ABCA4-related retinopathy
diseaseOn this page
Summary
ABCA4-related retinopathy (MONDO:0800406) is a disease caused by ABCA4 (GenCC Strong), with 1 cohort gene and 1 clinical trial.
At a glance
- Causal gene: ABCA4 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 130
- Clinical trials: 1
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | ABCA4-related retinopathy |
| Mondo ID | MONDO:0800406 |
| GARD | 0026556 |
| Is cancer (heuristic) | no |
Data availability: 130 ClinVar variants · 139 ClinGen variant curations · 1 GenCC gene-disease record.
Disease family
An umbrella term covering 3 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › ABCA4-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, AIPL1-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, 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 (3): severe early-childhood-onset retinal dystrophy, retinitis pigmentosa 19, cone-rod dystrophy 3
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
130 retrieved; paginated sample, class counts are floors:
78 pathogenic, 22 uncertain significance, 10 likely benign, 9 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic, 5 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 7901 | NM_000350.2(ABCA4):c.[1622T>C;3113C>T] | Pathogenic | reviewed by expert panel | |
| 1074381 | NM_000350.3(ABCA4):c.629del (p.Leu210fs) | ABCA4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1196428 | NM_000350.3(ABCA4):c.5584G>C (p.Gly1862Arg) | ABCA4 | Pathogenic | reviewed by expert panel |
| 1212117 | NM_000350.3(ABCA4):c.3328+2T>A | ABCA4 | Pathogenic | reviewed by expert panel |
| 1372740 | NM_000350.3(ABCA4):c.2879del (p.Ala960fs) | ABCA4 | Pathogenic | reviewed by expert panel |
| 1440605 | NM_000350.3(ABCA4):c.6568C>T (p.Gln2190Ter) | ABCA4 | Pathogenic | reviewed by expert panel |
| 1454986 | NM_000350.3(ABCA4):c.5554C>T (p.Gln1852Ter) | ABCA4 | Pathogenic | reviewed by expert panel |
| 1457683 | NM_000350.3(ABCA4):c.3943C>T (p.Gln1315Ter) | ABCA4 | Pathogenic | reviewed by expert panel |
| 1457719 | NM_000350.3(ABCA4):c.95CTTTAT[1] (p.Ser34_Leu35del) | ABCA4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1460063 | NM_000350.3(ABCA4):c.4720G>T (p.Glu1574Ter) | ABCA4 | Pathogenic | reviewed by expert panel |
| 2202779 | NM_000350.3(ABCA4):c.6410G>A (p.Cys2137Tyr) | ABCA4 | Pathogenic | reviewed by expert panel |
| 2202780 | NM_000350.3(ABCA4):c.6289C>T (p.Pro2097Ser) | ABCA4 | Pathogenic | reviewed by expert panel |
| 236109 | NM_000350.3(ABCA4):c.4195G>T (p.Glu1399Ter) | ABCA4 | Pathogenic | reviewed by expert panel |
| 236113 | NM_000350.3(ABCA4):c.4352+1G>A | ABCA4 | Pathogenic | reviewed by expert panel |
| 236114 | NM_000350.3(ABCA4):c.4354G>T (p.Glu1452Ter) | ABCA4 | Pathogenic | reviewed by expert panel |
| 236122 | NM_000350.3(ABCA4):c.4773+3A>G | ABCA4 | Pathogenic | reviewed by expert panel |
| 236129 | NM_000350.3(ABCA4):c.5318C>T (p.Ala1773Val) | ABCA4 | Pathogenic | reviewed by expert panel |
| 236516 | NM_000350.3(ABCA4):c.3098del (p.Lys1033fs) | ABCA4 | Pathogenic | reviewed by expert panel |
| 2585325 | NM_000350.3(ABCA4):c.5371dup (p.Ala1791fs) | ABCA4 | Pathogenic | reviewed by expert panel |
| 2664262 | NM_000350.3(ABCA4):c.2424C>G (p.Tyr808Ter) | ABCA4 | Pathogenic | reviewed by expert panel |
| 2733921 | NM_000350.3(ABCA4):c.4555del (p.Thr1519fs) | ABCA4 | Pathogenic | reviewed by expert panel |
| 2733935 | NM_000350.3(ABCA4):c.2616C>G (p.Tyr872Ter) | ABCA4 | Pathogenic | reviewed by expert panel |
| 2733942 | NM_000350.3(ABCA4):c.1519G>T (p.Asp507Tyr) | ABCA4 | Pathogenic | reviewed by expert panel |
| 280328 | NM_000350.3(ABCA4):c.3G>T (p.Met1Ile) | ABCA4 | Pathogenic | reviewed by expert panel |
| 289310 | NM_000350.3(ABCA4):c.3056C>T (p.Thr1019Met) | ABCA4 | Pathogenic | reviewed by expert panel |
| 298222 | NM_000350.3(ABCA4):c.6416G>C (p.Arg2139Pro) | ABCA4 | Pathogenic | reviewed by expert panel |
| 3381789 | NM_000350.3(ABCA4):c.4924_4927del (p.Ser1642fs) | ABCA4 | Pathogenic | reviewed by expert panel |
| 372290 | NM_000350.3(ABCA4):c.3210_3211dup (p.Ser1071fs) | ABCA4 | Pathogenic | reviewed by expert panel |
| 377407 | NM_000350.3(ABCA4):c.5646G>A (p.Met1882Ile) | ABCA4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 438100 | NM_000350.3(ABCA4):c.5196+1137G>A | ABCA4 | Pathogenic | reviewed by expert panel |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 12 · Orphanet: 3 · 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 |
|---|---|---|---|---|
| ABCA4 | Strong | Autosomal recessive | ABCA4-related retinopathy | 12 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| ABCA4 | Orphanet:1872 | Cone rod dystrophy |
| ABCA4 | Orphanet:791 | Retinitis pigmentosa |
| ABCA4 | Orphanet:827 | Stargardt disease |
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 |
|---|---|---|---|---|---|
| ABCA4 | HGNC:34 | ENSG00000198691 | P78363 | Retinal-specific phospholipid-transporting ATPase ABCA4 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| ABCA4 | Retinal-specific phospholipid-transporting ATPase ABCA4 | Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leafl… |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0
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 |
|---|---|---|---|
| Transporter | 1 | 77.8× | 0.013 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| ABCA4 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABCA4/ABCR |
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 |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| pigmented layer of retina | 1 |
| primordial germ cell in gonad | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| ABCA4 | 164 | tissue_specific | marker | pigmented layer of retina, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ABCA4 | 1,532 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| ABCA4 | P78363 | 8 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).
Pathways 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.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Defective visual phototransduction due to ABCA4 loss of function | 1 | 11420.0× | 9e-04 | ABCA4 |
| Retinoid cycle disease events | 1 | 2855.0× | 9e-04 | ABCA4 |
| Diseases associated with visual transduction | 1 | 2855.0× | 9e-04 | ABCA4 |
| Diseases of the neuronal system | 1 | 2855.0× | 9e-04 | ABCA4 |
| The canonical retinoid cycle in rods (twilight vision) | 1 | 519.1× | 0.004 | ABCA4 |
| Visual phototransduction | 1 | 259.6× | 0.006 | ABCA4 |
| ABC-family protein mediated transport | 1 | 121.5× | 0.012 | ABCA4 |
| Sensory Perception | 1 | 95.2× | 0.013 | ABCA4 |
| Transport of small molecules | 1 | 25.1× | 0.044 | ABCA4 |
| Disease | 1 | 13.1× | 0.076 | ABCA4 |
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 |
|---|---|---|---|---|
| phospholipid transfer to membrane | 1 | 5617.3× | 0.002 | ABCA4 |
| phototransduction, visible light | 1 | 1296.3× | 0.003 | ABCA4 |
| retinal metabolic process | 1 | 936.2× | 0.003 | ABCA4 |
| phospholipid translocation | 1 | 624.1× | 0.004 | ABCA4 |
| retinoid metabolic process | 1 | 495.6× | 0.004 | ABCA4 |
| photoreceptor cell maintenance | 1 | 358.6× | 0.004 | ABCA4 |
| lipid transport | 1 | 263.3× | 0.005 | ABCA4 |
| transmembrane transport | 1 | 168.5× | 0.007 | ABCA4 |
| visual perception | 1 | 79.5× | 0.013 | ABCA4 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| ABCA4 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
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 | 1 | ABCA4 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
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) |
|---|---|---|
| ABCA4 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01736293 | Not specified | ACTIVE_NOT_RECRUITING | Natural History of Eye Diseases Related to ABCA4 Mutations |
Related Atlas pages
- Cohort genes: ABCA4