NPY2R

Chr 4

neuropeptide Y receptor Y2

Also known as: NPY2-R

The NPY2R protein functions as a G-protein coupled receptor for neuropeptide Y and peptide YY, regulating appetite and energy homeostasis. Mutations cause autosomal recessive morbid obesity with early childhood onset. This gene shows low constraint to loss-of-function variants, consistent with a recessive inheritance pattern.

Summary from RefSeq, UniProt
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0
Active trials
25
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.88
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryNPY2R
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.036
Z-score 1.85
OE 0.38 (0.190.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.81Z-score
OE missense 0.84 (0.740.95)
178 obs / 211.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.190.88)
00.351.4
Missense OE0.84 (0.740.95)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 4 / 10.5Missense obs/exp: 178 / 211.2Syn Z: -1.28
DN
0.77top 25%
GOF
0.82top 10%
LOF
0.2289th %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

NPY2R · 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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