OPN1LW

Summary

OPN1LW (opsin 1, long wave sensitive, HGNC:9936) is a protein-coding gene on chromosome Xq28, encoding Long-wave-sensitive opsin 1 (P04000). Visual pigments are the light-absorbing molecules that mediate vision.

This gene encodes for a light absorbing visual pigment of the opsin gene family. The encoded protein is called red cone photopigment or long-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. This gene and the medium-wavelength opsin gene are tandemly arrayed on the X chromosome and frequent unequal recombination and gene conversion may occur between these sequences. X chromosomes may have fusions of the medium- and long-wavelength opsin genes or may have more than one copy of these genes. Defects in this gene are the cause of partial, protanopic colorblindness.

Source: NCBI Gene 5956 — RefSeq curated summary.

At a glance

• Gene–disease (curated): red color blindness (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 52 total — 9 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes
• MANE Select transcript: NM_020061

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9936
Approved symbol	OPN1LW
Name	opsin 1, long wave sensitive
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	COD5
Ensembl gene	ENSG00000102076
Ensembl biotype	protein_coding
OMIM	300822
Entrez	5956

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000369951, ENST00000442922, ENST00000463296

RefSeq mRNA: 1 — MANE Select: NM_020061 NM_020061

CCDS: CCDS14742

Canonical transcript exons

ENST00000369951 — 6 exons

Exon	Start	End
ENSE00001634443	154156294	154156533
ENSE00001788298	154154574	154154739
ENSE00001833335	154144243	154144395
ENSE00001842369	154158816	154159032
ENSE00003538309	154150656	154150952
ENSE00003678945	154152940	154153108

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 37.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0182 / max 23.8980, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198126	0.0146	3
198125	0.0035	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	37.91	gold quality
sural nerve	UBERON:0015488	37.76	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
skeletal muscle tissue	UBERON:0001134	35.02	gold quality
muscle tissue	UBERON:0002385	34.65	gold quality
smooth muscle tissue	UBERON:0001135	33.49	gold quality
bone marrow	UBERON:0002371	33.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
blood	UBERON:0000178	30.92	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
right uterine tube	UBERON:0001302	29.68	gold quality
vermiform appendix	UBERON:0001154	29.55	gold quality
prefrontal cortex	UBERON:0000451	29.39	gold quality
left uterine tube	UBERON:0001303	29.30	gold quality
lymph node	UBERON:0000029	29.01	gold quality
skin of leg	UBERON:0001511	28.22	silver quality
duodenum	UBERON:0002114	28.14	gold quality
urinary bladder	UBERON:0001255	27.98	gold quality
zone of skin	UBERON:0000014	27.47	silver quality
leukocyte	CL:0000738	27.10	gold quality
monocyte	CL:0000576	27.05	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
left adrenal gland cortex	UBERON:0035825	26.35	gold quality
fallopian tube	UBERON:0003889	26.32	silver quality
adrenal gland	UBERON:0002369	26.04	silver quality
gall bladder	UBERON:0002110	25.98	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	27.95
E-GEOD-137537	yes	4.98
E-ANND-3	no	0.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, MEF2C, SALL3

miRNA regulators (miRDB)

13 targeting OPN1LW, 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-4534	99.99	66.58	1907
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-625-5P	99.02	68.64	2031

Literature-anchored findings (GeneRIF, showing 33)

• In a Japanese male with congenital protan red/green color blindness the mutation Gly338Glu (GGG–>GAG) occurred in the single red gene resulting in no absorbance and loss of function (PMID:12051694)
• Abnormal distribution of cone red opsin is associated with autosomal dominant cone dystrophy (PMID:16020309)
• 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 inactivates expressed cone opsins, acting an inverse agonist (PMID:19386593)
• Immunoreactivity to anti-OPN1LW antibodies was seen in the basal 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)
• Novel and known mutations affecting the L-M opsin gene array were identified in families with X-linked cone-dominated phenotypes. (PMID:20220053)
• Mutations in the LW/MW cone opsin gene array can, therefore, lead to a spectrum of disease, ranging from color blindness to progressive cone dystrophy (XLCOD5). (PMID:20579627)
• Genomic rearrangements in the affected genes cause blue cone monochromatism. (PMID:21267011)
• Opsin expression in terminally differentiated mammalian cones remains subject to control by thyroid hormone through its receptor TRbeta2. (PMID:21451022)
• Missense mutation in both OPN1LW and OPN1MW cause X-linked cone dystrophy. (PMID:22183383)
• These results suggest that complete skipping of exon 3 at splicing, due to the unique haplotype of the exon, causes loss of expression of L-opsin in 119 Japanise men with protanopia color vision defect. (PMID:22732407)
• Identification of one single red-green OPN1LW/MW hybrid gene harboring a point mutation that associates with blue cone monochromatism. (PMID:22998501)
• The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. (PMID:23139274)
• Using several human ROP enhancer/promoter-luciferase reporter constructs, the study found that thyroid hormone receptor beta 2 increased luciferase activities through the 5’-UTR and intron 3-4 region. (PMID:24058409)
• We identified 76 individuals with an L-M array. Four had exonic mutations, but the other 72 had no mutation in the exons or flanking introns. Sixty-nine of the 72 individuals had a -71A>C substitution in the M gene promoter. (PMID:25820227)
• Our study confirms the findings that unique variants in OPN1LW are responsible for both syndromic and nonsyndromic X-linked high myopia mapped to MYP1. (PMID:26114493)
• The Ser180Ala polymorphisms on the L-opsin gene were found to influence the subject’s color discrimination and their sensitivity to spatio-chromatic patterns. (PMID:26368273)
• The study reports on a different regeneration mechanism among red and green cone opsins with retinal analogs using UV-Vis/fluorescence spectroscopic analyses, molecular modeling and site-directed mutagenesis. (PMID:26387074)
• In conclusion, we showed that normal-order gene array is frequently found in Japanese men with protan color-vision defect and that three novel mutations, Trp177STOP, -99T>G and +3A>C (intron 2) could have caused protanopia in the recently analyzed cases. (PMID:26967834)
• Investigated 24 affected males with blue cone monochromacy from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. (PMID:27339364)
• Findings show that OPN1LW mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus (PMID:27447086)
• 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)
• OPN1LW and OPN1MW restore M-cone function in a mouse model of human blue cone monochromacy. (PMID:29386880)
• Molecular genetic analysis of the OPN1LW/OPN1MW gene cluster revealed a novel deletion of about 73 kb in the patient encompassing the LCR. (PMID:29940872)
• These results suggest that O-glycosylation is a fundamental feature of red and green cone opsins, which may be relevant to their function or to cone cell development, and that differences in this post-translational modification also could contribute to the different morphologies of rod and cone photoreceptors. (PMID:30948514)
• Differential stability of variant OPN1LW gene transcripts in myopic Australian islander patients has been reported. (PMID:30996587)
• Visual and ocular findings in a family with X-linked cone dysfunction and protanopia. (PMID:34287097)
• Intermixing the OPN1LW and OPN1MW Genes Disrupts the Exonic Splicing Code Causing an Array of Vision Disorders. (PMID:34440353)
• Insight from OPN1LW Gene Haplotypes into the Cause and Prevention of Myopia. (PMID:35741704)
• Novel OPN1LW/OPN1MW Exon 3 Haplotype-Associated Splicing Defect in Patients with X-Linked Cone Dysfunction. (PMID:35743313)
• The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy. (PMID:35759666)
• Unique Haplotypes in OPN1LW as a Common Cause of High Myopia With or Without Protanopia: A Potential Window Into Myopic Mechanism. (PMID:37097228)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	opn1lw2	ENSDARG00000044861
danio_rerio	opn1lw1	ENSDARG00000044862
mus_musculus	Opn1mw	ENSMUSG00000031394
rattus_norvegicus	Opn1mw	ENSRNOG00000051529

Paralogs (9): OPN3 (ENSG00000054277), OPN4 (ENSG00000122375), OPN5 (ENSG00000124818), OPN1SW (ENSG00000128617), RHO (ENSG00000163914), OPN1MW2 (ENSG00000166160), RRH (ENSG00000180245), OPN1MW (ENSG00000268221), OPN1MW3 (ENSG00000269433)

Protein

Protein identifiers

Long-wave-sensitive opsin 1 — P04000 (reviewed: P04000)

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

All UniProt accessions (2): P04000, H0Y622

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.

Subcellular location. Membrane.

Tissue specificity. The three color pigments are found in the cone photoreceptor cells.

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

Disease relevance. Colorblindness, partial, protan series (CBP) [MIM:303900] An X-linked color vision defect characterized by a dichromasy in which red and green are confused, with loss of luminance and shift of brightness and hue curves toward the short wave end of the spectrum. Dichromasy is due to the use of only two types of photoreceptors, blue plus red in deuteranopia and blue plus green in protanopia. The disease is caused by variants affecting the gene represented in this entry. Blue cone monochromacy (BCM) [MIM:303700] A rare X-linked congenital stationary cone dysfunction syndrome characterized by the absence of functional long wavelength-sensitive and medium wavelength-sensitive cones in the retina. Color discrimination is severely impaired from birth, and vision is derived from the remaining preserved blue (S) cones and rod photoreceptors. BCM typically presents with reduced visual acuity, pendular nystagmus, and photophobia. Patients often have myopia. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_064445* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000378	Opsin_red/grn	Family
IPR001760	Opsin	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR027430	Retinal_BS	Binding_site
IPR050125	GPCR_opsins	Family

Pfam: PF00001

UniProt features (49 total): sequence variant 10, helix 10, topological domain 8, transmembrane region 7, turn 4, strand 4, glycosylation site 2, chain 1, region of interest 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8IU2	ELECTRON MICROSCOPY	3.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04000-F1	82.40	0.55

Antibody-complex structures (SAbDab): 1 — 8IU2

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): 312

Disulfide bonds (1): 126–203

Glycosylation sites (2): 22, 34

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-9918450	Defective visual phototransduction due to OPN1LW loss of function

MSigDB gene sets: 126 (showing top): NKX25_02, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_PHOTOTRANSDUCTION, GOBP_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIVISION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINESIS, GOBP_REGULATION_OF_CELL_DIVISION, 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), positive regulation of cytokinesis (GO:0032467), cellular response to light stimulus (GO:0071482), detection of visible light (GO:0009584)

GO Molecular Function (4): G protein-coupled photoreceptor activity (GO:0008020), photoreceptor activity (GO:0009881), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (4): photoreceptor outer segment (GO:0001750), plasma membrane (GO:0005886), photoreceptor disc membrane (GO:0097381), membrane (GO:0016020)

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
G protein-coupled receptor activity	2
signal transduction	2
detection of light stimulus	2
cellular anatomical structure	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
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
response to light stimulus	1
cellular response to radiation	1
detection of visible light	1
photoreceptor activity	1
signaling receptor activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
photoreceptor cell cilium	1
membrane	1
cell periphery	1
photoreceptor outer segment	1
organelle membrane	1

Protein interactions and networks

STRING

604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OPN1LW	TEX28	O15482	897
OPN1LW	NYX	Q9GZU5	804
OPN1LW	FRMD7	Q6ZUT3	767
OPN1LW	SLC25A14	O95258	668
OPN1LW	GPR143	P51810	663
OPN1LW	SOX3	P35714	624
OPN1LW	MYCBP2	O75592	585
OPN1LW	CACNA1F	O60840	581
OPN1LW	CDC42	P21181	571
OPN1LW	TKTL1	P51854	560
OPN1LW	GUCA1C	O95843	557
OPN1LW	PDE6C	P51160	501
OPN1LW	PDE6H	Q13956	497
OPN1LW	CA8	P35219	489
OPN1LW	A0A087WTN9	A0A087WTN9	480

IntAct

8 interactions, top by confidence:

A	B	Type	Score
TUSC5	OPN1LW	psi-mi:“MI:0915”(physical association)	0.560
OPN1LW	NRM	psi-mi:“MI:0915”(physical association)	0.560
OPN1LW	ACTBL2	psi-mi:“MI:0915”(physical association)	0.400
TUSC5	OPN1LW	psi-mi:“MI:0915”(physical association)	0.000
NRM	OPN1LW	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: O12948, O18910, O18912, O18913, O18914, O35476, O35478, O35599, O57605, O93441, O93459, P04000, P04001, P0DN77, P0DN78, P22329, P22330, P22331, P22332, P22671, P28683, P32309, P32310, P32311, P32312, P32313, P34989, P35357, P35358, P41591, P41592, P51471, P51472, P51474, P51488, P79863, P87365, P87366, P87367, Q8AYM7

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

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	2
Uncertain significance	27
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1012675	NM_020061.6(OPN1LW):c.354C>G (p.Tyr118Ter)	Pathogenic
10503	NM_020061.6(OPN1LW):c.739C>T (p.Arg247Ter)	Pathogenic
10505	NM_020061.6(OPN1LW):c.607T>C (p.Cys203Arg)	Pathogenic
10506	NM_020061.6(OPN1LW):c.1013G>A (p.Gly338Glu)	Pathogenic
10507	NC_000023.11:g.(154153459_154153462)_(154154925_154154928)del	Pathogenic
1299568	NM_020061.6(OPN1LW):c.269G>A (p.Trp90Ter)	Pathogenic
1299967	NM_020061.6(OPN1LW):c.891C>G (p.Tyr297Ter)	Pathogenic
2580330	GRCh37/hg19 Xq28(chrX:153247464-153522710)x3	Pathogenic
4755692	NM_020061.6(OPN1LW):c.529T>C (p.Trp177Arg)	Pathogenic
2671886	NM_020061.6(OPN1LW):c.764_765del (p.Glu255fs)	Likely pathogenic
3337423	NM_020061.6(OPN1LW):c.121G>T (p.Glu41Ter)	Likely pathogenic

SpliceAI

806 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154144393:GAG:G	donor_gain	1.0000
X:154144395:GGTG:G	donor_loss	1.0000
X:154144396:G:T	donor_loss	1.0000
X:154152938:A:AG	acceptor_gain	1.0000
X:154152939:G:GG	acceptor_gain	1.0000
X:154154737:GCG:G	donor_gain	1.0000
X:154156291:TA:T	acceptor_loss	1.0000
X:154156293:GGT:G	acceptor_gain	1.0000
X:154156531:CAG:C	donor_loss	1.0000
X:154156532:AGG:A	donor_loss	1.0000
X:154156534:G:GA	donor_loss	1.0000
X:154156535:T:G	donor_loss	1.0000
X:154144396:G:GG	donor_gain	0.9900
X:154144397:T:A	donor_loss	0.9900
X:154150948:GTGTG:G	donor_gain	0.9900
X:154150950:GTG:G	donor_gain	0.9900
X:154152938:A:AT	acceptor_loss	0.9900
X:154152938:AG:A	acceptor_gain	0.9900
X:154152938:AGG:A	acceptor_gain	0.9900
X:154152939:GG:G	acceptor_gain	0.9900
X:154152939:GGG:G	acceptor_gain	0.9900
X:154153104:AGCAG:A	donor_loss	0.9900
X:154153105:GCAG:G	donor_gain	0.9900
X:154153105:GCAGG:G	donor_loss	0.9900
X:154153106:CAGG:C	donor_loss	0.9900
X:154153107:AGGTA:A	donor_loss	0.9900
X:154153108:GGTA:G	donor_loss	0.9900
X:154153109:G:GT	donor_loss	0.9900
X:154153110:T:G	donor_loss	0.9900
X:154154568:CTCCA:C	acceptor_loss	0.9900

AlphaMissense

2391 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154150825:C:A	N94K	0.999
X:154150825:C:G	N94K	0.999
X:154150827:T:C	L95P	0.999
X:154150862:A:C	S107R	0.999
X:154150864:C:A	S107R	0.999
X:154150864:C:G	S107R	0.999
X:154150871:A:C	S110R	0.999
X:154150873:C:A	S110R	0.999
X:154150873:C:G	S110R	0.999
X:154153059:T:A	W177R	0.999
X:154153059:T:C	W177R	0.999
X:154153101:T:A	W191R	0.999
X:154153101:T:C	W191R	0.999
X:154154602:T:C	C203R	0.999
X:154154603:G:A	C203Y	0.999
X:154154604:C:G	C203W	0.999
X:154156486:A:C	S313R	0.999
X:154156488:T:A	S313R	0.999
X:154156488:T:G	S313R	0.999
X:154156503:C:A	N318K	0.999
X:154156503:C:G	N318K	0.999
X:154158816:T:C	F329L	0.999
X:154158817:T:G	F329C	0.999
X:154158818:T:A	F329L	0.999
X:154158818:T:G	F329L	0.999
X:154150718:T:A	W59R	0.998
X:154150718:T:C	W59R	0.998
X:154150743:C:A	S67Y	0.998
X:154150743:C:T	S67F	0.998
X:154150756:T:A	N71K	0.998

dbSNP variants (sampled 300 via entrez): RS1000356969 (X:154143583 C>T), RS1000543969 (X:154143391 C>T), RS1005366912 (X:154143800 C>T), RS1005855340 (X:154143977 C>G), RS1007305825 (X:154143291 A>G), RS1010348464 (X:154143367 G>A), RS1011894713 (X:154143593 C>T), RS1012379911 (X:154143751 G>A), RS1016100390 (X:154142268 C>T), RS1020293724 (X:154142849 C>T), RS1020653137 (X:154142979 T>C), RS1025559917 (X:154143784 C>A,T), RS1027230337 (X:154142452 G>A), RS1029687053 (X:154144014 C>A), RS1032082492 (X:154143584 G>A)

Disease associations

OMIM: gene MIM:300822 | disease phenotypes: MIM:303700, MIM:303900, MIM:300815

GenCC curated gene-disease

Disease	Classification	Inheritance
blue cone monochromacy	Definitive	X-linked
red color blindness	Strong	X-linked
cone-rod dystrophy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
red color blindness	Definitive	XL

Mondo (4): blue cone monochromacy (MONDO:0010563), red color blindness (MONDO:0010565), chromosome Xq28 duplication syndrome (MONDO:0010436), cone-rod dystrophy (MONDO:0015993)

Orphanet (3): Blue cone monochromatism (Orphanet:16), Proximal Xq28 duplication syndrome (Orphanet:1762), NON RARE IN EUROPE: Partial color blindness, protan type (Orphanet:319691)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000529	Progressive visual loss
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0001105	Retinal atrophy
HP:0001131	Corneal dystrophy
HP:0001419	X-linked recessive inheritance
HP:0007641	Dyschromatopsia
HP:0007663	Reduced visual acuity
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007843	Attenuation of retinal blood vessels
HP:0007939	Blue cone monochromacy
HP:0008002	Abnormal macular pigmentation
HP:0012043	Pendular nystagmus
HP:0012508	Metamorphopsia
HP:0025549	Eccentric visual fixation
HP:0030466	Abnormal full-field electroretinogram
HP:0030619	Reduced OCT-measured foveal thickness
HP:0200018	Protanomaly

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002388_280	Lymphocyte count	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
C536238	Blue cone monochromatism (supp.)
C567580	Chromosome Xq28 Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1949482 (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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases mutagenesis	3
2-methyl-4-isothiazolin-3-one	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1953562	Binding	Inverse agonist activity at human red cone opsin expressed in COS1 cells assessed as transducer activity at 200 uM by radioactive filter binding assay	Probing human red cone opsin activity with retinal analogues. — J Nat Prod

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT03513718	Not specified	COMPLETED	Acute Kidney Injury After Cardiac Surgery on CPB
NCT04034940	Not specified	UNKNOWN	Correlations Between Oxidative Stress Biomarkers, h-FABP and Left Ventricular Dysfunction in Patients With Acute Myocardial Infarction Undergoing Primary PCI
NCT06491615	Not specified	RECRUITING	National Ophthalmic Genotyping and Phenotyping Network (eyeGENE (Registered Trademark)), Stage 3 - Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases
NCT06467344	PHASE1/PHASE2	RECRUITING	Study to Evaluate ACDN-01 in ABCA4-related Stargardt Retinopathy (STELLAR)
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT00427180	Not specified	UNKNOWN	IRIS PILOT - Extended Pilot Study With a Retinal Implant System
NCT01864486	Not specified	COMPLETED	Restoring Vision With the Intelligent Retinal Implant System (IRIS V1)in Patients With Retinal Dystrophy
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02670980	Not specified	COMPLETED	Compensation for Blindness With the Intelligent Retinal Implant System (IRIS V2) in Patients With Retinal Dystrophy
NCT04658251	Not specified	TERMINATED	Study of New Mutations in Cone Disorders
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT06445322	Not specified	RECRUITING	Prescreening Study to Identify Potential Stargardt Participants for ACDN-01 Clinical Trials (STARPATH)
NCT07548944	Not specified	RECRUITING	Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance