OPRPN

Chr 4

opiorphin prepropeptide

Also known as: BPLP, PRL1, PROL1, opiorphin

The encoded protein (opiorphin) is an endogenous inhibitor of neprilysin and aminopeptidase N that prevents the breakdown of enkephalins and substance P, thereby modulating pain sensitivity through opioid-dependent pathways. No established Mendelian diseases are currently associated with mutations in this gene. The gene shows moderate tolerance to loss-of-function variants (pLI 0.39, LOEUF 1.73), suggesting haploinsufficiency is unlikely to cause severe developmental phenotypes.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.73
Clinical SummaryOPRPN
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.73LOEUF
pLI 0.389
Z-score 0.91
OE 0.00 (0.001.73)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.07Z-score
OE missense 0.98 (0.851.14)
130 obs / 132.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.001.73)
00.351.4
Missense OE0.98 (0.851.14)
00.61.4
Synonymous OE1.45
01.21.6
LoF obs/exp: 0 / 1.0Missense obs/exp: 130 / 132.3Syn Z: -2.54
DN
0.79top 25%
GOF
0.5563th %ile
LOF
0.1994th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

OPRPN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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