IGDRPT (Indian Genetic Disease Risk Prediction Tool)

Disease Name: Incontinetia pigmenti

1 .Inheritance

X-linked Dominants

2. Gene Name

NEMO

3. Protein Name

Serine/threonine-protein kinase NLK

4. Chromosomal Location

17q11.2

5. Protein Sequence

>sp|Q9UBE8|NLK_HUMAN Serine/threonine-protein kinase NLK OS=Homo sapiens OX=9606 GN=NLK PE=1 SV=2

MSLCGARANAKMMAAYNGGTSAAAAGHHHHHHHHLPHLPPPHLHHHHHPQHHLHPGSAAA

VHPVQQHTSSAAAAAAAAAAAAAMLNPGQQQPYFPSPAPGQAPGPAAAAPAQVQAAAAAT

VKAHHHQHSHHPQQQLDIEPDRPIGYGAFGVVWSVTDPRDGKRVALKKMPNVFQNLVSCK

RVFRELKMLCFFKHDNVLSALDILQPPHIDYFEEIYVVTELMQSDLHKIIVSPQPLSSDH

VKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEELDESRHMTQE

VVTQYYRAPEILMGSRHYSNAIDIWSVGCIFAELLGRRILFQAQSPIQQLDLITDLLGTP

SLEAMRTACEGAKAHILRGPHKQPSLPVLYTLSSQATHEAVHLLCRMLVFDPSKRISAKD

ALAHPYLDEGRLRYHTCMCKCCFSTSTGRVYTSDFEPVTNPKFDDTFEKNLSSVRQVKEI

IHQFILEQQKGNRVPLCINPQSAAFKSFISSTVAQPSEMPPSPLVWE

6. Gene Sequence

>NC_000017.11:28042677-28206074 Homo sapiens chromosome 17, GRCh38.p14 Primary Assembly

CTTTTGGCAACCCACACCCTTCCACACACGCTCACCCCAAAATTAAACACCAAGATCCTCTAACTTGTTT

GGATTGACTGATGAAGACATAAAGCTCTATGTTTTTTGAGGTGGAGTGAGTGGTTTTTCTTCATTTTTAA

ATGGCCAAATGACAGCTTGACCCAGTTTGCTTTCCAATCAAAGGGCATTTATTTTGAATGTCTCTTTGTG

GCGCAAGAGCCAACGCAAAAATGATGGCGGCTTACAATGGCGGTACATCTGCAGCAGCAGCAGGTCACCA

CCACCACCATCACCACCACCTTCCACACCTCCCTCCTCCTCACCTGCACCACCACCACCACCCTCAACAC

CATCTTCATCCGGGGTCGGCTGCCGCTGTACACCCTGTACAGCAGCACACCTCTTCGGCAGCTGCGGCAG

CCGCAGCAGCGGCTGCAGCTGCAGCCATGTTAAACCCTGGGCAACAACAGCCATATTTCCCATCACCGGC

ACCGGGGCAGGCTCCTGGACCAGCTGCAGCAGCCCCAGCTCAGGTACAGGCTGCCGCAGCTGCTACAGTT

AAGGCGCACCATCATCAGCACTCGCATCATCCACAGCAGCAGCTGGATATTGAGCCGGATAGACCTATTG

GATATGGAGCCTTTGGTGTTGTCTGGTGAGTATCCAAAGAAAAACACAACCTCTCATGGTTTCTTCTGTT

GGTTGTCATTGGATGAGTCCATCTCTAATGGTTGTCTCCATGTTGACCAAGGTGCAGCAAGCTTCTCAAC

CCAACTGTAGGAAGCCACCCTCACTTATGTGGTAAAGAGGCCTAATGCATTGGCTGTCTAGGCTCATGGC

AAGTTTTGGTGGAGCGCCTTCTCATGAGCAACACACATAAGTGTGCTGTCTACCAAACTTTTCTATTAGA

ACCTAAGCAAGCCACTGAACACAGGATCAGTAGATGAATGTATGCAATACTAATTCCTACGAAGACCTTG

GTCATCTCGTGTGTTTGATTCAGTGGCCCTGTGGCATTAAGTGTTAGCACCTGATCCAGACTGAATTCCT

TTATAATACTCTTGTCATTAGGATATACTTTGCATAACTACTTTCCTGTCCTTTCTGTCTTTTCACTTAT

TTTGTGATCTTGATCTCCAGAAGAAAGATAGGATTCATAGTTGAACCAGTTAAGATCATTGCTTGAGTGG

TTTATTTTAAACCATAAAGCTACAGTTGAGAAGTATGTAGCTGTAGCCTTTTGATAAGAATGCATTAAAT

ATAGCATCACACATGAGTACCACAAATGAGGTTAGTAGACTAGCTATGCAGTGGCCCACATTCAGTGTAA

TGTTTTAGTGTCATTTAGTGCCTCTTAAGTTGCTGTTATCTGTTGGTCAGTTGCTGTAGTAGGAAATAAT

ACTTTTTTAACAAATGACCCTACCTTTGCTAGTGCTAGGATATTTGTAAAAGCCTAAGGGCTTCTTAAAT

ATAACATTTTGGTCTATTTGGTCTAACCTTAGAAAGATTAGTAGTTTATAATAAAATATGTTTGTTCCTA

7. Motif

Pfam (7 motifs)

Pfam	Position(Independent E-value)	Description
Pkinase	141..427(4.6e-62)	PF00069, Protein kinase domain
PK_Tyr_Ser-Thr	141..335(5.1e-30)	PF07714, Protein tyrosine and serine/threonine kinase
Haspin_kinase	137..319(0.00029)	PF12330, Haspin like kinase domain
ABC1	229..297(0.0007)	PF03109, ABC1 atypical kinase-like domain
Pkinase_fungal	245..318(0.001)	PF17667, Fungal protein kinase
FTA2	245..286(0.049)	PF13095, Kinetochore Sim4 complex subunit FTA2
Kinase-like	197..312(0.06)	PF14531, Kinase-like

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 (-3732.46) 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 683 positions in the final dataset.

9. SNP

SNP	COORDINATE	AMINO ACID CHANGE	GENE ID	TRANSCRIPT ID	PROTEIN ID	SIFT SCORE	SIFT MEDIAN	SIFT PREDICTION
rs28934904	153296882	R133C	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934904	153296882	R145C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.004	2.69	DELETERIOUS
rs28934904	153296882	R133C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.022	2.67	DELETERIOUS
rs28934904	153296882	R133G	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934904	153296882	R145G	ENSG00000169057	ENST00000453960	ENSP00000395535	0.026	2.69	DELETERIOUS
rs28934904	153296882	R133G	ENSG00000169057	ENST00000303391	ENSP00000301948	0.085	2.67	TOLERATED
rs28934905	153296815	F167C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.005	2.81	DELETERIOUS
rs28934905	153296815	F155C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.015	2.66	DELETERIOUS
rs28934905	153296815	F167S	ENSG00000169057	ENST00000453960	ENSP00000395535	0.109	2.81	TOLERATED
rs28934905	153296815	F155S	ENSG00000169057	ENST00000303391	ENSP00000301948	0.119	2.66	TOLERATED
rs28934907	153297719	R106W	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934907	153297719	R106W	ENSG00000169057	ENST00000303391	ENSP00000301948	0.001	2.84	DELETERIOUS
rs28934907	153297719	R118W	ENSG00000169057	ENST00000453960	ENSP00000395535	0.008	2.82	DELETERIOUS
rs28934907	153297719	R106G	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934907	153297719	R106G	ENSG00000169057	ENST00000303391	ENSP00000301948	0.007	2.84	DELETERIOUS
rs28934907	153297719	R118G	ENSG00000169057	ENST00000453960	ENSP00000395535	0.158	2.82	TOLERATED
rs28934908	153296860	A140V	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934908	153296860	A152V	ENSG00000169057	ENST00000453960	ENSP00000395535	0.021	2.67	DELETERIOUS
rs28934908	153296860	A140V	ENSG00000169057	ENST00000303391	ENSP00000301948	0.042	2.61	DELETERIOUS
rs28935168	153297737	L100V	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28935168	153297737	L100V	ENSG00000169057	ENST00000303391	ENSP00000301948	0.197	2.67	TOLERATED
rs28935168	153297737	L112V	ENSG00000169057	ENST00000453960	ENSP00000395535	0.295	2.69	TOLERATED
rs28935468	153296363	R318C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.021	2.59	DELETERIOUS
rs28935468	153296363	R306C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.03	2.6	DELETERIOUS
rs56268439	153296090	E397*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs56268439	153296090	E409*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs56268439	153296090	E397K	ENSG00000169057	ENST00000303391	ENSP00000301948	0.992	2.49	TOLERATED
rs56268439	153296090	E409K	ENSG00000169057	ENST00000453960	ENSP00000395535	1	2.46	TOLERATED
rs61748389	153296881	R133L	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748389	153296881	R145L	ENSG00000169057	ENST00000453960	ENSP00000395535	0.178	2.69	TOLERATED
rs61748389	153296881	R133L	ENSG00000169057	ENST00000303391	ENSP00000301948	0.871	2.67	TOLERATED
rs61748389	153296881	R133H	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748389	153296881	R145H	ENSG00000169057	ENST00000453960	ENSP00000395535	0.032	2.69	DELETERIOUS
rs61748389	153296881	R133H	ENSG00000169057	ENST00000303391	ENSP00000301948	0.063	2.67	TOLERATED
rs61748390	153296878	S134F	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748390	153296878	S146F	ENSG00000169057	ENST00000453960	ENSP00000395535	0.003	2.69	DELETERIOUS
rs61748390	153296878	S134F	ENSG00000169057	ENST00000303391	ENSP00000301948	0.007	2.67	DELETERIOUS
rs61748390	153296878	S134C	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748390	153296878	S146C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.004	2.69	DELETERIOUS
rs61748390	153296878	S134C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.009	2.67	DELETERIOUS
rs61748391	153296876	K135E	ENSG00000169057	ENST00000407218	ENSP00000384865	0.008	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748391	153296876	K135E	ENSG00000169057	ENST00000303391	ENSP00000301948	0.568	2.67	TOLERATED
rs61748391	153296876	K147E	ENSG00000169057	ENST00000453960	ENSP00000395535	0.612	2.69	TOLERATED
rs61748392	153296869	E137G	ENSG00000169057	ENST00000407218	ENSP00000384865	0.004	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748392	153296869	E149G	ENSG00000169057	ENST00000453960	ENSP00000395535	0.01	2.79	DELETERIOUS
rs61748392	153296869	E137G	ENSG00000169057	ENST00000303391	ENSP00000301948	0.049	2.67	DELETERIOUS
rs61748395	153296857	Y141C	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748395	153296857	Y153C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.004	2.67	DELETERIOUS
rs61748395	153296857	Y141C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.007	2.68	DELETERIOUS
rs61748396	153296856	Y141*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748396	153296856	Y141*	ENSG00000169057	ENST00000407218	ENSP00000384865
rs61748396	153296856	Y153*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748396	153296856	Y141*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748396	153296856	Y141*	ENSG00000169057	ENST00000407218	ENSP00000384865
rs61748396	153296856	Y153*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748399	153296849	K144*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748399	153296849	K144*	ENSG00000169057	ENST00000407218	ENSP00000384865
rs61748399	153296849	K156*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748407	153296812	D168G	ENSG00000169057	ENST00000453960	ENSP00000395535	0.021	2.81	DELETERIOUS
rs61748407	153296812	D156G	ENSG00000169057	ENST00000303391	ENSP00000301948	0.03	2.66	DELETERIOUS
rs61748407	153296812	D168A	ENSG00000169057	ENST00000453960	ENSP00000395535	0.006	2.81	DELETERIOUS
rs61748407	153296812	D156A	ENSG00000169057	ENST00000303391	ENSP00000301948	0.107	2.66	TOLERATED
rs61748408	153296811	D156D	ENSG00000169057	ENST00000303391	ENSP00000301948	1	2.66	TOLERATED
rs61748408	153296811	D168D	ENSG00000169057	ENST00000453960	ENSP00000395535	1	2.81	TOLERATED
rs61748408	153296811	D168E	ENSG00000169057	ENST00000453960	ENSP00000395535	0.01	2.81	DELETERIOUS
rs61748408	153296811	D156E	ENSG00000169057	ENST00000303391	ENSP00000301948	0.157	2.66	TOLERATED
rs61748410	153296810	F169I	ENSG00000169057	ENST00000453960	ENSP00000395535	0.106	2.81	TOLERATED
rs61748410	153296810	F157I	ENSG00000169057	ENST00000303391	ENSP00000301948	0.289	2.66	TOLERATED
rs61748411	153296807	T170A	ENSG00000169057	ENST00000453960	ENSP00000395535	0.044	2.73	DELETERIOUS
rs61748411	153296807	T158A	ENSG00000169057	ENST00000303391	ENSP00000301948	0.05	2.66	TOLERATED
rs61748421	153296777	R168*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748421	153296777	R180*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748425	153296771	Q170*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748425	153296771	Q182*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748428	153296756	K175*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748428	153296756	K187*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749702	153296750	K177*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749702	153296750	K189*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749715	153296605	P237L	ENSG00000169057	ENST00000453960	ENSP00000395535	0.006	2.46	DELETERIOUS
rs61749715	153296605	P225L	ENSG00000169057	ENST00000303391	ENSP00000301948	0.007	2.5	DELETERIOUS
rs61749715	153296605		ENSG00000169057	ENST00000407218	ENSP00000384865
rs61749715	153296605	P237R	ENSG00000169057	ENST00000453960	ENSP00000395535	0.007	2.46	DELETERIOUS
rs61749715	153296605	P225R	ENSG00000169057	ENST00000303391	ENSP00000301948	0.115	2.5	TOLERATED
rs61749715	153296605		ENSG00000169057	ENST00000407218	ENSP00000384865
rs61749717	153296687	R198*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749717	153296687	R210*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749717	153296687	R161R	ENSG00000169057	ENST00000407218	ENSP00000384865	1	3.66	TOLERATED
rs61749718	153296681	K200*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749718	153296681	K212*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749718	153296681	P163P	ENSG00000169057	ENST00000407218	ENSP00000384865	1	3.66	TOLERATED
rs61749721	153296516	R255*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749721	153296516	R267*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749721	153296516		ENSG00000169057	ENST00000407218	ENSP00000384865
rs61749724	153296668	S204*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749724	153296668	S216*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749724	153296668	Q168E	ENSG00000169057	ENST00000407218	ENSP00000384865	0.289	4.32	TOLERATED

Evolutionary analysis of coding SNPs

SNP Id’s	Amino Acid Change	Probability of deleterious effect	Prediction score
rs28934904	R133C	probably damaging	0.81
rs28934904	R145C	probably damaging	0.85
rs28934904	R133C	probably damaging	0.65
rs28934904	R133G	probably damaging	0.84
rs28934904	R145G	probably damaging	0.95
rs28934904	R133G	probably damaging	0.98
rs28934905	F167C	probably damaging	0.68
rs28934905	F155C	probably damaging	0.88
rs28934905	F167S	probably damaging	0.57
rs28934905	F155S	probably damaging	0.75
rs28934907	R106W	probably damaging	0.85
rs28934907	R106W	probably damaging	0.85
rs28934907	R118W	probably damaging	0.75
rs28934907	R106G	probably benign	0.87
rs28934907	R106G	probably benign	0.97
rs28934907	R118G	probably benign	0.67
rs28934908	A140V	probably benign	0.57
rs28934908	A152V	probably damaging	0.84
rs28934908	A140V	probably damaging	0.85
rs28935168	L100V	probably damaging	0.69
rs28935168	L100V	probably benign	0.53
rs28935168	L112V	probably benign	0.93
rs28935468	R318C	probably damaging	0.95
rs28935468	R306C	probably benign	0.87
rs56268439	E397K	probably damaging	0.89
rs56268439	E409K	probably damaging	0.89
rs61748389	R133L	probably damaging	0.89
rs61748389	R145L	probably damaging	0.89
rs61748389	R133L	probably damaging	0.86
rs61748389	R133H	probably damaging	0.86
rs61748389	R145H	probably damaging	0.65
rs61748389	R133H	probably damaging	0.55
rs61748390	S134F	probably damaging	0.99
rs61748390	S146F	probably damaging	0.49
rs61748390	S134F	probably damaging	0.95
rs61748390	S134C	probably damaging	0.95
rs61748390	S146C	probably damaging	0.89
rs61748390	S134C	probably damaging	0.89
rs61748391	K135E	probably damaging	0.89
rs61748391	K135E	probability of deleterious effect	Pdel
rs61748391	K147E	probably damaging	0.89
rs61748392	E137G	probably damaging	0.95
rs61748392	E149G	probably damaging	0.65
rs61748392	E137G	probably damaging	0.64
rs61748395	Y141C	probably damaging	0.95
rs61748395	Y153C	probably damaging	0.78
rs61748395	Y141C	probably damaging	0.98
rs61748407	D168G	probably damaging	0.78
rs61748407	D156G	probably damaging	0.57
rs61748407	D168A	probably damaging	0.95
rs61748407	D156A	probably damaging	0.95
rs61748408	D156D	probably damaging	0.95
rs61748408	D168D	probably damaging	0.95
rs61748408	D168E	probably benign	0.57
rs61748408	D156E	probably benign	0.78
rs61748410	F169I	probably benign	0.68
rs61748410	F157I	probably benign	0.97
rs61748411	T170A	probably damaging	0.54
rs61748411	T158A	probably damaging	0.89
rs61749715	P237L	probably damaging	0.39
rs61749715	P225L	probably benign	0.63
rs61749715	P237R	probably benign	0.43
rs61749715	P225R	probably damaging	0.95
rs61749717	R161R	probably benign	0.27
rs61749718	P163P	probably damaging	0.89
rs61749724	Q168E	probably damaging	0.89

Provean

SNP Id’s	Amino Acid Change	Probability	Prediction	Score
rs28934904	R133C	Deleterious	Damaging	-8
rs28934904	R145C	Deleterious	Damaging	-7.99
rs28934904	R133C	Deleterious	Damaging	-7.99
rs28934904	R133G	Deleterious	Damaging	-7
rs28934904	R145G	Deleterious	Damaging	-7
rs28934904	R133G	Deleterious	Damaging	-7
rs28934905	F167C	Deleterious	Damaging	-7.41
rs28934905	F155C	Deleterious	Damaging	-7.41
rs28934905	F167S	Deleterious	Damaging	-7.27
rs28934905	F155S	Deleterious	Damaging	-7.27
rs28934907	R106W	Deleterious	Damaging	-7.55
rs28934907	R106W	Deleterious	Damaging	-7.59
rs28934907	R118W	Deleterious	Damaging	-7.59
rs28934907	R106G	Deleterious	Damaging	-6.57
rs28934907	R106G	Deleterious	Damaging	-6.59
rs28934907	R118G	Deleterious	Damaging	-6.59
rs28934908	A140V	Neutral	Tolerated	-2.43
rs28934908	A152V	Neutral	Damaging	-2.03
rs28934908	A140V	Neutral	Damaging	-2.03
rs28935168	L100V	Neutral	Tolerated	-1.2
rs28935168	L100V	Neutral	Damaging	-1.18
rs28935168	L112V	Neutral	Damaging	-1.23
rs28935468	R318C	Neutral	Damaging	-1.64
rs28935468	R306C	Neutral	Damaging	-1.64
rs56268439	E397K	Neutral	Tolerated	0.02
rs56268439	E409K	Neutral	Tolerated	0.02
rs61748389	R133L	Deleterious	Damaging	-7
rs61748389	R145L	Deleterious	Damaging	-7
rs61748389	R133L	Deleterious	Damaging	-7
rs61748389	R133H	Deleterious	Damaging	-5
rs61748389	R145H	Deleterious	Damaging	-5
rs61748389	R133H	Deleterious	Damaging	-5
rs61748390	S134F	Deleterious	Damaging	-6
rs61748390	S146F	Deleterious	Damaging	-6
rs61748390	S134F	Deleterious	Damaging	-6
rs61748390	S134C	Deleterious	Damaging	-5
rs61748390	S146C	Deleterious	Damaging	-5
rs61748390	S134C	Deleterious	Damaging	-5
rs61748391	K135E	Deleterious	Damaging	-3.56
rs61748391	K135E	Deleterious	Damaging	-3.46
rs61748391	K147E	Deleterious	Damaging	-3.46
rs61748392	E137G	Deleterious	Damaging	-4.2
rs61748392	E149G	Deleterious	Damaging	-3.76
rs61748392	E137G	Deleterious	Damaging	-3.76
rs61748395	Y141C	Deleterious	Damaging	-7.62
rs61748395	Y153C	Deleterious	Damaging	-7.86
rs61748395	Y141C	Deleterious	Damaging	-7.86
rs61748407	D168G	Deleterious	Damaging	-6.42
rs61748407	D156G	Deleterious	Damaging	-6.42
rs61748407	D168A	Deleterious	Damaging	-7.29
rs61748407	D156A	Deleterious	Damaging	-7.29
rs61748408	D156D	Neutral	Tolerated	0
rs61748408	D168D	Neutral	Tolerated	0
rs61748408	D168E	Deleterious	Damaging	-3.68
rs61748408	D156E	Deleterious	Damaging	-3.68
rs61748410	F169I	Deleterious	Damaging	-5.58
rs61748410	F157I	Deleterious	Damaging	-5.58
rs61748411	T170A	Deleterious	Damaging	-3.47
rs61748411	T158A	Deleterious	Damaging	-3.47
rs61749715	P237L	Deleterious	Damaging	-3.51
rs61749715	P225L	Deleterious	Damaging	-3.51
rs61749715	P237R	Deleterious	Damaging	-2.51
rs61749715	P225R	Deleterious	Damaging	-2.51
rs61749717	R161R	Neutral	Tolerated	0
rs61749718	P163P	Neutral	Tolerated	0
rs61749724	Q168E	Neutral	Damaging	-0.45

SNAP2

Wildetype Amino Acid	Position	Variant Amino Acid	Predicted Effect	Score	Expected Accurancy
Y	153	G	Effect	78	98%
Y	141	V	Effect	56	78%
D	168	A	Effect	56	98%
D	156	F	Effect	85	76%
D	156	D	Effect	96	98%
D	168	D	Effect	75	78%
D	168	E	Effect	26	98%
D	168	E	Effect	24	76%
D	156	I	Effect	98	98%
D	169	I	Effect	75	78%
D	157	A	Effect	65	98%
F	170	A	Effect	42	76%
F	158	L	Effect	35	98%
T	237	L	Effect	-29	78%
T	225	R	Effect	56	98%
P	237	R	Effect	36	76%
P	225	R	Effect	75	98%
P	161	P	Effect	63	76%
P	163	E	Effect	36	98%
R	16/1	D	Effect	25	78%
Q	168	E	Effect	36	98%
D	168	E	Effect	45	76%
D	168	I	Effect	26	98%
D	156	I	Effect	26	98%
F	169	A	Effect	-52	76%
F	157	A	Effect	96	98%
T	170	L	Effect	79	78%
T	158	L	Neutral	96	98%
P	237	L	Neutral	56	76%
P	225	R	Neutral	25	98%
P	237	R	Effect	36	78%
P	225	R	Effect	24	98%
R	161	P	Effect	75	76%
P	163	P	Neutral	98	98%

Polyphen 2

Rs_Id	Mutation Probability	Score
rs28934904	Probably damaging	0.999
rs28934904	Probably damaging	0.999
rs28934904	Possibly damaging	1.00
rs28934904	Probably damaging	0.999
rs28934904	Probably damaging	0.98
rs28934904	Possibly damaging	0.98
rs28934905	Possibly damaging	1.00
rs28934905	Probably damaging	0.999
rs28934905	Possibly damaging	1.00
rs28934905	Probably damaging	0.98
rs28934907	Possibly damaging	1.00
rs28934907	Probably damaging	0.999
rs28934907	Possibly damaging	0.98
rs28934907	Probably damaging	1.00
rs28934907	Probably damaging	0.999
rs28934907	Probably damaging	0.98
rs28934908	Possibly damaging	1.00
rs28934908	Probably damaging	0.999
rs28934908	Probably damaging	0.999
rs28935168	Probably damaging	0.98
rs28935168	Possibly damaging	1.00
rs28935168	Probably damaging	0.999
rs28935468	Possibly damaging	1.00
rs28935468	Probably damaging	1.00
rs56268439	Probably damaging	0.98
rs56268439	Possibly damaging	1.00
rs61748389	Probably damaging	0.999
rs61748389	Probably damaging	0.999
rs61748389	Possibly damaging	0.98
rs61748389	Probably damaging	1.00
rs61748389	Probably damaging	0.999
rs61748389	Possibly damaging	1.00
rs61748390	Probably damaging	0.999
rs61748390	Possibly damaging	1.00
rs61748390	Probably damaging	1.00
rs61748390	Probably damaging	0.999
rs61748390	Probably damaging	0.999
rs61748390	Probably damaging	0.999

Hope Prediction

Rs_Ids	Mutation	Mapping Issues	AA Variant	Function Impact	Score
rs28934904	NEMO_R133C	Uniprot Residue:L	R133C	High	10.84
rs28934904	NEMO_R145C		R145C	Medium	3.88
rs28934904	NEMO_R133C		R133C	Medium	4.46
rs28934904	NEMO_R133G		R133G	High	5.94
rs28934904	NEMO_R145G	Uniprot Residue:I	R145G	High	10.8
rs28934904	NEMO_R133G		R133G	High	6.52
rs28934905	NEMO_F167C		F167C	Medium	4.66
rs28934905	NEMO_F155C		F155C	Medium	4
rs28934905	NEMO_F167S	Uniprot Residue:M	F167S	Low	0.82
rs28934905	NEMO_F155S		F155S	Medium	5.23
rs28934907	NEMO_R106W		R106W	High	10.8
rs28934907	NEMO_R106W		R106W	Medium	4.88
rs28934907	NEMO_R118W		R118W	Medium	4.56
rs28934907	NEMO_R106G		R106G	High	5.94
rs28934907	NEMO_R106G	Uniprot Residue:C	R106G	High	10.8
rs28934907	NEMO_R118G		R118G	High	6.52
rs28934908	NEMO_A140V		A140V	Medium	4.66
rs28934908	NEMO_A152V		A152V	Low	0.59
rs28934908	NEMO_A140V		A140V	Medium	3.16
rs28935168	NEMO_L100V	Uniprot Residue:V	L100V	Medium	4.26
rs28935168	NEMO_L100V		L100V	High	6.62
rs28935168	NEMO_L112V		L112V	Low	0.98
rs28935468	NEMO_R318C		R318C	Medium	4.56
rs28935468	NEMO_R306C	Uniprot Residue:N	R306C	Medium	3.67
rs56268439	NEMO_E397K		E397K	Medium	2.86
rs56268439	NEMO_E409K		E409K	Low	0.65
rs61748389	NEMO_R133L		R133L	High	6.62
rs61748389	NEMO_R145L		R145L	Medium	2.96
rs61748389	NEMO_R133L		R133L	High	6.94
rs61748389	NEMO_R133H		R133H	High	10.6
rs61748389	NEMO_R145H		R145H	Low	0.32
rs61748389	NEMO_R133H	Uniprot Residue:L	R133H	Low	1.5
rs61748390	NEMO_S134F		S134F	High	5.02
rs61748390	NEMO_S146F		S146F	High	6.73
rs61748390	NEMO_S134F		S134F	High	8.52

10. Active Site

Rank	C-Score	Cluster Size	PDB Hit	Lig Name	Consensus Building Residues
1	0.84	1547	4othA	DRN	144,145,152,165,167,198,219, 220,221,222,224,225,268,269, 271,281,282
2	0.15	216	3vheA	42Q	144,152,165,167,185,188,189, 197,198,219,220,221,222,255, 262,271,280,281,282
3	0.12	185	3krwA	BA1	144,145,146,147,148,149,150, 152,165,167,169,185,198,220, 221,222,268,271,281,282,284
4	0.03	60	2y9qA	PEPTIDE	195,224,229,234,236,239,240, 243,246,247,250,273,274,275, 276,277,450,452,455
5	0.03	57	1golA	MG	269,282
6	0.02	52	3lfcA	Z86	152,165,167,181,184,185,188, 189,192,197,198,217,219,262, 281,282
7	0.01	22	4ux9C	PEPTIDE	222,224,228,234,236,239, 240,243,272,273,274,275, 276,429,431
8	0.01	15	3e87A	PEPTIDE	177,181,225,227,264,266,267, 268,301,302,303,304,305,306, 307,333,339,342
9	0.01	33	3owpA	PEPTIDE	148,149,178,225,227,228,231,266, 267,268,285,301,302,303,304,305, 307,333,337,338,339,342,343,344,349
10	0.01	17	3v6rA	CQQ	144,145,152,165,219,220,222,225, 227,228,266,267,268,271,281,306

11. Primary Sequence Analysis

Number of amino acids

527

Molecular weight

58282.84

Theoretical pI

8.35

Amino acid composition

Ala (A) 59 11.2%

Arg (R) 23 4.4%

Asn (N) 14 2.7%

Asp (D) 21 4.0%

Cys (C) 13 2.5%

Gln (Q) 32 6.1%

Glu (E) 21 4.0%

Gly (G) 25 4.7%

His (H) 41 7.8%

Ile (I) 25 4.7%

Leu (L) 50 9.5%

Lys (K) 23 4.4%

Met (M) 13 2.5%

Phe (F) 19 3.6%

Pro (P) 41 7.8%

Ser (S) 38 7.2%

Thr (T) 19 3.6%

Trp (W) 3 0.6%

Tyr (Y) 14 2.7%

Val (V) 33 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

C₂₅₉₈H₄₀₄₄N₇₅₀O₇₂₉S₂₆

Total number of atoms

8147

Instability index(II)

50.27

Stability

unstable

Aliphatic index(AI)

84.86

GRAVY

-0.218

12. Secondary structure analysis

Alpha helix (Hh) : 188 is 35.67%

310 helix (Gg) : 0 is 0.00%

Pi helix (Ii) : 0 is 0.00%

Beta bridge (Bb) : 0 is 0.00%

Extended strand (Ee) : 52 is 9.87%

Beta turn (Tt) : 0 is 0.00%

Bend region (Ss) : 0 is 0.00%

Random coil (Cc) : 287 is 54.46%

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	23
Asp-N endopeptidase	21
Asp-N endopeptidase + N-terminal Glu	42
BNPS-Skatole	3
CNBr	13
Caspasel	2
Chymotrypsin-high specificity (C-term to [FYW], not before P)	35
Chymotrypsin-low specificity (C-term to [FYWML], not before P)	127
Clostripain	23
Formic acid	21
Glutamylendopeptidase	21
Iodosobenzoic acid	1
Hydroxylamine	3
LysC	23
LysN	23
NTCB (2-nitro-5-thiocyanobenzoic acid)	13
Pepsin (pH1.3)	92
Pepsin (pH>2)	115
Proline-endopeptidase	7
Proteinase K	243
Staphylococcal peptidase I	19
Thermolysin	167
Trypsin	44

14. Epitope

Rank	Start position	Sequence	Score	Prediction
1	369	CEGAKAHILRGPHKQP	0.92	Epitope
2	46	HHHPQHHLHPGSAAAV	0.91	Epitope
3	429	EGRLRYHTCMCKCCFS	0.90	Epitope
4	308	APEILMGSRHYSNAID	0.89	Epitope
5	355	DLLGTPSLEAMRTACE	0.88	Epitope
5	137	DIEPDRPIGYGAFGVV	0.88	Epitope
6	88	GQQQPYFPSPAPGQAP	0.87	Epitope
7	152	VWSVTDPRDGKRVALK	0.85	Epitope
8	164	VALKKMPNVFQNLVSC	0.84	Epitope
9	54	HPGSAAAVHPVQQHTS	0.83	Epitope
9	258	AGILHRDIKPGNLLVN	0.83	Epitope
9	143	PIGYGAFGVVWSVTDP	0.83	Epitope
10	451	YTSDFEPVTNPKFDDT	0.82	Epitope
10	391	TLSSQATHEAVHLLCR	0.82	Epitope
10	288	VEELDESRHMTQEVVT	0.82	Epitope

15. Protein-Protein Interaction

No of Nodes	11
No of Edges	40
Avg node degree	7.27
avg. local clustering coefficient	0.939
expected number of e, dges	11
p-value	2.46e-11
Protein – Protein Interaction network

16. MRNA

RNA Base Pairing Probability Plot