DRD5
Chr 4ADdopamine receptor D5
Also known as: DBDR, DRD1B, DRD1L2
The D5 dopamine receptor is a G-protein coupled receptor that stimulates adenylyl cyclase and is highly expressed in limbic brain regions, with 10-fold higher dopamine affinity than the D1 subtype. Mutations cause autosomal dominant susceptibility to attention deficit-hyperactivity disorder and primary benign blepharospasm. This gene shows very low constraint against loss-of-function variants (pLI near zero), suggesting tolerance to such mutations.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
197 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 | 63 | 0 | 63 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 97 | 16 | 1 | 114 |
Likely Benign | 0 | 4 | 7 | 1 | 12 |
Benign | 0 | 2 | 2 | 0 | 4 |
Conflicting | — | 1 | |||
| Total | 0 | 103 | 91 | 2 | 197 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DRD5 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools