Gene Set Enrichment Analysis (GSEA). All nominally significant hippocampal correlates (uncorrected p ≤ 0.05, n = 2074, see ) of Hp1bp3 were extracted from whole-genome transcriptome data from BXD strains age-matched to those used for contextual fear conditioning. The genes were sorted based on correlation coefficient, with the most highly positively correlated genes at the top of the list. Graphs illustrate calculation of enrichment score, or deviation from random distribution throughout the preranked list. Each vertical black line below the graph represents a gene set member and its position in the preranked list (red=genes positively correlated with Hp1bp3, blue=genes negatively correlated with Hp1bp3). A FDR cut-off of q ≤ 0.25 was used to identify significantly enriched sets according to established methods. (a, top) Positive correlates were significantly enriched for localization to the nucleus. (a, bottom) Genes localized to the nucleus were also present in significantly enriched functional gene sets including RNA splicing, nuclear transport, chromosome organization, cell cycle, and transcription cofactor activity. Normalized enrichment score (NES) represents enrichment score after adjustment to account for size of the given gene set. (b) Positive correlates were significantly enriched for the KEGG pathway corresponding to insulin signaling. (c, top) Negative correlates of Hp1bp3 were significantly enriched for localization to the plasma membrane. (c, bottom) Genes localized to the plasma membrane were also present in significantly enriched functional gene sets including ion channel activity, substrate-specific channel activity, transmembrane transporter activity, voltage-gated channel activity, and G-protein coupled receptor activity. (d) Correlates of Hp1bp3 also show significant overlap with a set of genes determined by to be significantly differentially expressed between Alzheimer’s disease patients and corresponding controls.