NPSR1

Chr 7AD

neuropeptide S receptor 1

Also known as: ASRT2, FNSS3, GPR154, GPRA, NPSR, PGR14, VRR1

NCBI Gene: 387129ENSG00000187258UniProt: Q6W5P4

This gene encodes a member of the vasopressin/oxytocin subfamily of G protein-coupled receptors. The encoded membrane protein acts as a receptor for neuropeptide S and affects a variety of cellular processes through its signaling. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. Polymorphisms in this gene have also been associated with asthma susceptibility, panic disorders, inflammatory bowel disease, and rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

?Short sleep, familial natural, 3MIM #621336
AD
57
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NPSR1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 30 VUS of 57 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.16LOEUF
pLI 0.000
Z-score 0.99
OE 0.77 (0.52–1.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.38Z-score
OE missense 1.07 (0.96–1.20)
224 obs / 208.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.77 (0.52–1.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.96–1.20)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 16 / 20.9Missense obs/exp: 224 / 208.7Syn Z: 0.07

ClinVar Variant Classifications

57 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic3
VUS30
Likely Benign2
Benign5
17
Pathogenic
3
Likely Pathogenic
30
VUS
2
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
3
0
3
VUS
0
23
7
0
30
Likely Benign
0
1
0
1
2
Benign
0
2
2
1
5
Total02629257

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NPSR1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Short sleep, familial natural, 3

MIM #621336

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetics of generalized anxiety disorder and related traits.
Gottschalk MG et al.·Dialogues Clin Neurosci
2017Review
Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis.
Tapmeier TT et al.·Sci Transl Med
2021
A functional NPSR1 gene variant and environment shape personality and impulsive action: a longitudinal study.
Laas K et al.·J Psychopharmacol
2014Natural history
NPSR1-AS1 activates the MAPK pathway to facilitate thyroid cancer cell malignant behaviors via recruiting ELAVL1 to stabilize NPSR1 mRNA.
Ni T et al.·Cell Cycle
2022
Genetic factors in anxiety disorders.
Domschke K et al.·Mod Trends Pharmacopsychiatry
2013Review
Sex-specific association between functional neuropeptide S receptor gene (NPSR1) variants and cortisol and central stress responses.
Streit F et al.·Psychoneuroendocrinology
2017Functional
G protein-coupled receptor mutations and human genetic disease.
Thompson MD et al.·Methods Mol Biol
2014Review
Nocturnal asthma is affected by genetic interactions between RORA and NPSR1.
Gaertner VD et al.·Pediatr Pulmonol
2019
Impact of NPSR1 gene variation on the neural correlates of phasic and sustained fear in spider phobia-an imaging genetics and independent replication approach.
Leehr EJ et al.·Soc Cogn Affect Neurosci
2024
Neuropeptide S receptor gene variant and environment: contribution to alcohol use disorders and alcohol consumption.
Laas K et al.·Addict Biol
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools