AIPL1-related retinopathy
diseaseOn this page
Also known as AIPL1 Leber congenital amaurosisAIPL1 retinopathyamaurosis congenita of Leber, type 4cone-rod dystrophycone-rod dystrophy, AIPL1-relatedLCA4Leber congenital amaurosis 4Leber congenital amaurosis caused by mutation in AIPL1Leber congenital amaurosis type 4retinitis pigmentosa, juvenileretinitis pigmentosa, juvenile, AIPL1-related
Summary
AIPL1-related retinopathy (MONDO:0100438) is a disease caused by AIPL1 (GenCC Strong), with 1 cohort gene and 11 clinical trials. Top therapeutic interventions include cholesterol.
At a glance
- Causal gene: AIPL1 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 54
- Clinical trials: 11
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | AIPL1-related retinopathy |
| Mondo ID | MONDO:0100438 |
| GARD | 0026214 |
| Is cancer (heuristic) | no |
Also known as: AIPL1 Leber congenital amaurosis · AIPL1 retinopathy · amaurosis congenita of Leber, type 4 · cone-rod dystrophy · cone-rod dystrophy, AIPL1-related · LCA4 · Leber congenital amaurosis 4 · Leber congenital amaurosis caused by mutation in AIPL1 · Leber congenital amaurosis type 4 · retinitis pigmentosa, juvenile · retinitis pigmentosa, juvenile, AIPL1-related
Data availability: 54 ClinVar variants · 53 ClinGen variant curations · 1 GenCC gene-disease record · 2 cell lines.
Disease family
An umbrella term covering 1 Mondo subtype.
Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › AIPL1-related retinopathy
Related subtypes (104): retinal dystrophies primarily involving Bruch’s membrane, vitreoretinal dystrophy, dystrophies primarily involving the retinal pigment epithelium, retinal dystrophy in systemic or cerebroretinal lipidoses, age-related macular degeneration, helicoid peripapillary chorioretinal degeneration, Sorsby fundus dystrophy, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, pigmented paravenous retinochoroidal atrophy, retinoschisis, autosomal dominant, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, amaurosis-hypertrichosis syndrome, familial benign flecked retina, microcephaly and chorioretinopathy 1, ornithine aminotransferase deficiency, retinal degeneration-nanophthalmos-glaucoma syndrome, retinoschisis of fovea, Revesz syndrome, choroideremia, choroideremia-deafness-obesity syndrome, X-linked retinal dysplasia, X-linked retinoschisis, progressive bifocal chorioretinal atrophy, aceruloplasminemia, late-onset retinal degeneration, infantile cerebellar-retinal degeneration, progressive retinal dystrophy due to retinol transport defect, microcornea-myopic chorioretinal atrophy, retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies, macular degeneration, early-onset, cone-rod dystrophy, ectopia lentis-chorioretinal dystrophy-myopia syndrome, foveal hypoplasia-presenile cataract syndrome, MRCS syndrome, X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome, Leber congenital amaurosis, oligocone trichromacy, Oguchi disease, retinitis pigmentosa, hereditary macular dystrophy, RPE65-related recessive retinopathy, RPGR-related retinopathy, RP2-related retinopathy, RDH5-related retinopathy, RLBP1-related retinopathy, LCA5-related retinopathy, ATF6-related retinopathy, RAB28-related retinopathy, FLVCR1-related retinopathy with or without ataxia, RPE65-related dominant retinopathy, GUCY2D retinopathy, PDE6A-related retinopathy, ELOVL4-related maculopathy, MAK-related retinopathy, KIZ-related retinopathy, TOPORS-related retinopathy, PRPF8-related retinopathy, RD3-related retinopathy, BEST1-related dominant retinopathy, BEST1-related recessive retinopathy, IMPG2-related recessive retinopathy, IMPG2-related dominant retinopathy, CACNA1F-related retinopathy, CACNA2D4-related retinopathy, CDHR1-related retinopathy, GUCA1A-related retinopathy, RHO-related retinopathy, SNRNP200-related dominant retinopathy, RDH12-related recessive retinopathy, RDH12-related dominant retinopathy, NMNAT1-related retinopathy, CNGA3-related retinopathy, EYS-related retinopathy, GNAT2-related retinopathy, IDH3B-related retinopathy, MERTK-related retinopathy, PRPF31-related retinopathy, GPR179-related retinopathy, GRM6-related retinopathy, ADAM9-related retinopathy, RP1-related recessive retinopathy, RP1-related dominant retinopathy, CERKL-related retinopathy, TRPM1-related retinopathy, CNGB1-related retinopathy, PCARE-related retinopathy, CNGA1-related retinopathy, ABCA4-related retinopathy, NYX-related retinopathy, retinal dystrophy, X-linked, Gardner-Hardcastle type, PDE6C-related retinopathy, PDE6G-related retinopathy, LRIT3-related retinopathy, IMPG1-related dominant retinopathy, IMPG1-related recessive retinopathy, TTLL5-related retinopathy, HGSNAT-related retinopathy, IMPDH1-related retinopathy, PRPH2-related retinopathy, PROM1-related retinopathy, KCNV2-related retinopathy, CRX-related retinopathy, REEP6-related retinopathy, SPATA7-related retinopathy
Subtypes (1): Leber congenital amaurosis 4
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
54 retrieved; paginated sample, class counts are floors:
18 uncertain significance, 13 pathogenic, 11 benign, 9 likely pathogenic, 3 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1451640 | NM_014336.5(AIPL1):c.276+1G>A | AIPL1 | Pathogenic | reviewed by expert panel |
| 2736405 | NM_014336.5(AIPL1):c.809G>A (p.Arg270His) | AIPL1 | Pathogenic | reviewed by expert panel |
| 4087767 | NM_014336.5(AIPL1):c.618_619dup (p.Cys207fs) | AIPL1 | Pathogenic | reviewed by expert panel |
| 4087769 | NM_014336.5(AIPL1):c.126T>A (p.Cys42Ter) | AIPL1 | Pathogenic | reviewed by expert panel |
| 4087770 | NM_014336.5(AIPL1):c.216G>A (p.Trp72Ter) | AIPL1 | Pathogenic | reviewed by expert panel |
| 5565 | NM_014336.5(AIPL1):c.834G>A (p.Trp278Ter) | AIPL1 | Pathogenic | reviewed by expert panel |
| 5566 | NM_014336.5(AIPL1):c.1010_1011del (p.Glu337fs) | AIPL1 | Pathogenic | reviewed by expert panel |
| 574505 | NM_014336.5(AIPL1):c.265T>C (p.Cys89Arg) | AIPL1 | Pathogenic | reviewed by expert panel |
| 65709 | NM_014336.5(AIPL1):c.589G>C (p.Ala197Pro) | AIPL1 | Pathogenic | reviewed by expert panel |
| 65711 | NM_014336.5(AIPL1):c.784G>A (p.Gly262Ser) | AIPL1 | Pathogenic | reviewed by expert panel |
| 916622 | NM_014336.5(AIPL1):c.421C>T (p.Gln141Ter) | AIPL1 | Pathogenic | reviewed by expert panel |
| 99798 | NM_014336.5(AIPL1):c.277-2A>G | AIPL1 | Pathogenic | reviewed by expert panel |
| 99804 | NM_014336.5(AIPL1):c.487C>T (p.Gln163Ter) | AIPL1 | Pathogenic | reviewed by expert panel |
| 1419404 | NM_014336.5(AIPL1):c.724AAG[1] (p.Lys243del) | AIPL1 | Likely pathogenic | reviewed by expert panel |
| 2152271 | NM_014336.5(AIPL1):c.364G>A (p.Gly122Arg) | AIPL1 | Likely pathogenic | reviewed by expert panel |
| 2736407 | NM_014336.5(AIPL1):c.152A>G (p.Asp51Gly) | AIPL1 | Likely pathogenic | reviewed by expert panel |
| 4087766 | NM_014336.5(AIPL1):c.214T>C (p.Trp72Arg) | AIPL1 | Likely pathogenic | reviewed by expert panel |
| 5567 | NM_014336.5(AIPL1):c.715T>C (p.Cys239Arg) | AIPL1 | Likely pathogenic | reviewed by expert panel |
| 812219 | NM_014336.5(AIPL1):c.211G>T (p.Val71Phe) | AIPL1 | Likely pathogenic | reviewed by expert panel |
| 813151 | NM_014336.5(AIPL1):c.34dup (p.Val12fs) | AIPL1 | Likely pathogenic | reviewed by expert panel |
| 867104 | NM_014336.5(AIPL1):c.190G>A (p.Gly64Arg) | AIPL1 | Likely pathogenic | reviewed by expert panel |
| 870937 | NM_014336.5(AIPL1):c.50T>C (p.Leu17Pro) | AIPL1 | Likely pathogenic | reviewed by expert panel |
| 1364499 | NM_014336.5(AIPL1):c.172C>A (p.Pro58Thr) | AIPL1 | Uncertain significance | reviewed by expert panel |
| 1400984 | NM_014336.5(AIPL1):c.352G>A (p.Val118Met) | AIPL1 | Uncertain significance | reviewed by expert panel |
| 1486676 | NM_014336.5(AIPL1):c.281C>T (p.Thr94Met) | AIPL1 | Uncertain significance | reviewed by expert panel |
| 2178827 | NM_014336.5(AIPL1):c.868G>C (p.Val290Leu) | AIPL1 | Uncertain significance | reviewed by expert panel |
| 291000 | NM_014336.5(AIPL1):c.1090G>T (p.Ala364Ser) | AIPL1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2973015 | NM_014336.5(AIPL1):c.96+7G>T | AIPL1 | Uncertain significance | reviewed by expert panel |
| 324623 | NM_014336.5(AIPL1):c.73C>A (p.Pro25Thr) | AIPL1 | Uncertain significance | reviewed by expert panel |
| 3513086 | NM_014336.5(AIPL1):c.931C>T (p.Arg311Cys) | AIPL1 | Uncertain significance | reviewed by expert panel |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| AIPL1 | Strong | Semidominant | AIPL1-related retinopathy | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| AIPL1 | Orphanet:1872 | Cone rod dystrophy |
| AIPL1 | Orphanet:65 | Leber congenital amaurosis |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| AIPL1 | HGNC:359 | ENSG00000129221 | Q9NZN9 | Aryl-hydrocarbon-interacting protein-like 1 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| AIPL1 | Aryl-hydrocarbon-interacting protein-like 1 | May be important in protein trafficking and/or protein folding and stabilization. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| AIPL1 | Other/Unknown | no | TPR-like_helical_dom_sf, TPR_rpt, AIP/AIPL1/TTC9 |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| buccal mucosa cell | 1 |
| pancreatic ductal cell | 1 |
| tendon of biceps brachii | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| AIPL1 | 62 | tissue_specific | marker | buccal mucosa cell, pancreatic ductal cell, tendon of biceps brachii |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| AIPL1 | 891 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| AIPL1 | Q9NZN9 | 6 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| protein farnesylation | 1 | 5617.3× | 0.001 | AIPL1 |
| regulation of opsin-mediated signaling pathway | 1 | 1685.2× | 0.002 | AIPL1 |
| phototransduction, visible light | 1 | 1296.3× | 0.002 | AIPL1 |
| retina homeostasis | 1 | 1123.5× | 0.002 | AIPL1 |
| visual perception | 1 | 79.5× | 0.018 | AIPL1 |
| negative regulation of apoptotic process | 1 | 34.8× | 0.034 | AIPL1 |
| apoptotic process | 1 | 28.7× | 0.035 | AIPL1 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| AIPL1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| AIPL1 | 1 | Binding:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | AIPL1 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| AIPL1 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 11.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 8 |
| PHASE1/PHASE2 | 2 |
| PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01773278 | PHASE2 | RECRUITING | Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS) |
| NCT06467344 | PHASE1/PHASE2 | RECRUITING | Study to Evaluate ACDN-01 in ABCA4-related Stargardt Retinopathy (STELLAR) |
| NCT06789445 | PHASE1/PHASE2 | RECRUITING | A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO) |
| NCT02435940 | Not specified | RECRUITING | Inherited Retinal Degenerative Disease Registry |
| NCT05355415 | Not specified | RECRUITING | Adaptive Optics Imaging of Outer Retinal Diseases |
| NCT06445322 | Not specified | RECRUITING | Prescreening Study to Identify Potential Stargardt Participants for ACDN-01 Clinical Trials (STARPATH) |
| NCT07548944 | Not specified | RECRUITING | Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance |
| NCT00427180 | Not specified | UNKNOWN | IRIS PILOT - Extended Pilot Study With a Retinal Implant System |
| NCT01864486 | Not specified | COMPLETED | Restoring Vision With the Intelligent Retinal Implant System (IRIS V1)in Patients With Retinal Dystrophy |
| NCT02670980 | Not specified | COMPLETED | Compensation for Blindness With the Intelligent Retinal Implant System (IRIS V2) in Patients With Retinal Dystrophy |
| NCT04658251 | Not specified | TERMINATED | Study of New Mutations in Cone Disorders |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| CHOLESTEROL | 2 | 1 |
| CHEMBL1867358 | 0 | 1 |
| CHEMBL3184306 | 0 | 1 |
Related Atlas pages
- Cohort genes: AIPL1