Leucine to proline substitution by SNP at position 197 in Caspase-9 gene expression leads to neuroblastoma: a...

To understand the role of CASP9 (Caspase-9) gene products in relation to neuroblastoma disease, we have analyzed the single nucleotide polymorphisms (SNPs) associated with this gene. This can help us understand the genetic variations that can alter the function of the gene products. A total of 941 SNPs are investigated for CASP9 gene. To determine whether a non-synonymous SNP (nsSNP) in this gene affects its protein product, we used certain computational tools which predicted one nsSNP, rs1052574, to have deleterious phenotypic effect. This polymorphic variant results in amino acid substitution from leucine to proline at 197 position, i.e., from acyclic amino acid to a 5-membered amino acid which resides in the buried area of the protein with a high level of conservation. This amino acid substitution shows a transition from helix to coil in the mutant protein. Hence, due to the complete alteration in the structural property of the amino acid side chain, the stability of the protein is reduced which may affect the function of CASP9 protein, leading to deregulation of apoptosis and neuroblastoma development.