GPR142
Chr 17G protein-coupled receptor 142
Also known as: GPRg1b, PGR2
GPR142 encodes a G protein-coupled receptor that serves as a highly selective sensor for aromatic amino acids, particularly L-tryptophan and L-phenylalanine, and controls insulin secretion in the pancreas along with other gastrointestinal hormones to regulate glucose homeostasis. The gene shows very low intolerance to loss-of-function variants (pLI ~0, LOEUF 1.529), and the predicted mechanism of pathogenicity is gain-of-function. However, no specific disease associations or inheritance patterns have been established for GPR142 mutations based on the available data.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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.
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
126 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 11 | 0 | 11 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 85 | 0 | 0 | 85 |
Likely Benign | 1 | 9 | 6 | 3 | 19 |
Benign | 0 | 1 | 4 | 1 | 6 |
Conflicting | — | 1 | |||
| Total | 1 | 95 | 22 | 4 | 123 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GPR142 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools