NPSR1

protein-coding

neuropeptide S receptor 1, the group of Neuropeptide S receptor

Gene summary

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]

Previous symbols:

GPR154

MANE transcript

NM_207172.2

Inheritance

ClinVar variants

U:23B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr7:34,658,218-34,878,332

External References & Databases

Ensembl (ENSG00000187258)

Transcript & Mutation Effects

hg38 • Region Span ~220.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

asthma-related traits, susceptibility to, 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012067

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NPSR1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_207172.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense			23 clinvar	1 clinvar	1 clinvar	25
nonsense					1 clinvar	1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	23	2	3	28

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_207172.2	RefSeq	NP_997055.1	9	MANE Select
ENST00000360581.6	Ensembl	ENSP00000353788.1	9	MANE Select
NM_001300933.2	RefSeq	NP_001287862.1	9	Standard
NM_001300934.2	RefSeq	NP_001287863.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
G alpha (s) signalling events
Peptide ligand-binding receptors
Class A/1 (Rhodopsin-like receptors)

Biological Process

G protein-coupled receptor signaling pathway
neuropeptide signaling pathway
positive regulation of release of sequestered calcium ion into cytosol

Molecular Function

vasopressin receptor activity
neuropeptide receptor activity

Cellular Component

cytoplasm
plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359791
Coding exons: 9
Length: 220094
Individuals with no LoFs: 125137
Homozygous LoFs: 0
Heterozygous LoFs: 611
Defined: 125748
p: 0.00243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.376	224	209	1.07	0.0000110	2444
Missense (PolyPhen)		80	68.71	1.1643		871
Synonymous	0.0743	80	80.8	0.989	0.00000457	739
Loss of Function	0.989	16	20.9	0.766	0.00000123	205

Population LoF Frequency

Population	CAF	p-value	Status
African	0.027	0.027	notable
Latino/Admixed American	0.0015	0.0015	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00087	0.00087	rare
Finnish	0.0024	0.0024	notable
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00026	0.00026	rare
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: G-protein coupled receptor for neuropeptide S (NPS) (PubMed:16790440). Promotes mobilization of intracellular Ca(2+) stores (PubMed:16790440). Inhibits cell growth in response to NPS binding (PubMed:15947423). Involved in pathogenesis of asthma and other IgE-mediated diseases. {ECO:0000269|PubMed:15312648, ECO:0000269|PubMed:15947423, ECO:0000269|PubMed:16790440}.;

Recessive Scores

pRec: 0.193

Intolerance Scores

LoFtool: 0.895
RVIS EVS: 1.34
RVIS percentile EVS: 94.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.152

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High