
19:13002960		G>E	A:57	(12.21, 40.38, -26.16)
19:13002968		G>S	A:60	(9.75, 36.29, -25.53)
19:13002975		L>P	A:62	(7.68, 39.75, -29.06)
19:13002980		P>S	A:64	(4.15, 34.36, -28.95)
19:13002986		I>V	A:66	(5.74, 32.45, -34.19)
19:13002992		G>R	A:68	(10.51, 29.80, -34.54)
19:13004327		A>V	A:78	(-0.82, 32.42, -23.82)
19:13004329		Y>H	A:79	(-1.39, 36.57, -27.82)
19:13004330	COSM4167503 COSM4167505 COSM4167504	Y>C	A:79	(-1.39, 36.57, -27.82)
19:13004345		R>Q	A:84	(-5.71, 39.10, -18.45)
19:13004356	rs372429120 COSM565184 COSM1141546	R>W	A:88	(-4.13, 43.78, -15.46)
19:13004359		V>L	A:89	(-0.77, 48.28, -17.19)
19:13004378	rs139851890	S>L	A:95	(-1.15, 48.41, -28.72)
19:13004381	COSM991527	A>V	A:96	(2.68, 47.83, -29.22)
19:13004390	rs141456457	V>A	A:99	(1.50, 45.89, -33.86)
19:13004416		I>V	A:108	(6.62, 38.50, -42.20)
19:13004422		A>T	A:110	(2.22, 33.77, -43.54)
19:13004428		G>S	A:112	(6.31, 35.31, -46.70)
19:13004444		R>Q	A:117	(9.89, 33.64, -43.19)
19:13006818		L>R	A:129	(13.48, 45.74, -35.75)
19:13006828		C>W	A:132	(4.33, 49.38, -38.54)
19:13006832		G>R	A:134	(-0.43, 50.08, -43.02)
19:13006835	rs201714645 COSM3528913 COSM3528915 COSM3528914	L>F	A:135	(-4.67, 49.48, -43.70)
19:13006836		L>R	A:135	(-4.67, 49.48, -43.70)
19:13006841		E>Q	A:137	(-5.83, 55.59, -46.12)
19:13006848		N>I	A:139	(-10.41, 59.07, -47.24)
19:13006853	rs576948027	G>R	A:141	(-11.37, 52.62, -42.68)
19:13006857	COSM709901 COSM1148085	S>N	A:142	(-14.48, 51.04, -42.08)
19:13006859		D>N	A:143	(-14.06, 51.02, -46.93)
19:13006861	rs377580992	D>E	A:143	(-14.06, 51.02, -46.93)
19:13006866		S>T	A:145	(-12.25, 49.63, -50.93)
19:13006872	rs149120354	M>T	A:147	(-7.02, 51.81, -50.28)
19:13006899		S>C	A:156	(13.13, 48.06, -65.39)
19:13006920		N>S	A:163	(2.46, 57.11, -54.25)
19:13006925		T>A	A:165	(-1.32, 58.79, -46.75)
19:13006931		T>S	A:167	(-3.60, 57.81, -40.71)
19:13007041	rs375357230 COSM3796665 COSM3796667 COSM3796666 CM105713	D>N	A:176	(12.66, 50.35, -37.77)
19:13007062	rs368357056	R>W	A:183	(-5.79, 48.93, -54.71)
19:13007075	rs373998176	G>A	A:187	(-6.47, 45.30, -58.18)
19:13007077		C>G	A:188	(-4.84, 43.27, -56.28)
19:13007078		C>Y	A:188	(-4.84, 43.27, -56.28)
19:13007089		F>L	A:192	(4.28, 46.55, -50.59)
19:13007105		G>E	A:197	(15.31, 55.83, -45.19)
19:13007108		M>T	A:198	(13.12, 53.92, -47.92)
19:13007109		M>I	A:198	(13.12, 53.92, -47.92)
19:13007110	rs549254182 COSM1207999 COSM1208000 CM088185	R>W	A:199	(15.18, 59.64, -50.33)
19:13007111		R>Q	A:199	(15.18, 59.64, -50.33)
19:13007120	COSM3528919 COSM3528921 COSM3528920	S>L	A:202	(7.54, 60.31, -43.96)
19:13007128		R>G	A:205	(3.74, 62.92, -32.74)
19:13007147	COSM1711883 COSM1711884 CM002262	S>L	A:211	(-6.38, 57.90, -26.24)
19:13007152		R>W	A:213	(-1.55, 60.79, -23.84)
19:13007153		R>Q	A:213	(-1.55, 60.79, -23.84)
19:13007155	rs201076343	A>S	A:214	(1.75, 55.74, -24.09)
19:13007159	rs367699815 COSM352716	S>L	A:215	(1.24, 55.13, -27.84)
19:13007165	COSM1390678 COSM1390679	T>I	A:217	(0.44, 57.61, -32.98)
19:13007173		I>V	A:220	(2.93, 56.11, -43.31)
19:13007176		I>V	A:221	(3.94, 60.38, -45.83)
19:13007179		M>L	A:222	(4.06, 56.81, -49.12)
19:13007180		M>T	A:222	(4.06, 56.81, -49.12)
19:13007185		G>S	A:224	(7.90, 57.77, -54.20)
19:13007186		G>V	A:224	(7.90, 57.77, -54.20)
19:13007208		N>K	A:231	(10.72, 44.25, -49.94)
19:13007209		V>L	A:232	(6.70, 42.08, -52.01)
19:13007212	rs371654188	L>F	A:233	(4.34, 40.06, -48.65)
19:13007215		P>S	A:234	(4.57, 36.56, -51.55)
19:13007216		P>L	A:234	(4.57, 36.56, -51.55)
19:13007228		S>T	A:238	(-7.26, 40.97, -51.81)
19:13007733		G>S	A:244	(-6.05, 38.03, -41.12)
19:13007752	COSM1196731 COSM4074523 COSM1196732	R>Q	A:250	(-9.84, 41.94, -34.82)
19:13007757	rs539505767	G>S	A:252	(-5.97, 39.93, -28.16)
19:13007763	COSM1658971 COSM1658972	A>T	A:254	(-10.53, 40.26, -26.35)
19:13007764		A>V	A:254	(-10.53, 40.26, -26.35)
19:13007772		V>M	A:257	(-10.13, 44.51, -22.70)
19:13007781	rs373203481 CM002263	A>T	A:260	(-8.63, 46.72, -17.79)
19:13007787	rs375120783	E>Q	A:262	(-9.64, 42.25, -14.17)
19:13007808		R>W	A:269	(-13.05, 45.42, -3.72)
19:13007809		R>Q	A:269	(-13.05, 45.42, -3.72)
19:13007817	rs370059118	A>T	A:272	(-15.42, 51.03, -1.50)
19:13007823		D>N	A:274	(-10.66, 51.98, 1.77)
19:13008121		Q>K	A:277	(-18.76, 59.37, 3.07)
19:13008137		L>P	A:282	(-18.80, 53.82, -0.40)
19:13008162	rs376338666	K>N	A:290	(-26.11, 46.81, -9.29)
19:13008169		A>S	A:293	(-21.97, 42.74, -9.84)
19:13008175		M>V	A:295	(-18.10, 45.45, -12.96)
19:13008194		L>Q	A:301	(-19.60, 36.13, -19.33)
19:13008208		C>S	A:306	(-11.80, 34.11, -24.62)
19:13008220	COSM181121 CM980873 CM980874	G>S	A:310	(-8.39, 29.57, -28.01)
19:13008223		R>C	A:311	(-7.86, 26.05, -25.67)
19:13008224	COSM181122 CM980875	R>H	A:311	(-7.86, 26.05, -25.67)
19:13008519	rs114759170	A>D	A:318	(-11.40, 29.78, -35.77)
19:13008527	rs121434370	E>K	A:321	(-17.33, 35.44, -37.96)
19:13008536		S>A	A:324	(-16.06, 39.81, -34.15)
19:13008578	rs567564095 CM980878 CD111005	A>T	A:338	(-14.32, 52.22, -16.74)
19:13008581	rs150938052	R>C	A:339	(-17.65, 54.82, -19.46)
19:13008582		R>H	A:339	(-17.65, 54.82, -19.46)
19:13008598	rs538285397 COSM320556	M>I	A:344	(-17.52, 53.98, -8.05)
19:13008602	rs372983141 CM960717	G>R	A:346	(-15.25, 60.52, -8.09)
19:13008603		G>V	A:346	(-15.25, 60.52, -8.09)
19:13008632	rs121434372	V>M	A:356	(-9.90, 54.67, -13.78)
19:13008638	rs121434369	R>W	A:358	(-4.81, 55.12, -17.66)
19:13008644	rs201509112	A>T	A:360	(-11.58, 55.19, -20.04)
19:13008662	COSM1390680 COSM1390681	V>M	A:366	(-9.80, 49.79, -28.11)
19:13008674	rs147611168	E>K	A:370	(-8.67, 46.19, -35.25)
19:13010300	rs121434367	A>V	A:377	(-22.50, 43.91, -35.98)
19:13010324		T>M	A:385	(-28.82, 37.06, -42.41)
19:13010332		Q>K	A:388	(-24.65, 43.49, -47.29)
19:13010342	COSM181123	T>M	A:391	(-23.81, 48.91, -48.39)

1SIQ.A | GCDH.

1SIQ.A | GCDH

General Structure Information

Variant Set Distributions

Ripley’s K Analysis Plots

Variant Set Comparisons

Pathogenic Proximity Analysis

Mapped Variants

[+] ExAC Missense Variants

[+] ClinVar Missense Variants

[+] COSMIC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
19:13002761	COSM3937869	R>C	A:38	(8.00, 52.72, -17.31)
19:13002762	COSM1208003	R>H	A:38	(8.00, 52.72, -17.31)
19:13004318	COSM4686603	S>L	A:75	(-0.73, 28.98, -26.70)
19:13006811	COSM3932894	G>R	A:127	(13.37, 44.13, -30.48)
19:13007110	COSM1207999	R>W	A:199	(15.18, 59.64, -50.33)
19:13007752	COSM1196731	R>Q	A:250	(-9.84, 41.94, -34.82)
19:13008597	COSM4140285	M>R	A:344	(-17.52, 53.98, -8.05)
19:13008651	COSM3718091	N>T	A:362	(-7.00, 54.14, -23.26)