DRD3 G9S - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

DRD3 G9S

(DRD3 Gly9Ser)


Short 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.

Variant evidence
Computational -
Functional 4

“dopamine-mediated cAMP response was increased, and the mitogen-associated protein kinase (MAPK) signal was prolonged, as compared with the Ser-9 variant”

See Jeanneteau F et al. 2006 (16809426).

Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

“dopamine-mediated cAMP response was increased, and the mitogen-associated protein kinase (MAPK) signal was prolonged, as compared with the Ser-9 variant”

Allele frequency

  • T @ chr3:113890815: 53.3% (5734/10752) in EVS
  • T @ chr3:115373504: 51.6% (66/128) in GET-Evidence
  • Frequency shown in summary reports: 53.3% (5734/10752)

Publications
 

Jeanneteau F, Funalot B, Jankovic J, Deng H, Lagarde JP, Lucotte G, Sokoloff P. A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10753-8. Epub 2006 Jun 29. PubMed PMID: 16809426; PubMed Central PMCID: PMC1502303.

 

Adams DH, Close S, Farmen M, Downing AM, Breier A, Houston JP. Dopamine receptor D3 genotype association with greater acute positive symptom remission with olanzapine therapy in predominately caucasian patients with chronic schizophrenia or schizoaffective disorder. Hum Psychopharmacol. 2008 Jun;23(4):267-74. PubMed PMID: 18320559.

 

Liu YZ, Tang BS, Yan XX, Liu J, Ouyang DS, Nie LN, Fan L, Li Z, Ji W, Hu DL, Wang D, Zhou HH. Association of the DRD2 and DRD3 polymorphisms with response to pramipexole in Parkinson's disease patients. Eur J Clin Pharmacol. 2009 Jul;65(7):679-83. Epub 2009 Apr 25. PubMed PMID: 19396436.

 

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het T @ chr3:113890815

 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
hom T @ chr3:113890815

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het T @ chr3:113890815

 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
hom T @ chr3:113890815

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het T @ chr3:113890815

 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
het T @ chr3:113890815

 

 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
hom T @ chr3:113890815

 

hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
hom T @ chr3:113890815

 

hu2DBF2D - CGI sample GS01173-DNA_G02 from PGP sample 67180598
het T @ chr3:113890815

 

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
hom T @ chr3:113890815

 

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het T @ chr3:113890815

 

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
hom T @ chr3:113890815

 

hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
hom T @ chr3:113890815

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het T @ chr3:113890815

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het T @ chr3:113890815

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
hom T @ chr3:113890815

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het T @ chr3:113890815

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
hom T @ chr3:113890815

 

 

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
het T @ chr3:113890815

 

hu7A4AD1 - CGI sample GS01669-DNA_C05 from PGP sample 42408046
hom T @ chr3:113890815

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
hom T @ chr3:113890815

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
hom T @ chr3:113890815

 

hu92FD55 - CGI sample GS01669-DNA_A04 from PGP sample 08188426
het T @ chr3:113890815

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het T @ chr3:113890815

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
hom T @ chr3:113890815

 

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
hom T @ chr3:113890815

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het T @ chr3:113890815

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het T @ chr3:113890815

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het T @ chr3:113890815

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
hom T @ chr3:113890815

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
hom T @ chr3:113890815

 

huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
hom T @ chr3:113890815

 

huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
hom T @ chr3:113890815

 

huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
het T @ chr3:113890815

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
hom T @ chr3:113890815

 

huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
hom T @ chr3:113890815

 

GS06985 - var-GS06985-1100-36-ASM
hom T @ chr3:115373505

 

GS07357 - var-GS07357-1100-36-ASM
het T @ chr3:115373505

 

GS10851 - var-GS10851-1100-36-ASM
hom T @ chr3:115373505

 

GS12004 - var-GS12004-1100-36-ASM
hom T @ chr3:115373505

 

GS18508 - var-GS18508-1100-36-ASM
het T @ chr3:115373505

 

GS18526 - var-GS18526-1100-36-ASM
het T @ chr3:115373505

 

GS18537 - var-GS18537-1100-36-ASM
hom T @ chr3:115373505

 

GS18555 - var-GS18555-1100-36-ASM
het T @ chr3:115373505

 

GS18558 - var-GS18558-1100-36-ASM
hom T @ chr3:115373505

 

GS18940 - var-GS18940-1100-36-ASM
het T @ chr3:115373505

 

GS18942 - var-GS18942-1100-36-ASM
het T @ chr3:115373505

 

GS18947 - var-GS18947-1100-36-ASM
hom T @ chr3:115373505

 

GS18956 - var-GS18956-1100-36-ASM
het T @ chr3:115373505

 

GS19025 - var-GS19025-1100-36-ASM
het T @ chr3:115373505

 

GS19129 - var-GS19129-1100-36-ASM
het T @ chr3:115373505

 

GS19648 - var-GS19648-1100-36-ASM
hom T @ chr3:115373505

 

GS19669 - var-GS19669-1100-36-ASM
hom T @ chr3:115373505

 

GS19670 - var-GS19670-1100-36-ASM
hom T @ chr3:115373505

 

GS19735 - var-GS19735-1100-36-ASM
hom T @ chr3:115373505

 

GS19834 - var-GS19834-1100-36-ASM
het T @ chr3:115373505

 

GS20502 - var-GS20502-1100-36-ASM
hom T @ chr3:115373505

 

GS20509 - var-GS20509-1100-36-ASM
het T @ chr3:115373505

 

Other external references
 

    dbSNP
  • rs6280
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Essential Tremor]
    Risk or phenotype-associated allele: C. Phenotype: A study comparing 276 patients with essential tremor and 184 normal controls confirmed the association of the Gly-9 variant in the DRD-3 gene with risk and age-at-onset of essential tremor. Study size: 276. Study population/ethnicity: French.
    www.ncbi.nlm.nih.gov/pubmed/16809426
  • [Schizophrenia]
    [olanzapine]
    A study on 88 olanzapine-treated patients with schizophrenia found that the Gly/gly genotype was significantly associated with greater positive symptom improvement.
    www.ncbi.nlm.nih.gov/pubmed/18320559
  • [Parkinson Disease]
    [pramipexole]
    This variant in the DRD3 gene was significantly associated with the therapeutic efficacy of pramipexole in Chinese patients with Parkinson's disease in a study of 30 patients.
    www.ncbi.nlm.nih.gov/pubmed/19396436

Other in silico analyses
 

  • NBLOSUM100 score = 2
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

"GENE" or "GENE A123C":

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