DRD2

Chr 11

dopamine receptor D2

Also known as: D2DR, D2R

NCBI Gene: 1813 ENSG00000149295 UniProt: P14416 OMIM: 126450

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 OMIM 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 OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

357

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — DRD2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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

Background carrier burden — how many people carry a rare variant somewhere in DRD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

433 rare PASS variants

Rare truncating (LoF)

1 in 4,700

19 rare PASS variants

Rare synonymous (reference)

1 in 91

252 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DRD2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 6,500
South Asian	~43k	1 in 180	1 in 1,500
Remaining (unassigned)	~30k	1 in 170	≈ 1 in 30,000
European (Finnish)	~27k	1 in 600	none seen
Admixed American	~22k	1 in 180	none seen
African / African American	~21k	1 in 100	≈ 1 in 5,500
East Asian	~20k	1 in 130	none seen
Ashkenazi Jewish	~13k	1 in 490	none seen
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓