Potential Biological Processes Related to Brain SLC13A5 Across the Lifespan: Weighted Gene Co-Expression Network Analysis from Large Human Transcriptomic Data

<b>Background/Objectives:</b><i>SLC13A5</i> encodes a sodium-citrate cotransporter implicated in early-onset epileptic encephalopathy and metabolic brain dysfunction, yet its developmental regulation and molecular context in the human brain remain incompletely defined. <b>Methods:</b> Leveraging human developmental transcriptomes from the Evo-Devo resource, we delineated tissue trajectories and network context for <i>SLC13A5</i> across the fetal-postnatal life. <b>Results:</b> In the cerebrum, <i>SLC13A5</i> expression rises from late fetal stages to peak in the first postnatal year and then declines into adulthood, while cerebellar levels increase across the lifespan; liver shows a fetal decrease followed by sustained postnatal upregulation. A transcriptome-wide scan identified extensive positive and negative associations with <i>SLC13A5</i>, and a signed weighted gene co-expression network analysis (WGCNA) built on biweight midcorrelation placed <i>SLC13A5</i> in a large module. The module eigengene tracked brain maturation (Spearman rho = 0.802, <i>p</i> = 8.62 × 10^-6) and closely matched <i>SLC13A5</i> abundance (rho = 0.884, <i>p</i> = 2.73 × 10^-6), with a significant partial association after adjusting for developmental rank (rho = 0.672, <i>p</i> = 6.17 × 10^-4). Functional enrichment converged on oxidative phosphorylation and mitochondria. A force-directed subnetwork of the top intramodular members (|bicor| > 0.6) positioned <i>SLC13A5</i> adjacent to a densely connected nucleus including <i>CYP46A1</i>, <i>ITM2B</i>, <i>NRGN</i>, <i>GABRD</i>, <i>FBXO2</i>, <i>CHCHD10</i>, <i>CYSTM1</i>, and <i>MFSD4A</i>. <b>Conclusions:</b> Together, these results define a developmentally tuned, mitochondria-centered program that co-varies with <i>SLC13A5</i> in the human brain across the lifespan. It may provide insights to interrogate age-dependent phenotypes and therapeutic avenues for disorders involving citrate metabolism.