OPRPN

Summary

OPRPN (opiorphin prepropeptide, HGNC:17279) is a protein-coding gene on chromosome 4q13.3, encoding Opiorphin prepropeptide (Q99935). Opiorphin is an endogenous inhibitor of neprilysin and aminopeptidase N.

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.

Source: NCBI Gene 58503 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_021225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17279
Approved symbol	OPRPN
Name	opiorphin prepropeptide
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	BPLP, PRL1
Ensembl gene	ENSG00000171199
Ensembl biotype	protein_coding
OMIM	608936
Entrez	58503

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000399575, ENST00000505023, ENST00000514338

RefSeq mRNA: 2 — MANE Select: NM_021225 NM_001302807, NM_021225

CCDS: CCDS43235

Canonical transcript exons

ENST00000399575 — 3 exons

Exon	Start	End
ENSE00001171048	70397940	70398040
ENSE00001539149	70409380	70410195
ENSE00003626845	70399271	70399336

Expression profiles

Bgee: expression breadth broad, 58 present calls, max score 89.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5322 / max 2580.7320, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47929	1.5322	9

Top tissues by expression

245 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	89.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.68	gold quality
sperm	CL:0000019	79.06	silver quality
epithelium of mammary gland	UBERON:0003244	77.66	gold quality
male germ cell	CL:0000015	77.12	silver quality
mammary duct	UBERON:0001765	76.72	gold quality
saliva-secreting gland	UBERON:0001044	76.63	gold quality
minor salivary gland	UBERON:0001830	74.93	gold quality
parotid gland	UBERON:0001831	73.29	gold quality
mouth mucosa	UBERON:0003729	71.07	gold quality
cauda epididymis	UBERON:0004360	70.96	gold quality
tendon of biceps brachii	UBERON:0008188	70.66	gold quality
mammary gland	UBERON:0001911	65.73	gold quality
thoracic mammary gland	UBERON:0005200	65.53	gold quality
tibialis anterior	UBERON:0001385	65.28	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	62.05	gold quality
trachea	UBERON:0003126	62.02	gold quality
ileal mucosa	UBERON:0000331	60.73	silver quality
pancreatic ductal cell	CL:0002079	59.95	silver quality
mucosa of paranasal sinus	UBERON:0005030	59.41	gold quality
quadriceps femoris	UBERON:0001377	58.63	gold quality
vastus lateralis	UBERON:0001379	58.61	gold quality
palpebral conjunctiva	UBERON:0001812	57.81	silver quality
upper leg skin	UBERON:0004262	57.36	silver quality
hair follicle	UBERON:0002073	57.31	gold quality
deltoid	UBERON:0001476	56.70	gold quality
decidua	UBERON:0002450	56.55	gold quality
sural nerve	UBERON:0015488	55.37	silver quality
cranial nerve II	UBERON:0000941	54.46	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting OPRPN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-648	98.64	66.13	553
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-6823-5P	96.26	65.69	919

Literature-anchored findings (GeneRIF, showing 4)

• Results report the discovery of opiorphin, a previously uncharacterized physiological inhibitor of enkephalin-inactivating zinc ectopeptidases in humans. (PMID:17101991)
• All members of the human opiorphin family of genes can potentially modulate erectile physiology. Both hSMR3 and ProL1 are down-regulated in the corpora of men with ED, and therefore both genes can potentially act as markers of ED. (PMID:18410445)
• Role of opiorphin genes in prostate cancer growth and progression. (PMID:33593085)
• Relationship between saliva opiorphin levels, pain threshold, and cutting number in adolescents with non suicidal self injury. (PMID:35636040)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Opiorphin prepropeptide — Q99935 (reviewed: Q99935)

Alternative names: Basic proline-rich lacrimal protein, Proline-rich protein 1

All UniProt accessions (1): Q99935

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Secreted.

Tissue specificity. Abundantly expressed in lacrimal gland where it found in the secretory endpieces. Also expressed at modest levels in the submandibular gland.

Similarity. Belongs to the PROL1/PROL3 family.

RefSeq proteins (2): NP_001289736, NP_067048* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026288	SMR-like	Family

Pfam: PF15621

UniProt features (7 total): signal peptide 1, chain 1, peptide 1, region of interest 1, modified residue 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99935-F1	53.50	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 22

Glycosylation sites (1): 218

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): chr4q13, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_REGULATION_OF_SENSORY_PERCEPTION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, MORF_RAB3A, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_SENSORY_PERCEPTION, MORF_WNT1, ACEVEDO_LIVER_CANCER_UP, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, YOSHIMURA_MAPK8_TARGETS_UP, DANG_REGULATED_BY_MYC_DN

GO Biological Process (1): regulation of sensory perception of pain (GO:0051930)

GO Molecular Function (2): endopeptidase inhibitor activity (GO:0004866), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sensory perception of pain	1
regulation of sensory perception	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

8 interactions, top by confidence:

A	B	Type	Score
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
OPRPN	SLC5A4	psi-mi:“MI:0915”(physical association)	0.400
ITLN2	IGLC7	psi-mi:“MI:0914”(association)	0.350
FKBP14	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
LRRC8E	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): PROL1 (Affinity Capture-MS), PROL1 (Affinity Capture-MS), SLC5A4 (Affinity Capture-MS), PROL1 (Affinity Capture-MS), PROL1 (Affinity Capture-MS), PROL1 (Affinity Capture-MS), PROL1 (Affinity Capture-MS), PROL1 (Affinity Capture-RNA), PROL1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0G2K6Z9, A0A1D0BN92, A0A411D538, A1YQ92, B3A0Q4, D5L5Q8, H2A0M0, K9N4Q4, O08546, O15946, O35979, O35985, O36359, P06796, P07498, P0DMD3, P0DMD4, P11841, P13432, P15450, P18897, P34468, P54684, P55796, P79139, P81058, P81059, P83055, P83474, P86735, Q01493, Q09283, Q17RF5, Q28441, Q28451, Q28794, Q29135, Q29137, Q61900, Q7T6X1

Diamond homologs: P02814, P13432, Q99935, Q99954

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

3 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

274 predictions. Top by Δscore:

Variant	Effect	Δscore
4:70409378:A:AG	acceptor_gain	1.0000
4:70409379:G:GG	acceptor_gain	1.0000
4:70409379:GCCCA:G	acceptor_gain	1.0000
4:70409375:CACA:C	acceptor_loss	0.9900
4:70409376:ACAG:A	acceptor_loss	0.9900
4:70409377:CA:C	acceptor_loss	0.9900
4:70409378:A:C	acceptor_loss	0.9900
4:70409379:G:T	acceptor_loss	0.9900
4:70409379:GCCC:G	acceptor_gain	0.9900
4:70399337:G:GG	donor_gain	0.9800
4:70409370:A:AG	acceptor_gain	0.9800
4:70409371:T:G	acceptor_gain	0.9800
4:70409377:C:G	acceptor_gain	0.9800
4:70409379:GC:G	acceptor_gain	0.9800
4:70409379:GCC:G	acceptor_gain	0.9800
4:70409376:A:AG	acceptor_gain	0.9600
4:70398037:CAAG:C	donor_loss	0.9300
4:70398041:GTA:G	donor_loss	0.9300
4:70398042:T:G	donor_loss	0.9300
4:70399569:T:TA	donor_gain	0.9300
4:70399570:A:AA	donor_gain	0.9300
4:70409375:CACAG:C	acceptor_gain	0.9000
4:70409378:AGCC:A	acceptor_gain	0.9000
4:70409376:ACAGC:A	acceptor_gain	0.8900
4:70409377:CAGCC:C	acceptor_gain	0.8900
4:70409058:G:GA	donor_gain	0.8800
4:70399335:CA:C	donor_gain	0.8400
4:70409374:CCACA:C	acceptor_gain	0.8000
4:70399571:G:GG	donor_gain	0.7900
4:70408991:G:GG	donor_gain	0.7700

AlphaMissense

1577 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:70399331:T:C	F16L	0.897
4:70399333:C:A	F16L	0.897
4:70399333:C:G	F16L	0.897
4:70409623:T:C	F99L	0.861
4:70409625:T:A	F99L	0.861
4:70409625:T:G	F99L	0.861
4:70399317:C:A	A11D	0.855
4:70409647:T:C	F107L	0.855
4:70409649:C:A	F107L	0.855
4:70409649:C:G	F107L	0.855
4:70399307:G:C	G8R	0.851
4:70409560:T:C	F78L	0.817
4:70409562:T:A	F78L	0.817
4:70409562:T:G	F78L	0.817
4:70409521:T:C	F65L	0.814
4:70409523:T:A	F65L	0.814
4:70409523:T:G	F65L	0.814
4:70399298:T:C	F5L	0.786
4:70399300:C:A	F5L	0.786
4:70399300:C:G	F5L	0.786
4:70410067:T:C	F247L	0.771
4:70410069:T:A	F247L	0.771
4:70410069:T:G	F247L	0.771
4:70409389:A:C	S21R	0.765
4:70409391:T:A	S21R	0.765
4:70409391:T:G	S21R	0.765
4:70409398:T:C	F24L	0.759
4:70409400:C:A	F24L	0.759
4:70409400:C:G	F24L	0.759
4:70409698:T:C	F124L	0.750

dbSNP variants (sampled 300 via entrez): RS1000163988 (4:70400428 TA>T,TAA), RS1000239388 (4:70397911 T>A), RS1000493427 (4:70406578 A>C,T), RS1000562934 (4:70403469 T>C), RS1000626462 (4:70404825 G>A), RS1000782445 (4:70406193 T>C), RS1001398079 (4:70396578 C>T), RS1001746027 (4:70396881 C>G,T), RS1001831843 (4:70401778 G>A,C,T), RS1001862347 (4:70397630 T>C), RS1001907453 (4:70409239 C>T), RS1001970304 (4:70410663 G>C), RS1002500925 (4:70404782 G>A,T), RS1002553286 (4:70404422 C>T), RS1002564189 (4:70407958 G>A)

Disease associations

OMIM: gene MIM:608936 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Nickel	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.