OPN1SW

Summary

OPN1SW (opsin 1, short wave sensitive, HGNC:1012) is a protein-coding gene on chromosome 7q32.1, encoding Short-wave-sensitive opsin 1 (P03999). Visual pigments are the light-absorbing molecules that mediate vision.

This gene belongs to the G-protein coupled receptor 1 family, opsin subfamily. It encodes the blue cone pigment gene which is one of three types of cone photoreceptors responsible for normal color vision. Defects in this gene are the cause of tritan color blindness (tritanopia). Affected individuals lack blue and yellow sensory mechanisms while retaining those for red and green. Defective blue vision is characteristic.

Source: NCBI Gene 611 — RefSeq curated summary.

At a glance

• Gene–disease (curated): blue color blindness (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 284 total
• Phenotypes (HPO): 10
• MANE Select transcript: NM_001385125

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1012
Approved symbol	OPN1SW
Name	opsin 1, short wave sensitive
Location	7q32.1
Locus type	gene with protein product
Status	Approved
Aliases	BOP, CBT
Ensembl gene	ENSG00000128617
Ensembl biotype	protein_coding
OMIM	613522
Entrez	611

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000249389

RefSeq mRNA: 1 — MANE Select: NM_001385125 NM_001385125

CCDS: CCDS5806

Canonical transcript exons

ENST00000249389 — 5 exons

Exon	Start	End
ENSE00000882091	128772485	128772659
ENSE00000882092	128773649	128773888
ENSE00000882093	128774498	128774663
ENSE00000882095	128775439	128775794
ENSE00001208288	128774986	128775154

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 62.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0208 / max 26.9488, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86071	0.0208	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	62.23	gold quality
sural nerve	UBERON:0015488	55.64	silver quality
Brodmann (1909) area 46	UBERON:0006483	54.03	silver quality
stromal cell of endometrium	CL:0002255	53.24	silver quality
heart right ventricle	UBERON:0002080	53.00	gold quality
oocyte	CL:0000023	51.19	gold quality
pigmented layer of retina	UBERON:0001782	46.94	silver quality
amniotic fluid	UBERON:0000173	46.81	gold quality
calcaneal tendon	UBERON:0003701	46.59	silver quality
saphenous vein	UBERON:0007318	45.10	gold quality
bone marrow cell	CL:0002092	44.90	gold quality
tendon	UBERON:0000043	44.07	silver quality
trachea	UBERON:0003126	43.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
cartilage tissue	UBERON:0002418	43.02	gold quality
middle temporal gyrus	UBERON:0002771	42.71	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
pharyngeal mucosa	UBERON:0000355	42.50	gold quality
colonic epithelium	UBERON:0000397	42.22	gold quality
superior vestibular nucleus	UBERON:0007227	42.02	gold quality
cortical plate	UBERON:0005343	41.51	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
dorsal root ganglion	UBERON:0000044	41.33	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
dorsal plus ventral thalamus	UBERON:0001897	41.14	gold quality
descending thoracic aorta	UBERON:0002345	41.12	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
ventral tegmental area	UBERON:0002691	41.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CRX, NR2F1, NR2F2, NRL, RORA, RORB, THRB

Literature-anchored findings (GeneRIF, showing 9)

• A novel mutation(prolin/leucine) in the short-wavelength-sensitive cone pigment gene associated with a tritan color vision defect. (PMID:16961973)
• Results show that, although light absorption behaves differently in blue, green and red opsins, their low-frequency vibrational motions are similar. (PMID:19189139)
• 11-cis-retinol had no significant effect on the activity of human blue cone opsin (PMID:19386593)
• Immunoreactivity to anti-OPN1SW antibodies was seen in the upper layer of human epidermis & reconstructed skin. The opsin mRNA was seen in total RNA from human skin. Neither immunoreactivity nor mRNA expression was seen in cultured human keratinocytes. (PMID:19493002)
• Individuals with the T190I S-opsin mutation behaved as mild tritans at 12.3-92.3Td, but as tritanopes at 1.2-9.2Td, for both light-adapted and dark-adapted conditions. The results are consistent with the mutant opsin causing abnormal S-cone function. (PMID:23022137)
• A novel homozygous PDE6C mutation was identified as the cause of ACHM. In addition, we identified an OPN1SW mutation in the sibling with complete achromatopsia. (PMID:25605338)
• Data suggest that insights into dimerization interface of red cone opsin should aid investigations of the structure and function of GPCR cell signaling. (PMID:28045251)
• LVAVA haplotype of the OPN1LW gene and MVAVA haplotype of the OPN1MW gene cause apparently nonsyndromic high myopia in young patients but lead to progressive cone-rod dystrophy with deuteranopia and protanopia in middle-aged patients corresponding to a previously unknown disease course. (PMID:28358949)
• Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency. (PMID:32400513)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	opn1sw1	ENSDARG00000045677
mus_musculus	Opn1sw	ENSMUSG00000058831
rattus_norvegicus	Opn1sw	ENSRNOG00000006874

Paralogs (9): OPN3 (ENSG00000054277), OPN1LW (ENSG00000102076), OPN4 (ENSG00000122375), OPN5 (ENSG00000124818), RHO (ENSG00000163914), OPN1MW2 (ENSG00000166160), RRH (ENSG00000180245), OPN1MW (ENSG00000268221), OPN1MW3 (ENSG00000269433)

Protein

Protein identifiers

Short-wave-sensitive opsin 1 — P03999 (reviewed: P03999)

Alternative names: Blue cone photoreceptor pigment, Blue-sensitive opsin

All UniProt accessions (1): P03999

UniProt curated annotations — full annotation on UniProt →

Function. Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to cis-retinal. Required for the maintenance of cone outer segment organization in the ventral retina, but not essential for the maintenance of functioning cone photoreceptors. Involved in ensuring correct abundance and localization of retinal membrane proteins. May increase spectral sensitivity in dim light.

Subcellular location. Cell membrane. Photoreceptor inner segment. Cell projection. Cilium. Photoreceptor outer segment. Cytoplasm. Perinuclear region.

Tissue specificity. The three color pigments are found in the cone photoreceptor cells. Expressed throughout the epidermis and dermis, primarily in the stratum granulosum in the facial and abdominal skin (at protein level). Expressed in dermal fibroblasts (at protein level). Expressed in melanocytes (at protein level).

Post-translational modifications. Phosphorylated on some or all of the serine and threonine residues present in the C-terminal region.

Disease relevance. Tritan color blindness (CBT) [MIM:190900] A disorder of vision characterized by a selective deficiency of blue spectral sensitivity. The disease is caused by variants affecting the gene represented in this entry.

Induction. Induced by ultraviolet A light in dermal fibroblasts.

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

RefSeq proteins (1): NP_001372054* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001521	Opsin_blue	Family
IPR001760	Opsin	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 variant 4, chain 1, modified residue 1, glycosylation site 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8Y02	ELECTRON MICROSCOPY	2.61

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P03999-F1	87.23	0.63

Antibody-complex structures (SAbDab): 1 — 8Y02

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): 290

Disulfide bonds (1): 104–181

Glycosylation sites (1): 11

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2187335	The retinoid cycle in cones (daylight vision)
R-HSA-418594	G alpha (i) signalling events
R-HSA-419771	Opsins
R-HSA-9918443	Defective visual phototransduction due to OPN1SW loss of function

MSigDB gene sets: 112 (showing top): GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_PHOTOTRANSDUCTION, BROWNE_HCMV_INFECTION_48HR_DN, MODULE_205, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, TGCTGAY_UNKNOWN, chr7q32, GOBP_RESPONSE_TO_UV, GOBP_RESPONSE_TO_RADIATION, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS

GO Biological Process (8): signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), visual perception (GO:0007601), phototransduction (GO:0007602), absorption of visible light (GO:0016038), cellular response to light stimulus (GO:0071482), cellular response to UV-A (GO:0071492), detection of visible light (GO:0009584)

GO Molecular Function (5): G protein-coupled photoreceptor activity (GO:0008020), signaling receptor activity (GO:0038023), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), photoreceptor activity (GO:0009881)

GO Cellular Component (9): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), plasma membrane (GO:0005886), perinuclear region of cytoplasm (GO:0048471), photoreceptor disc membrane (GO:0097381), cone photoreceptor outer segment (GO:0120199), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Visual phototransduction	1
GPCR downstream signalling	1
Class A/1 (Rhodopsin-like receptors)	1
Retinoid cycle disease events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
G protein-coupled receptor activity	2
signal transduction	2
detection of light stimulus	2
photoreceptor outer segment	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
sensory perception of light stimulus	1
light absorption	1
response to light stimulus	1
cellular response to radiation	1
cellular response to UV	1
response to UV-A	1
detection of visible light	1
photoreceptor activity	1
molecular transducer activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
signaling receptor activity	1
photoreceptor cell cilium	1
membrane	1
cell periphery	1
cytoplasm	1
organelle membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OPN1SW	ARR3	P36575	893
OPN1SW	RBP3	P10745	811
OPN1SW	ZNF513	Q8N8E2	724
OPN1SW	GNAT2	P19087	676
OPN1SW	CRX	O43186	649
OPN1SW	PAX6	P26367	631
OPN1SW	RCVRN	P35243	619
OPN1SW	NR2E3	Q9Y5X4	611
OPN1SW	PDE6H	Q13956	609
OPN1SW	GNGT1	P63211	586
OPN1SW	GNAT1	P11488	585
OPN1SW	VSX2	P58304	554
OPN1SW	PDE6C	P51160	533
OPN1SW	GRM6	O15303	524
OPN1SW	GUCA1C	O95843	508

IntAct

5 interactions, top by confidence:

A	B	Type	Score
OPN1SW	MFF	psi-mi:“MI:0915”(physical association)	0.560
OPN1SW	HSPA8	psi-mi:“MI:0914”(association)	0.350
MFF	OPN1SW	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): MFF (Two-hybrid), HSPA8 (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS)

ESM2 similar proteins: O02464, O02465, O02667, O13018, O13092, O16017, O16018, O16019, O16020, O18312, O18481, O18485, O18486, O42266, O61303, O96107, P03999, P04950, P08099, P08255, P17646, P28679, P28680, P28684, P29404, P49146, P51473, P51490, P51491, P60015, P60573, P87368, P90680, P91657, P97295, Q17053, Q17292, Q17296, Q26495, Q5IS62

Diamond homologs: O12948, O13092, O13227, O18910, O18911, O18912, O18913, O18914, O35476, O35478, O35599, O42604, O57605, O62794, O93441, O93459, P03999, P04000, P04001, P0DN77, P0DN78, P22328, P22329, P22330, P22331, P22332, P22671, P28683, P28684, P32308, P32309, P32310, P32311, P32312, P32313, P34989, P35357, P35358, P35359, P35403

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	173
Likely benign	93
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

612 predictions. Top by Δscore:

Variant	Effect	Δscore
7:128772660:C:CC	acceptor_gain	1.0000
7:128773648:CCTG:C	donor_gain	1.0000
7:128773889:C:CG	acceptor_loss	1.0000
7:128773890:T:C	acceptor_loss	1.0000
7:128774496:A:AC	donor_gain	1.0000
7:128774497:C:CC	donor_gain	1.0000
7:128774497:CAG:C	donor_gain	1.0000
7:128775438:C:A	donor_loss	1.0000
7:128775477:TGGCG:T	donor_gain	1.0000
7:128775504:CAG:C	donor_gain	1.0000
7:128773643:CTTTA:C	donor_loss	0.9900
7:128773644:TTTA:T	donor_loss	0.9900
7:128773645:TTA:T	donor_loss	0.9900
7:128773646:TA:T	donor_loss	0.9900
7:128773647:A:AT	donor_loss	0.9900
7:128773648:C:CA	donor_loss	0.9900
7:128773887:AC:A	acceptor_gain	0.9900
7:128773888:CC:C	acceptor_gain	0.9900
7:128773889:C:CC	acceptor_gain	0.9900
7:128774490:CCACT:C	donor_loss	0.9900
7:128774491:CACTC:C	donor_loss	0.9900
7:128774492:ACTC:A	donor_loss	0.9900
7:128774493:CTCAC:C	donor_loss	0.9900
7:128774494:TCA:T	donor_loss	0.9900
7:128774495:CACAG:C	donor_loss	0.9900
7:128774496:ACAG:A	donor_gain	0.9900
7:128774497:C:CT	donor_loss	0.9900
7:128774497:CA:C	donor_gain	0.9900
7:128774497:CAGC:C	donor_gain	0.9900
7:128774497:CAGCT:C	donor_gain	0.9900

AlphaMissense

2284 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:128775035:A:G	W158R	0.995
7:128775035:A:T	W158R	0.995
7:128773694:A:C	S294R	0.994
7:128773694:A:T	S294R	0.994
7:128773696:T:G	S294R	0.994
7:128774993:A:G	W172R	0.994
7:128774993:A:T	W172R	0.994
7:128775566:G:C	N75K	0.994
7:128775566:G:T	N75K	0.994
7:128774623:A:G	W188R	0.993
7:128774623:A:T	W188R	0.993
7:128775026:C:G	G161R	0.993
7:128773697:C:A	K293N	0.992
7:128773697:C:G	K293N	0.992
7:128773785:G:C	P264R	0.992
7:128773802:G:C	F258L	0.992
7:128773802:G:T	F258L	0.992
7:128773804:A:G	F258L	0.992
7:128773801:A:G	C259R	0.991
7:128774621:C:A	W188C	0.991
7:128774621:C:G	W188C	0.991
7:128774988:G:C	S173R	0.991
7:128774988:G:T	S173R	0.991
7:128774990:T:G	S173R	0.991
7:128775140:A:G	W123R	0.991
7:128775140:A:T	W123R	0.991
7:128773785:G:T	P264H	0.990
7:128773713:G:C	P288R	0.989
7:128774517:A:G	L223P	0.989
7:128775025:C:T	G161D	0.989

dbSNP variants (sampled 300 via entrez): RS1000306050 (7:128776218 T>C), RS1000380076 (7:128776591 C>T), RS1000643486 (7:128777450 T>C), RS1000707105 (7:128777772 C>T), RS1000894026 (7:128776710 C>G,T), RS1001915473 (7:128777719 C>T), RS1002114779 (7:128772088 TTTTC>T), RS1002823775 (7:128774764 C>A,T), RS1002973888 (7:128773184 A>G), RS1003222394 (7:128776083 T>G), RS1004885246 (7:128774739 C>A,G), RS1005221207 (7:128775808 C>A,T), RS1006925509 (7:128776970 A>C,G), RS1007346947 (7:128772247 G>A,T), RS1007417450 (7:128772721 C>G,T)

Disease associations

OMIM: gene MIM:613522 | disease phenotypes: MIM:190900

GenCC curated gene-disease

Disease	Classification	Inheritance
blue color blindness	Strong	Autosomal dominant

Mondo (1): blue color blindness (MONDO:0008610)

Orphanet (1): Tritanopia (Orphanet:88629)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000479	Abnormal retinal morphology
HP:0000551	Color vision defect
HP:0000552	Tritanomaly
HP:0000613	Photophobia
HP:0007641	Dyschromatopsia
HP:0007663	Reduced visual acuity
HP:0008275	Abnormal light-adapted electroretinogram
HP:0012043	Pendular nystagmus
HP:0030584	Color vision test abnormality

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002030_2	Primary tooth development (time to first tooth eruption)	9.000000e-07
GCST002031_2	Primary tooth development (number of teeth)	4.000000e-09
GCST004401_3	Reading disability or specific language impairment (pleiotropy)	4.000000e-07
GCST004402_3	Reading disability or specific language impairment adjusted for intelligence quotient (pleiotropy)	3.000000e-07
GCST006061_93	Atrial fibrillation	2.000000e-08
GCST006414_126	Atrial fibrillation	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11653	CALU, OPN1SW		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Opsin receptors

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression	1
jinfukang	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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