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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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RLBP1
retinaldehyde binding protein 1
Chromosome 15 Β· 15q26.1
NCBI Gene: 6017Ensembl: ENSG00000140522.13HGNC: HGNC:10024UniProt: P12271
56PubMed Papers
23Diseases
0Drugs
52Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcytosolphosphatidylinositol bisphosphate bindingvitamin A metabolic processBothnia retinal dystrophyfundus albipunctatusNewfoundland cone-rod dystrophyretinitis punctata albescens
✦AI Summary

RLBP1 encodes cellular retinaldehyde binding protein (CRALBP), a soluble retinoid carrier essential for visual function in both rod and cone photoreceptors. CRALBP is predominantly expressed in the retinal pigment epithelium (RPE) but also in MΓΌller cells, where it functions as a chaperone for 11-cis-retinoids in the visual cycle 1. The protein participates in regenerating active 11-cis-retinol and 11-cis-retinaldehyde from inactive 11-trans products produced during the rhodopsin photocycle, enabling the cycling of retinoids between photoreceptor and RPE cells 2. Loss of RPE-expressed RLBP1 selectively impairs vision under low-light conditions, recapitulating the night blindness presentation in patients 1. Biallelic RLBP1 mutations cause three inherited retinal dystrophy subtypes: Bothnia dystrophy, retinitis punctata albescens, and Newfoundland rod-cone dystrophy 3. Progressive macular atrophy characterizes typical severe cases, though hypomorphic variants may cause milder phenotypes 4. Gene therapy using AAV8-RLBP1 subretinal delivery demonstrated preliminary safety and efficacy in patients, significantly improving dark adaptation kinetics and resolving disease-related retinal deposits 5. RLBP1 variants have also been identified in age-related macular degeneration through genome-wide transcriptome analysis 6.

Sources cited
1
CRALBP functions in the visual cycle by chaperoning 11-cis-retinoids, predominantly in RPE-expressed rlbp1b, with selective impairment of vision under dim light conditions upon loss
PMID: 40552921
2
AAV-mediated RLBP1 gene therapy improves dark adaptation rates in RLBP1-deficient mice
PMID: 26199951
3
RLBP1 variants cause three clinical subtypes (Bothnia dystrophy, retinitis punctata albescens, Newfoundland rod-cone dystrophy) and CRALBP functions in rod and cone visual cycles
PMID: 39385467
4
RLBP1-associated retinopathy typically features macular atrophy and progressive cone-rod dysfunction, though hypomorphic variants may cause milder phenotypes
PMID: 38945349
5
AAV8-RLBP1 gene therapy demonstrated safety and efficacy with improved dark adaptation and resolution of retinal deposits in RLBP1-associated retinal dystrophy patients
PMID: 39256350
6
RLBP1 was identified as a gene associated with age-related macular degeneration through transcriptome-wide association analysis
PMID: 30742112
Disease Associationsβ“˜23
Bothnia retinal dystrophyOpen Targets
0.73Strong
fundus albipunctatusOpen Targets
0.71Strong
Newfoundland cone-rod dystrophyOpen Targets
0.70Strong
retinitis punctata albescensOpen Targets
0.70Moderate
retinitis pigmentosaOpen Targets
0.68Moderate
Retinal dystrophyOpen Targets
0.52Moderate
Joubert syndrome and related disordersOpen Targets
0.51Moderate
RLBP1-related retinopathyOpen Targets
0.50Moderate
autosomal recessive retinitis pigmentosaOpen Targets
0.46Moderate
Posterior column ataxia - retinitis pigmentosaOpen Targets
0.37Weak
eye diseaseOpen Targets
0.37Weak
Alpers syndromeOpen Targets
0.34Weak
mitochondrial DNA depletion syndrome 4aOpen Targets
0.34Weak
age-related macular degenerationOpen Targets
0.32Weak
wet macular degenerationOpen Targets
0.31Weak
degeneration of macula and posterior poleOpen Targets
0.29Weak
Abnormality of limbsOpen Targets
0.27Weak
retinopathyOpen Targets
0.27Weak
Abnormality of the eyeOpen Targets
0.27Weak
dry age related macular degenerationOpen Targets
0.19Weak
Bothnia retinal dystrophyUniProt
Retinitis punctata albescensUniProt
Rod-cone dystrophy NewfoundlandUniProt
Pathogenic Variants52
NM_000326.5(RLBP1):c.677T>A (p.Met226Lys)Pathogenic
Retinitis punctata albescens|RLBP1-related disorder|Retinitis pigmentosa|Retinal dystrophy|not provided|Newfoundland cone-rod dystrophy;Pigmentary retinal dystrophy;Bothnia retinal dystrophy|Retinal disorder|Bothnia retinal dystrophy;Retinitis punctata albescens
β˜…β˜…β˜†β˜†2026β†’ Residue 226
NM_000326.5(RLBP1):c.282del (p.Phe95fs)Pathogenic
not provided|Newfoundland cone-rod dystrophy|Pigmentary retinal dystrophy|Bothnia retinal dystrophy;Pigmentary retinal dystrophy;Newfoundland cone-rod dystrophy|Retinitis pigmentosa
β˜…β˜…β˜†β˜†2026β†’ Residue 95
NM_000326.5(RLBP1):c.832del (p.Gln278fs)Pathogenic
not provided|Newfoundland cone-rod dystrophy;Pigmentary retinal dystrophy;Bothnia retinal dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 278
NM_000326.5(RLBP1):c.700C>T (p.Arg234Trp)Pathogenic
Bothnia retinal dystrophy|Retinitis punctata albescens|RLBP1-related disorder|Retinitis pigmentosa|not provided|Retinal dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 234
NM_000326.5(RLBP1):c.286_297del (p.Phe96_Phe99del)Pathogenic
not provided|Bothnia retinal dystrophy|Retinal dystrophy|Retinitis punctata albescens|Autosomal recessive retinitis pigmentosa|Abnormality of the eye|Retinitis pigmentosa|Pigmentary retinal dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 96
NM_000326.5(RLBP1):c.753C>A (p.Tyr251Ter)Pathogenic
Pigmentary retinal dystrophy|not provided|Retinitis pigmentosa
β˜…β˜…β˜†β˜†2025β†’ Residue 251
NM_000326.5(RLBP1):c.452G>A (p.Arg151Gln)Pathogenic
Pigmentary retinal dystrophy|Retinitis punctata albescens|Autosomal recessive retinitis pigmentosa|Retinitis pigmentosa|not provided|Newfoundland cone-rod dystrophy;Pigmentary retinal dystrophy;Bothnia retinal dystrophy|Bothnia retinal dystrophy|RLBP1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 151
NM_000326.5(RLBP1):c.190C>T (p.Arg64Ter)Pathogenic
Retinal dystrophy|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 64
NM_000326.5(RLBP1):c.141G>A (p.Lys47=)Pathogenic
Newfoundland cone-rod dystrophy|Retinitis punctata albescens|not provided|Retinitis pigmentosa
β˜…β˜…β˜†β˜†2025β†’ Residue 47
NM_000326.5(RLBP1):c.13-1G>CPathogenic
not provided|Retinitis pigmentosa|RLBP1-related disorder
β˜…β˜…β˜†β˜†2025
NM_000326.5(RLBP1):c.141+2T>CPathogenic
not provided|RLBP1-related disorder|Newfoundland cone-rod dystrophy|Bothnia retinal dystrophy;Newfoundland cone-rod dystrophy;Pigmentary retinal dystrophy
β˜…β˜…β˜†β˜†2025
NM_000326.5(RLBP1):c.466C>T (p.Arg156Ter)Pathogenic
not provided|Newfoundland cone-rod dystrophy;Pigmentary retinal dystrophy;Bothnia retinal dystrophy
β˜…β˜…β˜†β˜†2024β†’ Residue 156
NM_000326.5(RLBP1):c.12+2delLikely pathogenic
not provided|Newfoundland cone-rod dystrophy;Pigmentary retinal dystrophy;Bothnia retinal dystrophy
β˜…β˜…β˜†β˜†2024
NM_000326.5(RLBP1):c.451C>T (p.Arg151Trp)Pathogenic
Retinitis pigmentosa|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 151
NM_000326.5(RLBP1):c.333T>G (p.Tyr111Ter)Pathogenic
Retinal dystrophy|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 111
NM_000326.5(RLBP1):c.255_258dup (p.Arg87fs)Pathogenic
Retinitis pigmentosa|not provided
β˜…β˜…β˜†β˜†2020β†’ Residue 87
NM_000326.5(RLBP1):c.508G>T (p.Glu170Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 170
NM_000326.5(RLBP1):c.795+1G>APathogenic
not provided
β˜…β˜†β˜†β˜†2026
NM_000326.5(RLBP1):c.141+2T>GPathogenic
not provided
β˜…β˜†β˜†β˜†2026
NM_000326.5(RLBP1):c.346G>C (p.Gly116Arg)Pathogenic
Retinitis pigmentosa|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 116
View on ClinVar β†—
Related Genes
LRATProtein interaction95%AWAT2Protein interaction91%RDH11Protein interaction91%RDH8Protein interaction90%RDH5Protein interaction89%RGRProtein interaction89%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
97%
Ovary
3%
Liver
2%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
RLBP1LRATAWAT2RDH11RDH8RDH5RGR
PROTEIN STRUCTURE
Preparing viewer…
PDB3HX3 Β· 1.69 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.95LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.69 [0.50–0.95]
RankingsWhere RLBP1 stands among ~20K protein-coding genes
  • #8,128of 20,598
    Most Researched56
  • #1,297of 5,498
    Most Pathogenic Variants52 Β· top quartile
  • #8,950of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedRLBP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301590
1.00
2
Impact of Next Generation Sequencing in Unraveling the Genetics of 1036 Spanish Families With Inherited Macular Dystrophies.
PMID: 35119454
Invest Ophthalmol Vis Sci Β· 2022
0.90
3
Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration.
PMID: 30742112
Nat Genet Β· 2019
0.80
4
Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial.
PMID: 39256350
Nat Commun Β· 2024
0.70
5
Dual CRALBP isoforms unveiled: iPSC-derived retinal modeling and AAV2/5-RLBP1 gene transfer raise considerations for effective therapy.
PMID: 39385467
Mol Ther Β· 2024
0.60