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Biomarker Variants of Dopamine Receptor Genes Influence the Binding Interaction Between Dopamine Receptor and
Noor B Almandil1, Sayed AbdulAzeez2, Mohamed S Gomaa3
1Department of Clinical Pharmacy Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia.
Drug Design, Development and Therapy
|April 29, 2026
Summary
Genetic variations in dopamine receptor genes influence risperidone response. This study identified rs866976053 in DRD2 as the most deleterious SNP affecting risperidone binding, crucial for treating autism, schizophrenia, and bipolar mania.
Area of Science:
- Pharmacogenomics
- Computational Biology
- Neuroscience
Background:
- Risperidone is an atypical antipsychotic used for autism, schizophrenia, and bipolar mania.
- Patient response to risperidone varies due to genetic factors, particularly dopamine receptor genes.
Purpose of the Study:
- To predict deleterious single nucleotide polymorphisms (SNPs) in dopamine receptor genes (DRD1-5).
- To assess the impact of these SNPs on dopamine receptor protein function, structure, and risperidone binding.
Main Methods:
- Utilized in-silico tools (SIFT, PolyPhen2, etc.) to analyze 1581 non-synonymous SNPs (nsSNPs) in DRD1-5 genes.
- Evaluated the impact of nsSNPs on dopamine receptor protein function and risperidone binding affinity.
Main Results:
- Identified top deleterious nsSNPs: rs759268810 (DRD1), rs866976053 (DRD2), rs1274871399 (DRD3), rs745604469 (DRD4), and rs778635010 (DRD5).
- The F198C mutation in DRD2 (rs866976053) showed a significant reduction in binding free energy with risperidone (-7.29 kcal/mol vs. -8.73 kcal/mol).
- rs866976053 was identified as the most deleterious nsSNP among all analyzed dopamine receptor genes.
Conclusions:
- The F198C variant in DRD2 is a prioritized candidate for further wet lab investigation.
- Understanding these genetic variants can improve risperidone efficacy in managing autism, schizophrenia, and bipolar mania.
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