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Potential Biological Processes Related to Brain SLC13A5 Across the Lifespan: Weighted Gene Co-Expression Network

Bruna Klippel Ferreira¹, Patricia Fernanda Schuck¹, Gustavo Costa Ferreira¹

¹Laboratório de Erros Inatos do Metabolismo, Programa de Bioquímica e Biofísica Celular, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-599, Brazil.

|February 27, 2026

Summary

The sodium-citrate cotransporter SLC13A5 shows dynamic expression in the developing human brain, peaking in infancy. Its regulation is linked to a mitochondria-centered gene network, offering insights into brain development and metabolic disorders.

Keywords:

Na(+)/citrate cotransporter SLC13A5 cerebrum developmental and epileptic encephalopathy

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Area of Science:

Neuroscience
Genetics
Developmental Biology

Background:

The SLC13A5 gene encodes a sodium-citrate cotransporter.
Its role in early-onset epileptic encephalopathy and metabolic brain dysfunction is known.
Its precise developmental regulation and molecular context in the human brain require further definition.

Purpose of the Study:

To delineate the tissue-specific expression patterns of SLC13A5 during human brain development.
To identify the molecular network associated with SLC13A5 expression across the lifespan.
To explore the functional implications of SLC13A5 regulation in brain maturation and metabolic processes.

Main Methods:

Utilized human developmental transcriptomes from the Evo-Devo resource.
Performed transcriptome-wide association scans to identify co-expressed genes.
Applied weighted gene co-expression network analysis (WGCNA) to build gene networks.
Conducted functional enrichment analysis and subnetwork analysis.

Main Results:

SLC13A5 expression in the cerebrum peaks in the first postnatal year and declines in adulthood, while cerebellar levels increase across the lifespan.
WGCNA revealed a module eigengene closely tracking brain maturation and SLC13A5 abundance.
Functional enrichment analysis highlighted a link to oxidative phosphorylation and mitochondria.
SLC13A5 was positioned adjacent to key genes including CYP46A1, ITM2B, and GABRD in a densely connected subnetwork.

Conclusions:

A developmentally regulated, mitochondria-centered gene program co-varies with SLC13A5 in the human brain.
This program's regulation is tied to brain maturation across the lifespan.
Findings may inform research into age-dependent neurological phenotypes and citrate metabolism disorders.