NPBWR2

Chr 20

neuropeptides B and W receptor 2

Also known as: GPR8

NCBI Gene: 2832 ENSG00000125522 UniProt: P48146 OMIM: 600731

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is an integral membrane protein and G protein-coupled receptor. The encoded protein is similar in sequence to another G protein-coupled receptor (GPR7), and it is structurally similar to opioid and somatostatin receptors. This protein binds neuropeptides B and W. This gene is intronless and is expressed primarily in the frontal cortex of the brain. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.78

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.000

Z-score -0.02

OE 1.01 (0.55–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.56Z-score

OE missense 0.90 (0.80–1.00)

206 obs / 230.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.01 (0.55–1.78)

0≤0.351.4

Missense OE?0.90 (0.80–1.00)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 6 / 5.9Missense obs/exp: 206 / 230.0Syn Z: 0.29

Background carrier burden — how many people carry a rare variant somewhere in NPBWR2?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

413 rare PASS variants

Rare truncating (LoF)

1 in 4,100

49 rare PASS variants

Rare synonymous (reference)

1 in 150

221 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NPBWR2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 4,700
South Asian	~43k	1 in 84	1 in 1,200
Remaining (unassigned)	~30k	1 in 72	≈ 1 in 15,000
European (Finnish)	~26k	1 in 300	≈ 1 in 23,000
Admixed American	~22k	1 in 99	≈ 1 in 5,600
African / African American	~21k	1 in 67	1 in 3,500
East Asian	~20k	1 in 67	1 in 950
Ashkenazi Jewish	~13k	1 in 390	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 59	≈ 1 in 940

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓