GPR22

Chr 7

G protein-coupled receptor 22

NCBI Gene: 2845ENSG00000172209UniProt: Q99680

This gene is a member of the G-protein coupled receptor 1 family and encodes a multi-pass membrane protein. [provided by RefSeq, Jul 2008]

56
ClinVar variants
21
Pathogenic / LP
0.06
pLI score
0
Active trials
Clinical Summary— GPR22
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 34 VUS of 56 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.65LOEUF
pLI 0.060
Z-score 2.59
OE 0.31 (0.16–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.07Z-score
OE missense 0.61 (0.53–0.70)
137 obs / 224.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.16–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.53–0.70)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 5 / 16.3Missense obs/exp: 137 / 224.4Syn Z: 0.04

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
VUS34
Likely Benign1
21
Pathogenic
34
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
0
0
0
VUS
0
28
6
0
34
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total02827156

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

View in ClinVar →

Protein Context — Lollipop Plot

GPR22 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cardiomyocyte-specific overexpression of GPR22 ameliorates cardiac injury in mice with acute myocardial infarction.
Chang CC et al.·BMC Cardiovasc Disord
2024🔓 Open Access
An SNN retrocopy insertion upstream of GPR22 is associated with dark red coat color in Poodles.
Batcher K et al.·G3 (Bethesda)
2022🔓 Open Access
Orphan G-protein coupled receptor 22 (Gpr22) regulates cilia length and structure in the zebrafish Kupffer's vesicle.
Verleyen D et al.·PLoS One
2014🔓 Open AccessFunctional
Expression of orphan receptors GPR22 and GPR162 in streptozotocin-induced diabetic rats.
Ruiz-Hernández A et al.·J Recept Signal Transduct Res
2015
Myocardial expression, signaling, and function of GPR22: a protective role for an orphan G protein-coupled receptor.
Adams JW et al.·Am J Physiol Heart Circ Physiol
2008
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools