NPS

protein-coding

neuropeptide S, the group of Neuropeptides

Gene summary

Enables neuropeptide activity. Involved in phospholipase C-activating G protein-coupled receptor signaling pathway; positive regulation of ERK1 and ERK2 cascade; and positive regulation of cAMP/PKA signal transduction. Predicted to be located in obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001030013.2

Inheritance

—

ClinVar variants

U:6B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.39

Max pathogenic AF

—

Genomic locus

chr10:127,549,309-127,553,540

External References & Databases

Ensembl (ENSG00000214285)

Transcript & Mutation Effects

hg38 • Region Span ~4.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NPS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 6

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001030013.2. 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						0
missense			6 clinvar		1 clinvar	7
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	6	0	1	7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001030013.2	RefSeq	NP_001025184.1	3	MANE Select
ENST00000398023.3	Ensembl	ENSP00000381105.2	3	MANE Select

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
visual learning
positive regulation of circadian sleep/wake cycle, wakefulness
positive regulation of synaptic transmission, GABAergic

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398023
Coding exons: 3
Length: 3323
Individuals with no LoFs: 124761
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 124776
p: 0.0000601

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.531	53	43.2	1.23	0.00000196	569
Missense (PolyPhen)		17	11.459	1.4836		142
Synonymous	-0.976	22	16.9	1.30	8.05e-7	178
Loss of Function	-0.688	5	3.59	1.39	1.50e-7	48

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00028	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Modulates arousal and anxiety. May play an important anorexigenic role (By similarity). Binds to its receptor NPSR1 with nanomolar affinity to increase intracellular calcium concentrations (PubMed:15312648, PubMed:16790440). {ECO:0000250, ECO:0000269|PubMed:15312648, ECO:0000269|PubMed:16790440}.;

Recessive Scores

pRec: 0.0143

Intolerance Scores

LoFtool: 0.746
RVIS EVS: 0.88
RVIS percentile EVS: 88.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: N
Indispensability score: 0.00385

Gene Damage Prediction

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