NPY1R
Chr 4neuropeptide Y receptor Y1
Also known as: NPY1-R, NPYR
The protein is a G-protein-coupled receptor that mediates the function of neuropeptide Y (NPY), a neurotransmitter, and peptide YY (PYY), a gastrointestinal hormone, activating intracellular signaling pathways including calcium mobilization and adenylate cyclase inhibition. Mutations in this gene have been associated with autosomal recessive obesity and feeding disorders in pediatric patients. The gene shows tolerance to loss-of-function variants (LOEUF 0.84), suggesting that complete loss of function may be required for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
84 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 | 39 | 0 | 39 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 33 | 6 | 0 | 39 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 35 | 47 | 0 | 82 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NPY1R · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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