SAG

Summary

SAG (S-antigen visual arrestin, HGNC:10521) is a protein-coding gene on chromosome 2q37.1, encoding S-arrestin (P10523). Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G-proteins for the same binding site on RHO.

Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. S-arrestin, also known as S-antigen, is a major soluble photoreceptor protein that is involved in desensitization of the photoactivated transduction cascade. It is expressed in the retina and the pineal gland and inhibits coupling of rhodopsin to transducin in vitro. Additionally, S-arrestin is highly antigenic, and is capable of inducing experimental autoimmune uveoretinitis. Mutations in this gene have been associated with Oguchi disease, a rare autosomal recessive form of night blindness.

Source: NCBI Gene 6295 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 47 (Definitive, ClinGen) — +5 more curated relationships
• Clinical variants (ClinVar): 509 total — 25 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 49
• MANE Select transcript: NM_000541

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10521
Approved symbol	SAG
Name	S-antigen visual arrestin
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	ARRESTIN, RP47
Ensembl gene	ENSG00000130561
Ensembl biotype	protein_coding
OMIM	181031
Entrez	6295

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 retained_intron, 5 protein_coding_CDS_not_defined, 3 protein_coding, 1 nonsense_mediated_decay

ENST00000409110, ENST00000412969, ENST00000415974, ENST00000447536, ENST00000453143, ENST00000461532, ENST00000462487, ENST00000469222, ENST00000471884, ENST00000473771, ENST00000474206, ENST00000474220, ENST00000476500, ENST00000479450, ENST00000483231, ENST00000492629

RefSeq mRNA: 1 — MANE Select: NM_000541 NM_000541

CCDS: CCDS46545

Canonical transcript exons

ENST00000409110 — 16 exons

Exon	Start	End
ENSE00001133716	233307816	233308022
ENSE00003464870	233346807	233347055
ENSE00003470363	233346403	233346412
ENSE00003477282	233334962	233335099
ENSE00003518771	233338676	233338753
ENSE00003533833	233316075	233316135
ENSE00003538916	233322946	233323005
ENSE00003540398	233328478	233328613
ENSE00003568397	233309162	233309264
ENSE00003580155	233327121	233327197
ENSE00003614246	233318751	233318795
ENSE00003621140	233340455	233340478
ENSE00003638036	233329493	233329577
ENSE00003640789	233320630	233320823
ENSE00003674787	233342271	233342326
ENSE00003694247	233331640	233331712

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 76.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5347 / max 1482.1456, expressed in 14 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26042	0.8471	5
26040	0.3950	3
26041	0.2107	7
26045	0.0473	3
202615	0.0111	3
26044	0.0107	4
26043	0.0084	2
202614	0.0045	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	76.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.59	gold quality
left testis	UBERON:0004533	75.30	gold quality
testis	UBERON:0000473	74.61	gold quality
right testis	UBERON:0004534	73.56	gold quality
caudate nucleus	UBERON:0001873	68.71	gold quality
putamen	UBERON:0001874	68.17	gold quality
monocyte	CL:0000576	59.75	gold quality
leukocyte	CL:0000738	59.32	gold quality
granulocyte	CL:0000094	59.30	gold quality
bone marrow cell	CL:0002092	58.37	silver quality
bone marrow	UBERON:0002371	58.27	gold quality
mucosa of transverse colon	UBERON:0004991	58.20	gold quality
blood	UBERON:0000178	55.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	53.96	silver quality
placenta	UBERON:0001987	53.38	gold quality
temporal lobe	UBERON:0001871	52.92	gold quality
amygdala	UBERON:0001876	52.76	gold quality
lower esophagus mucosa	UBERON:0035834	50.97	gold quality
endometrium	UBERON:0001295	50.86	gold quality
muscle tissue	UBERON:0002385	50.30	gold quality
skeletal muscle tissue	UBERON:0001134	50.29	gold quality
stromal cell of endometrium	CL:0002255	49.51	silver quality
Ammon’s horn	UBERON:0001954	49.44	gold quality
calcaneal tendon	UBERON:0003701	49.16	silver quality
brain	UBERON:0000955	48.65	gold quality
endocervix	UBERON:0000458	48.40	gold quality
substantia nigra	UBERON:0002038	47.99	gold quality
muscle of leg	UBERON:0001383	47.92	gold quality
primary visual cortex	UBERON:0002436	47.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	4239.56
E-MTAB-5061	no	1.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CRX, NFKBIA, NFKBID, NRL, RAX, VSX2

miRNA regulators (miRDB)

6 targeting SAG, 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-3151-5P	99.86	63.83	1069
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-10399-3P	96.95	67.92	111
HSA-MIR-4764-3P	96.81	67.94	580
HSA-MIR-1180-3P	95.98	66.88	65

Literature-anchored findings (GeneRIF, showing 21)

• Rhodopsin-arrestin complexes alter the morphology of endosomal compartments and severely damage receptor-mediated endocytic functions in retinitis pigmentosa. (PMID:15232620)
• The existence of 2 novel mutations of the arrestin gene in 2 unrelated Japanese patients strongly supports the previous data that arrestin gene mutations are associated with Oguchi’s disease (PMID:15234147)
• Mutation 926delA of the SAG gene is the main cause of Oguchi disease in Japanese. This mutation appears to have been inherited from a single founder. (PMID:15295660)
• studies suggest that IRBP and S-Ag can initiate innate and, in sensitive individuals, adaptive immune response by attracting iDCs and T and B cells expressing CXCR3 and CXCR5 (PMID:15713799)
• The tetramer form of arrestin increases the arrestin-binding capacity of microtubules while readily dissociating to supply active monomer when it is needed to quench rhodopsin signaling. (PMID:17332750)
• two models of interaction for the human S-arrestin/rhodopsin complex (PMID:18175313)
• ARRESTIN binds to different phosphorylated regions of the thyrotropin-releasing hormone receptor with distinct functional consequences. (PMID:18413662)
• S-Ag specific T cells are present in certain active Behcet’s disease patients, and most of them are activated memory CD4(+) T cells. (PMID:18685727)
• maintenance of low levels of the active monomer is the biological role of arrestin-1 self-association (PMID:21288033)
• Macular dysfunction can occur in Oguchi disease with the 1147delA mutation in the SAG gene. (PMID:21447990)
• Identification of autoantibodies specific for two retinal antigens (CRALBP and S-Ag) supports the concept of an autoimmunological origin of the disease. (PMID:21904838)
• the arrestin 1147delA, which has been known as a frequent cause of Oguchi disease, also may be related to the pathogenesis of autosomal recessive RP. (PMID:21922265)
• We describe a case of Oguchi disease with unusual findings caused by a putative heterozygous mutation in the SAG gene. (PMID:21987685)
• Compound heterozygosity of a nonsense R193X mutation and a heterozygous deletion of 3,224 bp encompassing exon 2 in the SAG gene is the cause of Oguchi’s disease in a Chinese family. (PMID:22419846)
• Based on their observed affinity for arrestin-1, P-opsin and inactive P-Rh very likely affect the physiological monomer-dimer-tetramer equilibrium of arrestin-1, and should therefore be taken into account when modeling photoreceptor function. (PMID:23277586)
• This is the first dominant-acting mutation identified in SAG, a founder mutation possibly originating in Mexico several centuries ago. The phenotype is clearly adRP and is distinct from the previously reported phenotypes of recessive null mutations, that is, Oguchi disease and recessive RP. (PMID:28549094)
• Arrestin-1 was found to be expressed in RCC (58.7% of cases) and renal oncocytoma (90% of cases) cells, while being absent in healthy kidney. The expression of arrestin-1 in RCC metastases was more prominent than in primary tumours. Hypomethylation of the SAG gene promoter is unlikely to be the mechanism for the aberrant expression of arrestin-1. (PMID:30389514)
• Retinitis pigmentosa with SAG mutations often shows a characteristic golden sheen surrounding posterior pigmentary retinal degeneration. Oguchi disease can show progressive degeneration in adulthood, rarely resulting in RP. (PMID:31257036)
• Oguchi disease caused by a homozygous novel SAG splicing alteration associated with the multiple evanescent white dot syndrome: A 15-month follow-up. (PMID:32333190)
• Progressive sector retinitis pigmentosa due to c.440G>T mutation in SAG in an Australian family. (PMID:33047631)
• Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease. (PMID:35549688)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	saga	ENSDARG00000012610
danio_rerio	sagb	ENSDARG00000038378
mus_musculus	Sag	ENSMUSG00000056055
rattus_norvegicus	Sag	ENSRNOG00000018185
drosophila_melanogaster	krz	FBGN0040206
caenorhabditis_elegans		WBGENE00000195

Paralogs (3): ARR3 (ENSG00000120500), ARRB1 (ENSG00000137486), ARRB2 (ENSG00000141480)

Protein

Protein identifiers

S-arrestin — P10523 (reviewed: P10523)

Alternative names: 48 kDa protein, Retinal S-antigen, Rod photoreceptor arrestin

All UniProt accessions (4): P10523, C9JSX4, E7ESX4, F8WCN5

UniProt curated annotations — full annotation on UniProt →

Function. Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G-proteins for the same binding site on RHO. May play a role in preventing light-dependent degeneration of retinal photoreceptor cells.

Subunit / interactions. Monomer. Homodimer. Homotetramer. Interacts with RHO (via the phosphorylated C-terminus).

Subcellular location. Cell projection. Cilium. Photoreceptor outer segment. Membrane.

Tissue specificity. Detected in retina, in the proximal portion of the outer segment of rod photoreceptor cells (at protein level).

Disease relevance. Night blindness, congenital stationary, Oguchi type 1 (CSNBO1) [MIM:258100] A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. Congenital stationary night blindness Oguchi type is an autosomal recessive form associated with fundus discoloration and abnormally slow dark adaptation. The disease is caused by variants affecting the gene represented in this entry. Retinitis pigmentosa 47 (RP47) [MIM:613758] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry. Retinitis pigmentosa 96 (RP96) [MIM:620228] An autosomal dominant form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminus interferes with binding to non-phosphorylated RHO. Interaction with phosphorylated RHO triggers displacement of the C-terminus and leads to a conformation change that mediates high-affinity RHO binding.

Similarity. Belongs to the arrestin family.

RefSeq proteins (1): NP_000532* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000698	Arrestin	Family
IPR011021	Arrestin-like_N	Domain
IPR011022	Arrestin-like_C	Domain
IPR014752	Arrestin-like_C_sf	Homologous_superfamily
IPR014753	Arrestin_N	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR017864	Arrestin_CS	Conserved_site

Pfam: PF00339, PF02752

UniProt features (21 total): sequence variant 13, sequence conflict 6, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10523-F1	85.44	0.61

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): 234

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2485179	Activation of the phototransduction cascade
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-2187338	Visual phototransduction
R-HSA-2514856	The phototransduction cascade
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 199 (showing top): GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, RORA1_01, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_PHOTOTRANSDUCTION, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PHOTOTRANSDUCTION_VISIBLE_LIGHT, SIG_PIP3_SIGNALING_IN_B_LYMPHOCYTES, GOBP_RECEPTOR_INTERNALIZATION, GOBP_RESPONSE_TO_RADIATION, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_RADIATION

GO Biological Process (5): G protein-coupled receptor internalization (GO:0002031), cell surface receptor signaling pathway (GO:0007166), sensory perception (GO:0007600), G protein-coupled opsin signaling pathway (GO:0016056), signal transduction (GO:0007165)

GO Molecular Function (6): G protein-coupled receptor binding (GO:0001664), opsin binding (GO:0002046), protein phosphatase inhibitor activity (GO:0004864), spectrin binding (GO:0030507), phosphoprotein binding (GO:0051219), protein binding (GO:0005515)

GO Cellular Component (5): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), cytosol (GO:0005829), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
The phototransduction cascade	2
Sensory Perception	1
Visual phototransduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein binding	2
desensitization of G protein-coupled receptor signaling pathway	1
receptor internalization	1
signal transduction	1
nervous system process	1
G protein-coupled receptor signaling pathway	1
phototransduction	1
phototransduction, visible light	1
cellular response to light stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signaling receptor binding	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
cytoskeletal protein binding	1
protein-containing complex binding	1
binding	1
photoreceptor cell cilium	1
cytoplasm	1

Protein interactions and networks

STRING

1907 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAG	RHO	P08100	999
SAG	ADRB2	P07550	984
SAG	GRK1	Q15835	975
SAG	GRK7	Q8WTQ7	957
SAG	GRK2	P25098	909
SAG	GRK3	P35626	884
SAG	SRC	P12931	873
SAG	KIF3A	Q9Y496	867
SAG	PPP1R9B	Q96SB3	863
SAG	RCVRN	P35243	832
SAG	DRD2	P14416	827
SAG	PDE4A	P27815	810
SAG	GRK5	P34947	802
SAG	RBP3	P10745	781
SAG	CALML4	Q96GE6	779

IntAct

11 interactions, top by confidence:

A	B	Type	Score
SAG	CLK3	psi-mi:“MI:0915”(physical association)	0.560
ARRB1	SAG	psi-mi:“MI:0914”(association)	0.530
ARRB1		psi-mi:“MI:0914”(association)	0.350
ARRB2		psi-mi:“MI:0914”(association)	0.350
ARRB1	SAG	psi-mi:“MI:0914”(association)	0.350
SAG	CLK3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): SAG (Reconstituted Complex), SAG (Affinity Capture-MS), CLK3 (Two-hybrid), RHO (Reconstituted Complex), SAG (Affinity Capture-RNA), SAG (Affinity Capture-MS), ALB (Cross-Linking-MS (XL-MS)), SAG (Affinity Capture-MS), SAG (Affinity Capture-MS)

ESM2 similar proteins: A7YW45, O14744, P08168, P10523, P15372, P15887, P19107, P19108, P20443, P25455, P32122, P36575, P51432, P51477, P51478, P51479, P51481, P51482, P51483, P51484, P51485, P51486, P51487, P52566, P55274, P79260, Q0VCA2, Q1JQD4, Q28281, Q498D9, Q4R4K0, Q4R5M3, Q5DRQ4, Q5FWL4, Q5R5L7, Q5R698, Q61599, Q66KM2, Q6NUA1, Q6TXF1

Diamond homologs: P08168, P10523, P15372, P15887, P17870, P19107, P19108, P20443, P29066, P29067, P32120, P32121, P32122, P36575, P36576, P49407, P51466, P51467, P51468, P51477, P51478, P51479, P51481, P51482, P51483, P51484, P51485, P51486, P51487, P55274, P79260, Q28281, Q4R562, Q5DRQ4, Q5RCR4, Q7YS78, Q8BWG8, Q91YI4, Q95223, Q9EQP6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NEDD4	“down-regulates quantity by destabilization”	SAG	polyubiquitination
SAG	“up-regulates quantity by stabilization”	CUL5	binding
NEDD4	“down-regulates quantity”	SAG	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	20
Uncertain significance	243
Likely benign	134
Benign	50

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
102422	NM_000541.5(SAG):c.523C>T (p.Arg175Ter)	Pathogenic
1066818	NC_000002.11:g.(?234224701)(234224801_?)dup	Pathogenic
1069163	NC_000002.11:g.(?234217836)(234217930_?)del	Pathogenic
12951	NM_000541.5(SAG):c.926del (p.Asn309fs)	Pathogenic
1356012	NM_000541.5(SAG):c.858dup (p.Leu288fs)	Pathogenic
1389528	NM_000541.5(SAG):c.695_704del (p.Asn232fs)	Pathogenic
1440983	NM_000541.5(SAG):c.619del (p.Leu207fs)	Pathogenic
1449236	NM_000541.5(SAG):c.178_181del (p.Lys60fs)	Pathogenic
1452228	NM_000541.5(SAG):c.74C>A (p.Ser25Ter)	Pathogenic
1460172	NC_000002.11:g.(?234237727)(234247303_?)del	Pathogenic
1901641	NM_000541.5(SAG):c.807delA (p.Glu270fs)	Pathogenic
1940817	NM_000541.5(SAG):c.341dup (p.Leu115fs)	Pathogenic
2423272	NC_000002.11:g.(?234224701)(234224801_?)del	Pathogenic
2851019	NM_000541.5(SAG):c.544C>T (p.Gln182Ter)	Pathogenic
41895	NM_000541.5(SAG):c.577C>T (p.Arg193Ter)	Pathogenic
41897	NM_000541.5(SAG):c.874C>T (p.Arg292Ter)	Pathogenic
41898	NM_000541.5(SAG):c.916G>T (p.Glu306Ter)	Pathogenic
4531166	SAG, 1-BP DEL, 636T	Pathogenic
4531167	S133L	Pathogenic
4699726	NM_000541.5(SAG):c.376-2A>G	Pathogenic
801912	NM_000541.5(SAG):c.571C>T (p.Gln191Ter)	Pathogenic
831716	NC_000002.12:g.(?233316075)(233316135_?)del	Pathogenic
862338	NM_000541.5(SAG):c.440G>T (p.Cys147Phe)	Pathogenic
984410	NM_000541.5(SAG):c.648+1G>C	Pathogenic
989451	NM_000541.5(SAG):c.649-1G>C	Pathogenic
1066985	NM_000541.5(SAG):c.1047-2A>G	Likely pathogenic
1067757	NM_000541.5(SAG):c.76-2A>C	Likely pathogenic
1479039	NM_000541.5(SAG):c.649-1G>A	Likely pathogenic
1490119	NM_000541.5(SAG):c.435+1G>A	Likely pathogenic
1511520	NM_000541.5(SAG):c.72_75+15del	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2655 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:233320653:T:C	F69L	0.999
2:233320655:C:A	F69L	0.999
2:233320655:C:G	F69L	0.999
2:233328501:G:C	R179P	0.999
2:233316084:T:G	Y29D	0.998
2:233316098:A:C	R33S	0.998
2:233316098:A:T	R33S	0.998
2:233320636:T:A	V63D	0.998
2:233320649:C:G	C67W	0.998
2:233327143:T:A	V153D	0.998
2:233335048:C:A	A298D	0.998
2:233335087:C:A	A311D	0.998
2:233335092:A:C	S313R	0.998
2:233335094:C:A	S313R	0.998
2:233335094:C:G	S313R	0.998
2:233309243:G:C	K18N	0.997
2:233309243:G:T	K18N	0.997
2:233318754:G:A	G47D	0.997
2:233320654:T:C	F69S	0.997
2:233328500:C:A	R179S	0.997
2:233338708:G:A	G326E	0.997
2:233346838:T:C	F382L	0.997
2:233346840:T:A	F382L	0.997
2:233346840:T:G	F382L	0.997
2:233316088:T:C	L30P	0.996
2:233316097:G:C	R33T	0.996
2:233320647:T:C	C67R	0.996
2:233320695:T:C	F83L	0.996
2:233320697:C:A	F83L	0.996
2:233320697:C:G	F83L	0.996

dbSNP variants (sampled 300 via entrez): RS1000120721 (2:233320216 C>T), RS1000141 (2:233333701 C>T), RS1000252882 (2:233322510 T>A,C), RS1000409585 (2:233316813 A>G), RS1000443898 (2:233318109 G>A), RS1000459249 (2:233327100 T>C), RS1000492418 (2:233345158 A>C), RS1000547 (2:233326824 A>C,G,T), RS1000548 (2:233326656 T>C), RS1000604905 (2:233322077 C>T), RS1000616434 (2:233324462 A>C), RS1000689416 (2:233315007 T>G), RS1000724491 (2:233321279 A>G), RS1000777294 (2:233319497 C>A,G,T), RS1000825236 (2:233315327 C>G)

Disease associations

OMIM: gene MIM:181031 | disease phenotypes: MIM:258100, MIM:613758, MIM:620228, MIM:268000, MIM:613411

GenCC curated gene-disease

Disease	Classification	Inheritance
Oguchi disease-1	Definitive	Autosomal recessive
retinitis pigmentosa 47	Definitive	Autosomal dominant
retinitis pigmentosa 96	Strong	Autosomal dominant
retinal disorder	Moderate	Autosomal recessive
Oguchi disease	Supportive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
retinitis pigmentosa 47	Definitive	AR

Mondo (9): Oguchi disease (MONDO:0019152), Oguchi disease-1 (MONDO:0009775), retinitis pigmentosa 47 (MONDO:0013407), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 96 (MONDO:0859367), retinitis pigmentosa (MONDO:0019200), Oguchi disease-2 (MONDO:0013259), retinal disorder (MONDO:0005283), cone dystrophy (MONDO:0000455)

Orphanet (4): Oguchi disease (Orphanet:75382), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Progressive cone dystrophy (Orphanet:1871)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000533	Chorioretinal atrophy
HP:0000539	Abnormality of refraction
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000608	Macular degeneration
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000651	Diplopia
HP:0000654	Decreased light- and dark-adapted electroretinogram amplitude
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001123	Visual field defect
HP:0001133	Constriction of peripheral visual field

GWAS associations

0 associations (top):

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C537743	Oguchi disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
aflatoxin B2	decreases methylation	1
2-palmitoylglycerol	increases expression	1
Cadmium	decreases expression, increases abundance	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Zinc Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy