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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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AIPL1
AIP like 1 HSP90 co-chaperone
Chromosome 17 Β· 17p13.2
NCBI Gene: 23746Ensembl: ENSG00000129221.16HGNC: HGNC:359UniProt: F1T0B5
88PubMed Papers
21Diseases
0Drugs
80Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein farnesylationnucleuscytoplasmprotein bindingLeber congenital amaurosis 4Leber congenital amaurosisAIPL1-related retinopathyCone rod dystrophy
✦AI Summary

AIPL1 is a specialized HSP90 co-chaperone essential for photoreceptor cell function and survival. It serves as a critical chaperone for phosphodiesterase 6 (PDE6), the effector enzyme of the phototransduction cascade, ensuring proper folding, stability, and trafficking of this multimeric protein complex 1. AIPL1 is expressed early during retinal development in both rod and cone photoreceptors, with sustained expression in adult rods 2. Biallelic AIPL1 mutations cause Leber congenital amaurosis 4 (LCA4), one of the most severe inherited retinal dystrophies, characterized by rapid photoreceptor degeneration beginning in infancy 3. Patients typically present before age one with perception-limited vision, nystagmus, and nearly undetectable electroretinographic responses 4. AIPL1 mutations account for approximately 11% of LCA cases, with p.Q141X being the most prevalent mutation in Chinese populations 5. Clinically significant therapeutic advances have been achieved: subretinal gene supplementation therapy using rAAV8.hRKp.AIPL1 improved visual acuity from light perception to measurable levels in young children, with preserved retinal structure and functional visual cortex activation 6. Complementary approaches including human cone photoreceptor transplantation have demonstrated functional rescue even in end-stage disease models 7, suggesting multiple therapeutic pathways for this severe blinding condition.

Sources cited
1
AIPL1 is a specialized HSP90 co-chaperone for phosphodiesterase 6 (PDE6) ensuring proper protein folding, stability, and trafficking in the phototransduction cascade
PMID: 28939106
2
AIPL1 is expressed early during retinal development in both rods and cones, with continued expression in adult rods; it is critical for photoreceptor cell survival and function
PMID: 24664679
3
AIPL1 mutations cause Leber congenital amaurosis, one of the most severe forms of inherited retinal degeneration with rapid and extensive photoreceptor degeneration
PMID: 31884595
4
AIPL1 is one of the five most frequently mutated genes in Leber congenital amaurosis (11.0% frequency), with p.Q141X as the most common mutation in Chinese cohorts
PMID: 31630094
5
LCA4 (AIPL1-related) presents in infancy with severe vision loss, nystagmus, and nearly undetectable ERG responses; shows gradual progression over decades
PMID: 30578499
6
Subretinal rAAV8.hRKp.AIPL1 gene therapy improved visual acuity in young children with AIPL1-associated retinal dystrophy, with preserved retinal structure and functional improvement
PMID: 39986747
7
Human cone photoreceptor transplantation rescued light-evoked activity and visual function in AIPL1-deficient mice, demonstrating therapeutic feasibility in severe retinal dystrophy
PMID: 40154478
8
AIPL1 is associated with Leber congenital amaurosis/early-onset severe retinal dystrophy as part of the spectrum of inherited retinal diseases
PMID: 38278208
Disease Associationsβ“˜21
Leber congenital amaurosis 4Open Targets
0.78Strong
Leber congenital amaurosisOpen Targets
0.73Strong
AIPL1-related retinopathyOpen Targets
0.67Moderate
Cone rod dystrophyOpen Targets
0.59Moderate
retinitis pigmentosaOpen Targets
0.52Moderate
Rod-cone dystrophyOpen Targets
0.50Moderate
Retinal dystrophyOpen Targets
0.50Moderate
cone-rod dystrophyOpen Targets
0.50Moderate
myopia 25, autosomal dominantOpen Targets
0.28Weak
Abnormality of the eyeOpen Targets
0.27Weak
cone-rod dystrophy 2Open Targets
0.27Weak
crystal arthropathyOpen Targets
0.23Weak
chondrocalcinosisOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
autosomal dominant retinitis pigmentosaOpen Targets
0.19Weak
Posterior column ataxia - retinitis pigmentosaOpen Targets
0.19Weak
eye diseaseOpen Targets
0.19Weak
metabolic diseaseOpen Targets
0.16Weak
hypothyroidismOpen Targets
0.16Weak
connective tissue diseaseOpen Targets
0.15Weak
Leber congenital amaurosis 4UniProt
Pathogenic Variants80
NM_014336.5(AIPL1):c.834G>A (p.Trp278Ter)Pathogenic
Leber congenital amaurosis 4|not provided|AIPL1-related disorder|Leber congenital amaurosis|Retinal dystrophy|Leber congenital amaurosis 4;Retinitis pigmentosa|AIPL1-related retinopathy|Retinal disorder
β˜…β˜…β˜…β˜†2025β†’ Residue 278
NM_014336.5(AIPL1):c.421C>T (p.Gln141Ter)Pathogenic
Leber congenital amaurosis 4|Leber congenital amaurosis|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 141
NM_014336.5(AIPL1):c.1010_1011del (p.Glu337fs)Pathogenic
Leber congenital amaurosis 4|not provided|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 337
NM_014336.5(AIPL1):c.214T>C (p.Trp72Arg)Likely pathogenic
AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 72
NM_014336.5(AIPL1):c.211G>T (p.Val71Phe)Likely pathogenic
Leber congenital amaurosis|Leber congenital amaurosis 4|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 71
NM_014336.5(AIPL1):c.34dup (p.Val12fs)Likely pathogenic
Leber congenital amaurosis|Leber congenital amaurosis 4|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 12
NM_014336.5(AIPL1):c.190G>A (p.Gly64Arg)Likely pathogenic
Retinal dystrophy|Leber congenital amaurosis 4|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 64
NM_014336.5(AIPL1):c.50T>C (p.Leu17Pro)Likely pathogenic
not provided|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 17
NM_014336.5(AIPL1):c.265T>C (p.Cys89Arg)Pathogenic
Leber congenital amaurosis 4|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 89
NM_014336.5(AIPL1):c.487C>T (p.Gln163Ter)Pathogenic
not provided|Leber congenital amaurosis 4|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 163
NM_014336.5(AIPL1):c.277-2A>GPathogenic
not provided|Leber congenital amaurosis 4|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025
NM_014336.5(AIPL1):c.216G>A (p.Trp72Ter)Pathogenic
AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 72
NM_014336.5(AIPL1):c.784G>A (p.Gly262Ser)Pathogenic
Leber congenital amaurosis 4|not provided|AIPL1-related disorder|CONE-ROD DYSTROPHY, AIPL1-RELATED;Juvenile retinitis pigmentosa, AIPL1-related;Leber congenital amaurosis 4;AIPL1-related disorder|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 262
NM_014336.5(AIPL1):c.724AAG[1] (p.Lys243del)Likely pathogenic
Leber congenital amaurosis 4|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 243
NM_014336.5(AIPL1):c.126T>A (p.Cys42Ter)Pathogenic
AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 42
NM_014336.5(AIPL1):c.364G>A (p.Gly122Arg)Likely pathogenic
Leber congenital amaurosis 4|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 122
NM_014336.5(AIPL1):c.618_619dup (p.Cys207fs)Pathogenic
AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 207
NM_014336.5(AIPL1):c.589G>C (p.Ala197Pro)Pathogenic
Leber congenital amaurosis 4|not provided|AIPL1-related retinopathy|Leber congenital amaurosis
β˜…β˜…β˜…β˜†2025β†’ Residue 197
NM_014336.5(AIPL1):c.152A>G (p.Asp51Gly)Likely pathogenic
Leber congenital amaurosis 4|not provided|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 51
NM_014336.5(AIPL1):c.809G>A (p.Arg270His)Pathogenic
Leber congenital amaurosis 4|Leber congenital amaurosis|AIPL1-related retinopathy
β˜…β˜…β˜…β˜†2025β†’ Residue 270
View on ClinVar β†—
Related Genes
IMPG1Shared pathway100%ROM1Shared pathway100%PRR4Shared pathway100%NYXShared pathway100%IMPG2Shared pathway100%RAXShared pathway100%
Tissue Expression6 tissues
Ovary
100%
Lung
86%
Liver
79%
Brain
61%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
AIPL1IMPG1ROM1PRR4NYXIMPG2RAX
PROTEIN STRUCTURE
Preparing viewer…
PDB6PX0 Β· 1.55 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.01LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.72 [0.53–1.01]
RankingsWhere AIPL1 stands among ~20K protein-coding genes
  • #5,396of 20,598
    Most Researched88
  • #931of 5,498
    Most Pathogenic Variants80 Β· top quartile
  • #9,826of 17,882
    Most Constrained (LOEUF)1.01
Genes detectedAIPL1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study.
PMID: 39986747
Lancet Β· 2025
1.00
2
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
PMID: 38278208
Prog Retin Eye Res Β· 2024
0.90
3
Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy.
PMID: 31630094
Br J Ophthalmol Β· 2020
0.80
4
Gene and Cell Therapy for AIPL1-Associated Leber Congenital Amaurosis: Challenges and Prospects.
PMID: 31884595
Adv Exp Med Biol Β· 2019
0.70
5
Human cone photoreceptor transplantation stimulates remodeling and restores function in AIPL1 model of end-stage Leber congenital amaurosis.
PMID: 40154478
Stem Cell Reports Β· 2025
0.60