PNOC
protein-codingprepronociceptin, the group of Neuropeptides
Gene summary
This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include nociceptin, nocistatin, and orphanin FQ2 (OFQ2). Nociceptin, also known as orphanin FQ, is a 17-amino acid neuropeptide that binds to the nociceptin receptor to induce increased pain sensitivity, and may additionally regulate body temperature, learning and memory, and hunger. Another product of the encoded preproprotein, nocistatin, may inhibit the effects of nociceptin. [provided by RefSeq, Jul 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.4 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 PNOC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006228.5. 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 | 1 | 1 | ||||
| missense | 34 | 1 | 35 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 34 | 1 | 1 | 36 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006219.1 | 2 | MANE Select | |
| Ensembl | ENSP00000301908.3 | 2 | MANE Select | |
| RefSeq | NP_001271173.1 | 1 | Standard | |
| Ensembl | ENSP00000428059.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pnocb | Danio rerio | Structure: solid lens vesicle Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vitamin D Receptor Pathway
- Signaling by GPCR
- Signal Transduction
- Peptide ligand-binding receptors
- Class A/1 (Rhodopsin-like receptors)
Biological Process
- signal transduction
- G protein-coupled receptor signaling pathway
- neuropeptide signaling pathway
- chemical synaptic transmission
- female pregnancy
Molecular Function
- opioid peptide activity
- neuropeptide hormone activity
- opioid receptor binding
Cellular Component
- extracellular region
- plasma membrane
- dendrite
- neuronal cell body
- axon terminus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000301908
- Coding exons
- 2
- Length
- 26370
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125732
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.639 | 90 | 109 | 0.827 | 0.00000653 | 1164 |
| Missense (PolyPhen) | 21 | 30.788 | 0.68209 | 331 | ||
| Synonymous | 0.725 | 38 | 44.1 | 0.861 | 0.00000262 | 336 |
| Loss of Function | 1.38 | 4 | 8.29 | 0.483 | 5.25e-7 | 76 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| 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 | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Nociceptin: Ligand of the opioid receptor-like receptor OPRL1. It may act as a transmitter in the brain by modulating nociceptive and locomotor behavior. May be involved in neuronal differentiation and development. {ECO:0000250|UniProtKB:P55791}.; FUNCTION: Orphanin FQ2: Has potent analgesic activity. {ECO:0000250|UniProtKB:Q64387}.;
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- LoFtool
- 0.362
- RVIS EVS
- -0.3
- RVIS percentile EVS
- 32.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |