3EE6.A | TPP1 – ASTRID

3EE6.A | TPP1

General Structure Information

PDB ID	3ee6
HGNC Gene Label(s)	TPP1
Structure Name	crystal structure analysis of tripeptidyl peptidase -i
Resolution	2.35Å
Reference	AUTH A.PAL,R.KRAETZNER,T.GRUENE,M.GRAPP,K.SCHREIBER,M.GRONBORG,AUTH 2 H.URLAUB,S.BECKER,A.R.ASIF,J.GARTNER,G.M.SHELDRICK,AUTH 3 R.STEINFELDTITL STRUCTURE OF TRIPEPTIDYL-PEPTIDASE I PROVIDES INSIGHT INTOTITL 2 THE MOLECULAR BASIS OF LATE INFANTILE NEURONAL CEROIDTITL 3 LIPOFUSCINOSISREF J.BIOL.CHEM. V. 284 3976 2009REFN ISSN 0021-9258PMID 19038966DOI 10.1074/JBC.M806947200

Variant Set Distributions

ExAC Variants

Number Of Residues	528
Number Of SNVs	136
Number Of Permutations	26524
Optimal Distance Threshold	10.0
K Statistic	0.034
p-value	0.304

ClinVar

Number Of Residues	528
Number Of SNVs	15
Number Of Permutations	2553
Optimal Distance Threshold	11.0
K Statistic	0.152
p-value	0.006

COSMIC

Number Of Residues	528
Number Of SNVs	4
Number Of Permutations	478
Optimal Distance Threshold	17.0
K Statistic	0.333
p-value	0.568

Ripley’s K Analysis Plots

ExACClinVarCOSMIC

Variant Set Comparisons

ClinVar vs. ExAC

Number Of ExAC SNVs	136
Number Of ClinVar SNVs	13
Optimal Distance Threshold	11.0
K Statistic	0.119
p-value	0.006

Cosmic vs. ExAC

Number Of ExAC SNVs	136
Number Of COSMIC SNVs	4
Optimal Distance Threshold	17.0
K Statistic	0.187
p-value	0.884

Pathogenic Proximity Analysis

ClinVar PathProx Analysis

COSMIC PathProx Analysis

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
11:6640458		S>R	A:20	(106.53, 4.30, 42.24)
11:6640443	rs373323264	P>T	A:25	(109.13, 13.25, 50.31)
11:6640438		D>E	A:26	(108.23, 16.64, 52.18)
11:6640437		Q>E	A:27	(106.54, 14.49, 56.61)
11:6640433	rs369126677	R>Q	A:28	(109.44, 16.13, 61.04)
11:6640434		R>W	A:28	(109.44, 16.13, 61.04)
11:6640121		G>S	A:39	(107.84, -2.46, 68.04)
11:6640117	rs549309216 COSM1509612	R>H	A:40	(107.55, -4.24, 62.48)
11:6640114		A>V	A:41	(103.91, -4.13, 63.84)
11:6640103		E>K	A:45	(97.96, -4.62, 64.43)
11:6640098		E>D	A:46	(93.50, -4.28, 61.78)
11:6640087		T>I	A:50	(92.73, 8.69, 56.15)
11:6640088		T>A	A:50	(92.73, 8.69, 56.15)
11:6640085		F>V	A:51	(93.16, 6.79, 51.98)
11:6640051	rs2734715	S>L	A:62	(89.89, 30.51, 45.64)
11:6640048		E>V	A:63	(87.88, 32.29, 42.14)
11:6640034		V>M	A:68	(82.19, 35.10, 50.08)
11:6640030		S>L	A:69	(85.49, 37.28, 51.94)
11:6640027		D>G	A:70	(86.10, 41.10, 49.59)
11:6640015		P>L	A:74	(78.87, 41.61, 45.20)
11:6638988	COSM930827	E>D	A:83	(75.80, 19.35, 49.02)
11:6638980		A>G	A:86	(80.46, 18.89, 47.34)
11:6638981	rs140663603	A>T	A:86	(80.46, 18.89, 47.34)
11:6638976		D>E	A:87	(78.38, 19.61, 44.12)
11:6638977	rs148064565	D>G	A:87	(78.38, 19.61, 44.12)
11:6638975		L>M	A:88	(83.05, 22.62, 43.73)
11:6638972		V>M	A:89	(85.34, 19.65, 45.73)
11:6638953	rs535584300	T>S	A:95	(89.12, 9.31, 41.39)
11:6638944	rs140726254	T>M	A:98	(90.60, 4.13, 40.69)
11:6638942		V>M	A:99	(90.38, 4.66, 45.13)
11:6638924	rs368435226	A>S	A:105	(92.12, -5.50, 46.40)
11:6638918	rs201613668	G>R	A:107	(91.18, -5.40, 51.90)
11:6638914	rs374132017	A>V	A:108	(89.69, -2.68, 52.61)
11:6638901	rs199539943	H>Q	A:112	(83.57, 5.11, 57.30)
11:6638897	rs552111650	V>M	A:114	(82.66, 12.55, 53.83)
11:6638885		D>N	A:118	(87.23, 14.75, 49.95)
11:6638859	COSM3869960	I>M	A:126	(99.91, -3.84, 59.37)
11:6638857	rs121908204	R>L	A:127	(99.01, -8.37, 55.67)
11:6638651		E>G	A:130	(103.23, -3.14, 54.75)
11:6638633		A>V	A:136	(105.77, 0.86, 54.65)
11:6638612		G>E	A:143	(102.89, 8.74, 74.10)
11:6638610		G>R	A:144	(102.27, 10.63, 76.87)
11:6638603		T>M	A:146	(99.13, 10.14, 77.78)
11:6638604		T>A	A:146	(99.13, 10.14, 77.78)
11:6638594		H>R	A:149	(98.41, 2.96, 70.23)
11:6638591		V>A	A:150	(100.31, 5.52, 67.50)
11:6638579		P>L	A:154	(109.79, 5.01, 60.19)
11:6638567		Q>P	A:158	(106.14, 4.51, 47.14)
11:6638561		P>L	A:160	(100.78, 3.22, 43.07)
11:6638536		D>E	A:168	(96.56, 14.16, 47.71)
11:6638381		G>E	A:171	(96.89, 8.96, 56.82)
11:6638369		R>H	A:175	(101.33, 13.44, 59.99)
11:6638370		R>C	A:175	(101.33, 13.44, 59.99)
11:6638363		P>L	A:177	(99.72, 12.96, 68.12)
11:6638364		P>T	A:177	(99.72, 12.96, 68.12)
11:6638285		S>F	A:203	(86.29, 39.73, 85.54)
11:6638276	rs121908209	R>H	A:206	(83.27, 40.38, 80.39)
11:6638277	rs28940573	R>C	A:206	(83.27, 40.38, 80.39)
11:6638270		R>Q	A:208	(91.62, 45.89, 78.71)
11:6638259		T>A	A:212	(78.85, 44.76, 79.78)
11:6638255		S>L	A:213	(76.68, 42.69, 82.31)
11:6638241		S>P	A:218	(70.09, 36.18, 73.35)
11:6638232		S>G	A:221	(69.46, 31.93, 67.89)
11:6638228	rs372787642 COSM179520	N>S	A:222	(70.81, 28.53, 65.56)
11:6638225	rs538565229	N>S	A:223	(74.83, 31.81, 67.35)
11:6638080		Q>R	A:233	(93.34, 16.53, 77.88)
11:6638044	COSM1356196	R>H	A:245	(79.75, 27.00, 91.09)
11:6638023		A>V	A:252	(74.92, 35.44, 81.73)
11:6638021		H>Y	A:253	(76.31, 31.63, 83.06)
11:6638008		V>A	A:257	(78.35, 21.72, 76.57)
11:6638005		A>D	A:258	(75.37, 21.48, 73.88)
11:6638006		A>S	A:258	(75.37, 21.48, 73.88)
11:6638002	rs140176031	R>H	A:259	(77.25, 18.17, 69.75)
11:6638003		R>C	A:259	(77.25, 18.17, 69.75)
11:6637996	rs146136938	V>A	A:261	(82.12, 15.63, 69.11)
11:6637997	COSM1193836	V>L	A:261	(82.12, 15.63, 69.11)
11:6637981		R>Q	A:266	(84.88, 7.52, 83.07)
11:6637982	rs200138397	R>W	A:266	(84.88, 7.52, 83.07)
11:6637978		G>D	A:267	(88.88, 10.60, 82.95)
11:6637976	COSM3810150	R>W	A:268	(92.56, 13.22, 85.72)
11:6637966		I>T	A:271	(95.13, 22.43, 82.12)
11:6637951		D>V	A:276	(89.97, 25.99, 75.46)
11:6637949	rs121908207	V>M	A:277	(85.46, 25.24, 77.31)
11:6637940		L>V	A:280	(84.44, 30.08, 74.41)
11:6637935		M>I	A:281	(81.23, 29.42, 77.80)
11:6637919	rs578253592	I>V	A:287	(76.76, 31.57, 73.23)
11:6637732	rs553122824 COSM930823	R>W	A:297	(94.45, 10.92, 70.56)
11:6637715		E>D	A:302	(96.27, 12.26, 61.61)
11:6637713		P>L	A:303	(93.63, 13.98, 65.57)
11:6637704	rs201192562	Q>L	A:306	(89.61, 12.43, 61.63)
11:6637696		M>V	A:309	(86.93, 14.23, 57.78)
11:6637690		L>F	A:311	(84.26, 20.35, 59.51)
11:6637674	rs149463616	A>D	A:316	(74.91, 22.35, 60.76)
11:6637665		H>R	A:319	(78.42, 30.44, 62.61)
11:6637656		T>I	A:322	(88.22, 28.02, 68.83)
11:6637653		V>A	A:323	(91.67, 25.81, 66.86)
11:6637637		D>E	A:328	(107.18, 22.96, 63.22)
11:6637639	rs202086458 COSM930822	D>H	A:328	(107.18, 22.96, 63.22)
11:6637629		S>F	A:331	(107.37, 19.28, 59.44)
11:6637618	rs146927291	A>T	A:335	(100.46, 17.49, 50.34)
11:6637614	COSM1509616	Y>C	A:336	(98.95, 17.89, 55.96)
11:6637605		R>Q	A:339	(93.56, 18.44, 51.14)
11:6637606		R>W	A:339	(93.56, 18.44, 51.14)
11:6637594	rs121908197	E>K	A:343	(89.72, 21.25, 53.72)
11:6637586		M>I	A:345	(89.85, 27.31, 51.12)
11:6637587		M>T	A:345	(89.85, 27.31, 51.12)
11:6637588	rs141482368	M>L	A:345	(89.85, 27.31, 51.12)
11:6637578	rs370144405	A>D	A:348	(85.39, 30.11, 54.31)
11:6637563	rs145966505	T>N	A:353	(85.13, 31.91, 61.89)
11:6637300		S>G	A:361	(107.92, 29.74, 70.78)
11:6637291		G>R	A:364	(111.50, 30.64, 66.96)
11:6637287	rs119455954	C>Y	A:365	(114.57, 28.09, 66.70)
11:6637285		W>R	A:366	(114.61, 25.67, 60.91)
11:6637265		H>Q	A:372	(120.35, 29.62, 64.01)
11:6637267	rs371314926	H>Y	A:372	(120.35, 29.62, 64.01)
11:6637264	rs112812685	Q>E	A:373	(116.25, 30.08, 59.94)
11:6637257	rs546003291 COSM1605082	R>H	A:375	(110.95, 26.16, 63.50)
11:6637258	rs368914445 COSM295107	R>C	A:375	(110.95, 26.16, 63.50)
11:6637236		S>N	A:382	(96.97, 29.91, 56.79)
11:6636791		P>H	A:383	(96.15, 32.26, 54.25)
11:6636750		F>L	A:397	(97.33, 45.14, 91.72)
11:6636747	rs149319579	L>F	A:398	(96.56, 47.94, 87.25)
11:6636720		I>V	A:407	(104.99, 33.13, 74.65)
11:6636698	rs146798796	N>I	A:414	(108.88, 29.66, 54.50)
11:6636686	rs138744051	R>Q	A:418	(102.95, 39.36, 51.27)
11:6636687	rs143584882	R>W	A:418	(102.95, 39.36, 51.27)
11:6636673	rs121908200	Q>H	A:422	(98.89, 40.95, 54.70)
11:6636547	rs201034755	T>M	A:427	(104.88, 47.10, 53.44)
11:6636548		T>S	A:427	(104.88, 47.10, 53.44)
11:6636530		S>G	A:433	(110.77, 48.58, 61.93)
11:6636520	rs150039898	L>P	A:436	(113.76, 44.51, 61.49)
11:6636499	rs139343938	N>S	A:443	(110.71, 34.90, 53.68)
11:6636500		N>H	A:443	(110.71, 34.90, 53.68)
11:6636496		A>D	A:444	(109.29, 38.84, 53.58)
11:6636487	rs119455956	R>H	A:447	(100.29, 34.61, 56.69)
11:6636431	rs78970155	V>M	A:466	(91.48, 21.74, 91.15)
11:6636409		G>A	A:473	(98.74, 31.02, 76.45)
11:6636410	rs121908203	G>R	A:473	(98.74, 31.02, 76.45)
11:6636403	rs121908202	S>L	A:475	(95.42, 28.36, 73.83)
11:6636213		P>A	A:479	(89.31, 31.23, 73.25)
11:6636197		I>T	A:484	(84.46, 38.67, 71.61)
11:6636191		S>Y	A:486	(80.22, 34.82, 68.62)
11:6636187	rs532438658 COSM165096	L>F	A:487	(78.61, 38.53, 71.01)
11:6636182		N>S	A:489	(78.15, 36.55, 64.51)
11:6636158	rs549928656	R>H	A:497	(73.78, 42.39, 58.83)
11:6636159	rs377700188	R>C	A:497	(73.78, 42.39, 58.83)
11:6636134	rs138941580	P>R	A:505	(89.63, 40.34, 54.52)
11:6636125		Y>C	A:508	(94.41, 42.95, 57.71)
11:6636122	rs149529997	Q>R	A:509	(89.21, 46.77, 54.19)
11:6635910	rs368697480	R>H	A:520	(105.96, 49.77, 75.10)
11:6635911	rs371204585	R>S	A:520	(105.96, 49.77, 75.10)
11:6635887	rs375364589	D>N	A:528	(121.79, 33.26, 68.93)
11:6635877		V>A	A:531	(119.03, 37.19, 67.90)
11:6635859		C>Y	A:537	(109.32, 43.83, 67.71)
11:6635856		S>C	A:538	(105.97, 45.66, 68.92)
11:6635835		V>A	A:545	(103.93, 39.79, 67.91)
11:6635832		T>I	A:546	(100.07, 41.45, 68.29)
11:6635810		F>L	A:553	(82.46, 44.53, 72.22)
11:6635788	rs566120191	L>I	A:561	(77.18, 45.61, 63.22)
11:6635781		P>H	A:563	(78.05, 48.66, 56.64)

3EE6.A | TPP1.

3EE6.A | TPP1

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
11:6640007	rs121908195	G>R	A:77	(77.96, 36.49, 52.42)
11:6638938	rs1800746	Q>R	A:100	(86.29, 2.44, 45.43)
11:6638288	rs121908205	P>L	A:202	(86.44, 35.90, 83.70)
11:6638277	rs28940573	R>C	A:206	(83.27, 40.38, 80.39)
11:6637951	rs763162812	D>V	A:276	(89.97, 25.99, 75.46)
11:6637945	rs796053439	Q>R	A:278	(86.45, 27.05, 81.47)
11:6637933	rs796053440	S>N	A:282	(83.35, 33.73, 79.43)
11:6637927	rs119455957	G>V	A:284	(80.89, 33.99, 74.97)
11:6637921	rs119455958	N>S	A:286	(74.12, 32.76, 77.27)
11:6637606	rs750428882	R>W	A:339	(93.56, 18.44, 51.14)
11:6637287	rs119455954	C>Y	A:365	(114.57, 28.09, 66.70)
11:6637288	rs119455953	C>R	A:365	(114.57, 28.09, 66.70)
11:6636673	rs121908200	Q>H	A:422	(98.89, 40.95, 54.70)
11:6636487	rs119455956	R>H	A:447	(100.29, 34.61, 56.69)
11:6636451	rs864309505	Y>S	A:459	(94.16, 32.95, 81.45)
11:6636430	rs398122959	V>G	A:466	(91.48, 21.74, 91.15)

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
11:6638369	COSM3726910	R>H	A:175	(101.33, 13.44, 59.99)
11:6638044	COSM1356196	R>H	A:245	(79.75, 27.00, 91.09)
11:6637257	COSM1605082	R>L	A:375	(110.95, 26.16, 63.50)
11:6637258	COSM295107	R>C	A:375	(110.95, 26.16, 63.50)
11:6636493	COSM1675801	S>N	A:445	(107.37, 36.87, 50.87)