DRD3
Chr 3ADdopamine receptor D3
Also known as: D3DR, ETM1, FET1
The DRD3 protein encodes a dopamine receptor primarily expressed in limbic brain areas that inhibits adenylyl cyclase via G protein coupling and regulates cognitive, emotional, and endocrine functions. Mutations cause autosomal dominant hereditary essential tremor type 1, with genetic variants also associated with increased susceptibility to schizophrenia. This gene shows low constraint against loss-of-function variants (pLI 0.002), suggesting that complete loss of function may be tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
107 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 31 | 0 | 31 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 1 | 42 | 4 | 0 | 47 |
Likely Benign | 0 | 3 | 4 | 9 | 16 |
Benign | 0 | 0 | 3 | 4 | 7 |
Conflicting | — | 2 | |||
| Total | 1 | 45 | 43 | 13 | 104 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DRD3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Efficacy of a Prediction Model-based Algorithm to PREVENT Drug-induced Impulse Control Disorders in Parkinson's Disease
NOT YET RECRUITINGmRNA Expression and Genetic Polymorphisms Affecting DRD3 (rs6280) and HTR2A (rs6313) in Bruxism
NOT YET RECRUITINGPain, Central Sensitization and Psychoemotional State in Patients With Chronic Masticatory Muscle Pain
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools