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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GRK1
G protein-coupled receptor kinase 1
Chromosome 13 Β· 13q34
NCBI Gene: 6011Ensembl: ENSG00000185974.7HGNC: HGNC:10013UniProt: Q15835
51PubMed Papers
21Diseases
0Drugs
21Pathogenic Variants
FUNCTIONAL ROLE
Kinase
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of opsin-mediated signaling pathwayrhodopsin kinase activityregulation of signal transductioncytoplasmOguchi disease-2Oguchi diseaseRetinal dystrophycongenital stationary night blindness
✦AI Summary

GRK1 (G protein-coupled receptor kinase 1) is a retina-specific kinase that phosphorylates rhodopsin to terminate phototransduction signaling 1. This rapid desensitization of the activated rhodopsin receptor is essential for scotopic vision and enables quick adaptation to changes in light illumination 2. GRK1 functions as part of a negative feedback loop in vertebrate phototransduction, with its activity regulated in a calcium-dependent manner by the protein recoverin 2. The kinase operates through multipoint substrate attachment mechanisms independent of second messengers 1. Pathogenic variants in GRK1 cause Oguchi disease, a rare autosomal recessive form of congenital stationary night blindness (CSNB) 34. Clinical manifestations include severe night blindness, characteristic fundus appearance (Mizuo-Nakamura phenomenon), attenuated rod electroretinogram responses, and negative ERG waveforms, while visual acuity and visual fields typically remain normal 3. GRK1 mutations account for a significant portion of inherited retinal disease cases 5. Structurally, disease-causing variants show a hotspot in the kinase domain 4. GRK1 serves as a promoter element in gene therapy applications for retinal photoreceptor diseases 6, and the protein interacts with the molecular chaperone Hsp90 to maintain retinal proteostasis 7.

Sources cited
1
GRK1 (rhodopsin kinase) catalyzes phosphorylation of activated rhodopsin G-protein-coupled receptor through multipoint kinase-substrate attachment independent of second messengers
PMID: 1664548
2
GRK1 and recoverin interact in a calcium-dependent manner, with recoverin acting as a negative regulator of rhodopsin kinase in phototransduction and light adaptation
PMID: 12596917
3
GRK1 mutations cause Oguchi disease with clinical features including night blindness, Mizuo-Nakamura phenomenon, attenuated rod responses, and negative ERG waveforms
PMID: 36417138
4
Biallelic GRK1 mutations cause Oguchi disease, a rare CSNB subtype, with missense variants showing a hotspot in the kinase domain
PMID: 33252155
5
GRK1 is among genes encoding phototransduction proteins whose pathogenic variants cause significant vision impairment and inherited retinal disease
PMID: 40013354
6
GRK1 is a retinal client protein that interacts with Hsp90 chaperone for proteostatic maintenance in photoreceptors
PMID: 35883534
7
GRK1 promoter is used in gene therapy for retinal photoreceptor diseases
PMID: 22308428
Disease Associationsβ“˜21
Oguchi disease-2Open Targets
0.66Moderate
Oguchi diseaseOpen Targets
0.51Moderate
Retinal dystrophyOpen Targets
0.50Moderate
congenital stationary night blindnessOpen Targets
0.26Weak
neuroinflammatory disorderOpen Targets
0.22Weak
epilepsyOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
alopecia areataOpen Targets
0.15Weak
pancreas diseaseOpen Targets
0.14Weak
metabolic diseaseOpen Targets
0.14Weak
age-related macular degenerationOpen Targets
0.07Suggestive
X-linked retinal dysplasiaOpen Targets
0.07Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.06Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.05Suggestive
Stargardt diseaseOpen Targets
0.05Suggestive
Familial drusenOpen Targets
0.04Suggestive
X-linked retinoschisisOpen Targets
0.04Suggestive
age related macular degeneration 11Open Targets
0.04Suggestive
age related macular degeneration 4Open Targets
0.04Suggestive
age related macular degeneration 7Open Targets
0.04Suggestive
Night blindness, congenital stationary, Oguchi type 2UniProt
Pathogenic Variants21
NM_002929.3(GRK1):c.1139T>A (p.Val380Asp)Pathogenic
Oguchi disease-2|not provided|Retinal dystrophy
β˜…β˜…β˜†β˜†2022β†’ Residue 380
NM_002929.3(GRK1):c.1177C>T (p.Arg393Ter)Pathogenic
Oguchi disease-2
β˜…β˜†β˜†β˜†2024β†’ Residue 393
NM_002929.3(GRK1):c.712_714del (p.Glu238del)Likely pathogenic
Oguchi disease-2
β˜…β˜†β˜†β˜†2024β†’ Residue 238
NM_002929.3(GRK1):c.142_145del (p.Glu48fs)Pathogenic
Oguchi disease-2|Retinal dystrophy
β˜…β˜†β˜†β˜†2024β†’ Residue 48
NM_002929.3(GRK1):c.1312C>T (p.Arg438Cys)Likely pathogenic
Oguchi disease-2|Retinal dystrophy
β˜…β˜†β˜†β˜†2022β†’ Residue 438
NM_002929.3(GRK1):c.55C>T (p.Arg19Ter)Likely pathogenic
Oguchi disease-2
β˜…β˜†β˜†β˜†β†’ Residue 19
NM_002929.3(GRK1):c.508_516del (p.Tyr170_Leu172del)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2022β†’ Residue 170
NM_002929.3(GRK1):c.1384C>T (p.Gln462Ter)Likely pathogenic
Congenital stationary night blindness|Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 462
NM_002929.3(GRK1):c.470T>C (p.Leu157Pro)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 157
NM_002929.3(GRK1):c.1129G>C (p.Ala377Pro)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 377
NM_002929.3(GRK1):c.1138G>T (p.Val380Phe)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 380
NM_002929.3(GRK1):c.971del (p.Leu324fs)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 324
NM_002929.3(GRK1):c.1411_1412del (p.Pro471fs)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 471
NM_002929.3(GRK1):c.1549_1559del (p.Pro517fs)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 517
NM_002929.3(GRK1):c.1084G>A (p.Glu362Lys)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 362
NM_002929.3(GRK1):c.827+625_883delLikely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019
NM_002929.3(GRK1):c.614C>A (p.Ser205Ter)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 205
NM_002929.3(GRK1):c.1172C>A (p.Pro391His)Pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 391
NM_002929.3(GRK1):c.595G>C (p.Gly199Arg)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 199
NM_002929.3(GRK1):c.923T>C (p.Leu308Pro)Likely pathogenic
Oguchi disease-2
β˜†β˜†β˜†β˜†2019β†’ Residue 308
View on ClinVar β†—
Related Genes
RHOProtein interaction100%CXCR4Protein interaction99%NCS1Protein interaction97%SAGProtein interaction92%ARRB1Protein interaction91%ARRB2Protein interaction91%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
92%
Heart
42%
Lung
3%
Ovary
3%
Liver
0%
Gene Interaction Network
Click a node to explore
GRK1RHOCXCR4NCS1SAGARRB1ARRB2
PROTEIN STRUCTURE
Preparing viewer…
PDB5AFP Β· 2.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.10LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.74 [0.50–1.10]
RankingsWhere GRK1 stands among ~20K protein-coding genes
  • #8,681of 20,598
    Most Researched51
  • #2,157of 5,498
    Most Pathogenic Variants21
  • #11,278of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedGRK1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Monogenic Retinal Diseases Associated With Genes Encoding Phototransduction Proteins: A Review.
PMID: 40013354
Clin Exp Ophthalmol Β· 2025
1.00
2
Ginsenoside RK1 Promotes Hepatic Stellate Cell Glycolysis-Mediated Ferroptosis by Activating the HK2/ACSL4/LPCAT3/ALOX5 Signaling Pathway.
PMID: 40570179
J Agric Food Chem Β· 2025
0.90
3
G-protein-coupled receptor kinases.
PMID: 1664548
Trends Biochem Sci Β· 1991
0.80
4
The Role of Hsp90 in Retinal Proteostasis and Disease.
PMID: 35883534
Biomolecules Β· 2022
0.70
5
Genetic analysis and clinical features of three Chinese patients with Oguchi disease.
PMID: 36417138
Doc Ophthalmol Β· 2023
0.60