GPR20

Chr 8

G protein-coupled receptor 20

NCBI Gene: 2843 ENSG00000204882 UniProt: Q99678 OMIM: 601908

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).

OMIM ResearchSummary from RefSeq, UniProt

Enables G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. Part of receptor complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.87

Clinical Summary— GPR20

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.18) despite low pLI — interpret in context.

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ClinVar Variants

83 VUS of 93 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.87LOEUF

pLI 0.441

Z-score 1.77

OE 0.18 (0.06–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.75Z-score

OE missense 0.87 (0.78–0.97)

226 obs / 260.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.06–0.87)

0≤0.351.4

Missense OE?0.87 (0.78–0.97)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 1 / 5.5Missense obs/exp: 226 / 260.0Syn Z: 0.23

This gene — mechanism propensity

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

93 submitted variants in ClinVar

ClinVar

Classification Summary

VUS83

Likely Benign9

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	83	0	83
Likely Benign	6	3	9
Benign	0	0	0
Total	89	3	92

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 7) ClinVar copy-number / structural variants overlap GPR20 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →