In silico analysis of single nucleotide polymorphisms (SNPs) in human HGD gene which is associated with Alkaptonuria

Alkaptonuria, resulting from homogentisate ۱,۲-dioxygenase deficiency, presents with darkurine, ochronosis, and arthritis. Manifestations include pigment deposition and complications such asvalve calcification, renal stones, and hypothyroidism. Early recognition is crucial for effectivemanagement. The HGD gene encodes homogentisate ۱,۲-dioxygenase and in this study sought todiscover disease-causing single nucleotide polymorphisms (SNPs) in the HGD gene usingbioinformatics servers. One SNP rs۲۸۹۴۱۷۸۳ (G۱۶۱R) was studied using SIFT, PolyPhen-۲, I-Mutant۲.۰, and Hope servers. The result showed that rs۲۸۹۴۱۷۸۳ affected protein function with a score of ۰.۰۰by the SIFT and was predicted to be possibly damaging with a score of ۱.۰۰۰ by PolyPhen-۲. Moreover,a large decrease in the stability of protein was predicted by I-Mutant (DDG = -۱.۵۹). Hope serverindicated that mutation of wild-type residue, glycine, can abolish the protein's function because glycineis the most flexible of all residues and this flexibility might be necessary for the protein's structure andfunction. The mutated residue is located in a domain and in contact with another domain that isimportant for the activity of the protein. The interaction between these domains could be disturbed bythe mutation, which might affect the function of the protein. This interaction may be important for thecorrect function of the protein. Ultimately, the study suggests that the G۱۶۱R variant of HGD genecould affect protein function.

کلیدواژه ها:

HGD gene ، SIFT ، PolyPhen-۲ ، I-Mutant ، Hope