OGFR

Summary

OGFR (opioid growth factor receptor, HGNC:15768) is a protein-coding gene on chromosome 20q13.33, encoding Opioid growth factor receptor (Q9NZT2). Receptor for opioid growth factor (OGF), also known as Met-enkephalin.

The protein encoded by this gene is a receptor for opioid growth factor (OGF), also known as [Met(5)]-enkephalin. OGF is a negative regulator of cell proliferation and tissue organization in a variety of processes. The encoded unbound receptor for OGF has been localized to the outer nuclear envelope, where it binds OGF and is translocated into the nucleus. The coding sequence of this gene contains a polymorphic region of 60 nt tandem imperfect repeat units. Several transcripts containing between zero and eight repeat units have been reported.

Source: NCBI Gene 11054 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 132 total
• Druggable target: yes
• MANE Select transcript: NM_007346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15768
Approved symbol	OGFR
Name	opioid growth factor receptor
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	7-60
Ensembl gene	ENSG00000060491
Ensembl biotype	protein_coding
OMIM	606459
Entrez	11054

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000290291, ENST00000370461, ENST00000450048, ENST00000892717, ENST00000892718, ENST00000967036

RefSeq mRNA: 1 — MANE Select: NM_007346 NM_007346

CCDS: CCDS13504

Canonical transcript exons

ENST00000290291 — 7 exons

Exon	Start	End
ENSE00001210611	62812230	62814000
ENSE00001280931	62811462	62811610
ENSE00002438831	62809585	62809663
ENSE00002440273	62810499	62810565
ENSE00002499201	62808247	62808325
ENSE00002507804	62807537	62807605
ENSE00002728822	62804835	62805030

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 96.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.8234 / max 1160.2352, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185759	43.8234	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.51	gold quality
monocyte	CL:0000576	95.76	gold quality
mononuclear cell	CL:0000842	95.59	gold quality
leukocyte	CL:0000738	95.55	gold quality
sural nerve	UBERON:0015488	95.06	gold quality
right frontal lobe	UBERON:0002810	94.66	gold quality
right lobe of liver	UBERON:0001114	94.64	gold quality
endometrium epithelium	UBERON:0004811	94.44	gold quality
spleen	UBERON:0002106	93.95	gold quality
right lung	UBERON:0002167	93.27	gold quality
right uterine tube	UBERON:0001302	93.16	gold quality
tibial nerve	UBERON:0001323	92.85	gold quality
cingulate cortex	UBERON:0003027	92.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.67	gold quality
anterior cingulate cortex	UBERON:0009835	92.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.50	gold quality
mucosa of stomach	UBERON:0001199	92.46	gold quality
upper lobe of left lung	UBERON:0008952	92.37	gold quality
apex of heart	UBERON:0002098	92.24	gold quality
left ovary	UBERON:0002119	92.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.14	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.14	gold quality
right lobe of thyroid gland	UBERON:0001119	92.10	gold quality
adenohypophysis	UBERON:0002196	92.08	gold quality
frontal pole	UBERON:0002795	92.04	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.96	gold quality
lower esophagus	UBERON:0013473	91.95	gold quality
left lobe of thyroid gland	UBERON:0001120	91.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.93	gold quality
paraflocculus	UBERON:0005351	91.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

18 targeting OGFR, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-1178-5P	95.83	64.12	504

Literature-anchored findings (GeneRIF, showing 15)

• Gene therapy to reinstate more OGFr and enhance OGFr function, could serve as a useful treatment for inhibiting tumor progression in head and neck cancers. (PMID:16685459)
• Opioid growth factor receptor is unaltered with the progression of human pancreatic and colon cancers (PMID:16820893)
• These data indicate that the OGF receptor is integral to cell replication of SCCHN, and support treatment modalities that amplify OGFr in order to decrease the growth of these neoplasias. (PMID:17273790)
• supports opioid growth factor receptor (OGFr) gene function as a regulator of cell proliferation that impacts on tumorigenic expression, and suggest that molecular and pharmacological manipulation of OGFr may prevent or delay human pancreatic cancer. (PMID:18636152)
• Results indicate that both p16(INK4a) and p21(WAF1/CIP1) are required for the opioid growth factor (OGF)-OGF receptor axis to inhibit cell proliferation in normal cells. (PMID:18923142)
• the regulation of cell proliferation by the OGF-OGFr axis is dependent on nucleocytoplasmic translocation and reliant on the integrity of two NLSs in OGFr to interact with transport receptors. (PMID:19244545)
• Cell proliferation of human ovarian cancer is regulated by the opioid growth factor-opioid growth factor receptor axis. (PMID:19297547)
• Opioid growth factor-opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers. (PMID:19675283)
• OGF and OGFR are present in follicular-derived thyroid cancers, and that OGF serves in a inhibitory manner to maintain homeostasis of cell proliferation. (PMID:19835629)
• These data are the first to report that theOGFr system is a native biological regulator of cell proliferation in Hepatocellular carcinoma (PMID:19923357)
• OGF-OGFr axis is a determinant of the progression of human ovarian cancer (PMID:22328595)
• The OGF-OGFr axis may be a feasible target for treatment of cancer of the ovary (i) in a prophylactic fashion, (ii) following cytoreduction or (iii) in conjunction with standard chemotherapy for additive effectiveness (PMID:23856908)
• The blockade of OGF signaling by MNTX releases cells from their arrest and boosts the effect of Doc (PMID:25853862)
• Morphine interacts with OGFR and may suppress lung cancer proliferation and progression. (PMID:27167686)
• beta-endorphin and opioid growth factor as biomarkers of physical ability in multiple sclerosis. (PMID:33677409)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ogfr2	ENSDARG00000024815
danio_rerio	ogfr	ENSDARG00000037837
danio_rerio	ogfr1	ENSDARG00000099409
danio_rerio		ENSDARG00000103677
mus_musculus	Ogfr	ENSMUSG00000049401
rattus_norvegicus	Ogfr	ENSRNOG00000009355

Paralogs (1): OGFRL1 (ENSG00000119900)

Protein

Protein identifiers

Opioid growth factor receptor — Q9NZT2 (reviewed: Q9NZT2)

Alternative names: Protein 7-60, Zeta-type opioid receptor

All UniProt accessions (3): Q9NZT2, A0A0A0MRN5, Q4VXW3

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for opioid growth factor (OGF), also known as Met-enkephalin. Seems to be involved in growth regulation.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in the heart and liver, moderately in skeletal muscle and kidney and to a lesser extent in brain and pancreas. Expressed in fetal tissues including liver and kidney.

Similarity. Belongs to the opioid growth factor receptor family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZT2-1	1	yes
Q9NZT2-2	2

RefSeq proteins (1): NP_031372* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006757	OGF_rcpt	Domain
IPR006770	OGF_rcpt_rpt	Repeat
IPR039574	OGFr	Family

Pfam: PF04664, PF04680

UniProt features (53 total): sequence conflict 15, modified residue 14, compositionally biased region 8, repeat 7, region of interest 4, sequence variant 2, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZT2-F1	63.00	0.34

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 (14): 1, 299, 315, 349, 361, 378, 382, 403, 420, 484, 537, 557, 617, 637

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 135 (showing top): MORF_RAB5A, GOBP_GROWTH, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, RODRIGUES_NTN1_TARGETS_DN, AMIT_EGF_RESPONSE_120_HELA, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, SCHLOSSER_SERUM_RESPONSE_AUGMENTED_BY_MYC, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_CELL_GROWTH, GOBP_REGULATION_OF_GROWTH, SANSOM_APC_MYC_TARGETS, GARY_CD5_TARGETS_UP

GO Biological Process (1): regulation of cell growth (GO:0001558)

GO Molecular Function (3): opioid growth factor receptor activity (GO:0140625), protein binding (GO:0005515), signaling receptor activity (GO:0038023)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
peptide receptor activity	1
binding	1
molecular transducer activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

560 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OGFR	PENK	P01210	987
OGFR	OPRD1	P41143	428
OGFR	HAP1	P54257	422
OGFR	OPRM1	P35372	410
OGFR	IVNS1ABP	Q9Y6Y0	288
OGFR	PGBD4	Q96DM1	273
OGFR	SPATA2L	Q8IUW3	254
OGFR	CYB5D1	Q6P9G0	251
OGFR	CYB561D1	Q8N8Q1	247
OGFR	RBM38	Q9H0Z9	244
OGFR	PNOC	Q13519	241
OGFR	PPP1R14B	Q96C90	229
OGFR	CDH4	P55283	221
OGFR	FAM53A	Q6NSI3	220
OGFR	CCNQ	Q8N1B3	220

IntAct

19 interactions, top by confidence:

A	B	Type	Score
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
WASF3	HOXB9	psi-mi:“MI:0914”(association)	0.530
OGFR	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
OGFR	CDK4	psi-mi:“MI:0915”(physical association)	0.400
TERF1	OGFR	psi-mi:“MI:0915”(physical association)	0.370
OGFR	GPR182	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
PRKCE	SRP54	psi-mi:“MI:0914”(association)	0.350
PRKCE	CST4	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
OAS1	UBA6	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
GSTK1	OGFR	psi-mi:“MI:0915”(physical association)	0.000
OGFR	TERF2IP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (60): OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), CDK4 (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS), OGFR (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YX94, A0A0J9YXQ4, A0A0J9YY54, A0A494C1R9, A5D7L8, A6NDY0, A6NKD2, A7E321, E9PGG2, F6SZT2, O14771, O19110, O75807, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0CW24, P17564, P78358, Q01534, Q0P5N2, Q15735, Q2KI51, Q2M329, Q587J8, Q5DTT8, Q5R5G8, Q5R6R8, Q5SV97, Q60465, Q62881, Q69ZB3, Q6P752, Q86V59, Q8BSI6, Q8IWY8, Q8N3D4, Q8VD63

Diamond homologs: A2VCV0, Q4KLH3, Q5TC84, Q8VE52, Q99PG2, Q9NZT2, Q9QXY4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	25
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1272 predictions. Top by Δscore:

Variant	Effect	Δscore
20:62804983:G:GT	donor_gain	1.0000
20:62805026:TCCAG:T	donor_loss	1.0000
20:62805027:CCAG:C	donor_loss	1.0000
20:62805028:CAG:C	donor_loss	1.0000
20:62805030:GGTGC:G	donor_loss	1.0000
20:62805031:G:GA	donor_loss	1.0000
20:62805032:T:A	donor_loss	1.0000
20:62807535:A:AG	acceptor_gain	1.0000
20:62807536:G:GT	acceptor_gain	1.0000
20:62807536:GTCC:G	acceptor_gain	1.0000
20:62807536:GTCCA:G	acceptor_gain	1.0000
20:62808236:T:A	acceptor_gain	1.0000
20:62808237:G:A	acceptor_gain	1.0000
20:62808242:TTCA:T	acceptor_loss	1.0000
20:62808245:A:AG	acceptor_gain	1.0000
20:62808245:AG:A	acceptor_gain	1.0000
20:62808245:AGGAT:A	acceptor_loss	1.0000
20:62808246:G:GC	acceptor_gain	1.0000
20:62808246:GG:G	acceptor_gain	1.0000
20:62808246:GGA:G	acceptor_gain	1.0000
20:62808246:GGAT:G	acceptor_gain	1.0000
20:62808246:GGATC:G	acceptor_gain	1.0000
20:62808323:ACG:A	donor_gain	1.0000
20:62808323:ACGG:A	donor_loss	1.0000
20:62808324:CGG:C	donor_loss	1.0000
20:62808325:GGTA:G	donor_loss	1.0000
20:62808326:G:GG	donor_gain	1.0000
20:62808326:GTA:G	donor_loss	1.0000
20:62809573:T:TA	acceptor_gain	1.0000
20:62809574:G:A	acceptor_gain	1.0000

AlphaMissense

4406 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:62808292:T:C	F96L	0.998
20:62808294:C:A	F96L	0.998
20:62808294:C:G	F96L	0.998
20:62809662:T:A	W133R	0.998
20:62809662:T:C	W133R	0.998
20:62810529:C:A	N143K	0.998
20:62810529:C:G	N143K	0.998
20:62811525:T:C	F177L	0.998
20:62811527:C:A	F177L	0.998
20:62811527:C:G	F177L	0.998
20:62812465:T:C	F284L	0.998
20:62812467:C:A	F284L	0.998
20:62812467:C:G	F284L	0.998
20:62808293:T:C	F96S	0.997
20:62811531:G:T	G179W	0.997
20:62812436:C:A	A274D	0.997
20:62808295:T:G	Y97D	0.996
20:62808302:A:T	N99I	0.996
20:62810503:T:C	F135L	0.996
20:62810505:T:A	F135L	0.996
20:62810505:T:G	F135L	0.996
20:62811532:G:A	G179E	0.996
20:62812269:G:C	K218N	0.996
20:62812269:G:T	K218N	0.996
20:62810499:G:C	W133C	0.995
20:62810499:G:T	W133C	0.995
20:62810504:T:C	F135S	0.995
20:62810546:T:A	L149H	0.995
20:62812471:T:A	W286R	0.995
20:62812471:T:C	W286R	0.995

dbSNP variants (sampled 300 via entrez): RS1000234821 (20:62807370 C>T), RS1000334423 (20:62812138 G>A,C), RS1000523811 (20:62806246 G>A,C), RS1000677977 (20:62811081 G>A), RS1000719986 (20:62813854 G>C,T), RS1000979370 (20:62805970 C>A,G,T), RS1000983980 (20:62805827 T>A,C,G), RS1001067217 (20:62805191 G>A,C), RS1001099773 (20:62805071 GC>G,GCC), RS1001312721 (20:62807301 G>A), RS1001326023 (20:62804812 C>CTTTCGG), RS1001853305 (20:62810700 C>G,T), RS1001918010 (20:62811785 A>G), RS1002450782 (20:62809053 CAAT>C), RS1002877725 (20:62811796 G>A)

Disease associations

OMIM: gene MIM:606459 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007917_12	Estimated glomerular filtration rate	2.000000e-07
GCST007919_21	Creatinine levels	3.000000e-08
GCST012226_840	Waist circumference adjusted for body mass index	7.000000e-14
GCST012231_17	A body shape index	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105797 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.71	Kd	195.6	nM	CHEMBL5653589
6.71	ED50	195.6	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 14 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148912: Binding affinity to human OGFR incubated for 45 mins by Kinobead based pull down assay	kd	0.1956	uM

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	3
Estradiol	increases expression, increases phosphorylation	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Tretinoin	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	decreases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Acrolein	increases abundance, affects cotreatment, decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Cannabidiol	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4044464	Binding	Antagonist activity at OGFR in human SKOV3 cells assessed as increase in cell growth at 10 uM after 24 hrs by hemacytometric method	Selective opioid growth factor receptor antagonists based on a stilbene isostere. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1ZI	Abcam HeLa OGFR KO	Cancer cell line	Female

Clinical trials (associated diseases)

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