NPFFR2
protein-codingneuropeptide FF receptor 2, the group of Neuropeptide FF receptors
Gene summary
This gene encodes a member of a subfamily of G-protein-coupled neuropeptide receptors. This protein is activated by the neuropeptides A-18-amide (NPAF) and F-8-amide (NPFF) and may function in pain modulation and regulation of the opioid system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]
- GPR74
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~116.4 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 NPFFR2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004885.3. 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 | 46 | 4 | 2 | 52 | ||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 49 | 4 | 2 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004876.3 | 3 | MANE Select | |
| Ensembl | ENSP00000307822.7 | 3 | MANE Select | |
| RefSeq | NP_001138228.1 | 4 | Standard | |
| RefSeq | NP_444264.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- GPCRs, Class A Rhodopsin-like
- Signaling by GPCR
- Signal Transduction
- Orexin and neuropeptides FF and QRFP bind to their respective receptors
Biological Process
- G protein-coupled receptor signaling pathway
- neuropeptide signaling pathway
- detection of abiotic stimulus
- cellular response to hormone stimulus
- regulation of MAPK cascade
Molecular Function
- G protein-coupled receptor activity
- neuropeptide receptor activity
- opioid receptor binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000308744
- Coding exons
- 4
- Length
- 116264
- Individuals with no LoFs
- 125515
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 232
- Defined
- 125748
- p
- 0.000927
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.17 | 336 | 281 | 1.20 | 0.0000136 | 3461 |
| Missense (PolyPhen) | 101 | 89.161 | 1.1328 | 1200 | ||
| Synonymous | -1.62 | 126 | 105 | 1.20 | 0.00000533 | 992 |
| Loss of Function | 1.15 | 13 | 18.3 | 0.711 | 8.70e-7 | 199 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0.0024 | 0.0023 | notable |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00096 | 0.00096 | rare |
| South Asian | 0.0010 | 0.00098 | notable |
| Other | 0.0026 | 0.0026 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system.;
Recessive Scores
- pRec
- 0.0777
Intolerance Scores
- LoFtool
- 0.932
- RVIS EVS
- 0.36
- RVIS percentile EVS
- 74.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0771
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |