Supplementary Figure 8: Model for rs13102260 (G/A) as a bidirectional genetic modifier of HD age of onset.

rs13102260 (G/A) is located in the identified NF-κB TFBS in the HTT promoter immediately proximal to the 5’UTR of the HTT gene. The rs13102260 (A) sequence variant impaired NF-κB binding, and reduced transcriptional activity of the HTT gene and HTT protein levels. Presence of the rs13102260 (A) variant on the wild-type allele associated with reduced wild-type HTT protein levels and earlier AO, while the (A) variant on the HD disease allele associated with lower mutant HTT (mHTT) protein levels and delayed AO in HD patients.