IN-SILICO ANALYSIS OF P.LYS131ASN MISSENSE-DONOR LOSS VARIANT IN MINAR2
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Keywords
Autosomal recessive, deafness, hearing loss, MINAR2, NOTCH2, In-silico analysis of MINAR2 variant, p.Lys131Asn
Abstract
In-silico analysis of underlying variants ensures the fact that the variant is pathogenic, and on top of it, this assists scientists and clinicians reach conclusion on the basis of guidelines provided by American College of Medical Genetics and Genomics. Discovery of deafness genes and elucidating their functions have substantially contributed to our understanding of hearing physiology and its pathologies. Here we report in-silico analysis of a variant in MINAR2 (membrane integral NOTCH2-associated receptor) underlying autosomal recessive non-syndromic deafness. MINAR2 is a recently annotated gene with limited functional understanding. We have reported three MINAR2 variants, p.Trp48*, p.Arg138Valfs*10, and p.Lys131Asn previously, in 13 individuals with congenital or prelingual-onset severe to profound sensorineural hearing loss in recent past. The p.Lys131Asn variant is shown to disrupt a splice donor site. Here, we conclude that MINAR2 is essential for hearing in humans and its disruption leads to sensorineural hearing loss. In-silico analysis of MINAR2 variant p.Lys131Asn corroborates our previously reported findings and supports the fact that deleterious variants in MINAR2 underlie inherited non-syndromic hearing loss and MINAR2 plays an important role in normal hearing and development.
This in-silico work aims to determine whether mutation in MINAR2 protein affects the activity and stability of the protein, and also determines the pathogenicity of the p.Lys131Asn variant in MINAR2. Prediction of pathogenicity of variant will reveal if the mutation has a damaging effect on the native structure of protein or not. Prediction of protein stability will reveal whether the mutation has a stabilizing or destabilizing effect on the protein.
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Mangesh Deokar
Oriental College of Pharmacy and Research, Oriental University, Indore, MP, India
Nitu Singh
Oriental College of Pharmacy and Research, Oriental University, Indore, MP, India