In silico analysis of CDC73 gene revealing 11 novel SNPs with possible association to Hyperparathyroidism-Jaw Tumor syndrome

dbSNP rs#*	Sub*	Sift prediction	Sift score	Provean prediction	PROVEAN score	Polyphen2 prediction	Polyphen2 score	Snap2 prediction	Snap2 Score
rs28942098	M1I	afect	0	Deleterious	-2.586	probably damaging	0.999	effect	41
rs1296841626	L5F	afect	0	Deleterious	2.676	probably damaging	1	efect	43
rs770544416	S6G	afect	0	Deleterious	-2.539	possibly damaging	0.567	efect	8
rs1054465259	G28A	afect	0	Deleterious	-3.745	possibly damaging	0.816	efect	47
rs777541949	T38S	afect	0	Deleterious	-2.785	probably damaging	1	efect	49
rs1019931450	Y40C	afect	0	Deleterious	-5.114	probably damaging	1	efect	56
rs200806263	G49C	afect	0	Deleterious	-5.363	probably damaging	1	efect	14
rs1454615241	T56I	afect	0	Deleterious	-4.102	probably damaging	1	efect	48
rs1060500015	L63P	afect	0	Deleterious	-4.277	probably damaging	1	efect	25
rs121434264	L64P	afect	0	Deleterious	-4.435	probably damaging	0.999	efect	60
rs778467088	D90H	afect	0	Deleterious	-5.36	probably damaging	1	efect	17
rs1186176634	S174P	afect	0	Deleterious	-2.64	probably damaging	1	efect	23
rs770439843	R222G	afect	0	Deleterious	-3.272	possibly damaging	0.955	efect	49
rs776394390	D223G	afect	0	Deleterious	-3.71	probably damaging	0.994	efect	25
rs1330160847	I224T	afect	0	Deleterious	-3.072	probably damaging	0.991	efect	25
rs1060500022	W231R	afect	0	Deleterious	-7.888	probably damaging	0.996	efect	64
rs1452051467	R234Q	afect	0	Deleterious	-3.063	probably damaging	1	efect	72
rs973863694	I249T	afect	0	Deleterious	-3.648	probably damaging	0.999	efect	33
rs878855091	R263C	afect	0	Deleterious	-3.402	probably damaging	1	efect	17
rs1244272523	R330W	afect	0	Deleterious	-3.789	probably damaging	0.996	efect	56
rs770734388	P360S	afect	0	Deleterious	-6.86	probably damaging	1	efect	59
rs769288212	P365L	afect	0.04	Deleterious	-8.661	probably damaging	1	efect	75
rs113200235	A367V	afect	0.05	Deleterious	-3.178	probably damaging	0.996	efect	66
rs866465727	V387A	afect	0	Deleterious	-3.326	possibly damaging	0.656	efect	48
rs866793539	G396C	afect	0.02	Deleterious	-7.128	probably damaging	1	efect	25
rs754454928	R441C	afect	0	Deleterious	-7.186	probably damaging	1	efect	58
rs778432682	R441H	afect	0	Deleterious	-4.441	probably damaging	1	efect	64
rs1225502334	R484C	afect	0.05	Deleterious	-3.972	probably damaging	0.994	efect	32
rs1292596060	R504S	afect	0	Deleterious	-5.296	probably damaging	1	efect	74
rs759222387	R504H	afect	0	Deleterious	-4.43	probably damaging	1	efect	73
rs1060500011	R513W	afect	0.04	Deleterious	-3.834	probably damaging	0.977	efect	59

[i] dbSNP rs*: is a locus accession for a variant type assigned by dbSNP, Sub*: substitution

Table 2

Functional analysis of single nucleotide polymorphisms (SNPs) by SNPs&GO, PHD and PMUT servers, showing eleven pathogenic SNPs.

dbSNP rs#*	Sub*	SNPandGO Prediction	RI*	snp and go score	PHD Prediction	RI	PHD probability	PMut prediction	PMut score
rs200806263	G49C	Disease	7	0.829	Disease	8	0.893	Disease	0.54 (80%)
rs1060500015	L63P	Disease	3	0.657	Disease	7	0.861	Disease	0.68 (85%)
rs121434264	L64P	Disease	5	0.729	Disease	8	0.875	Disease	0.75 (87%)
rs778467088	D90H	Disease	4	0.708	Disease	7	0.867	Disease	0.70 (86%)
rs770439843	R222G	Disease	1	0.553	Disease	6	0.782	Disease	0.53 (80%)
rs1060500022	W231R	Disease	1	0.544	Disease	1	0.56	Disease	0.64 (84%)
rs770734388	P360S	Disease	3	0.65	Disease	0	0.503	Disease	0.84 (90%)
rs754454928	R441C	Disease	5	0.743	Disease	5	0.775	Disease	0.61 (83%)
rs778432682	R441H	Disease	3	0.669	Disease	5	0.753	Disease	0.70 (86%)
rs1292596060	R504S	Disease	6	0.823	Disease	7	0.867	Disease	0.86 (91%)
rs759222387	R504H	Disease	6	0.811	Disease	7	0.857	Disease	0.72 (86%)

[i] dbSNP rs*: is a locus accession for a variant type assigned by dbSNP, Sub*: substitution, RI*: Reliability Index

Table 3

stability analysis of 11 single nucleotides polymorphism using I-MUTANT showing decrease in the related protein stability. Variant effect on cancer was analyzed by COSMIC tool, which show the related type of mutations. Finally, the frequency alleles of the SNPs analyzed by dbSNP Short Genetic Variations that shows a frequency ranging from 0.0 to 0.00001.

dbSNP rs#	sub	I-MUTANT prediction	SCORE	RI	COSMIC Mutation type	Frequency alleles
rs200806263	G49C	Decrease	-0.91	5	N/A	0.00000
rs1060500015	L63P	Decrease	-1.61	2	Deletion - Frameshift	N/A*
rs121434264	L64P	Decrease	-1.58	2	N/A	0.0000
rs778467088	D90H	Decrease	-1.19	9	N/A	0.00001
rs770439843	R222G	Decrease	-1.23	6	Substitution - Nonsense	0.00001
rs1060500022	W231R	Decrease	-1.07	8	Substitution - Nonsense	N/A
rs770734388	P360S	Decrease	-1.45	8	N/A	0.00001
rs754454928	R441C	Decrease	-0.91	7	Substitution - Missense	0.00001
rs778432682	R441H	Decrease	-1.31	9	N/A	0.00001
rs1292596060	R504S	Decrease	-1.3	9	N/A	N/A
rs759222387	R504H	Decrease	-1.52	9	N/A	0.00004

[i] dbSNP rs*: is a locus accession for a variant type assigned by dbSNP, Sub*: substitution, RI*: Reliability Index, N/A: not available

Paper workflow, which shows the used methods and soft wares in the paper.

Table 4

CDC73 gene Functions and its appearance in network and genome as predicted by Gene mania. Showing the function, number of genes in network and in the genomes.

Function	FDR	Genes in network	Genes in genome
transcription elongation factor complex	2.52E-09	6	28
regulation of transcription elongation from RNA polymerase II promoter	2.52E-09	5	10
transcription elongation from RNA polymerase II promoter	6.60E-09	7	75
DNA-templated transcription, elongation	5.45E-08	7	108
positive regulation of DNA-templated transcription, elongation	5.45E-08	5	20
mRNA polyadenylation	7.21E-08	5	22
RNA polyadenylation	9.97E-08	5	24
regulation of DNA-templated transcription, elongation	2.01E-07	5	28
histone modification	3.31E-07	8	260
covalent chromatin modification	3.47E-07	8	265
DNA-directed RNA polymerase II, holoenzyme	3.50E-07	6	81
endodermal cell fate commitment	3.50E-07	4	10
RNA polymerase complex	7.92E-07	6	96
DNA-directed RNA polymerase complex	7.92E-07	6	95
nuclear DNA-directed RNA polymerase complex	7.92E-07	6	95
endodermal cell differentiation	8.50E-07	4	13
negative regulation of myeloid cell differentiation	1.03424E-06	5	44
cell fate commitment involved in formation of primary germ layer	2.50852E-06	4	17
histone monoubiquitination	3.86491E-06	4	19
endoderm formation	5.6616E-06	4	21
mRNA processing	1.22928E-05	7	287
endoderm development	1.28119E-05	4	26
histone ubiquitination	2.24022E-05	4	30
mRNA 3’-end processing	2.5645E-05	5	88
regulation of myeloid cell differentiation	4.02517E-05	5	97
protein monoubiquitination	4.41323E-05	4	37
formation of primary germ layer	4.41323E-05	4	37
RNA 3’-end processing	4.41323E-05	5	101
regulation of mRNA processing	0.000289177	4	59
positive regulation of mRNA 3’-end processing	0.000313172	3	15
regulation of mRNA 3’-end processing	0.000372752	3	16
myeloid cell diferentiation	0.000446549	5	165
Gastrulation	0.000451884	4	68
positive regulation of mRNA processing	0.000804394	3	21
histone H3-K4 methylation	0.001915467	3	28
cell fate commitment	0.002956445	4	111
negative regulation of cell differentiation	0.004090933	5	267
stem cell maintenance	0.005276884	3	40
histone lysine methylation	0.006873226	3	44
regulation of histone modification	0.011780086	3	53
histone methylation	0.01357129	3	56
stem cell diferentiation	0.013955822	4	171
cellular response to lipopolysaccharide	0.01758198	3	62
regulation of chromatin organization	0.018029071	3	63
cellular response to molecule of bacterial origin	0.020035617	3	66
embryonic morphogenesis	0.020035617	4	192
RNA polymerase II core binding	0.020433712	2	10
peptidyl-lysine trimethylation	0.022132906	2	11
basal transcription machinery binding	0.022132906	2	11
basal RNA polymerase II transcription machinery binding	0.022132906	2	11
mRNA cleavage	0.022132906	2	11
transcriptionally active chromatin	0.022132906	2	11
regulation of histone H3-K4 methylation	0.022132906	2	11
protein alkylation	0.022434688	3	73
protein methylation	0.022434688	3	73
cellular response to biotic stimulus	0.022949254	3	74
mRNA cleavage factor complex	0.024254179	2	12
RNA polymerase core enzyme binding	0.024254179	2	12
positive regulation of histone methylation	0.028159975	2	13
response to lipopolysaccharide	0.037153654	3	90
stem cell development	0.037153654	3	90
regulation of chromosome organization	0.037153654	3	90
RNA polymerase binding	0.040493707	2	16
regulation of histone methylation	0.04514658	2	17
response to molecule of bacterial origin	0.049891593	3	101
peptidyl-lysine methylation	0.054973868	2	19
macromolecule methylation	0.080506456	3	120

[i] *FDR: false discovery rate is greater than or equal to the probability that this is a false positive

Table 5

The gene co-expressed, share domain and interaction with CDC73 gene network, as predicted by Gene mania. Showing the type of interaction between different genes and CDC73 gene.

Gene 1	Gene 2	Weight	Network group
AP3S1	HSP90AA1	0.013259681	Co-expression
CTR9	CDC73	0.008208696	Co-expression
CTR9	LEO1	0.003100712	Co-expression
WDR61	LEO1	0.007506342	Co-expression
WDR61	CTR9	0.003934787	Co-expression
KMT2C	BCL9L	0.01605392	Co-expression
CDK9	CPSF4	0.007431932	Co-expression
GTF2F1	PAF1	0.004063675	Co-expression
GTF2F1	KMT2C	0.008976047	Co-expression
AURKB	TKT	0.011608324	Co-expression
NUP98	CTR9	0.014227687	Co-expression
CPSF4	TKT	0.00430011	Co-expression
CPSF4	AURKB	0.006637127	Co-expression
CHUK	CSTF3	0.016616315	Co-expression
CSTF2	AURKB	0.004579851	Co-expression
CHUK	CDC73	0.001583963	Co-expression
CHUK	NUP98	0.004846978	Co-expression
GTF2F1	TKT	0.009125041	Co-expression
CPSF4	CSTF3	0.014529244	Co-expression
CHUK	NUP98	0.008912819	Co-expression
NUP98	CDC73	0.00588025	Co-expression
CHUK	CDC73	0.001885684	Co-expression
CSTF2	LEO1	0.006971632	Co-expression
CSTF3	CTR9	0.006781118	Co-expression
CHUK	CDC73	0.011535326	Co-expression
CHUK	CTR9	0.00340099	Co-expression
AP3S1	CTR9	0.004597292	Co-expression
GTF2F1	PAF1	0.010657921	Co-expression
GTF2F1	CPSF4	0.011196721	Co-expression
CSTF2	CTR9	0.011377413	Co-expression
CDK9	CPSF4	0.009146069	Co-expression
AURKB	CSTF3	0.006553773	Co-expression
SPCS3	CHUK	0.00718225	Co-expression
AURKB	NUP98	0.004425747	Pathway
CPSF4	CSTF3	0.11179613	Pathway
CHUK	HSP90AA1	0.006348364	Pathway
CSTF2	CSTF3	0.009734826	Pathway
CSTF2	CPSF4	0.11179613	Pathway
GTF2F1	CSTF3	0.005905584	Pathway
GTF2F1	CSTF2	0.005905584	Pathway
GTF2F1	CDK9	0.011108032	Pathway
CSTF2	CSTF3	0.011789562	Pathway
GTF2F1	CSTF3	0.008021638	Pathway
GTF2F1	CSTF2	0.007878398	Pathway
GTF2F1	CDK9	0.014240757	Pathway
CHUK	HSP90AA1	0.088913664	Pathway
LEO1	CDC73	0.122442566	Physical Interactions
PAF1	CDC73	0.21769759	Physical Interactions
PAF1	LEO1	0.15407903	Physical Interactions
CTR9	CDC73	0.21769759	Physical Interactions
CTR9	LEO1	0.15407903	Physical Interactions
CTR9	PAF1	0.27394587	Physical Interactions
WDR61	CDC73	0.21769759	Physical Interactions
WDR61	LEO1	0.15407903	Physical Interactions
WDR61	PAF1	0.27394587	Physical Interactions
WDR61	CTR9	0.27394587	Physical Interactions
HSP90AA1	CDC73	0.3958806	Physical Interactions
CDK9	HSP90AA1	0.20299108	Physical Interactions
CDK9	CDC73	0.119673245	Physical Interactions
AURKB	CDC73	0.1827706	Physical Interactions
AURKB	HSP90AA1	0.042777777	Physical Interactions
PAF1	CDC73	0.13507365	Physical Interactions
CTR9	CDC73	0.18643428	Physical Interactions
NUP98	CDC73	0.203537	Physical Interactions
NUP98	PAF1	0.31207067	Physical Interactions
CHUK	CDC73	0.1774874	Physical Interactions
CHUK	PAF1	0.2721304	Physical Interactions
CDK9	HSP90AA1	0.040214784	Physical Interactions
LEO1	CDC73	0.20954604	Physical Interactions
PAF1	CDC73	0.16041815	Physical Interactions
PAF1	LEO1	0.08672058	Physical Interactions
CTR9	CDC73	0.24223034	Physical Interactions
CTR9	LEO1	0.1309475	Physical Interactions
CTR9	PAF1	0.10024697	Physical Interactions
CSTF2	CSTF3	0.24596581	Physical Interactions
GTF2F1	CDC73	0.1822143	Physical Interactions
GTF2F1	CDK9	0.077137925	Physical Interactions
LEO1	CDC73	0.3225924	Physical Interactions
PAF1	CDC73	0.3225924	Physical Interactions
CTR9	CDC73	0.3225924	Physical Interactions
WDR61	CDC73	0.17647609	Physical Interactions
CSTF3	CDC73	0.3225924	Physical Interactions
FIP1L1	CDC73	0.3225924	Physical Interactions
CPSF4	CDC73	0.17647609	Physical Interactions
CHUK	HSP90AA1	0.02887361	Physical Interactions
KMT2C	CDC73	0.15483053	Physical Interactions
CSTF2	CDC73	0.16203262	Physical Interactions
LEO1	CDC73	0.09317254	Physical Interactions
PAF1	CDC73	0.08377836	Physical Interactions
PAF1	LEO1	0.07275753	Physical Interactions
CTR9	CDC73	0.09010142	Physical Interactions
CTR9	LEO1	0.078248814	Physical Interactions
CTR9	PAF1	0.07035932	Physical Interactions
WDR61	CDC73	0.114276804	Physical Interactions
WDR61	LEO1	0.09924398	Physical Interactions
WDR61	PAF1	0.089237645	Physical Interactions
WDR61	CTR9	0.09597274	Physical Interactions
AP3S1	CDC73	0.2352175	Physical Interactions
CSTF2	CSTF3	0.077111326	Physical Interactions
LEO1	CDC73	0.049589828	Physical Interactions
PAF1	CDC73	0.10079521	Physical Interactions
PAF1	LEO1	0.11382505	Physical Interactions
CTR9	CDC73	0.01533186	Physical Interactions
CTR9	LEO1	0.017313818	Physical Interactions
CTR9	PAF1	0.035191692	Physical Interactions
WDR61	CDC73	0.041940387	Physical Interactions
WDR61	LEO1	0.047362044	Physical Interactions
WDR61	PAF1	0.09626707	Physical Interactions
WDR61	CTR9	0.014643089	Physical Interactions
FIP1L1	CSTF3	0.113308094	Physical Interactions
CPSF4	FIP1L1	0.14965165	Physical Interactions
CSTF2	FIP1L1	0.10615889	Physical Interactions
CDK9	CTR9	0.0411037	Physical Interactions
LEO1	CDC73	0.05172406	Physical Interactions
PAF1	CDC73	0.028004196	Physical Interactions
PAF1	LEO1	0.054951686	Physical Interactions
CTR9	CDC73	0.04297603	Physical Interactions
CTR9	LEO1	0.08433042	Physical Interactions
CTR9	PAF1	0.045657773	Physical Interactions
WDR61	CDC73	0.04966663	Physical Interactions
WDR61	LEO1	0.09745915	Physical Interactions
WDR61	PAF1	0.05276587	Physical Interactions
WDR61	CTR9	0.080975994	Physical Interactions
CSTF3	CDC73	0.06669109	Physical Interactions
FIP1L1	CSTF3	0.14174445	Physical Interactions
AURKB	HSP90AA1	0.002030884	Physical Interactions
CPSF4	CDC73	0.09574746	Physical Interactions
CPSF4	FIP1L1	0.20350051	Physical Interactions
CHUK	HSP90AA1	0.001720827	Physical Interactions
BCL9L	CDC73	0.2791709	Physical Interactions
KMT2C	CDC73	0.04642578	Physical Interactions
CSTF2	CDC73	0.0463337	Physical Interactions
CSTF2	CSTF3	0.11722768	Physical Interactions
CDK9	PAF1	0.01438359	Physical Interactions
GTF2F1	CDK9	0.013446528	Physical Interactions
AURKB	HSP90AA1	0.03819712	Physical Interactions
CDK9	HSP90AA1	0.03819712	Physical Interactions
LEO1	CDC73	0.5193767	Physical Interactions
PAF1	CDC73	0.5193767	Physical Interactions
CTR9	CDC73	0.37205398	Physical Interactions
WDR61	CDC73	0.5193767	Physical Interactions
AURKB	HSP90AA1	0.080966905	Physical Interactions
CDK9	HSP90AA1	0.036444858	Physical Interactions
LEO1	CDC73	0.0771831	Physical Interactions
PAF1	CDC73	0.031383026	Physical Interactions
PAF1	LEO1	0.14005615	Physical Interactions
CTR9	CDC73	0.058806863	Physical Interactions
CTR9	PAF1	0.10671071	Physical Interactions
WDR61	CTR9	0.34459004	Physical Interactions
CPSF4	FIP1L1	0.44817418	Physical Interactions
CHUK	HSP90AA1	0.0081622	Physical Interactions
HSF2BP	CDC73	0.31519976	Physical Interactions
CDK9	HSP90AA1	0.010792454	Physical Interactions
HSF2BP	CDC73	0.58701295	Physical Interactions
CPSF4	FIP1L1	0.6677753	Physical Interactions
CHUK	HSP90AA1	0.007963367	Physical Interactions
CSTF2	CSTF3	0.2417784	Physical Interactions
CTR9	LEO1	0.09094542	Predicted
CTR9	LEO1	0.0869592	Predicted
LEO1	CDC73	1	Predicted
CPSF4	FIP1L1	1	Predicted
CSTF3	LEO1	0.020077549	Predicted
FIP1L1	CSTF3	0.015798066	Predicted
NUP98	CTR9	0.047920566	Predicted
SPCS3	CDC73	0.25866398	Predicted
CTR9	LEO1	0.34126943	Predicted
TKT	CDC73	1	Predicted
TKT	CDC73	1	Predicted
CHUK	AURKB	0.006874138	Shared protein domains
CDK9	AURKB	0.003942981	Shared protein domains
CDK9	CHUK	0.006889931	Shared protein domains
CHUK	AURKB	0.003882364	Shared protein domains
CDK9	AURKB	0.002896895	Shared protein domains
CDK9	CHUK	0.004389529	Shared protein domains

SNPs ID: rs200806263: G49C: The amino acid Glycine (green color) changed to Cysteine (red color) at position 49. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs1060500015: L63P: The amino acids Leucine (green color) changed to Proline (red color) at position 63. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs121434264: L64P: The amino acid Leucine (green color) changed to Proline (red color) at position 64. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs778467088: D90H: The amino acid Aspartic acid (green color) changed to Histidine (red color) at position 90. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs770439843: R222G: The amino acid Arginine (green color) changed to Glycine (red color) at position 222. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs1060500022: W231R: The amino acid Tryptophan (green color) changed to Arginine (red color) at position 231. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs770734388:P360S: The amino acid Proline (green color) changed to Serine (red color) at position 360. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs754454928: R441C: The amino acid Arginine (green color) changed to Cysteine ( red color) at position 441. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs778432682: R441H: The amino acid Arginine (green color) changed to Histidine (red color) at position 441. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs1292596060: R504S: The amino acid Arginine (green color) changed to Serine (red color) at position 504. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

SNPs ID: rs759222387: R504H: The amino acid Arginine (green color) changed to Histidine (red color) at position 504. Illustration was done by UCSF Chimera (v 1.10.2.) and project HOPE.

Interaction between *CDC73* gene and related genes using Gene MANIA software showing the different types of interactions between these genes. With physical interactions being the most significant type (76.64%).

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DOI: https://doi.org/10.2478/ebtj-2020-0008 | Journal eISSN: 2564-615X

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Language: English

Page range: 67 - 81

Published on: Apr 30, 2020

Published by: European Biotechnology Thematic Network Association

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

SNPs,

PHPT,

HPT-JT,

Related subjects:

© 2020 Abdelrahman H. Abdelmoneim, Alaa I. Mohammed, Esraa O. Gadim, Mayada Alhibir Mohammed, Sara H. Hamza, Sara A. Mirghani, Thwayba A. Mahmoud, Mohamed A. Hassan, published by European Biotechnology Thematic Network Association
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Volume 4 (2020): Issue 2 (April 2020)

In silico analysis of CDC73 gene revealing 11 novel SNPs with possible association to Hyperparathyroidism-Jaw Tumor syndrome

Figures & Tables

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Table 5

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