PPY
protein-codingpancreatic polypeptide, the group of Neuropeptides
Gene summary
This gene encodes a member of the neuropeptide Y (NPY) family of peptides. The encoded 95 aa preproprotein is synthesized in the pancreatic islets of Langerhans and proteolytically processed to generate two peptide products. These products include the active pancreatic hormone of 36 aa and an icosapeptide of unknown function. This hormone acts as a regulator of pancreatic and gastrointestinal functions and may be important in the regulation of food intake. Plasma level of this hormone has been shown to be reduced in conditions associated with increased food intake and elevated in anorexia nervosa. In addition, infusion of this hormone in obese rodents has shown to decrease weight gain. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.7 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 PPY variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002722.5. 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 | 11 | 1 | 12 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 11 | 1 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002713.1 | 3 | MANE Select | |
| Ensembl | ENSP00000225992.3 | 3 | MANE Select | |
| RefSeq | NP_001306138.1 | 4 | Standard | |
| Ensembl | ENSP00000465711.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling by GPCR
- Signal Transduction
- GPCR signaling-G alpha q
- GPCR signaling-cholera toxin
- GPCR signaling-pertussis toxin
Biological Process
- G protein-coupled receptor signaling pathway
- neuropeptide signaling pathway
- protein secretion
- regulation of signaling receptor activity
Molecular Function
- G protein-coupled receptor binding
- hormone activity
- neuropeptide hormone activity
Cellular Component
- extracellular region
- extracellular space
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000591228
- Coding exons
- 3
- Length
- 1665
- Individuals with no LoFs
- 125472
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 264
- Defined
- 125739
- p
- 0.00106
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.758 | 40 | 56.0 | 0.715 | 0.00000327 | 582 |
| Missense (PolyPhen) | 8 | 14.489 | 0.55215 | 164 | ||
| Synonymous | -1.43 | 36 | 26.6 | 1.35 | 0.00000166 | 207 |
| Loss of Function | 0.478 | 3 | 4.04 | 0.743 | 1.71e-7 | 47 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.0083 | 0.0082 | notable |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Pancreatic hormone is synthesized in pancreatic islets of Langerhans and acts as a regulator of pancreatic and gastrointestinal functions.;
Recessive Scores
- pRec
- 0.286
Intolerance Scores
- LoFtool
- 0.394
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 74.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |