OPN5

Summary

OPN5 (opsin 5, HGNC:19992) is a protein-coding gene on chromosome 6p12.3, encoding Opsin-5 (Q6U736). G-protein coupled receptor which selectively activates G(i) type G proteins via ultraviolet A (UVA) light-mediated activation in the retina.

Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This opsin gene is expressed in the eye, brain, testes, and spinal cord. This gene belongs to the seven-exon subfamily of mammalian opsin genes that includes peropsin (RRH) and retinal G protein coupled receptor (RGR). Like these other seven-exon opsin genes, this family member may encode a protein with photoisomerase activity. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 221391 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 23 total
• Druggable target: yes
• MANE Select transcript: NM_181744

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19992
Approved symbol	OPN5
Name	opsin 5
Location	6p12.3
Locus type	gene with protein product
Status	Approved
Aliases	neuropsin, dJ402H5.1
Ensembl gene	ENSG00000124818
Ensembl biotype	protein_coding
OMIM	609042
Entrez	221391

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000244799, ENST00000371211, ENST00000393699, ENST00000489301, ENST00000510695

RefSeq mRNA: 1 — MANE Select: NM_181744 NM_181744

CCDS: CCDS4923

Canonical transcript exons

ENST00000371211 — 7 exons

Exon	Start	End
ENSE00001351272	47786515	47786634
ENSE00003495757	47808154	47808395
ENSE00003601560	47791802	47791972
ENSE00003606116	47795229	47795563
ENSE00003679795	47811674	47811731
ENSE00003978354	47823983	47826381
ENSE00003978355	47782032	47782196

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 80.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0176 / max 14.8858, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68175	0.0127	3
68174	0.0049	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.56	silver quality
ileal mucosa	UBERON:0000331	80.55	silver quality
tibialis anterior	UBERON:0001385	73.23	silver quality
left testis	UBERON:0004533	72.62	gold quality
right testis	UBERON:0004534	72.30	gold quality
testis	UBERON:0000473	70.83	gold quality
sperm	CL:0000019	67.93	silver quality
pancreatic ductal cell	CL:0002079	64.78	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.38	gold quality
upper leg skin	UBERON:0004262	59.14	gold quality
gingival epithelium	UBERON:0001949	55.94	gold quality
skin of hip	UBERON:0001554	55.49	silver quality
epithelial cell of pancreas	CL:0000083	55.23	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
epithelium of nasopharynx	UBERON:0001951	54.26	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
heart left ventricle	UBERON:0002084	53.29	gold quality
cardiac ventricle	UBERON:0002082	52.92	gold quality
epithelium of mammary gland	UBERON:0003244	52.59	gold quality
mammary duct	UBERON:0001765	52.55	gold quality
tibia	UBERON:0000979	52.02	gold quality
parotid gland	UBERON:0001831	52.00	gold quality
gingiva	UBERON:0001828	51.38	gold quality
myocardium	UBERON:0002349	51.02	gold quality
lower lobe of lung	UBERON:0008949	50.16	silver quality
quadriceps femoris	UBERON:0001377	49.96	gold quality
nasal cavity epithelium	UBERON:0005384	49.93	gold quality
tendon of biceps brachii	UBERON:0008188	47.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting OPN5, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4698	99.84	71.41	4303

Literature-anchored findings (GeneRIF, showing 7)

• Genetic variation of the hNP gene may contribute to molecular mechanisms of bipolar disorder and some aspects of memory and intelligence. (PMID:18354391)
• UV photoreceptor in human beings OPN5 triggers a UV-sensitive Gi-mediated signaling pathway in the mammalian tissues. (PMID:22043319)
• Opn5m may work exclusively as a short wavelength sensor in the brain as well as in the retina with the assistance of an 11-cis-retinal-supplying system. (PMID:24403072)
• It dissects a schizophrenic susceptibility gene, NRG1. (PMID:24614639)
• Data indicate that opsin5 (OPN5) photoreceptor mediates light-induced Ca(2+) response. (PMID:24941910)
• Expression of the hNP gene on the mRNA level, evaluated based on peripheral blood, is significantly higher in the patients with MRD than in the healthy subjects. (PMID:28636578)
• Neuropsin in mental health. (PMID:32414324)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	opn5	ENSDARG00000070110
mus_musculus	Opn5	ENSMUSG00000043972
rattus_norvegicus	Opn5	ENSRNOG00000012689
caenorhabditis_elegans		WBGENE00005641
caenorhabditis_elegans		WBGENE00017176

Paralogs (9): OPN3 (ENSG00000054277), OPN1LW (ENSG00000102076), OPN4 (ENSG00000122375), OPN1SW (ENSG00000128617), RHO (ENSG00000163914), OPN1MW2 (ENSG00000166160), RRH (ENSG00000180245), OPN1MW (ENSG00000268221), OPN1MW3 (ENSG00000269433)

Protein

Protein identifiers

Opsin-5 — Q6U736 (reviewed: Q6U736)

Alternative names: G-protein coupled receptor 136, G-protein coupled receptor PGR12, Neuropsin, Transmembrane protein 13

All UniProt accessions (3): D6RDV4, Q6U736, J3KPQ2

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor which selectively activates G(i) type G proteins via ultraviolet A (UVA) light-mediated activation in the retina. Preferentially binds the chromophore 11-cis retinal and is a bistable protein that displays emission peaks at 380 nm (UVA light) and 470 nm (blue light). Required for the light-response in the inner plexiform layer, and contributes to the regulation of the light-response in the nerve fiber layer, via phosphorylated DAT/SLC6A3 dopamine uptake. Involved in local corneal and retinal circadian rhythm photoentrainment via modulation of the UVA light-induced phase-shift of the retina clock. Acts as a circadian photoreceptor in the outer ear, via modulation of circadian clock-gene expression in response to violet light during the light-to-dark transition phase and night phase of the circadian cycle. Required in the retina to negatively regulate hyaloid vessel regression during postnatal development via light-dependent OPN5-SLC32A1-DRD2-VEGFR2 signaling. Involved in the light-dependent regulation of retina and vitreous compartment dopamine levels.

Subcellular location. Cell membrane.

Tissue specificity. Detected in brain and retina and cell lines derived from neural retina.

Post-translational modifications. It is uncertain whether Cys-315 or Cys-316 is palmitoylated.

Similarity. Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.

RefSeq proteins (1): NP_859528* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR002962	Peropsin	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR027430	Retinal_BS	Binding_site
IPR050125	GPCR_opsins	Family

Pfam: PF00001

UniProt features (24 total): topological domain 8, transmembrane region 7, sequence conflict 3, lipid moiety-binding region 2, chain 1, modified residue 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6U736-F1	83.83	0.63

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 (3): 296, 315, 316

Disulfide bonds (1): 106–183

Glycosylation sites (1): 4

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-419771	Opsins

MSigDB gene sets: 94 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_PHOTOPERIODISM, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_PHOTOTRANSDUCTION, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_ANATOMICAL_STRUCTURE_REGRESSION, chr6p12, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, WTGAAAT_UNKNOWN, GOBP_RESPONSE_TO_UV, OCT1_06, GOBP_RESPONSE_TO_RADIATION, GOBP_ENTRAINMENT_OF_CIRCADIAN_CLOCK, GOBP_DETECTION_OF_LIGHT_STIMULUS

GO Biological Process (10): G protein-coupled receptor signaling pathway (GO:0007186), visual perception (GO:0007601), phototransduction (GO:0007602), phototransduction, UV (GO:0007604), entrainment of circadian clock by photoperiod (GO:0043153), cellular response to light stimulus (GO:0071482), cellular response to UV-A (GO:0071492), hyaloid vascular plexus regression (GO:1990384), signal transduction (GO:0007165), detection of visible light (GO:0009584)

GO Molecular Function (4): 11-cis retinal binding (GO:0005502), G protein-coupled photoreceptor activity (GO:0008020), G protein-coupled receptor activity (GO:0004930), photoreceptor activity (GO:0009881)

GO Cellular Component (4): photoreceptor outer segment (GO:0001750), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
G protein-coupled receptor activity	2
signal transduction	2
detection of light stimulus	2
cellular response to UV	2
sensory perception of light stimulus	1
phototransduction	1
detection of UV	1
photoperiodism	1
entrainment of circadian clock	1
response to light stimulus	1
cellular response to radiation	1
response to UV-A	1
camera-type eye development	1
anatomical structure regression	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
retinal binding	1
detection of visible light	1
photoreceptor activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
signaling receptor activity	1
photoreceptor cell cilium	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OPN5	ALDH18A1	P54886	775
OPN5	OPHN1	O60890	624
OPN5	TSHB	P01222	500
OPN5	DIO2	Q92813	475
OPN5	TSHR	P16473	472
OPN5	ZNF875	P10072	458
OPN5	MEDAG	Q5VYS4	441
OPN5	DIO3	P55073	432
OPN5	PER2	O15055	415
OPN5	GNAT2	P19087	413
OPN5	NRL	P54845	410
OPN5	CNGA3	Q16281	408
OPN5	EYA3	Q99504	403
OPN5	CRY1	Q16526	388
OPN5	SPP1	P10451	388

IntAct

2 interactions, top by confidence:

A	B	Type	Score
OPN5	LGALS7	psi-mi:“MI:0914”(association)	0.350

BioGRID (2): LGALS7B (Affinity Capture-MS), PKP1 (Affinity Capture-MS)

ESM2 similar proteins: O01668, O02464, O02465, O13018, O16005, O16017, O16018, O16019, O16020, O18312, O18315, O18481, O18485, O18486, O42266, O61303, O96107, P04950, P06002, P08099, P08255, P09241, P17646, P22269, P24603, P28678, P28679, P28680, P29404, P31356, P35356, P35360, P35361, P35362, P87368, P90680, P91657, Q17053, Q17094, Q17292

Diamond homologs: O01668, O01670, O02464, O02465, O15973, O16005, O16017, O16018, O16019, O16020, O18312, O18315, O18481, O18485, O18486, O57422, O61303, O96107, P04950, P06002, P08099, P08255, P08913, P09241, P17646, P22269, P22909, P24603, P28678, P28679, P28680, P29404, P31356, P35356, P35360, P35361, P35362, P90680, P91657, Q01338

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1244 predictions. Top by Δscore:

Variant	Effect	Δscore
6:47782194:TTGG:T	donor_loss	1.0000
6:47782195:TGG:T	donor_loss	1.0000
6:47782196:GGT:G	donor_loss	1.0000
6:47782197:G:GC	donor_loss	1.0000
6:47782197:G:GG	donor_gain	1.0000
6:47782198:T:G	donor_loss	1.0000
6:47786630:TTCAG:T	donor_loss	1.0000
6:47786631:TCAGG:T	donor_loss	1.0000
6:47786632:CAG:C	donor_loss	1.0000
6:47786633:AGG:A	donor_loss	1.0000
6:47786634:GG:G	donor_loss	1.0000
6:47786635:GTAAC:G	donor_loss	1.0000
6:47786636:T:G	donor_loss	1.0000
6:47795227:AGG:A	acceptor_gain	1.0000
6:47795228:GGG:G	acceptor_gain	1.0000
6:47795433:T:TA	acceptor_gain	1.0000
6:47795440:AAC:A	acceptor_gain	1.0000
6:47795441:AC:A	acceptor_gain	1.0000
6:47795442:C:CA	acceptor_gain	1.0000
6:47782157:G:GT	donor_gain	0.9900
6:47782157:G:T	donor_gain	0.9900
6:47782192:AATTG:A	donor_gain	0.9900
6:47782193:ATTG:A	donor_gain	0.9900
6:47782194:TTG:T	donor_gain	0.9900
6:47786509:TTGTA:T	acceptor_loss	0.9900
6:47786510:TGTAG:T	acceptor_loss	0.9900
6:47786511:GTAG:G	acceptor_loss	0.9900
6:47786512:TA:T	acceptor_loss	0.9900
6:47786513:A:AC	acceptor_loss	0.9900
6:47786513:A:AG	acceptor_gain	0.9900

AlphaMissense

2288 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:47791848:G:C	W99C	0.999
6:47791848:G:T	W99C	0.999
6:47791933:A:C	S128R	0.999
6:47791935:C:A	S128R	0.999
6:47791935:C:G	S128R	0.999
6:47808178:T:C	F261L	0.999
6:47808180:C:A	F261L	0.999
6:47808180:C:G	F261L	0.999
6:47808190:T:A	W265R	0.999
6:47808190:T:C	W265R	0.999
6:47786606:T:A	N74K	0.998
6:47786606:T:G	N74K	0.998
6:47791846:T:A	W99R	0.998
6:47791846:T:C	W99R	0.998
6:47791943:G:C	R131P	0.998
6:47795276:T:A	W157R	0.998
6:47795276:T:C	W157R	0.998
6:47795294:T:A	W163R	0.998
6:47795294:T:C	W163R	0.998
6:47808197:C:A	P267H	0.998
6:47782196:G:A	G44R	0.997
6:47782196:G:C	G44R	0.997
6:47786625:G:A	G81R	0.997
6:47786625:G:C	G81R	0.997
6:47791880:G:A	G110E	0.997
6:47791909:A:C	S120R	0.997
6:47791911:C:A	S120R	0.997
6:47791911:C:G	S120R	0.997
6:47795355:G:A	C183Y	0.997
6:47795356:C:G	C183W	0.997

dbSNP variants (sampled 300 via entrez): RS1000023136 (6:47780826 G>A), RS1000030318 (6:47821933 C>A,T), RS1000097851 (6:47805954 C>G,T), RS1000198570 (6:47823390 A>T), RS1000271561 (6:47798498 G>A), RS1000321644 (6:47823681 C>A,G), RS1000323961 (6:47810479 G>A), RS1000412985 (6:47788716 A>C), RS1000436252 (6:47804512 A>G,T), RS1000466801 (6:47788926 A>G), RS1000480999 (6:47815463 T>A), RS1000493010 (6:47799449 C>A), RS1000585659 (6:47794947 C>A,T), RS1000615712 (6:47799705 T>C), RS1000658747 (6:47811872 G>A,T)

Disease associations

OMIM: gene MIM:609042 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002397_149	Mean spheric corpuscular volume	3.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523878 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Opsin receptors

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
testosterone undecanoate	affects cotreatment, increases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
CGP 52608	increases reaction, affects binding	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	decreases methylation	1
Ethanol	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Malathion	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	decreases methylation	1
Levonorgestrel	affects cotreatment, increases expression	1
Permethrin	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883556	Binding	PRESTO-Tango GPCRome screening (OPN5)	Data for DCP probe UCSF924

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KY67	PathHunter CHO-K1 OPN5 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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