In Silico Characterization of Pathogenic Homeodomain Missense Mutations in the PITX2 Gene

Overview

Journal Biochem Genet

Specialty Molecular Biology

Date 2024 May 27

PMID 38802693

Authors

Yogesh Vetriselvan

Aarthi Manoharan

Manoranjani Murugan

Swetha Jayakumar

Chandramohan Govindasamy

Sambandam Ravikumar

Affiliations

Soon will be listed here.

Abstract

Paired homologous domain transcription factor 2 (PITX2) is critically involved in ocular and cardiac development. Mutations in PITX2 are consistently reported in association with Axenfeld-Rieger syndrome, an autosomal dominant genetic disorder and atrial fibrillation, a common cardiac arrhythmia. In this study, we have mined missense mutations in PITX2 gene from NCBI-dbSNP and Ensembl databases, evaluated the pathogenicity of the missense variants in the homeodomain and C-terminal region using five in silico prediction tools SIFT, PolyPhen2, GERP, Mutation Assessor and CADD. Fifteen homeodomain mutations G42V, G42R, R45W, S49Y, R53W, E53D, E55V, R62H, P65S, R69H, G75R, R84G, R86K, R87W, R91P were found to be highly pathogenic by both SIFT, PolyPhen2 were further functionally characterized using I-Mutant 2.0, Consurf, MutPred and Project Hope. The findings of the study can be used for prioritizing mutations in the context of genetic studies.

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