IGDRPT (Indian Genetic Disease Risk Prediction Tool)

Disease Name: Purpura

1 .Inheritance

Autosomal Recessive

2. Gene Name

PROC

3. Protein Name

Vitamin K-dependent protein C

4. Chromosomal Location

2q13-q14

5. Protein Sequence

>sp|P04070|PROC_HUMAN Vitamin K-dependent protein C OS=Homo sapiens OX=9606 GN=PROC PE=1 SV=1

MWQLTSLLLFVATWGISGTPAPLDSVFSSSERAHQVLRIRKRANSFLEELRHSSLERECI

EEICDFEEAKEIFQNVDDTLAFWSKHVDGDQCLVLPLEHPCASLCCGHGTCIDGIGSFSC

DCRSGWEGRFCQREVSFLNCSLDNGGCTHYCLEEVGWRRCSCAPGYKLGDDLLQCHPAVK

FPCGRPWKRMEKKRSHLKRDTEDQEDQVDPRLIDGKMTRRGDSPWQVVLLDSKKKLACGA

VLIHPSWVLTAAHCMDESKKLLVRLGEYDLRRWEKWELDLDIKEVFVHPNYSKSTTDNDI

ALLHLAQPATLSQTIVPICLPDSGLAERELNQAGQETLVTGWGYHSSREKEAKRNRTFVL

NFIKIPVVPHNECSEVMSNMVSENMLCAGILGDRQDACEGDSGGPMVASFHGTWFLVGLV

SWGEGCGLLHNYGVYTKVSRYLDWIHGHIRDKEAPQKSWAP

6. Gene Sequence

>NM_000312.3 Homo sapiens protein C, inactivator of coagulation factors Va and VIIIa (PROC), transcript variant 10, mRNA

ATGGATTAACTCGAACTCCAGGCTGTCATGGCGGCAGGACGGCGAACTTGCAGTATCTCCACGACCCGCC

CCTACAGGTGCCAGTGCCTCCAGAATGTGGCAGCTCACAAGCCTCCTGCTGTTCGTGGCCACCTGGGGAA

TTTCCGGCACACCAGCTCCTCTTGACTCAGTGTTCTCCAGCAGCGAGCGTGCCCACCAGGTGCTGCGGAT

CCGCAAACGTGCCAACTCCTTCCTGGAGGAGCTCCGTCACAGCAGCCTGGAGCGGGAGTGCATAGAGGAG

ATCTGTGACTTCGAGGAGGCCAAGGAAATTTTCCAAAATGTGGATGACACACTGGCCTTCTGGTCCAAGC

ACGTCGACGGTGACCAGTGCTTGGTCTTGCCCTTGGAGCACCCGTGCGCCAGCCTGTGCTGCGGGCACGG

CACGTGCATCGACGGCATCGGCAGCTTCAGCTGCGACTGCCGCAGCGGCTGGGAGGGCCGCTTCTGCCAG

CGCGAGGTGAGCTTCCTCAATTGCTCGCTGGACAACGGCGGCTGCACGCATTACTGCCTAGAGGAGGTGG

GCTGGCGGCGCTGTAGCTGTGCGCCTGGCTACAAGCTGGGGGACGACCTCCTGCAGTGTCACCCCGCAGT

GAAGTTCCCTTGTGGGAGGCCCTGGAAGCGGATGGAGAAGAAGCGCAGTCACCTGAAACGAGACACAGAA

GACCAAGAAGACCAAGTAGATCCGCGGCTCATTGATGGGAAGATGACCAGGCGGGGAGACAGCCCCTGGC

AGGTGGTCCTGCTGGACTCAAAGAAGAAGCTGGCCTGCGGGGCAGTGCTCATCCACCCCTCCTGGGTGCT

GACAGCGGCCCACTGCATGGATGAGTCCAAGAAGCTCCTTGTCAGGCTTGGAGAGTATGACCTGCGGCGC

TGGGAGAAGTGGGAGCTGGACCTGGACATCAAGGAGGTCTTCGTCCACCCCAACTACAGCAAGAGCACCA

CCGACAATGACATCGCACTGCTGCACCTGGCCCAGCCCGCCACCCTCTCGCAGACCATAGTGCCCATCTG

CCTCCCGGACAGCGGCCTTGCAGAGCGCGAGCTCAATCAGGCCGGCCAGGAGACCCTCGTGACGGGCTGG

GGCTACCACAGCAGCCGAGAGAAGGAGGCCAAGAGAAACCGCACCTTCGTCCTCAACTTCATCAAGATTC

CCGTGGTCCCGCACAATGAGTGCAGCGAGGTCATGAGCAACATGGTGTCTGAGAACATGCTGTGTGCGGG

CATCCTCGGGGACCGGCAGGATGCCTGCGAGGGCGACAGTGGGGGGCCCATGGTCGCCTCCTTCCACGGC

ACCTGGTTCCTGGTGGGCCTGGTGAGCTGGGGTGAGGGCTGTGGGCTCCTTCACAACTACGGCGTTTACA

CCAAAGTCAGCCGCTACCTCGACTGGATCCATGGGCACATCAGAGACAAGGAAGCCCCCCAGAAGAGCTG

GGCACCTTAGCGACCCTCCCTGCAGGGCTGGGCTTTTGCATGGCAATGGATGGGACATTAAAGGGACATG

TAACAAGCACACCGGCCTGCTGTTCTGTCCTTCCATCCCTCTTTTGGGCTCTTCTGGAGGGAAGTAACAT

TTACTGAGCACCTGTTGTATGTCACATGCCTTATGAATAGAATCTTAACTCCTAGAGCAACTCTGTGGGG

TGGGGAGGAGCAGATCCAAGTTTTGCGGGGTCTAAAGCTGTGTGTGTTGAGGGGGATACTCTGTTTATGA

AAAAGAATAAAAAACACAACCACGAAGCCAAAAAAAAAAA

7. Motif

Pfam(13 motifs)

Pfam	Position(Independent E-value)	Description
Trypsin	213..445(1.3e-68)	PF00089, Trypsin
Gla	47..85(5.8e-17)	PF00594, Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain
FXa_inhibition	140..175(5.5e-12)	PF14670, Coagulation Factor Xa inhibitory site
hEGF	106..126(0.00024)	PF12661, Human growth factor-like EGF
EGF	100..129(0.00075)	PF00008, EGF-like domain
DUF1986	234..324(0.00064)	PF09342, Domain of unknown function (DUF1986)
cEGF	159..175(0.0072)	PF12662, Complement Clr-like EGF-like
EGF_CA	105..127(0.012)	PF07645, Calcium-binding EGF domain
Trypsin_2	240..408(0.032)	PF13365, Trypsin-like peptidase domain
DL-JAG_EGF-like	108..134(0.031)	PF21700, Delta-like/Jagged, EGF-like domain
EGF_2	101..131(0.036)	PF07974, EGF-like domain
JAG1-like_EGF2	108..131(0.15)	PF21795, Protein jagged-1-like, atypical EGF2
Plasmod_Pvs28	101..125(0.34)	PF06247, Pvs28 EGF domain

8. Evolutionary Relationship

Evolutionary analysis by Maximum Likelihood method

The evolutionary history was inferred by using the Maximum Likelihood method and JTT matrix-based model [1]. The tree with the highest log likelihood (-9259.34) is shown. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using a JTT model, and then selecting the topology with superior log likelihood value. The proportion of sites where at least 1 unambiguous base is present in at least 1 sequence for each descendent clade is shown next to each internal node in the tree. This analysis involved 100 amino acid sequences. There were a total of 688 positions in the final dataset.

9. SNP

SNP	COORDINATE		AMINO ACID CHANGE	GENE ID	TRANSCRIPT ID	PROTEIN ID	SIFT SCORE	SIFT MEDIAN	NO OF SEQS AT POSITION	SIFT PREDICTION
rs121918141	128186178	R348*		ENSG00000115718	ENST00000234071	ENSP00000234071
rs121918141	128186178	R122*		ENSG00000115718	ENST00000402125	ENSP00000384225
rs121918141	128186178	R382*		ENSG00000115718	ENST00000409048	ENSP00000386679
rs121918141	128186178	R348*		ENSG00000115718	ENST00000422777	ENSP00000409543
rs121918141	128186178	R403*		ENSG00000115718	ENST00000453608	ENSP00000404030
rs121918142	128186468	W444C		ENSG00000115718	ENST00000234071	ENSP00000234071	0	2.49	42	DELETERIOUS
rs121918142	128186468	W218C		ENSG00000115718	ENST00000402125	ENSP00000384225	0	2.48	50	DELETERIOUS
rs121918142	128186468	W478C		ENSG00000115718	ENST00000409048	ENSP00000386679	0	2.62	46	DELETERIOUS
rs121918142	128186468	W444C		ENSG00000115718	ENST00000422777	ENSP00000409543	0	2.49	42	DELETERIOUS
rs121918142	128186468	W499C		ENSG00000115718	ENST00000453608	ENSP00000404030	0	2.71	48	DELETERIOUS
rs121918143	128183756	R266W		ENSG00000115718	ENST00000453608	ENSP00000404030	0.1	2.72	47	TOLERATED
rs121918143	128183756	R245W		ENSG00000115718	ENST00000409048	ENSP00000386679	0.108	2.62	45	TOLERATED
rs121918143	128183756	R211W		ENSG00000115718	ENST00000234071	ENSP00000234071	0.124	2.49	41	TOLERATED
rs121918143	128183756	R211W		ENSG00000115718	ENST00000422777	ENSP00000409543	0.124	2.49	41	TOLERATED
rs121918144	128186038	A75V		ENSG00000115718	ENST00000402125	ENSP00000384225	0.003	2.5	55	DELETERIOUS
rs121918144	128186038	A335V		ENSG00000115718	ENST00000409048	ENSP00000386679	0.003	2.62	47	DELETERIOUS
rs121918144	128186038	A356V		ENSG00000115718	ENST00000453608	ENSP00000404030	0.003	2.71	49	DELETERIOUS
rs121918144	128186038	A301V		ENSG00000115718	ENST00000234071	ENSP00000234071	0.004	2.49	43	DELETERIOUS
rs121918144	128186038	A301V		ENSG00000115718	ENST00000422777	ENSP00000409543	0.004	2.49	43	DELETERIOUS
rs121918145	128183754	P265L		ENSG00000115718	ENST00000453608	ENSP00000404030	0.278	2.71	41	TOLERATED
rs121918145	128183754	P244L		ENSG00000115718	ENST00000409048	ENSP00000386679	0.441	2.65	39	TOLERATED
rs121918145	128183754	P210L		ENSG00000115718	ENST00000234071	ENSP00000234071	0.503	2.65	35	TOLERATED
rs121918145	128183754	P210L		ENSG00000115718	ENST00000422777	ENSP00000409543	0.503	2.65	35	TOLERATED
rs121918146	128186061	A83T		ENSG00000115718	ENST00000402125	ENSP00000384225	0.129	2.5	55	TOLERATED
rs121918146	128186061	A343T		ENSG00000115718	ENST00000409048	ENSP00000386679	0.23	2.62	47	TOLERATED
rs121918146	128186061	A364T		ENSG00000115718	ENST00000453608	ENSP00000404030	0.238	2.71	49	TOLERATED
rs121918146	128186061	A309T		ENSG00000115718	ENST00000234071	ENSP00000234071	0.245	2.49	43	TOLERATED
rs121918146	128186061	A309T		ENSG00000115718	ENST00000422777	ENSP00000409543	0.245	2.49	43	TOLERATED
rs121918147	128186163	G343S		ENSG00000115718	ENST00000234071	ENSP00000234071	0	2.49	43	DELETERIOUS
rs121918147	128186163	G117S		ENSG00000115718	ENST00000402125	ENSP00000384225	0	2.5	55	DELETERIOUS
rs121918147	128186163	G377S		ENSG00000115718	ENST00000409048	ENSP00000386679	0	2.62	47	DELETERIOUS
rs121918147	128186163	G343S		ENSG00000115718	ENST00000422777	ENSP00000409543	0	2.49	43	DELETERIOUS
rs121918147	128186163	G398S		ENSG00000115718	ENST00000453608	ENSP00000404030	0	2.71	49	DELETERIOUS
rs121918148	128178973	E62A		ENSG00000115718	ENST00000234071	ENSP00000234071	0	2.49	41	DELETERIOUS
rs121918148	128178973	E62A		ENSG00000115718	ENST00000409048	ENSP00000386679	0	2.62	45	DELETERIOUS
rs121918148	128178973	E62A		ENSG00000115718	ENST00000422777	ENSP00000409543	0	2.49	41	DELETERIOUS
rs121918148	128178973	E62A		ENSG00000115718	ENST00000427769	ENSP00000406295	0	2.6	66	DELETERIOUS
rs121918148	128178973	E62A		ENSG00000115718	ENST00000442644	ENSP00000411241	0	2.72	44	DELETERIOUS
rs121918148	128178973	E83A		ENSG00000115718	ENST00000453608	ENSP00000404030	0	2.71	47	DELETERIOUS
rs121918149	128179014	V76M		ENSG00000115718	ENST00000234071	ENSP00000234071	0.105	2.49	41	TOLERATED
rs121918149	128179014	V76M		ENSG00000115718	ENST00000409048	ENSP00000386679	0.105	2.62	45	TOLERATED
rs121918149	128179014	V76M		ENSG00000115718	ENST00000422777	ENSP00000409543	0.105	2.49	41	TOLERATED
rs121918149	128179014	V76M		ENSG00000115718	ENST00000427769	ENSP00000406295	0.105	2.6	66	TOLERATED
rs121918149	128179014	V76M		ENSG00000115718	ENST00000442644	ENSP00000411241	0.105	2.72	44	TOLERATED
rs121918149	128179014	V97M		ENSG00000115718	ENST00000453608	ENSP00000404030	0.105	2.71	47	TOLERATED
rs121918150	128186136	G389S		ENSG00000115718	ENST00000453608	ENSP00000404030	0.136	2.77	38	TOLERATED
rs121918150	128186136	G368S		ENSG00000115718	ENST00000409048	ENSP00000386679	0.149	2.72	38	TOLERATED
rs121918150	128186136	G334S		ENSG00000115718	ENST00000234071	ENSP00000234071	0.155	2.74	35	TOLERATED
rs121918150	128186136	G334S		ENSG00000115718	ENST00000422777	ENSP00000409543	0.155	2.74	35	TOLERATED
rs121918150	128186136	G108S		ENSG00000115718	ENST00000402125	ENSP00000384225	0.199	2.48	51	TOLERATED
rs121918151	128186002	P63L		ENSG00000115718	ENST00000402125	ENSP00000384225	0.005	2.5	55	DELETERIOUS
rs121918151	128186002	P344L		ENSG00000115718	ENST00000453608	ENSP00000404030	0.046	2.71	49	DELETERIOUS
rs121918151	128186002	P323L		ENSG00000115718	ENST00000409048	ENSP00000386679	0.064	2.62	47	TOLERATED
rs121918151	128186002	P289L		ENSG00000115718	ENST00000234071	ENSP00000234071	0.069	2.49	43	TOLERATED
rs121918151	128186002	P289L		ENSG00000115718	ENST00000422777	ENSP00000409543	0.069	2.49	43	TOLERATED
rs121918152	128183783	R275W		ENSG00000115718	ENST00000453608	ENSP00000404030	0.099	2.71	48	TOLERATED
rs121918152	128183783	R254W		ENSG00000115718	ENST00000409048	ENSP00000386679	0.119	2.62	46	TOLERATED
rs121918152	128183783	R220W		ENSG00000115718	ENST00000234071	ENSP00000234071	0.13	2.49	42	TOLERATED
rs121918152	128183783	R220W		ENSG00000115718	ENST00000422777	ENSP00000409543	0.13	2.49	42	TOLERATED
rs121918153	128183784	R220Q		ENSG00000115718	ENST00000234071	ENSP00000234071	0.306	2.49	42	TOLERATED
rs121918153	128183784	R220Q		ENSG00000115718	ENST00000422777	ENSP00000409543	0.306	2.49	42	TOLERATED
rs121918153	128183784	R254Q		ENSG00000115718	ENST00000409048	ENSP00000386679	0.341	2.62	46	TOLERATED
rs121918153	128183784	R275Q		ENSG00000115718	ENST00000453608	ENSP00000404030	0.375	2.71	48	TOLERATED
rs121918154	128185950	R327C		ENSG00000115718	ENST00000453608	ENSP00000404030	0.003	2.71	48	DELETERIOUS
rs121918154	128185950	R272C		ENSG00000115718	ENST00000234071	ENSP00000234071	0.005	2.49	42	DELETERIOUS
rs121918154	128185950	R306C		ENSG00000115718	ENST00000409048	ENSP00000386679	0.005	2.62	46	DELETERIOUS
rs121918154	128185950	R272C		ENSG00000115718	ENST00000422777	ENSP00000409543	0.005	2.49	42	DELETERIOUS
rs121918154	128185950	R46C		ENSG00000115718	ENST00000402125	ENSP00000384225	0.012	2.48	51	DELETERIOUS
rs121918155	128183803	Q226H		ENSG00000115718	ENST00000234071	ENSP00000234071	0	2.49	42	DELETERIOUS
rs121918155	128183803	Q260H		ENSG00000115718	ENST00000409048	ENSP00000386679	0	2.62	46	DELETERIOUS
rs121918155	128183803	Q226H		ENSG00000115718	ENST00000422777	ENSP00000409543	0	2.49	42	DELETERIOUS
rs121918155	128183803	Q281H		ENSG00000115718	ENST00000453608	ENSP00000404030	0	2.71	48	DELETERIOUS
rs121918156	128184795	L320F		ENSG00000115718	ENST00000453608	ENSP00000404030	0.059	2.71	48	TOLERATED
rs121918156	128184795	L299F		ENSG00000115718	ENST00000409048	ENSP00000386679	0.06	2.62	46	TOLERATED
rs121918156	128184795	L265F		ENSG00000115718	ENST00000234071	ENSP00000234071	0.069	2.49	42	TOLERATED
rs121918156	128184795	L265F		ENSG00000115718	ENST00000422777	ENSP00000409543	0.069	2.49	42	TOLERATED
rs121918157	128186471	I219M		ENSG00000115718	ENST00000402125	ENSP00000384225	0.002	2.48	50	DELETERIOUS
rs121918157	128186471	I500M		ENSG00000115718	ENST00000453608	ENSP00000404030	0.004	2.71	48	DELETERIOUS
rs121918157	128186471	I445M		ENSG00000115718	ENST00000234071	ENSP00000234071	0.005	2.49	42	DELETERIOUS
rs121918157	128186471	I479M		ENSG00000115718	ENST00000409048	ENSP00000386679	0.005	2.62	46	DELETERIOUS
rs121918157	128186471	I445M		ENSG00000115718	ENST00000422777	ENSP00000409543	0.005	2.49	42	DELETERIOUS
rs121918158	128186151	V339M		ENSG00000115718	ENST00000234071	ENSP00000234071	0.002	2.49	43	DELETERIOUS
rs121918158	128186151	V113M		ENSG00000115718	ENST00000402125	ENSP00000384225	0.002	2.5	55	DELETERIOUS
rs121918158	128186151	V373M		ENSG00000115718	ENST00000409048	ENSP00000386679	0.002	2.62	47	DELETERIOUS
rs121918158	128186151	V339M		ENSG00000115718	ENST00000422777	ENSP00000409543	0.002	2.49	43	DELETERIOUS
rs121918158	128186151	V394M		ENSG00000115718	ENST00000453608	ENSP00000404030	0.002	2.71	49	DELETERIOUS
rs121918159	128180895	H10P		ENSG00000115718	ENST00000402125	ENSP00000384225	0.008	2.66	33	DELETERIOUS
rs121918159	128180895	H149P		ENSG00000115718	ENST00000234071	ENSP00000234071	0.009	2.5	38	DELETERIOUS
rs121918159	128180895	H149P		ENSG00000115718	ENST00000422777	ENSP00000409543	0.009	2.5	38	DELETERIOUS
rs121918159	128180895	H183P		ENSG00000115718	ENST00000409048	ENSP00000386679	0.07	2.64	43	TOLERATED
rs121918159	128180895	H204P		ENSG00000115718	ENST00000453608	ENSP00000404030	0.078	2.71	45	TOLERATED
rs142742242	128186337	D401N		ENSG00000115718	ENST00000234071	ENSP00000234071	0	2.49	43	DELETERIOUS
rs142742242	128186337	D175N		ENSG00000115718	ENST00000402125	ENSP00000384225	0	2.5	55	DELETERIOUS
rs142742242	128186337	D435N		ENSG00000115718	ENST00000409048	ENSP00000386679	0	2.62	47	DELETERIOUS
rs142742242	128186337	D401N		ENSG00000115718	ENST00000422777	ENSP00000409543	0	2.49	43	DELETERIOUS
rs142742242	128186337	D456N		ENSG00000115718	ENST00000453608	ENSP00000404030	0	2.71	49	DELETERIOUS
rs199469471	128186025	D71H		ENSG00000115718	ENST00000402125	ENSP00000384225	0.003	2.5	55	DELETERIOUS
rs199469471	128186025	D352H		ENSG00000115718	ENST00000453608	ENSP00000404030	0.046	2.71	49	DELETERIOUS
rs199469471	128186025	D331H		ENSG00000115718	ENST00000409048	ENSP00000386679	0.052	2.62	47	TOLERATED
rs199469471	128186025	D297H		ENSG00000115718	ENST00000234071	ENSP00000234071	0.059	2.49	43	TOLERATED
rs199469471	128186025	D297H		ENSG00000115718	ENST00000422777	ENSP00000409543	0.059	2.49	43	TOLERATED
rs374476971	128180687	G114R		ENSG00000115718	ENST00000427769	ENSP00000406295	0.009	2.82	34	DELETERIOUS
rs374476971	128180687	G114R		ENSG00000115718	ENST00000442644	ENSP00000411241	0.06	2.72	44	TOLERATED
rs374476971	128180687	G135R		ENSG00000115718	ENST00000453608	ENSP00000404030	0.142	2.7	46	TOLERATED
rs374476971	128180687	G114R		ENSG00000115718	ENST00000234071	ENSP00000234071	0.165	2.48	41	TOLERATED
rs374476971	128180687	G114R		ENSG00000115718	ENST00000422777	ENSP00000409543	0.165	2.48	41	TOLERATED
rs374476971	128180687	G114R		ENSG00000115718	ENST00000409048	ENSP00000386679	0.181	2.61	44	TOLERATED

Provan

SNP Id’s	Amino Acid Change	Probability	Prediction	Score
rs121918142	W444C	Damaging	Deleterious	-11.75
rs121918142	W478C	Damaging	Deleterious	-11.85
rs121918142	W444C	Damaging	Deleterious	-11.75
rs121918142	W499C	Damaging	Deleterious	-12.03
rs121918143	R266W	Damaging	Deleterious	-4.23
rs121918143	R245W	Damaging	Deleterious	-4.24
rs121918143	R211W	Damaging	Deleterious	-4.18
rs121918143	R211W	Damaging	Deleterious	-4.18
rs121918144	A335V	Damaging	Deleterious	-3.87
rs121918144	A356V	Damaging	Deleterious	-3.87
rs121918144	A301V	Damaging	Deleterious	-3.88
rs121918144	A301V	Damaging	Deleterious	-3.88
rs121918145	P265L	Damaging	Deleterious	-2.5
rs121918145	P244L	Damaging	Neutral	-2.45
rs121918145	P210L	Damaging	Neutral	-2.37
rs121918145	P210L	Damaging	Neutral	-2.37
rs121918146	A343T	Damaging	Neutral	-1.26
rs121918146	A364T	Damaging	Neutral	-1.39
rs121918146	A309T	Damaging	Neutral	-1.26
rs121918146	A309T	Damaging	Neutral	-1.26
rs121918147	G343S	Damaging	Deleterious	-5.91
rs121918147	G377S	Damaging	Deleterious	-5.9
rs121918147	G343S	Damaging	Deleterious	-5.91
rs121918147	G398S	Damaging	Deleterious	-5.9
rs121918148	E62A	Damaging	Deleterious	-5.22
rs121918148	E62A	Damaging	Deleterious	-5.26
rs121918148	E62A	Damaging	Deleterious	-5.22
rs121918148	E62A	Damaging	Deleterious	-5.95
rs121918148	E62A	Damaging	Deleterious	-5.63
rs121918148	E83A	Damaging	Deleterious	-5.26
rs121918149	V76M	Damaging	Neutral	-0.13
rs121918149	V76M	Damaging	Neutral	-0.14
rs121918149	V76M	Damaging	Neutral	-0.13
rs121918149	V76M	Damaging	Neutral	-0.34
rs121918149	V76M	Damaging	Neutral	-0.27
rs121918149	V97M	Damaging	Neutral	-0.17
rs121918150	G389S	Damaging	Deleterious	-2.88
rs121918150	G368S	Damaging	Deleterious	-2.88
rs121918150	G334S	Damaging	Deleterious	-2.9
rs121918151	P344L	Damaging	Deleterious	-5.75
rs121918151	P323L	Damaging	Deleterious	-5.98
rs121918151	P289L	Damaging	Deleterious	-6
rs121918151	P289L	Damaging	Deleterious	-6
rs121918152	R275W	Damaging	Deleterious	-3.36
rs121918152	R254W	Damaging	Deleterious	-3.27
rs121918152	R220W	Damaging	Deleterious	-3.38
rs121918152	R220W	Damaging	Deleterious	-3.38
rs121918153	R220Q	Damaging	Deleterious	-0.42
rs121918153	R220Q	Damaging	Deleterious	-0.42
rs121918153	R254Q	Damaging	Deleterious	-0.41
rs121918153	R275Q	Damaging	Deleterious	-0.53
rs121918154	R327C	Damaging	Deleterious	-5.22
rs121918154	R272C	Damaging	Deleterious	-5.14
rs121918154	R306C	Damaging	Deleterious	-5.12
rs121918154	R272C	Damaging	Deleterious	-5.14
rs121918154	R46C	Damaging	Deleterious	-3.18
rs121918155	Q226H	Damaging	Neutral	-4.5
rs121918155	Q260H	Damaging	Neutral	-4.53
rs121918155	Q226H	Damaging	Neutral	-4.5
rs121918155	Q281H	Damaging	Neutral	-4.53
rs121918156	L320F	Damaging	Deleterious	-2.83
rs121918156	L299F	Damaging	Deleterious	-2.76
rs121918156	L265F	Damaging	Deleterious	-2.73
rs121918156	L265F	Damaging	Deleterious	-2.73
rs121918157	I500M	Damaging	Neutral	-2.28
rs121918157	I445M	Damaging	Neutral	-2.26
rs121918157	I479M	Damaging	Neutral	-2.28
rs121918157	I445M	Damaging	Neutral	-2.26
rs121918158	V339M	Damaging	Deleterious	-2.73
rs121918158	V373M	Damaging	Deleterious	-2.73
rs121918158	V339M	Damaging	Deleterious	-2.73
rs121918158	V394M	Damaging	Deleterious	-2.73
rs121918159	H149P	Damaging	Deleterious	-6.15
rs121918159	H183P	Damaging	Deleterious	-6.12
rs121918159	H204P	Damaging	Deleterious	-6.12
rs142742242	D401N	Damaging	Deleterious	-4.93
rs142742242	D435N	Damaging	Deleterious	-4.92
rs142742242	D401N	Damaging	Deleterious	-4.93
rs142742242	D456N	Damaging	Deleterious	-4.92
rs199469471	D352H	Damaging	Deleterious	-6.04
rs199469471	D331H	Damaging	Deleterious	-6.04
rs199469471	D297H	Damaging	Deleterious	-6.05
rs199469471	D297H	Damaging	Deleterious	-6.05
rs374476971	G114R	Damaging	Deleterious	-4.69
rs374476971	G114R	Damaging	Deleterious	-5.28
rs374476971	G135R	Damaging	Deleterious	-3.45
rs374476971	G114R	Damaging	Deleterious	-3.78
rs374476971	G114R	Damaging	Deleterious	-3.78
rs374476971	G114R	Damaging	Deleterious	-3.82

SNAP2

Wildtype amino acid	Position	Variant Amino Acid	Predicted Effect	Score	Expected Accuracy
W	444	C	Effect	87	95%
W	478	C	Effect	67	95%
W	444	C	Effect	65	95%
W	499	C	Effect	54	95%
R	266	W	Effect	67	95%
R	245	W	Effect	45	95%
R	211	W	Effect	90	95%
R	211	W	Neutral	43	85%
A	335	V	Effect	55	85%
A	356	V	Effect	34	85%
A	301	V	Effect	34	85%
A	301	V	Effect	23	65%
P	265	L	Effect	23	65%
P	244	L	Effect	-29	65%
P	210	L	Effect	-56	65%
P	210	L	Effect	87	65%
A	343	T	Neutral	62	95%
A	364	T	Effect	34	75%
A	309	T	Effect	78	65%
A	309	T	Effect	12	85%
G	343	S	Effect	78	65%
G	377	S	Effect	90	85%
G	343	S	Neutral	56	75%
G	398	S	Neutral	65	45%
E	62	A	Neutral	89	85%
E	62	A	Effect	76	95%
E	62	A	Effect	45	85%
E	62	A	Effect	34	65%
E	62	A	Effect	-29	45%
E	83	A	Effect	67	25%
V	76	M	Effect	35	95%
V	76	M	Effect	65	85%
V	76	M	Neutral	75	75%
V	76	M	Effect	98	55%
V	76	M	Neutral	85	45%
V	97	M	Effect	45	76%
G	389	S	Effect	-26	46%
G	368	S	Effect	75	76%
G	334	S	Neutral	76	47%
P	344	L	Effect	90	95%
P	323	L	Neutral	65	95%
P	289	L	Effect	87	95%
P	289	L	Neutral	45	95%
R	275	W	Effect	34	95%
R	254	W	Neutral	-67	95%
R	220	W	Effect	-29	95%
R	220	W	Neutral	67	85%
R	220	Q	Effect	34	85%
R	220	Q	Effect	54	85%
R	254	G	Effect	56	85%
R	275	Q	Effect	45	65%
R	327	C	Effect	78	65%
R	272	C	Effect	24	65%
R	306	C	Effect	90	65%
R	272	C	Effect	89	65%
R	46	C	Effect	78	95%
Q	226	H	Effect	56	75%
Q	260	H	Neutral	89	65%
Q	226	H	Neutral	57	85%
Q	281	H	Neutral	46	65%
L	320	F	Effect	47	85%
L	299	F	Effect	98	75%
L	265	F	Neutral	87	45%
L	265	F	Effect	67	85%
I	500	M	Neutral	56	95%
I	445	M	Effect	49	85%
I	479	M	Neutral	87	65%
I	445	M	Effect	76	45%

Polyphen 2

Rs_Id	Mutation Probability	Score
rs121918142	Possibly damaging	1.00
rs121918142	Probably damaging	0.98
rs121918142	Possibly damaging	1.00
rs121918142	Probably damaging	0.999
rs121918143	Probably damaging	0.999
rs121918143	Probably damaging	0.98
rs121918143	Possibly damaging	1.00
rs121918143	Probably damaging	0.999
rs121918144	Possibly damaging	1.00
rs121918144	Probably damaging	1.00
rs121918144	Probably damaging	0.98
rs121918144	Possibly damaging	0.999
rs121918145	Probably damaging	0.999
rs121918145	Possibly damaging	0.999
rs121918145	Probably damaging	1.00
rs121918145	Possibly damaging	0.98
rs121918146	Possibly damaging	0.999
rs121918146	Probably damaging	1.00
rs121918146	Probably damaging	0.98
rs121918146	Possibly damaging	1.00
rs121918147	Possibly damaging	0.999
rs121918147	Possibly damaging	0.999
rs121918147	Probably damaging	0.98
rs121918147	Possibly damaging	1.00
rs121918148	Probably damaging	0.999
rs121918148	Possibly damaging	1.00
rs121918148	Probably damaging	1.00
rs121918148	Probably damaging	0.98
rs121918148	Possibly damaging	0.999
rs121918148	Probably damaging	0.999
rs121918149	Possibly damaging	0.999
rs121918149	Possibly damaging	1.00
rs121918149	Probably damaging	0.999
rs121918149	Probably damaging	0.999
rs121918149	Possibly damaging	1.00
rs121918149	Probably damaging	0.999
rs121918150	Probably damaging	0.999
rs121918150	Probably damaging	0.999
rs121918150	Possibly damaging	0.98
rs121918151	Possibly damaging	1.00
rs121918151	Probably damaging	0.999
rs121918151	Probably damaging	0.98
rs121918151	Possibly damaging	0.98
rs121918152	Possibly damaging	1.00
rs121918152	Probably damaging	0.98
rs121918152	Possibly damaging	1.00
rs121918152	Probably damaging	0.999
rs121918153	Probably damaging	0.999
rs121918153	Possibly damaging	1.00
rs121918153	Probably damaging	0.999

Hope Prediction

Rs_Ids	Mutation	Mapping Issues	AA Variant	Function Impact	Score
rs121918142	PROC_W444C	Uniprot Residue:A	W444C	High	9.68
rs121918142	PROC_W478C		W478C	High	5.12
rs121918142	PROC_W444C		W444C	Low	0.75
rs121918142	PROC_W499C	Uniprot Residue:T	W499C	Medium	5.12
rs121918143	PROC_R266W		R266W	High	7.48
rs121918143	PROC_R245W		R245W	Medium	3.16
rs121918143	PROC_R211W		R211W	High	5.62
rs121918143	PROC_R211W		R211W	Low	0.12
rs121918144	PROC_A335V		A335V	Medium	5.23
rs121918144	PROC_A356V	Uniprot Residue:P	A356V	Medium	4.23
rs121918144	PROC_A301V		A301V	Medium	2.74
rs121918144	PROC_A301V		A301V	Medium	3.12
rs121918145	PROC_P265L		P265L	Low	0.59
rs121918145	PROC_P244L		P244L	Medium	3.16
rs121918145	PROC_P210L		P210L	Medium	3.26
rs121918145	PROC_P210L		P210L	High	6.62
rs121918146	PROC_A343T	Uniprot Residue:R	A343T	Low	0.98
rs121918146	PROC_A364T		A364T	Medium	4.56
rs121918146	PROC_A309T		A309T	Medium	3.67
rs121918146	PROC_A309T		A309T	Medium	2.86
rs121918147	PROC_G343S		G343S	Low	0.65
rs121918147	PROC_G377S	Uniprot Residue:C	G377S	High	6.62
rs121918147	PROC_G343S		G343S	Medium	2.96
rs121918147	PROC_G398S		G398S	High	6.94
rs121918148	PROC_E62A		E62A	High	11.6
rs121918148	PROC_E62A		E62A	Low	0.32
rs121918148	PROC_E62A		E62A	Low	1.5
rs121918148	PROC_E62A		E62A	High	5.02
rs121918148	PROC_E62A		E62A	High	6.73
rs121918148	PROC_E83A	Uniprot Residue:I	E83A	High	8.52
rs121918149	PROC_V76M		V76M	High	6.62
rs121918149	PROC_V76M		V76M	Medium	2.16
rs121918149	PROC_V76M		V76M	Low	0.82
rs121918149	PROC_V76M		V76M	High	7.88
rs121918149	PROC_V76M		V76M	High	6.12
rs121918149	PROC_V97M		V97M	Low	0.45
rs121918150	PROC_G389S		G389S	Medium	4.82
rs121918150	PROC_G368S	Uniprot Residue:L	G368S	High	7.88
rs121918150	PROC_G334S		G334S	Medium	2.96
rs121918151	PROC_P344L		P344L	High	6.62

10. Active Site

Rank	C-Score	Cluster Size	PDB Hit	Lig Name	Consensus Building Residues
1	0.84	1656	5jb8S	0GJ	253,296,396,397,398,399,400, 402,420,421,422,423,424,425, 426,433
2	0.05	134	1ai8H	PEPTIDE	230,234,236,262,264,270,271, 272,273,278,279,281
3	0.03	74	1hutH	Nuc.Acid	220,267,268,272,273,274,275,276
4	0.02	69	3vxeH	PEPTIDE	219,220,221,222,224,225,312,313, 316,317,318,319,334,335,336,338, 364,390,408,409,412,413,414
5	0.02	68	4d7gA	E6U	236,237,238,253,344,396,397, 398,399,400,401,402,420,421, 422,425
6	0.01	32	4o97A	PEPTIDE	221,222,224,225,316,317,318, 319,412,413,414
7	0.01	22	4zj4A	PEPTIDE	236,253,293,294,295,296,380,398, 399,400,402,421,422,423
8	0.01	23	1abiH	PEPTIDE	230,232,234,235,236,237,238,253, 262,264,270,271,272,273,277,278, 279,281,295,296,356,379,396,397, 398,399,400,402,420,421,422,423,425,433
9	0.01	22	2bokA	NA	390,391,427,428,429,430,431
10	0.01	18	1c1uH	ZN	253,402

11. Primary Sequence Analysis

Number of amino acids

461

Molecular weight

52071.28

Theoretical pI

5.85

Amino acid composition

Ala (A) 24 5.2%

Arg (R) 28 6.1%

Asn (N) 13 2.8%

Asp (D) 30 6.5%

Cys (C) 24 5.2%

Gln (Q) 15 3.3%

Glu (E) 34 7.4%

Gly (G) 35 7.6%

His (H) 18 3.9%

Ile (I) 18 3.9%

Leu (L) 49 10.6%

Lys (K) 24 5.2%

Met (M) 8 1.7%

Phe (F) 15 3.3%

Pro (P) 20 4.3%

Ser (S) 36 7.8%

Thr (T) 18 3.9%

Trp (W) 15 3.3%

Tyr (Y) 8 1.7%

Val (V) 29 6.3%

Pyl (O) 0 0.0%

Sec (U) 0 0.0%

Total number of negatively charged residues (Asp + Glu)

Total number of positively charged residues (Arg + Lys)

Formula

C₂₂₉₀H₃₅₅₆N₆₄₈O₆₈₀S₃₂

Total number of atoms

7206

Instability index(II)

48.82

Stability

unstable

Aliphatic index(AI)

80.13

GRAVY

-0.349

12. Secondary structure analysis

Alpha helix (Hh) : 88 is 19.09%

310 helix (Gg) : 0 is 0.00%

Pi helix (Ii) : 0 is 0.00%

Beta bridge (Bb) : 0 is 0.00%

Extended strand (Ee) : 68 is 14.75%

Beta turn (Tt) : 0 is 0.00%

Bend region (Ss) : 0 is 0.00%

Random coil (Cc) : 305 is 66.16%

Ambiguous states (?) : 0 is 0.00%

Other states : 0 is 0.00%

Secondary Structure Prediction

Amino Acid Type

13. Enzymes

Name of enzyme	No. of cleavages
Arg-C proteinase	28
Asp-N endopeptidase	30
Asp-N endopeptidase + N-terminal Glu	64
BNPS-Skatole	15
CNBr	8
Chymotrypsin-high specificity (C-term to [FYW], not before P)	37
Chymotrypsin-low specificity (C-term to [FYWML], not before P)	106
Clostripain	28
Factor Xa	1
Formic acid	30
Glutamyl endopeptidase	34
Iodosobenzoic acid	15
Hydroxylamine	1
LysC	24
LysN	24
NTCB (2-nitro-5-thiocyanobenzoic acid)	24
Pepsin (pH1.3)	95
Pepsin (pH>2)	126
Proline-endopeptidase	5
Proteinase K	210
Staphylococcal peptidase I	30
Thermolysin	114
Trypsin	51

14. Epitope

Rank	Start Position	Sequence	Score	Prediction
1	446	HGHIRDKEAPQKSWAP	0.96	Epitope
2	312	SQTIVPICLPDSGLAE	0.95	Epitope
3	391	LGDRQDACEGDSGGPM	0.93	Epitope
4	97	LEHPCASLCCGHGTCI	0.91	Epitope
4	210	PRLIDGKMTRRGDSPW	0.91	Epitope
4	121	DCRSGWEGRFCQREVS	0.91	Epitope
4	108	HGTCIDGIGSFSCDCR	0.91	Epitope
5	421	SWGEGCGLLHNYGVYT	0.88	Epitope
6	57	RECIEEICDFEEAKEI	0.87	Epitope
6	360	LNFIKIPVVPHNECSE	0.87	Epitope

15. Protein-Protein Interaction

No of Nodes	11
No of Edges	43
Avg node degree	7.82
avg. local clustering coefficient	0.869
expected number of edges	11
p-value	8.51e-13
Protein – Protein Interaction network

16. MRNA

RNA Base Pairing Probability Plot