Interpreting missense mutations in Human TRIM5alpha by computational methods

The human restriction factor TRIM5alpha may play an important role in regulation of the human immunodeficiency virus (HIV). It is unclear whether non-synonymous single nucleotide polymorphisms (nsSNP) in TRIM5alpha affect the clinical course of HIV infection.

We surveyed the literature for TRIM5alpha nsSNPs and used comparative sequence analysis to predict the effect of each polymorphism on protein function. Twenty-eight nsSNPs were identified with available functional data, clinical data, or both. The four comparative method programs assessed included SIFT, PolyPhen, A-GVGD, and average BLOSUM62 pairwise score. Two common polymorphisms, H43Y and R136Q, were predicted to be benign based on comparative sequence analysis. The nsSNPs P323R, K324N, I328M, G330Q, R332P, I348V, and T369S were all predicted to affect protein function.

Comparative sequence analysis offers a functional tool to analyze unknown nsSNPs in TRIM5alpha.