Identification of pivotal genes and pathways in Chorea-acanthocytosis using comprehensive bioinformatic analysis

Chorea-acanthocytosis (ChAc), an autosomal recessive disorder, is associated with cognitive and behavioral abnormalities. Previous studies were focused around exploring the functional annotation of VPS13A gene in ChAc, whereas the genetic labyrinth underlying this disease and plausible drug targets were underexplored. In the present study, we have identified the pivotal genes and molecular pathways implicated in ChAc using comprehensive bioinformatics analysis. In our analysis we found 27 distinct genes in Homo sapiens linked to ChAc, out of which 15 were selected as candidate genes for enrichment analysis based on their Gene Ontology (GO) annotations and involvement in relevant molecular pathways. By constructing a Protein-Protein Interaction (PPI) network consisting of 26 nodes and 62 edges, we identified two gene modules. Subsequently, using the MCODE algorithm, we identified 6 hub genes-ATN1, JPH3, TBP, VPS13A, DMD, and HTT-as core candidates. These hub genes are primarily associated with processes such as neuron development and differentiation, the CAMKK-AMPK signaling cascade, ion transmembrane transport systems, and protein localization. Furthermore, using drug gene databank we identified 23 FDA-approved drugs that possess the propensity to target 3 out of the 6 identified hub genes. We believe that our findings could open promising avenues for potential therapeutic interventions in ChAc.