Annotated PGx Gene Information for DRD2
Submitted by: Huijun Z. Ring, Ruhong Jiang, Caryn Lerman, Huaiyu Mi, Paul Thomas (The Pharmacogenetics of Nicotine Addiction and Treatment (PNAT) Research Consortium)
Reviewed by: Under Review
Submitted date: March 7, 2007
| Gene HGNC Name: |
DRD2 |
|---|---|
| Gene Common Name: | Dopamine Receptor D2 |
| Introductory Information: | DRD2 is one of five different dopamine receptor genes that have been identified in humans and shows high expression in both the pituitary gland and the central nervous system [PMID: 9760208]. DRD2, DRD3, and DRD4 belong to a distinct subfamily of G protein-coupled receptors that likely derives from gene duplication prior to the vertebrate expansion; these receptors are also known to share similar pharmacological profiles [Watson, S, and Arkinstall, S, The G-Protein Linked Receptor Facts Book, ISBN:0127384405]. In 1989, Grandy et al. cloned [PMID: 2532362] and mapped the DRD2 gene to the 11q22-q23 junction by in situ hybridization [PMID: 2573278]. The gene is interrupted by 6 introns [PMID: 2532362]. Signaling through dopamine D2 receptors governs physiologic functions related to locomotion, hormone production, and drug abuse. The human dopamine D2 receptor is also a known target for many antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia [PMID: 9209827]. Many of the known agonists and antagonists of DRD2 are listed in the IUPHAR database. More than 200 polymorphisms have been identified in the DNA encompassing the genomic sequence of this gene; most are in the introns and the downstream flanking region [PMID: 2573278, 1979357, 1679742, 1837284, 1684859, 8471125, 7910578, 8533775], but some are in the coding [PMID: 8277546] and the upstream promoter regions [PMID: 9097961]. Allele frequencies of a number of these polymorphisms have been determined in a number of diiferent populations (http://alfred.med.yale.edu/alfred/recordinfo.asp?condition=loci.locus_uid='LO000168P). Alternative splicing of this gene results in two transcript variants encoding different isoforms: short (D2S) and long (D2L) [PMID: 2531847]. The short isoform is also known as D2(415), whereas the long form is known as D2(444). The difference between the long and short isoforms is the inclusion of an alternatively spliced exon that accounts for the 29 extra amino acids found in the long form. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing [PMID: 10719223]. |
| Key PubMed IDs: | 9760208, 2532362, 9209827, 2573278, 1979357, 1679742, 1837284, 1684859, 8471125, 7910578, 8533775, 9097961, 2531847; 8277546 |
| Drugs/Substrates: | antipsychotics 9209827 ; for agonists and antagonists see IUPHAR database |
| Phenotypes/Diseases: | Schizophrenia 9209827 9097961 |
| Important Variants: | -141C Ins/Del, Ser311Cys, Taq1A (C32806T), C957T |
| Important Splice Variants: | Long Form, Short Form |