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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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ARR3
arrestin 3
Chromosome X Β· Xq13.1
NCBI Gene: 407Ensembl: ENSG00000120500.19HGNC: HGNC:710UniProt: P36575
54PubMed Papers
21Diseases
0Drugs
10Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingphotoreceptor inner segmentG protein-coupled receptor bindingG protein-coupled receptor internalizationmyopia 26, X-linked, female-limitedgenetic disorderrefractive errorRare isolated myopia
✦AI Summary

ARR3 (arrestin 3) encodes cone arrestin, a retinal protein that plays a critical role in cone phototransduction by inactivating phosphorylated opsins and terminating cone cell signals 1. The protein is specifically expressed in cone photoreceptors where it binds to photoactivated-phosphorylated red/green opsins to regulate visual signal transduction 2. Pathogenic variants in ARR3 are the most frequently implicated genetic cause of Mendelian early-onset high myopia (eoHM), following an X-linked female-limited inheritance pattern 3. The disease mechanism involves cone dysfunction, with affected patients showing mild-to-moderately reduced cone responses on electroretinography and progressive color vision defects 34. Clinical significance includes severe myopia ranging from -5.00 to -28.75 diopters, with most patients developing mild myopic fundus changes that can progress to pathologic myopia 3. The cone dysfunction observed in ARR3-associated myopia is specifically linked to the genetic mutation rather than being a consequence of eye elongation 4. Various pathogenic variants have been identified, including truncation mutations, missense variants, and splicing variants, all leading to similar phenotypes of early-onset high myopia with cone dysfunction 56.

Sources cited
1
ARR3 encodes cone arrestin that inactivates phosphorylated-opsins and prevents cone signals
PMID: 37268727
2
ARR3 is involved in phototransduction and binds to photoactivated-phosphorylated opsins
PMID: 40013354
3
ARR3 is the most frequently implicated gene for Mendelian early-onset high myopia with X-linked female-limited inheritance
PMID: 36180177
4
ARR3 mutations cause cone dysfunction with reduced cone responses on electroretinography
PMID: 39420435
5
Various pathogenic variants including splicing variants cause early-onset high myopia
PMID: 38517428
6
Truncation mutations in ARR3 lead to nonsense-mediated decay and pathogenic mechanisms
PMID: 34966409
Disease Associationsβ“˜21
myopia 26, X-linked, female-limitedOpen Targets
0.61Moderate
genetic disorderOpen Targets
0.19Weak
refractive errorOpen Targets
0.19Weak
Rare isolated myopiaOpen Targets
0.18Weak
neoplasmOpen Targets
0.11Weak
myopiaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
SepsisOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.07Suggestive
Miyoshi myopathyOpen Targets
0.06Suggestive
leukemiaOpen Targets
0.05Suggestive
prostate cancerOpen Targets
0.05Suggestive
respiratory depressionOpen Targets
0.04Suggestive
hypertriglyceridemia 2Open Targets
0.04Suggestive
liver cancerOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
childhood leukemiaOpen Targets
0.04Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.04Suggestive
glioblastoma multiformeOpen Targets
0.04Suggestive
non-small cell lung carcinomaOpen Targets
0.03Suggestive
Myopia 26, X-linked, female-limitedUniProt
Pathogenic Variants10
NM_004312.3(ARR3):c.767+1G>APathogenic
not provided|Myopia 26, X-linked, female-limited
β˜…β˜…β˜†β˜†2024
NM_004312.3(ARR3):c.1A>G (p.Met1Val)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1
NM_004312.3(ARR3):c.905+2delPathogenic
Myopia 26, X-linked, female-limited
β˜…β˜†β˜†β˜†2025
NM_004312.3(ARR3):c.193G>T (p.Glu65Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 65
NM_004312.3(ARR3):c.214C>T (p.Arg72Ter)Pathogenic
Myopia 26, X-linked, female-limited|ARR3-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 72
NM_004312.3(ARR3):c.917del (p.Gly306fs)Likely pathogenic
ARR3-related disorder
β˜†β˜†β˜†β˜†2024β†’ Residue 306
NM_004312.3(ARR3):c.330C>A (p.Tyr110Ter)Likely pathogenic
ARR3-related disorder
β˜†β˜†β˜†β˜†2023β†’ Residue 110
NM_004312.3(ARR3):c.239T>C (p.Leu80Pro)Pathogenic
Myopia 26, X-linked, female-limited
β˜†β˜†β˜†β˜†2017β†’ Residue 80
NM_004312.3(ARR3):c.298C>T (p.Arg100Ter)Pathogenic
Myopia 26, X-linked, female-limited
β˜†β˜†β˜†β˜†2017β†’ Residue 100
NM_004312.3(ARR3):c.893C>A (p.Ala298Asp)Pathogenic
Myopia 26, X-linked, female-limited
β˜†β˜†β˜†β˜†2017β†’ Residue 298
View on ClinVar β†—
Related Genes
GRK2Protein interaction99%NR2E3Protein interaction97%RHOProtein interaction94%RCVRNProtein interaction91%OPN1SWProtein interaction91%PDE6HProtein interaction89%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
74%
Lung
66%
Liver
53%
Heart
34%
Brain
9%
Gene Interaction Network
Click a node to explore
ARR3GRK2NR2E3RHORCVRNOPN1SWPDE6H
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P36575
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.62LoF Tolerant
pLIβ“˜
0.46Tolerant
Observed/Expected LoF0.40 [0.26–0.62]
RankingsWhere ARR3 stands among ~20K protein-coding genes
  • #8,279of 20,598
    Most Researched54
  • #2,869of 5,498
    Most Pathogenic Variants10
  • #4,318of 17,882
    Most Constrained (LOEUF)0.62 Β· top quartile
Genes detectedARR3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetic and clinical landscape of
PMID: 36180177
Br J Ophthalmol Β· 2023
1.00
2
Monogenic Retinal Diseases Associated With Genes Encoding Phototransduction Proteins: A Review.
PMID: 40013354
Clin Exp Ophthalmol Β· 2025
0.90
3
The causal mutation in ARR3 gene for high myopia and progressive color vision defect.
PMID: 37268727
Sci Rep Β· 2023
0.80
4
Novel Splicing Variants in the ARR3 Gene Cause the Female-Limited Early-Onset High Myopia.
PMID: 38517428
Invest Ophthalmol Vis Sci Β· 2024
0.70
5
Cone dysfunction in ARR3-mutation-associated early-onset high myopia: an electrophysiological study.
PMID: 39420435
Orphanet J Rare Dis Β· 2024
0.60