OPRPN

Chr 4

opiorphin prepropeptide

Also known as: BPLP, PRL1, PROL1, opiorphin

NCBI Gene: 58503 ENSG00000171199 UniProt: Q99935 OMIM: 608936

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.73

Clinical Summary— OPRPN

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

2 VUS of 2 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.389

Z-score 0.91

OE 0.00 (0.00–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.07Z-score

OE missense 0.98 (0.85–1.14)

130 obs / 132.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.73)

0≤0.351.4

Missense OE?0.98 (0.85–1.14)

0≤0.61.4

Synonymous OE?1.45

0≤1.21.6

LoF obs/exp: 0 / 1.0Missense obs/exp: 130 / 132.3Syn Z: -2.54

This gene — mechanism propensity

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

2 submitted variants in ClinVar

ClinVar

Classification Summary

VUS2

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	2	2
Likely Benign	0	0
Benign	0	0
Total	2	2

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

23 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap OPRPN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →