OPRPN
protein-codingopiorphin prepropeptide
Gene summary
This gene encodes a member of the proline-rich protein family. The encoded protein has multiple proposed functions, including roles in pain suppression, penile erection, and protection of the eye surface. The QRFSR pentapeptide, known as opiorphin, is derived from the N-terminal of this protein. Opiorphin inhibits the enkephalin-inactivating peptidases neprilysin and aminopeptidase N, and this activity is thought to reduce sensitivity to painful stimuli by effecting enkephalin-related activation of opioid-dependent pathways. Opiorphin may also act as an anti-depressant. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
- PROL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.3 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 OPRPN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021225.5. 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 | 2 | 2 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 2 | 0 | 0 | 2 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067048.4 | 2 | MANE Select | |
| Ensembl | ENSP00000382485.2 | 2 | MANE Select | |
| RefSeq | NP_001289736.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- retina homeostasis
- negative regulation of endopeptidase activity
- regulation of sensory perception of pain
Molecular Function
- endopeptidase inhibitor activity
- peptidase inhibitor activity
Cellular Component
- extracellular region
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000399575
- Coding exons
- 2
- Length
- 12313
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0720 | 130 | 132 | 0.982 | 0.00000662 | 1568 |
| Missense (PolyPhen) | 4 | 4.0581 | 0.9857 | 51 | ||
| Synonymous | -2.54 | 74 | 51.0 | 1.45 | 0.00000264 | 564 |
| Loss of Function | 0.908 | 0 | 0.960 | 0.00 | 4.05e-8 | 12 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| 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 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Opiorphin is an endogenous inhibitor of neprilysin and aminopeptidase N. Inhibits the breakdown of substance P, Mca-BK2 and Met-enkephalin by neprilysin in vitro with IC(50) values of 29 uM, 33 uM and 33 uM respectively. Inhibits the breakdown of Ala- pNA by aminopeptidase N in vitro with an IC(50) of 65 uM. Has a potent analgesic effect when administered to rats by intravenous injection. {ECO:0000269|PubMed:17101991}.;
Recessive Scores
- pRec
- 0.0420
Intolerance Scores
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 37.11
Essentials
- Essential (gene trap)
- N