On this page
AIPL1
AIP like 1 HSP90 co-chaperone
AIPL1 is located on the short (p) arm of chromosome 17, at band 17p13.2. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 17 in the library →Available at Jeen Health
Clinical tests that include this
Overview
AIPL1 (AIP like 1 HSP90 co-chaperone) produces a specialised co-chaperone protein predominantly expressed in retinal photoreceptor cells. The AIPL1 protein works alongside heat shock protein 90 (HSP90) to ensure correct folding and stability of proteins essential for phototransduction, the process by which light signals are converted into electrical signals in the retina.
Pathogenic variants in AIPL1 are primarily associated with inherited retinal disorders, most notably Leber congenital amaurosis, a severe form of early-onset retinal degeneration. The gene is recognised on NHS Genomic Medicine Service panels for retinal disorders, reflecting its clinical importance in diagnosing inherited blindness. Understanding AIPL1 function provides insight into the molecular mechanisms underlying photoreceptor survival and retinal disease.
What the gene does
The AIPL1 protein functions as a co-chaperone that modulates the activity of HSP90, a molecular chaperone critical for maintaining cellular protein homeostasis. Within photoreceptor cells, AIPL1 assists in the maturation and stabilisation of phosphodiesterase 6 (PDE6), an enzyme central to the phototransduction cascade that enables vision in dim light conditions.
AIPL1 facilitates the proper assembly of PDE6 subunits and helps maintain the structural integrity of this enzyme complex. Without functional AIPL1, PDE6 fails to achieve its correct three-dimensional configuration, leading to degradation of the enzyme and impaired signal transduction in rod photoreceptors. The protein's co-chaperone activity is essential during photoreceptor development and throughout adult life for maintaining the delicate biochemical machinery required for light detection. Loss of AIPL1 function results in photoreceptor cell death, typically manifesting in infancy or early childhood as progressive vision loss.
Video: Genetics 101
Chromosome location
AIPL1 is located on chromosome 17 at band p13.2, a region on the short arm of chromosome 17. The gene spans approximately 11 kilobases of genomic DNA and contains six exons that encode the mature messenger RNA. The chromosomal region 17p13.2 contains several genes involved in neurological and developmental processes, though AIPL1 exhibits highly tissue-specific expression predominantly in the retina.
Protein structure
The AIPL1 protein comprises 384 amino acids organised into functionally distinct domains that enable its co-chaperone activity. The N-terminal region contains a PPIase FKBP-type domain spanning amino acids 53 to 145, which exhibits peptidyl-prolyl isomerase activity and contributes to protein folding processes.
The C-terminal portion of the protein features three consecutive tetratricopeptide repeat (TPR) motifs: TPR 1 (amino acids 178-211), TPR 2 (amino acids 230-263), and TPR 3 (amino acids 264-297). These TPR domains mediate protein-protein interactions, particularly binding to HSP90, and are critical for AIPL1's function in stabilising client proteins such as PDE6. The extreme C-terminus contains a disordered region from amino acids 328 to 384, which may provide flexibility for conformational changes during chaperone cycling.
Key variants
Pathogenic variants in AIPL1 are distributed throughout the gene, with both missense and loss-of-function variants reported. Many disease-causing variants affect the TPR domains, disrupting the protein's ability to interact with HSP90 or stabilise PDE6. Null variants that result in complete absence of functional protein typically cause the most severe phenotypes with earliest onset of vision loss. The spectrum of variant severity correlates broadly with residual AIPL1 function and age of symptom onset.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.126T>A | p.Cys42Ter | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
c.216G>A | p.Trp72Ter | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
c.265T>C | p.Cys89Arg | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
c.276+1G>A | - | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
c.276+2T>C | - | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
c.277-2A>G | - | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
c.421C>T | p.Gln141Ter | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
c.487C>T | p.Gln163Ter | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
c.618_619dup | p.Cys207fs | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
c.784G>A | p.Gly262Ser | Pathogenic | ★★★☆ | AIPL1-related retinopathy |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in AIPL1 cause inherited retinal disorders characterised by progressive photoreceptor degeneration. The most common presentation is Leber congenital amaurosis, a severe form of retinal dystrophy evident from birth or early infancy, with profound vision impairment and nystagmus. Some individuals with less severe AIPL1 variants develop juvenile-onset retinitis pigmentosa, with progressive night blindness and peripheral vision loss beginning in childhood or adolescence. The clinical severity depends on the specific variants present and the degree to which AIPL1 function is compromised.
No disease links recorded for this gene in our reference set.
UK clinical status
AIPL1 is included on multiple NHS Genomic Medicine Service gene panels relevant to inherited eye disorders. The gene holds green classification status on the national Developmental Disorders Gene-to-Phenotype (DDG2P) panel and the Retinal disorders panel (R32), indicating robust evidence linking AIPL1 variants to specific clinical phenotypes. This classification means AIPL1 is routinely analysed when genetic testing is requested for individuals presenting with early-onset retinal degeneration or suspected Leber congenital amaurosis through NHS clinical genetics services.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What conditions are caused by AIPL1 variants?
Pathogenic variants in AIPL1 primarily cause Leber congenital amaurosis, a severe inherited retinal disorder present from birth or early infancy. Some variants are associated with juvenile-onset retinitis pigmentosa, a milder form of progressive vision loss. Both conditions result from photoreceptor cell degeneration in the retina.
How is AIPL1 inherited?
AIPL1-related conditions follow autosomal recessive inheritance, meaning an affected individual typically inherits one pathogenic variant from each parent. Parents who each carry one variant are generally unaffected carriers with normal vision. When both parents are carriers, each child has a 25% chance of inheriting both variants and being affected.
Is AIPL1 tested on the NHS?
Yes, AIPL1 is included on NHS Genomic Medicine Service panels for retinal disorders and holds green classification status. Genetic testing that includes AIPL1 analysis is available through NHS clinical genetics services for individuals meeting clinical criteria for inherited retinal disease, typically those with early-onset vision loss or family history of retinal disorders.