In silico screening and analysis of single-nucleotide polymorphic variants of the ABCC2 gene affecting Dubin–Johnson syndrome

Sharma, Parul; Sharma, Siddharth

doi:10.1016/j.ajg.2022.03.003

Cited by 2 publications

(2 citation statements)

References 45 publications

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“…The assessment of the potentially pathogenic nature of the detected mutation was performed using the online software tools PROVEAN (http://sift.jcvi.org/www/SIFT_enst_submit.html) [32], MutationTaster web application (http://www.mutationtaster.org) [33,34], and Mutpred2 (http://mutpred2.mutdb.org/index.html) [35,36]. For the analysis using these resources, we inputted the amino acid sequences following the algorithms provided by the respective developers.…”

Section: In Silico Analysismentioning

confidence: 99%

In Silico Analysis and In-depth Assessment of a Female Patient with a Missense Mutation in the F12 Gene Associated with Hereditary Angioedema Symptoms: A Case Study

Pechnikova,

Yaremenko,

Saitgalina

et al. 2023

Preprint

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Hereditary angioedema (HAE) is a complex genetic disorder characterized by recurrent episodes of localized skin and mucosal swelling, with potential life-threatening complications, particularly in the upper respiratory tract. While much is understood about the mutations behind HAE I-II types, the genetic landscape of type III remains complex. Our study provides a comprehensive exploration of an undiagnosed case of a 13-year-old female presenting with HAE symptoms. Despite undergoing thorough clinical evaluations including blood, immunochemical, coprological, and allergen tests, no correlations with allergies or HAE I-II types were observed. Leveraging whole-exome sequencing, a unique missense mutation in the F12gene (NC_000005.9: g.176831826 C > G, Ala207Pro) was identified in the patient's genetic profile, which she inherited from both parents. Subsequent comprehensive in silico analyses suggest this mutation could be a potent contributor to HAE's III type manifestation, notably in homozygous females. The data brought forth intricate relationships between age-related hormonal changes (estrogen fluctuations), specific genetic variance, and the multifaceted bradykinin pathway's involvement in HAE episodes. Significantly, the mutation's position within the EGF-like 2 domain hints at possible effects on protein structure, which might impact its structural stability and subsequent function. Advanced bioinformatics approaches greatly streamlined the identification and comprehension of this pathogenic mutation, demonstrating their invaluable role, especially in atypical cases. We believe that merging in silico methodologies with clinical observations offers a promising avenue for a comprehensive understanding of genetic disorders, emphasizing an integrated approach essential for the development of personalized diagnostic and treatment approaches for diseases such as HAE.

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Section: In Silico Analysismentioning

confidence: 99%

In Silico Analysis and In-depth Assessment of a Female Patient with a Missense Mutation in the F12 Gene Associated with Hereditary Angioedema Symptoms: A Case Study

Pechnikova,

Yaremenko,

Saitgalina

et al. 2023

Preprint

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“…Alternatively, several computational methods are widely used for predicting deleterious genetic mutations and determining their molecular mechanism [Thusberg and Vihinen, 2009;Leong et al, 2015;Singh and Mistry, 2016;Naveed et al, 2019;Kakar et al, 2021]. Indeed, pathogenic SNPs of various genes have been identified using these computational approaches including genes implicated in cancer, such as BRCA1, KRAS, and FGF4 [Rajasekaran et al, 2007;Wang et al, 2019;Lim et al, 2022]; in infection susceptibility, such as ACE2 and IFNAR2 [Saih et al, 2021;Akter et al, 2022], or in hereditary disease like MRE11 and ABCC2 [Tarapara and Shah, 2022;Sharma and Sharma, 2022].…”

mentioning

confidence: 99%

Identification of High-Risk Single Nucleotide Polymorphisms in the Human CYB5R3 Gene Responsible for Recessive Congenital Methemoglobinemia: A Computational Approach

Bouatrous,

Nouira,

Menif

et al. 2023

Mol Syndromol

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Introduction: NADH-cytochrome b5 reductase deficiency due to pathogenic variants in the CYB5R3 gene causes recessive congenital methemoglobinemia (RCM) type I or type II. In type I, cyanosis from birth is the only major symptom, and the enzyme deficiency is restricted only to erythrocytes. Whereas in type II, cyanosis is associated with severe neurological manifestations, and the enzyme deficiency is generalized to all tissues. Methods: In this study, several computational methods (SIFT, Polyphen-2, PROVEAN, Mutation Assessor, Panther, Phd-SNP, SNPs&GO, SNAP2, Align, GVGD, MutPred2, I-Mutant 2.0, MUpro, Duet, ConSurf and Netsurf-2.0 tools) were used to find the most deleterious nsSNPs in the CYB5R3 gene. Furthermore, structural analysis by Swiss-PDB viewer, protein-ligand docking using FTSite, and protein-protein interaction using STRING were carried out to evaluate the impact of these nsSNPs on the protein structure and function. Results: Our in silico analysis suggested that out of 339 nsSNPs of the CYB5R3 gene, 17 (L47H, L47P, R61P, L73R G76D, G76C, P96H, G104C, S128P, G144D, P145S, L149P, Y151H, M177T, I178T, I216N, and G251V), are the most deleterious. Among them, two (P96H and S128P) were reported to be associated with the severe form RCM type II, six are related to RCM type I (G104C, G144D, P145S, L149P, M177T, and I178T), and the remaining nine high-risk nsSNPs have not yet been reported in RCM patients. Discussion: This study highlighted the potential pathogenic nsSNPs of the CYB5R3 gene. To comprehend how these most harmful nsSNPs contribute to disease, it is crucial to experimentally validate their functional effects.

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In silico screening and analysis of single-nucleotide polymorphic variants of the ABCC2 gene affecting Dubin–Johnson syndrome

Cited by 2 publications

References 45 publications

In Silico Analysis and In-depth Assessment of a Female Patient with a Missense Mutation in the F12 Gene Associated with Hereditary Angioedema Symptoms: A Case Study

In Silico Analysis and In-depth Assessment of a Female Patient with a Missense Mutation in the F12 Gene Associated with Hereditary Angioedema Symptoms: A Case Study

Identification of High-Risk Single Nucleotide Polymorphisms in the Human CYB5R3 Gene Responsible for Recessive Congenital Methemoglobinemia: A Computational Approach

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