Predicted Impact of the 107G>A HFE Variant on Hereditary Hemochromatosis

Hereditary Hemochromatosis is a genetic disorder in which the body stores excess iron from food, allowing it to build up and eventually damage organs such as the pancreas, liver, and heart. Fatigue, abdominal pain, and joint pain are common in the early stages of HC, and patients may develop liver disease, heart abnormalities, and skin discoloration later on. Mutations in the HFE gene, which codes for the HFE protein, have been linked with development of HC. However, many mutations lack full interpretation of their impacts - it is unknown whether they are pathogenic or benign. By combining and analyzing findings from various genetic databases and prediction algorithms, one can attempt to discern the impact of such mutations. This study investigates the effect of a guanine to adenine switch in position 107 of the HFE gene (NM_000410.4(HFE):c.107G>A (p.Gly36Asp)), resulting in an aspartic acid instead of glycine at position 36 of its protein. The prediction algorithms used concluded that this mutation was likely pathogenic, as the properties of glycine and aspartic acid differ greatly. Additionally, the mutation was found to be in a highly conserved portion of the gene, indicating the intolerance of that region to a change. Taken together, this study indicates that the mutation NM_000410.4(HFE):c.107G>A (p.Gly36Asp) is likely related to Hereditary Hemochromatosis in human patients.