Abstract Background The ABCD1 gene is a part of the ABC transporter family that encodes proteins involved in lipid and metabolite transport. Numerous non-synonymous single nucleotide polymorphisms (nsSNPs) have been identified within the coding region of the ABCD1 gene, some of which are associated with a rare genetic disorder X-linked adrenoleukodystrophy (ALD). However, the structural changes resulting from these nsSNPs remain poorly understood. Methods This study utilized multiple bioinformatics tools to predict the high-risk pathogenic nsSNPs in ABCD1 and evaluate their potential impact on the structure and function of the adrenoleukodystrophy protein (ALDP). nsSNPs extracted from ENSEMBL and the Indian population-specific 1000 genomes project were analyzed using various in-silico tools to predict the pathogenic consequences of nsSNPs and their impact on physical, chemical, and structural changes in the protein. Results A total of 80 high-risk pathogenic nsSNPs (HRPₙsSNPs) were identified in ABCD1 which were predicted pathogenic, located at highly conserved residues with a conservation score of 9 and were associated with decreased protein stability. Notably, 3 novel nsSNPs specific to the Indian population were highlighted. These HRPₙsSNPs significantly affect amino acid properties such as size, charge, and hydrophobicity. Among the 80 HRPₙsSNPs, 60 have been previously linked to ALD, while 20 are newly identified. Conclusion This study revealed that among thousands of nsSNPs, 80 were the HRPₙsSNPs that altered the physical and chemical properties of amino acids, led to structural changes in the protein, disruption of domain interactions, and impaired protein function. The work offers valuable insights for prioritizing pathogenic ABCD1 nsSNPs and studying the pathogenesis of ALD.
Reshmi et al. (Wed,) studied this question.