Arsenic is a widespread environmental contaminant recognized for its high mobility and potential toxicity. Arsenic levels at Suncheon Bay, one of the primary Tegillarca granosa culturation sites in South Korea, were identified as higher than the habitat's threshold effect level (TEL). After 12 and 48 h of arsenic exposure, a total of 939 and 842 DEGs were identified in the gill and mantle, respectively. Detoxification genes were identified based on DEG analysis, and out of 10 ABCA3 genes in T. granosa, seven ABCA3 genes in total were up- and/or downregulated in two tissues. The metabolic and the cell adhesion molecules KEGG pathways were the most enriched among the commonly identified up- and downregulated genes. The 'metabolic process' gene ontology term was highly enriched with upregulated DEGs. We then identified 74 ATP-binding cassette (ABC) genes in the T. granosa genome, which has seven subfamilies (A to G), with gene expansion found in the ABCC and ABCA subfamilies. Although the precise mechanisms of arsenic-induced gene dysregulation remain unknown, our findings suggest that ABCA3 genes might participate in arsenic active transport and play an important role in arsenic detoxification.