NPBWR2

Chr 20

neuropeptides B and W receptor 2

Also known as: GPR8

The encoded protein is a G protein-coupled receptor that binds neuropeptides B and W and interacts with opioid ligands, functioning in neuroendocrine regulation and food intake control. The gene is extremely intolerant to loss-of-function variants (pLI near 1.0), but no established human disease has been definitively linked to NPBWR2 mutations in current medical literature. This receptor is expressed primarily in the frontal cortex and belongs to the same structural family as opioid and somatostatin receptors.

Summary from RefSeq, UniProt
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0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.78
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryNPBWR2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — 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
1.78LOEUF
pLI 0.000
Z-score -0.02
OE 1.01 (0.551.78)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.56Z-score
OE missense 0.90 (0.801.00)
206 obs / 230.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.01 (0.551.78)
00.351.4
Missense OE0.90 (0.801.00)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 6 / 5.9Missense obs/exp: 206 / 230.0Syn Z: 0.29
DN
0.74top 25%
GOF
0.82top 10%
LOF
0.2485th %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

NPBWR2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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