DRD2

Chr 11

dopamine receptor D2

Also known as: D2DR, D2R

NCBI Gene: 1813 ENSG00000149295 UniProt: P14416

The D2 dopamine receptor is a G-protein coupled receptor that inhibits adenylyl cyclase activity and plays a role in dopaminergic signaling pathways. Mutations cause myoclonus-dystonia, typically with childhood to adolescent onset involving involuntary muscle contractions and brief shock-like movements. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants (LOEUF 0.439).

GeneReviews ResearchSummary from RefSeq, UniProt

This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.44

Clinical Summary— DRD2

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

66 VUS of 175 total submissions

💊

Clinical Trials

8 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — DRD2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.747

Z-score 3.23

OE 0.17 (0.08–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.62Z-score

OE missense 0.56 (0.50–0.64)

162 obs / 287.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.08–0.44)

0≤0.351.4

Missense OE?0.56 (0.50–0.64)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 3 / 17.7Missense obs/exp: 162 / 287.2Syn Z: -0.51

This gene — mechanism propensity

0.6647th %ile

GOF

0.73top 25%

LOF

0.4825th %ile

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.

GOFprediction above median

DNprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

175 submitted variants in ClinVar

ClinVar

Classification Summary

VUS66

Likely Benign52

Benign48

Conflicting4

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	63	2	1	66
Likely Benign	0	1	11	40	52
Benign	0	2	35	11	48
Conflicting	—				4
Total	0	66	48	52	170

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap DRD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →