GPR20

Chr 8

G protein-coupled receptor 20

The protein is an orphan G protein-coupled receptor with constitutive G(i) signaling activity that activates cyclic AMP and is located in the plasma membrane. GPR20 mutations have not been definitively associated with human disease. The gene shows moderate tolerance to loss-of-function variants (pLI 0.44, LOEUF 0.87).

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.87
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryGPR20
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.18) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.441
Z-score 1.77
OE 0.18 (0.060.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.75Z-score
OE missense 0.87 (0.780.97)
226 obs / 260.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.060.87)
00.351.4
Missense OE0.87 (0.780.97)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 1 / 5.5Missense obs/exp: 226 / 260.0Syn Z: 0.23
DN
0.7035th %ile
GOF
0.84top 5%
LOF
0.3261th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GPR20 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC