NPFF
protein-codingneuropeptide FF-amide peptide precursor, the group of Neuropeptides
Gene summary
This gene encodes a member of the FMRFamide related peptide (FARP) family of neuropeptides. The encoded preproprotein is proteolytically processed to generate multiple amidated peptides. These peptides may play a role in the regulation of heart rate and blood pressure and the modulation of morphine-induced antinociception. Patients with hypertension exhibit decreased expression of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~0.8 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 NPFF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003717.4. 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 | 0 | |||||
| missense | 13 | 3 | 2 | 18 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 13 | 3 | 2 | 18 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003708.1 | 3 | MANE Select | |
| Ensembl | ENSP00000267017.3 | 3 | MANE Select | |
| RefSeq | NP_001307225.1 | 2 | Standard | |
| Ensembl | ENSP00000610453.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling by GPCR
- Signal Transduction
- Orexin and neuropeptides FF and QRFP bind to their respective receptors
- Peptide ligand-binding receptors
- Class A/1 (Rhodopsin-like receptors)
Biological Process
- acute inflammatory response to antigenic stimulus
- regulation of membrane depolarization
- G protein-coupled receptor signaling pathway
- positive regulation of cytosolic calcium ion concentration
- neuropeptide signaling pathway
Molecular Function
- G protein-coupled receptor binding
- signaling receptor binding
- neuropeptide hormone activity
Cellular Component
- extracellular region
- extracellular space
- dendrite
- vesicle
- perikaryon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000267017
- Coding exons
- 3
- Length
- 949
- Individuals with no LoFs
- 125691
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125709
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.461 | 52 | 62.2 | 0.836 | 0.00000341 | 716 |
| Missense (PolyPhen) | 16 | 16.577 | 0.96518 | 215 | ||
| Synonymous | 1.86 | 15 | 27.3 | 0.549 | 0.00000145 | 235 |
| Loss of Function | -0.545 | 6 | 4.72 | 1.27 | 2.02e-7 | 51 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00087 | 0.00086 | 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) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Morphine modulating peptides. Have wide-ranging physiologic effects, including the modulation of morphine-induced analgesia, elevation of arterial blood pressure, and increased somatostatin secretion from the pancreas. Neuropeptide FF potentiates and sensitizes ASIC1 and ASIC3 channels. {ECO:0000269|PubMed:11587714}.;
Intolerance Scores
- LoFtool
- 0.770
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 61.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0284
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |