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From SNPedia

Geno Mag Summary
(C;C) better response to olanzapine
(C;T) 0 normal
(T;T) 0 normal
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
1000 genomesrs6280
23andMe allrs6280
SNP Nexus

GWAS Ctlgrs6280
Max Magnitude0
? (C;C) (C;T) (T;T) 28
rs6280, also known as Ser9Gly, is a SNP in the dopamine receptor D3 DRD3 gene. The rs6280(C) allele encodes a glycine, and the (T) allele encodes a serine (in dbSNP orientation).

In a study of 88 patients being treated for schizophrenia with olanzapine, those who were rs6280(C;C) homozygotes had greater positive symptom remission (endpoint rating of minimal or none on all PANSS clinical response positive items, 39.1%), as compared with (C;T) or (T;T) genotypes (13.8%; p = 0.033). [PMID 18320559]

Ser9Gly has been implicated in executive function in some studies, but the results are conflicting.

  • [PMID 18351593] Gly/Gly carriers showed significantly (p = 0.002) poorer performance than Ser/Ser carriers on executive functioning tasks in a somewhat small Caucasian sample (84 patients with first-episode psychosis and 85 controls).
  • [PMID 2186374OA-icon.png] Gly/Ser heterozygotes had 23% more preservative errors on the WCST compared to Ser/Ser homozygotes in a small (216) healthy Han Chinese sample (p = 0.009). Differences between homozygotes were not statistically significant.
  • [PMID 15785860] No association between WCST scores and Ser9Gly was found in 138 schizophrenic patients.

[PMID 18348205] Associated in a family association study and pooled sample of 2,037 with nicotine dependence in Americans of European descent.

[PMID 16583407] Preliminary evidence for an association between a dopamine D3 receptor gene variant and obsessive-compulsive personality disorder in patients with major depression. DRD3 polymorphism for an individual with Gly/Gly (C;C) genotype is 2.4 (P = 0.017) times more likely to be diagnosed with OCPD. Male gender was also found to be a significant predictor of OCPD diagnosis (OR = 2.82, P = 0.001). DRD3 may contribute to the development of OCPD. This association was tested using two independent groups of individuals with a history of depression, from a clinical sample (n = 149) and a family study (n = 213).

[PMID 19358223] The DRD3 rs6280 polymorphism and prevalence of tardive dyskinesia: A meta-analysis.

[PMID 20236178] Dopamine receptor 3(DRD3) polymorphism and risk for migraine

[PMID 21491142OA-icon.png] Dopamine receptor D3 genetic polymorphism (rs6280TC) is associated with rates of cognitive impairment in methamphetamine-dependent men with HIV: preliminary findings

[PMID 22569179] Rs1076560, a functional variant of the dopamine D2 receptor gene, confers risk of schizophrenia in Han Chinese

Risk rs6280(T;T)
Alt rs6280(T;T)
Reference rs6280(C;C)
Significance Other
Disease Schizophrenia Essential tremor
Variation info
Gene DRD3
CLNDBN Schizophrenia, susceptibility to Essential tremor, susceptibility to
Reversed 0
HGVS NC_000003.11:g.113890815C>T
CLNSRC OMIM Allelic Variant
CLNACC RCV000018257.2, RCV000018258.2,

[PMID 16380908OA-icon.png] Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder.

[PMID 16893532] Novel, replicated associations between dopamine D3 receptor gene polymorphisms and schizophrenia in two independent samples.

[PMID 17466074OA-icon.png] Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study.

[PMID 17630406OA-icon.png] Dopamine genes and schizophrenia: case closed or evidence pending?

[PMID 18366720OA-icon.png] Association of dopaminergic pathway gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes.

[PMID 18593715OA-icon.png] Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation.

[PMID 18603647OA-icon.png] Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.

[PMID 18698231OA-icon.png] Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.

[PMID 18781856] Genetic underpinnings of tardive dyskinesia: passing the baton to pharmacogenetics.

[PMID 18987889] A common haplotype of DRD3 affected by recent positive selection is associated with protection from schizophrenia.

[PMID 19197363OA-icon.png] A genome-wide investigation of SNPs and CNVs in schizophrenia.

[PMID 19207358OA-icon.png] Further evidence for an association between the gamma-aminobutyric acid receptor A, subunit 4 genes on chromosome 4 and Fagerstrom Test for Nicotine Dependence.

[PMID 19302829] Effects of the DRD3 Ser9Gly polymorphism on aripiprazole efficacy in schizophrenic patients as modified by clinical factors.

[PMID 19379518OA-icon.png] Development of a fingerprinting panel using medically relevant polymorphisms.

[PMID 19604093OA-icon.png] Genetic polymorphisms, their allele combinations and IFN-beta treatment response in Irish multiple sclerosis patients.

[PMID 19669131OA-icon.png] Clinical and pharmacogenetic determinants for the discontinuation of non-ergoline dopamine agonists in Parkinson's disease.

[PMID 19693267OA-icon.png] Financial and psychological risk attitudes associated with two single nucleotide polymorphisms in the nicotine receptor (CHRNA4) gene.

[PMID 20565774OA-icon.png] Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

[PMID 21162693OA-icon.png] Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction.

[PMID 21595009] Converging evidence implicates the dopamine D3 receptor gene in vulnerability to schizophrenia.

[PMID 21663922OA-icon.png] Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium.

GET Evidence
aa_change Gly9Ser
aa_change_short G9S
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.533296
summary Dopamine agonist for the D3 receptor - increases receptor affinity for dopamine by 4-5 times. So a gain-of-function mutation that could have positive or negative effects depending on the person's brain.

[PMID 24398431] DRD3 variation associates with early-onset heroin dependence, but not specific personality traits

[PMID 22940547] Preliminary evidence for association between schizophrenia and polymorphisms in the regulatory Regions of the ADRA2A, DRD3 and SNAP-25 Genes.

[PMID 23312624] Dopamine receptor D3 (DRD3) gene rs6280 variant and risk for restless legs syndrome.

[PMID 24776816] DRD3 Gene rs6280 Polymorphism May Be Associated with Alcohol Dependence Overall and with Lesch Type I Alcohol Dependence in Koreans

[PMID 25660313] Meta-analysis of six genes (BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA) involved in neuroplasticity and the risk for alcohol dependence

[PMID 25698199] Association between Tourette syndrome and the dopamine D3 receptor gene rs6280

[PMID 27325396] Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson's disease patients.