NPY
protein-codingneuropeptide Y, the group of Neuropeptides
Gene summary
This gene encodes a neuropeptide that is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. The neuropeptide functions through G protein-coupled receptors to inhibit adenylyl cyclase, activate mitogen-activated protein kinase (MAPK), regulate intracellular calcium levels, and activate potassium channels. A polymorphism in this gene resulting in a change of leucine 7 to proline in the signal peptide is associated with elevated cholesterol levels, higher alcohol consumption, and may be a risk factor for various metabolic and cardiovascular diseases. The protein also exhibits antimicrobial activity against bacteria and fungi. [provided by RefSeq, Oct 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.7 kbGenCC 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 NPY variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000905.4. 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 | 1 | 2 | |||
| missense | 9 | 1 | 10 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 10 | 2 | 1 | 13 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000896.1 | 3 | MANE Select | |
| Ensembl | ENSP00000242152.2 | 3 | MANE Select | |
| Ensembl | ENSP00000385282.1 | 3 | Standard | |
| Ensembl | ENSP00000385282.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| npy | Danio rerio | Structure: feeding behavior Quality: decreased process quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of lipolysis in adipocytes - Homo sapiens (human)
- Adipocytokine signaling pathway - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Alcoholism - Homo sapiens (human)
- Sympathetic Nerve Pathway (Neuroeffector Junction)
Biological Process
- calcium ion transport
- G protein-coupled receptor signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- neuropeptide signaling pathway
- chemical synaptic transmission
Molecular Function
- G protein-coupled receptor binding
- G protein-coupled receptor activity
- signaling receptor binding
- neuropeptide hormone activity
- calcium channel regulator activity
Cellular Component
- extracellular region
- extracellular space
- cell
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000407573
- Coding exons
- 3
- Length
- 7703
- Individuals with no LoFs
- 124672
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 124676
- p
- 0.0000160
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.643 | 42 | 55.5 | 0.757 | 0.00000256 | 595 |
| Missense (PolyPhen) | 11 | 23.456 | 0.46896 | 242 | ||
| Synonymous | 0.0280 | 25 | 25.2 | 0.993 | 0.00000112 | 210 |
| Loss of Function | 1.47 | 2 | 5.81 | 0.344 | 3.45e-7 | 56 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.;
Recessive Scores
- pRec
- 0.641
Intolerance Scores
- LoFtool
- 0.252
- RVIS EVS
- 0.21
- RVIS percentile EVS
- 67.72
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.110
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |