OPN3

Summary

OPN3 (opsin 3, HGNC:14007) is a protein-coding gene on chromosome 1q43, encoding Opsin-3 (Q9H1Y3). G protein-coupled receptor which selectively activates G(i/o) proteins via ultraviolet A (UVA) light-mediated activation in the skin, thereby decreasing cellular cAMP.

Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. In addition to the visual opsins, mammals possess several photoreceptive non-visual opsins that are expressed in extraocular tissues. This gene, opsin 3, is strongly expressed in brain and testis and weakly expressed in liver, placenta, heart, lung, skeletal muscle, kidney, and pancreas. The gene may also be expressed in the retina. The protein has the canonical features of a photoreceptive opsin protein.

Source: NCBI Gene 23596 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 34 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_014322

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14007
Approved symbol	OPN3
Name	opsin 3
Location	1q43
Locus type	gene with protein product
Status	Approved
Aliases	ERO, NMO-1, encephalopsin, PPP1R116
Ensembl gene	ENSG00000054277
Ensembl biotype	protein_coding
OMIM	606695
Entrez	23596

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 1 protein_coding

ENST00000366554, ENST00000462265, ENST00000463155, ENST00000469376, ENST00000478849, ENST00000490673, ENST00000635737

RefSeq mRNA: 1 — MANE Select: NM_014322 NM_014322

CCDS: CCDS31072

Canonical transcript exons

ENST00000366554 — 4 exons

Exon	Start	End
ENSE00000793718	241604260	241604579
ENSE00001868270	241639882	241640369
ENSE00001957919	241593124	241594691
ENSE00003631971	241597746	241597997

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 95.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.8366 / max 55.0043, expressed in 1637 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18300	12.8275	1760
18299	4.5086	1517
18298	1.3280	888

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	95.27	gold quality
placenta	UBERON:0001987	95.15	gold quality
tibia	UBERON:0000979	93.16	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.13	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.98	gold quality
palpebral conjunctiva	UBERON:0001812	91.86	gold quality
visceral pleura	UBERON:0002401	91.24	gold quality
prefrontal cortex	UBERON:0000451	90.59	gold quality
amniotic fluid	UBERON:0000173	90.53	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.51	gold quality
monocyte	CL:0000576	90.44	gold quality
mononuclear cell	CL:0000842	90.33	gold quality
leukocyte	CL:0000738	90.09	gold quality
superior frontal gyrus	UBERON:0002661	90.00	gold quality
orbitofrontal cortex	UBERON:0004167	89.96	gold quality
colonic mucosa	UBERON:0000317	89.32	gold quality
primary visual cortex	UBERON:0002436	89.24	gold quality
mucosa of transverse colon	UBERON:0004991	88.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.56	gold quality
postcentral gyrus	UBERON:0002581	88.48	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.35	gold quality
decidua	UBERON:0002450	88.33	gold quality
metanephric glomerulus	UBERON:0004736	88.30	gold quality
frontal cortex	UBERON:0001870	88.23	gold quality
renal glomerulus	UBERON:0000074	88.04	gold quality
parietal lobe	UBERON:0001872	88.01	gold quality
adrenal tissue	UBERON:0018303	88.00	gold quality
occipital lobe	UBERON:0002021	87.96	gold quality
esophagus squamous epithelium	UBERON:0006920	87.78	gold quality
endothelial cell	CL:0000115	87.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	99.66
E-MTAB-6701	yes	75.86
E-ANND-3	yes	4.02
E-MTAB-8060	no	217.64
E-MTAB-7249	no	58.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting OPN3, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-217-5P	99.49	69.93	1419

Literature-anchored findings (GeneRIF, showing 21)

• Assignment of panopsin (OPN3) to human chromosome band 1q43 (PMID:12063405)
• Human OPN3 gene consists of six exons and expresses various splice variants. (PMID:12242008)
• Related persons with heterozygous germline deletions of 1q42.3, which includes EXO1, RGS7, KMO, CHML, and OPN3, showed no phenotypic abnormalities other than multiple leiomyomatosis. (PMID:14623461)
• Polymorphisms in the OPN3 and CHML genes are associated with asthma and atopic asthma. (PMID:18344558)
• Decreased OPN3 levels in Bel7402(5-FU) cells activated the anti-apoptotic pathway through increasing phospho-Akt and the Bcl2/Bax ratio, while overexpression of OPN3 inactivated this pathway. (PMID:22313545)
• OPN3 and the multimeric tyrosinase/tyrosinase-related protein complex induced after its activation appear as new potential targets for regulating melanogenesis but also to protect dark skins against blue light in physiological conditions and in pigmentary disorders. (PMID:28842328)
• This is the first demonstration of photorelaxation in airway smooth muscle via an OPN receptor-mediated pathway. (PMID:30284927)
• OPN3 and MC1R colocalize at both the plasma membrane. (PMID:31097585)
• Illuminating insights into opsin 3 function in the skin. (PMID:31653550)
• Opsin3 Downregulation Induces Apoptosis of Human Epidermal Melanocytes via Mitochondrial Pathway. (PMID:31730232)
• Expression of OPN3 in lung adenocarcinoma promotes epithelial-mesenchymal transition and tumor metastasis. (PMID:31802643)
• Activation of an Endogenous Opsin 3 Light Receptor Mediates Photo-Relaxation of Pre-Contracting Late Gestation Human Uterine Smooth Muscle Ex Vivo. (PMID:32166706)
• Identification of OPN3 as associated with non-syndromic oligodontia in a Japanese population. (PMID:33611338)
• Expression of OPN3 in acral lentiginous melanoma and its associated with clinicohistopathologic features and prognosis. (PMID:33955704)
• TGFbeta2 Upregulates Tyrosinase Activity through Opsin-3 in Human Skin Melanocytes In Vitro. (PMID:34029574)
• OPN3 Regulates Melanogenesis in Human Congenital Melanocytic Nevus Cells through Functional Interaction with BRAF(V600E). (PMID:35577105)
• The effects of missense OPN3 mutations in melanocytic lesions on protein structure and light-sensitive function. (PMID:36017595)
• Opsin 3 mediates UVA-induced keratinocyte supranuclear melanin cap formation. (PMID:36869204)
• Opsin 3 expression in human Langerhans cell histiocytosis and its mediation of ELD-1 cellular function. (PMID:37823488)
• In vitro differentiation of human amniotic epithelial stem cells into keratinocytes regulated by OPN3. (PMID:38284195)
• Downregulation of OPN3 Gene Induces Ferroptosis, Apoptosis, and Pyroptosis of Human Dermal Fibroblasts In Vitro. (PMID:38548258)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	opn3	ENSDARG00000052775
mus_musculus	Opn3	ENSMUSG00000026525
rattus_norvegicus	Opn3	ENSRNOG00000003778
drosophila_melanogaster	ninaE	FBGN0002940
drosophila_melanogaster	Rh2	FBGN0003248
drosophila_melanogaster	Rh3	FBGN0003249
drosophila_melanogaster	Rh4	FBGN0003250
drosophila_melanogaster	Rh5	FBGN0014019

Paralogs (9): OPN1LW (ENSG00000102076), OPN4 (ENSG00000122375), OPN5 (ENSG00000124818), OPN1SW (ENSG00000128617), RHO (ENSG00000163914), OPN1MW2 (ENSG00000166160), RRH (ENSG00000180245), OPN1MW (ENSG00000268221), OPN1MW3 (ENSG00000269433)

Protein

Protein identifiers

Opsin-3 — Q9H1Y3 (reviewed: Q9H1Y3)

Alternative names: Encephalopsin, Panopsin

All UniProt accessions (4): A0A1B0GUF8, Q6GMT1, Q6P5W7, Q9H1Y3

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor which selectively activates G(i/o) proteins via ultraviolet A (UVA) light-mediated activation in the skin, thereby decreasing cellular cAMP. Binds both 11-cis retinal and all-trans retinal. Regulates melanogenesis in melanocytes by specifically inhibiting MC1R-evoked cAMP signaling, modulating calcium flux, regulating CAMK2 phosphorylation, and subsequently phosphorylating CREB, p38, ERK and MITF, probably in a constitutive, light-independent manner. In the paraventricular nucleus of the hypothalamus, inhibits MC4R-mediated cAMP signaling and activates KCNJ13 channel opening in a constitutive manner, thereby promoting food intake and modulating spontaneous firing of neurons. Plays a role in melanocyte survival through regulation of intracellular calcium levels and subsequent BCL2/RAF1 signaling. Additionally regulates apoptosis via cytochrome c release and subsequent activation of the caspase cascade. Required for TYR and DCT blue light-induced complex formation in melanocytes. Involved in keratinocyte differentiation in response to blue-light. Required for the UVA-mediated induction of calcium and mitogen-activated protein kinase signaling resulting in the expression of MMP1, MMP2, MMP3, MMP9 and TIMP1 in dermal fibroblasts. Plays a role in light-mediated glucose uptake, mitochondrial respiration and fatty acid metabolism in brown adipocyte tissues. May be involved in photorelaxation of airway smooth muscle cells, via blue-light dependent GPCR signaling pathways.

Subunit / interactions. Interacts with MC1R; the interaction results in a decrease in MC1R-mediated cAMP signaling and ultimately a decrease in melanin production in melanocytes. Forms a complex with KCNJ13 and MC4R; OPN3 inhibits MC4R signaling and potentiates KCNJ13.

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Expressed in tracheal airway smooth muscle (at protein level). Expressed throughout the epidermis and dermis, predominantly in the basal layer on the facial and abdominal skin (at protein level). Expressed in dermal fibroblasts (at protein level). Expressed in melanocytes (at protein level). Expressed in keratinocytes. Expressed in the retina.

Induction. Induced by low-level blue light (453nm) during epithelial wound healing. Induced by ultraviolet A light in dermal fibroblasts.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H1Y3-1	1, 1-4b-5-6	yes
Q9H1Y3-2	2, 1-2-5-6

RefSeq proteins (1): NP_055137* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00001

UniProt features (26 total): topological domain 8, transmembrane region 7, glycosylation site 2, sequence variant 2, chain 1, modified residue 1, lipid moiety-binding region 1, disulfide bond 1, splice variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1Y3-F1	80.71	0.69

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 (2): 299, 325

Disulfide bonds (1): 114–188

Glycosylation sites (2): 5, 198

Mutagenesis-validated functional residues (1):

Position	Phenotype
299	abolishes binding of 11-cis retinal and all-trans retinal. no effect on g-alpha (i) protein signaling.

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: 283 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_BEHAVIOR, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_PHOTOTRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_EPIDERMAL_CELL_DIFFERENTIATION

GO Biological Process (18): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), phototransduction (GO:0007602), detection of light stimulus (GO:0009583), response to blue light (GO:0009637), keratinocyte differentiation (GO:0030216), regulation of circadian rhythm (GO:0042752), negative regulation of apoptotic process (GO:0043066), positive regulation of D-glucose import across plasma membrane (GO:0046326), negative regulation of melanin biosynthetic process (GO:0048022), positive regulation of melanin biosynthetic process (GO:0048023), cellular response to light stimulus (GO:0071482), cellular response to UV-A (GO:0071492), positive regulation of cellular respiration (GO:1901857), positive regulation of eating behavior (GO:1904000), signal transduction (GO:0007165), detection of visible light (GO:0009584), positive regulation of metabolic process (GO:0009893)

GO Molecular Function (6): G protein-coupled receptor activity (GO:0004930), 11-cis retinal binding (GO:0005502), all-trans retinal binding (GO:0005503), G protein-coupled photoreceptor activity (GO:0008020), photoreceptor activity (GO:0009881), protein binding (GO:0005515)

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
response to light stimulus	3
cellular anatomical structure	3
G protein-coupled receptor activity	2
signal transduction	2
detection of light stimulus	2
melanin biosynthetic process	2
regulation of melanin biosynthetic process	2
retinal binding	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
detection of external stimulus	1
detection of abiotic stimulus	1
epidermal cell differentiation	1
skin development	1
circadian rhythm	1
regulation of biological process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
negative regulation of secondary metabolite biosynthetic process	1
positive regulation of secondary metabolite biosynthetic process	1
cellular response to radiation	1
cellular response to UV	1
response to UV-A	1
positive regulation of metabolic process	1
regulation of cellular respiration	1
cellular respiration	1
eating behavior	1
regulation of eating behavior	1
positive regulation of feeding behavior	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
metabolic process	1
regulation of metabolic process	1

Protein interactions and networks

STRING

706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OPN3	CHML	P26374	974
OPN3	KMO	O15229	861
OPN3	MAP1LC3C	Q9BXW4	757
OPN3	OPHN1	O60890	622
OPN3	WDR64	B1ANS9	582
OPN3	OSBPL3	Q9H4L5	424
OPN3	MC3R	P41968	408
OPN3	ITPR1	Q14643	407
OPN3	DNER	Q8NFT8	405
OPN3	EVA1A	Q9H8M9	405
OPN3	ARHGAP26	Q9UNA1	398
OPN3	EFCAB3	Q8N7B9	389
OPN3	MITF	O75030	383
OPN3	ATG5	Q9H1Y0	383
OPN3	MC1R	Q01726	382

IntAct

23 interactions, top by confidence:

A	B	Type	Score
OPN3	MC1R	psi-mi:“MI:0915”(physical association)	0.560
MC1R	OPN3	psi-mi:“MI:0915”(physical association)	0.560
OPN3	MC1R	psi-mi:“MI:0403”(colocalization)	0.560
OPN3	EIF2B2	psi-mi:“MI:0914”(association)	0.530
RAMP1	OPN3	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	OPN3	psi-mi:“MI:0915”(physical association)	0.400
OPN3	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
OPN3	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
OPN3	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): EIF2B5 (Affinity Capture-MS), EIF2B4 (Affinity Capture-MS), EIF2B2 (Affinity Capture-MS), EIF2B3 (Affinity Capture-MS), EIF2B3 (Affinity Capture-MS), EIF2B2 (Affinity Capture-MS), EIF2B4 (Affinity Capture-MS), EIF2B5 (Affinity Capture-MS), OPN3 (Affinity Capture-RNA), OPN3 (Affinity Capture-MS), OPN3 (Affinity Capture-MS), OPN3 (Affinity Capture-MS), EIF2B2 (Affinity Capture-MS), EIF2B4 (Affinity Capture-MS), EIF2B5 (Affinity Capture-MS)

ESM2 similar proteins: G4WMX4, O02836, O42329, O43613, O97512, O97661, P05363, P16177, P16610, P21452, P25931, P29371, P30098, P30549, P30559, P30560, P30975, P32306, P37288, P47937, P48043, P49146, P51144, P56449, P56494, P56718, P58307, P70536, P79113, P79218, P97295, P97926, Q0GBZ5, Q28756, Q5DUB2, Q5IS62, Q62463, Q63447, Q64077, Q90252

Diamond homologs: O02664, O13227, O14718, O15973, O16005, O35214, O57422, O60431, O77408, O88634, P02699, P02700, P09241, P14416, P21918, P22328, P24603, P28682, P31356, P32309, P32310, P35403, P41590, P41591, P41983, P49912, P51472, P52702, P60026, P61168, P61169, P79756, P79798, P79807, P79809, P79812, P79863, P79902, P79914, Q17094

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	26
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
831850	NC_000001.10:g.(?241661128)(242034263_?)del	Pathogenic

SpliceAI

2042 predictions. Top by Δscore:

Variant	Effect	Δscore
1:241594692:C:CC	acceptor_gain	1.0000
1:241594697:C:CT	acceptor_gain	1.0000
1:241597993:CGAAG:C	acceptor_gain	1.0000
1:241597998:C:CC	acceptor_gain	1.0000
1:241639942:T:A	donor_gain	1.0000
1:241594689:AAAC:A	acceptor_loss	0.9900
1:241594690:AA:A	acceptor_gain	0.9900
1:241594691:AC:A	acceptor_loss	0.9900
1:241594692:CTGGG:C	acceptor_loss	0.9900
1:241594698:A:T	acceptor_gain	0.9900
1:241597740:GCTTA:G	donor_loss	0.9900
1:241597741:CTTA:C	donor_loss	0.9900
1:241597742:TTAC:T	donor_loss	0.9900
1:241597743:TAC:T	donor_loss	0.9900
1:241597744:ACC:A	donor_loss	0.9900
1:241597745:C:A	donor_loss	0.9900
1:241597745:CCTTT:C	donor_gain	0.9900
1:241597994:GAAG:G	acceptor_gain	0.9900
1:241597996:AG:A	acceptor_gain	0.9900
1:241604366:T:TA	donor_gain	0.9900
1:241639876:ACT:A	donor_loss	0.9900
1:241639877:CT:C	donor_loss	0.9900
1:241639878:TCACC:T	donor_loss	0.9900
1:241639879:CAC:C	donor_loss	0.9900
1:241639880:A:AC	donor_gain	0.9900
1:241639880:ACCG:A	donor_loss	0.9900
1:241639881:C:CC	donor_gain	0.9900
1:241590470:G:T	donor_gain	0.9800
1:241594687:CGAAA:C	acceptor_gain	0.9800
1:241594688:GAAA:G	acceptor_gain	0.9800

AlphaMissense

2597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:241594539:G:C	F366L	0.989
1:241594539:G:T	F366L	0.989
1:241594541:A:G	F366L	0.989
1:241594518:A:C	F373L	0.974
1:241594518:A:T	F373L	0.974
1:241594520:A:G	F373L	0.974
1:241640003:G:C	S84R	0.973
1:241640003:G:T	S84R	0.973
1:241640005:T:G	S84R	0.973
1:241604427:A:G	W176R	0.969
1:241604427:A:T	W176R	0.969
1:241640009:G:C	N82K	0.968
1:241640009:G:T	N82K	0.968
1:241594540:A:G	F366S	0.966
1:241594519:A:G	F373S	0.958
1:241604347:A:C	F202L	0.958
1:241604347:A:T	F202L	0.958
1:241604349:A:G	F202L	0.958
1:241604469:A:G	W162R	0.949
1:241604469:A:T	W162R	0.949
1:241594551:T:A	K362N	0.948
1:241594551:T:G	K362N	0.948
1:241604537:C:G	R139P	0.948
1:241604425:C:A	W176C	0.942
1:241604425:C:G	W176C	0.942
1:241597942:T:A	E250V	0.939
1:241604423:T:A	N177I	0.938
1:241639898:A:C	F119L	0.937
1:241639898:A:T	F119L	0.937
1:241639900:A:G	F119L	0.937

dbSNP variants (sampled 300 via entrez): RS1000283356 (1:241636743 G>A), RS1000378858 (1:241626775 A>T), RS1000467306 (1:241630269 C>T), RS1000493510 (1:241632826 G>A), RS1000499225 (1:241602244 A>G), RS1000585332 (1:241630010 G>C), RS1000589016 (1:241640626 G>A,C), RS1000593167 (1:241623646 C>T), RS1000769891 (1:241616574 T>C), RS1000819049 (1:241596843 G>C), RS1000898995 (1:241621768 A>G), RS1001049907 (1:241603383 A>G), RS1001094360 (1:241603602 A>G), RS1001109224 (1:241628155 G>T), RS1001182542 (1:241628326 T>C)

Disease associations

OMIM: gene MIM:606695 | disease phenotypes: MIM:606812

GenCC curated gene-disease

Mondo (1): fumaric aciduria (MONDO:0011730)

Orphanet (1): Fumaric aciduria (Orphanet:24)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003518_79	Daytime sleep phenotypes	4.000000e-06
GCST012178_3	Pancreatic ductal adenocarcinoma x smoking interaction	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0006527	smoking status measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538191	Fumaric aciduria (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523919 (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

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
Cyclosporine	decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
lead acetate	decreases expression	1
beta-lapachone	decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
periodate-oxidized adenosine	affects expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Cyclophosphamide	affects response to substance	1
Doxorubicin	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
CHEMBL4883555	Binding	PRESTO-Tango GPCRome screening (OPN3)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04387500	PHASE2	UNKNOWN	Sintilimab Injection Combined With Inlyta in Fumarate Hydratase- Deficient Renal Cell Carcinoma
NCT04623502	Not specified	RECRUITING	An Investigation of Kidney and Urothelial Tumor Metabolism in Patients Undergoing Surgical Resection and/or Biopsy