Isolated macular dystrophy
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Summary
Isolated macular dystrophy (MONDO:0957048) is a disease with 12 cohort genes.
At a glance
- Cohort genes: 12
- ClinVar variants: 21
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | isolated macular dystrophy |
| Mondo ID | MONDO:0957048 |
| Orphanet | 519302 |
| UMLS | C5681367 |
| MedGen | 1842262 |
| GARD | 0022097 |
| Is cancer (heuristic) | no |
Data availability: 21 ClinVar variants.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › isolated macular dystrophy
Related subtypes (8): vitelliform macular dystrophy, degeneration of macula and posterior pole, macular retinal edema, autosomal recessive bestrophinopathy, occult macular dystrophy, macular degeneration, early-onset, Stargardt disease, patterned macular dystrophy
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
21 retrieved; paginated sample, class counts are floors:
7 conflicting classifications of pathogenicity, 7 pathogenic/likely pathogenic, 6 pathogenic, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 813128 | NM_000350.3(ABCA4):c.1912C>T (p.Pro638Ser) | ABCA4 | Pathogenic | criteria provided, single submitter |
| 813130 | NM_000350.3(ABCA4):c.2294G>C (p.Ser765Thr) | ABCA4 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 813132 | NM_000350.3(ABCA4):c.2579T>C (p.Val860Ala) | ABCA4 | Pathogenic | criteria provided, single submitter |
| 813146 | NM_000350.3(ABCA4):c.2588-161_2615del | ABCA4 | Pathogenic | criteria provided, single submitter |
| 444253 | NM_004183.4(BEST1):c.37C>G (p.Arg13Gly) | BEST1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 623772 | NM_004183.4(BEST1):c.247+2del | BEST1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 807800 | NM_033380.3(COL4A5):c.2315G>T (p.Gly772Val) | COL4A5 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 802212 | NM_001384910.1(GUCA1A):c.359G>T (p.Arg120Leu) | GUCA1A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 493439 | NM_001563.4(IMPG1):c.378G>A (p.Trp126Ter) | IMPG1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 444672 | NM_001242957.3(MAK):c.1700_1703del (p.Asn567fs) | MAK | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2628029 | NM_006204.4(PDE6C):c.2368-2A>T | PDE6C | Pathogenic | criteria provided, single submitter |
| 813204 | NM_006017.3(PROM1):c.1767+4A>G | PROM1 | Pathogenic | criteria provided, single submitter |
| 624247 | NM_000322.5(PRPH2):c.331del (p.Ile111fs) | PRPH2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3336852 | NM_001163692.2(UBAP1L):c.120+1G>T | UBAP1L | Likely pathogenic | criteria provided, single submitter |
| 424902 | NM_000350.3(ABCA4):c.2875A>T (p.Thr959Ser) | ABCA4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 806169 | NM_000350.3(ABCA4):c.463G>A (p.Asp155Asn) | ABCA4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 813140 | NM_000350.3(ABCA4):c.5329A>T (p.Met1777Leu) | ABCA4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 813148 | NM_000350.3(ABCA4):c.5198T>C (p.Met1733Thr) | ABCA4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1354645 | NM_001098.3(ACO2):c.934C>T (p.Arg312Trp) | ACO2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 425251 | NM_201548.5(CERKL):c.1546_1565dup (p.Gly523fs) | CERKL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 425378 | NM_000322.5(PRPH2):c.653C>T (p.Ser218Leu) | PRPH2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 39 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| ACO2 | Orphanet:313850 | Infantile cerebellar-retinal degeneration |
| ACO2 | Orphanet:98676 | Autosomal recessive isolated optic atrophy |
| BEST1 | Orphanet:1243 | Best vitelliform macular dystrophy |
| BEST1 | Orphanet:139455 | Autosomal recessive bestrophinopathy |
| BEST1 | Orphanet:263347 | MRCS syndrome |
| BEST1 | Orphanet:3086 | Autosomal dominant vitreoretinochoroidopathy |
| BEST1 | Orphanet:35612 | Nanophthalmos |
| BEST1 | Orphanet:791 | Retinitis pigmentosa |
| BEST1 | Orphanet:99000 | Adult-onset foveomacular vitelliform dystrophy |
| CERKL | Orphanet:791 | Retinitis pigmentosa |
| COL4A5 | Orphanet:1018 | X-linked Alport syndrome-diffuse leiomyomatosis |
| COL4A5 | Orphanet:653722 | Digenic Alport syndrome |
| COL4A5 | Orphanet:88917 | X-linked Alport syndrome |
| ABCA4 | Orphanet:1872 | Cone rod dystrophy |
| ABCA4 | Orphanet:791 | Retinitis pigmentosa |
| ABCA4 | Orphanet:827 | Stargardt disease |
| UBAP1L | Orphanet:1872 | Cone rod dystrophy |
| GUCA1A | Orphanet:1871 | Progressive cone dystrophy |
| GUCA1A | Orphanet:1872 | Cone rod dystrophy |
| GUCA1A | Orphanet:75377 | Central areolar choroidal dystrophy |
| IMPG1 | Orphanet:251287 | Benign concentric annular macular dystrophy |
| IMPG1 | Orphanet:791 | Retinitis pigmentosa |
| IMPG1 | Orphanet:99000 | Adult-onset foveomacular vitelliform dystrophy |
| MAK | Orphanet:791 | Retinitis pigmentosa |
| PDE6C | Orphanet:1871 | Progressive cone dystrophy |
| PDE6C | Orphanet:49382 | Achromatopsia |
| PROM1 | Orphanet:1872 | Cone rod dystrophy |
| PROM1 | Orphanet:319640 | Retinal macular dystrophy type 2 |
| PROM1 | Orphanet:791 | Retinitis pigmentosa |
| PROM1 | Orphanet:827 | Stargardt disease |
| PRPH2 | Orphanet:1872 | Cone rod dystrophy |
| PRPH2 | Orphanet:227796 | Fundus albipunctatus |
| PRPH2 | Orphanet:52427 | Retinitis punctata albescens |
| PRPH2 | Orphanet:75377 | Central areolar choroidal dystrophy |
| PRPH2 | Orphanet:791 | Retinitis pigmentosa |
| PRPH2 | Orphanet:827 | Stargardt disease |
| PRPH2 | Orphanet:99000 | Adult-onset foveomacular vitelliform dystrophy |
| PRPH2 | Orphanet:99001 | Butterfly-shaped pigment dystrophy |
| PRPH2 | Orphanet:99003 | Multifocal pattern dystrophy simulating fundus flavimaculatus |
Cohort genes → proteins
12 cohort genes, 12 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 12 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| ACO2 | HGNC:118 | ENSG00000100412 | Q99798 | Aconitate hydratase, mitochondrial | clinvar |
| BEST1 | HGNC:12703 | ENSG00000167995 | O76090 | Bestrophin-1 | clinvar |
| CERKL | HGNC:21699 | ENSG00000188452 | Q49MI3 | Ceramide kinase-like protein | clinvar |
| COL4A5 | HGNC:2207 | ENSG00000188153 | P29400 | Collagen alpha-5(IV) chain | clinvar |
| ABCA4 | HGNC:34 | ENSG00000198691 | P78363 | Retinal-specific phospholipid-transporting ATPase ABCA4 | clinvar |
| UBAP1L | HGNC:40028 | ENSG00000246922 | F5GYI3 | Ubiquitin-associated protein 1-like | clinvar |
| GUCA1A | HGNC:4678 | ENSG00000048545 | P43080 | Guanylyl cyclase-activating protein 1 | clinvar |
| IMPG1 | HGNC:6055 | ENSG00000112706 | Q17R60 | Interphotoreceptor matrix proteoglycan 1 | clinvar |
| MAK | HGNC:6816 | ENSG00000111837 | P20794 | Serine/threonine-protein kinase MAK | clinvar |
| PDE6C | HGNC:8787 | ENSG00000095464 | P51160 | Cone cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha' | clinvar |
| PROM1 | HGNC:9454 | ENSG00000007062 | O43490 | Prominin-1 | clinvar |
| PRPH2 | HGNC:9942 | ENSG00000112619 | P23942 | Peripherin-2 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| ACO2 | Aconitate hydratase, mitochondrial | Catalyzes the isomerization of citrate to isocitrate via cis-aconitate. |
| BEST1 | Bestrophin-1 | Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+). |
| CERKL | Ceramide kinase-like protein | Has no detectable ceramide-kinase activity. |
| COL4A5 | Collagen alpha-5(IV) chain | Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen. |
| 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… |
| GUCA1A | Guanylyl cyclase-activating protein 1 | Stimulates retinal guanylyl cyclase when free calcium ions concentration is low and inhibits guanylyl cyclase when free calcium ions concentration is elevated. |
| IMPG1 | Interphotoreceptor matrix proteoglycan 1 | Chondroitin sulfate-, heparin- and hyaluronan-binding protein. |
| MAK | Serine/threonine-protein kinase MAK | Essential for the regulation of ciliary length and required for the long-term survival of photoreceptors. |
| PDE6C | Cone cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha’ | As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP. |
| PROM1 | Prominin-1 | May play a role in cell differentiation, proliferation and apoptosis. |
| PRPH2 | Peripherin-2 | Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure. |
Protein-family classification
Druggable: 4 · Difficult: 1 · Unknown: 7 · Druggable fraction: 0.33
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 |
|---|---|---|---|
| Kinase | 2 | 4.6× | 0.338 |
| Transporter | 1 | 6.5× | 0.360 |
| Other/Unknown | 7 | 1.1× | 0.788 |
| Enzyme (other) | 1 | 1.0× | 0.788 |
| Transcription factor | 1 | 0.7× | 0.788 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| ACO2 | Enzyme (other) | yes | 4.2.1.3 | AconitaseA/IPMdHydase_ssu_swvl, Acoase/IPM_deHydtase_lsu_aba, Aconitase_mito-like |
| BEST1 | Other/Unknown | no | Bestrophin, Bestrophin-like | |
| CERKL | Kinase | yes | Diacylglycerol_kinase_cat_dom, NAD/diacylglycerol_kinase_sf, ATP-NAD_kinase_N | |
| COL4A5 | Other/Unknown | no | Collagen_IV_NC, Collagen, CTDL_fold | |
| ABCA4 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABCA4/ABCR | |
| UBAP1L | Other/Unknown | no | UMA, UBAP1, UBAP1_C | |
| GUCA1A | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS | |
| IMPG1 | Other/Unknown | no | SEA_dom, EGF, SEA_dom_sf | |
| MAK | Kinase | yes | 2.7.11.22 | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf |
| PDE6C | Transcription factor | no | PDEase_catalytic_dom, GAF, HD/PDEase_dom | |
| PROM1 | Other/Unknown | no | Prominin | |
| PRPH2 | Other/Unknown | no | Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS |
Expression context
Cohort genes with no expression data: 0.
11 cohort genes 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) | 12 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 4 |
| pigmented layer of retina | 2 |
| cerebellar hemisphere | 2 |
| nucleus accumbens | 2 |
| secondary oocyte | 2 |
| apex of heart | 1 |
| heart right ventricle | 1 |
| left ventricle myocardium | 1 |
| inferior olivary complex | 1 |
| lateral globus pallidus | 1 |
| islet of Langerhans | 1 |
| olfactory segment of nasal mucosa | 1 |
| lower esophagus muscularis layer | 1 |
| mucosa of stomach | 1 |
| ventricular zone | 1 |
| primordial germ cell in gonad | 1 |
| cerebellar cortex | 1 |
| right hemisphere of cerebellum | 1 |
| hypothalamus | 1 |
| putamen | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| ACO2 | 291 | ubiquitous | marker | heart right ventricle, apex of heart, left ventricle myocardium |
| BEST1 | 209 | ubiquitous | marker | pigmented layer of retina, lateral globus pallidus, inferior olivary complex |
| CERKL | 122 | tissue_specific | marker | islet of Langerhans, olfactory segment of nasal mucosa, male germ line stem cell (sensu Vertebrata) in testis |
| COL4A5 | 267 | ubiquitous | marker | mucosa of stomach, ventricular zone, lower esophagus muscularis layer |
| ABCA4 | 164 | tissue_specific | marker | pigmented layer of retina, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis |
| UBAP1L | 171 | tissue_specific | yes | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| GUCA1A | 52 | broad | marker | nucleus accumbens, putamen, hypothalamus |
| IMPG1 | 155 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, nucleus accumbens, secondary oocyte |
| MAK | 184 | broad | marker | sperm, male germ cell, choroid plexus epithelium |
| PDE6C | 159 | tissue_specific | marker | secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere |
| PROM1 | 252 | broad | marker | bronchial epithelial cell, epithelium of bronchus, bronchus |
| PRPH2 | 176 | tissue_specific | marker | quadriceps femoris, vastus lateralis, hindlimb stylopod muscle |
Protein interactions among cohort
Intra-cohort edges: 9.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ACO2 | 4,776 |
| PROM1 | 3,302 |
| COL4A5 | 1,738 |
| ABCA4 | 1,532 |
| GUCA1A | 1,434 |
| PRPH2 | 1,234 |
| MAK | 966 |
| BEST1 | 959 |
| CERKL | 959 |
| PDE6C | 903 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ABCA4 | BEST1 | string_interaction |
| ABCA4 | CERKL | string_interaction |
| ABCA4 | IMPG1 | string_interaction |
| ABCA4 | PROM1 | string_interaction |
| ABCA4 | PRPH2 | string_interaction |
| BEST1 | IMPG1 | string_interaction |
| BEST1 | PRPH2 | string_interaction |
| IMPG1 | PRPH2 | string_interaction |
| MAK | PRPH2 | string_interaction |
Structural data
PDB: 5 · AlphaFold-only: 7 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| BEST1 | O76090 | 19 |
| ABCA4 | P78363 | 8 |
| PDE6C | P51160 | 7 |
| COL4A5 | P29400 | 2 |
| PRPH2 | P23942 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ACO2 | Q99798 | 95.44 |
| PROM1 | O43490 | 85.68 |
| CERKL | Q49MI3 | 79.82 |
| GUCA1A | P43080 | 71.28 |
| UBAP1L | F5GYI3 | 66.48 |
| MAK | P20794 | 62.74 |
| IMPG1 | Q17R60 | 59.26 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 37. Enrichment computed across 12 evidence-associated genes (6 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 6 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 | 1903.3× | 0.019 | ABCA4 |
| Retinoid cycle disease events | 1 | 475.8× | 0.019 | ABCA4 |
| Diseases associated with visual transduction | 1 | 475.8× | 0.019 | ABCA4 |
| Diseases of the neuronal system | 1 | 475.8× | 0.019 | ABCA4 |
| Anchoring fibril formation | 1 | 126.9× | 0.044 | COL4A5 |
| Fibronectin matrix formation | 1 | 95.2× | 0.044 | COL4A5 |
| Crosslinking of collagen fibrils | 1 | 95.2× | 0.044 | COL4A5 |
| Maturation of TCA enzymes and regulation of TCA cycle | 1 | 95.2× | 0.044 | ACO2 |
| The canonical retinoid cycle in rods (twilight vision) | 1 | 86.5× | 0.044 | ABCA4 |
| Attachment of bacteria to epithelial cells | 1 | 82.8× | 0.044 | COL4A5 |
| Citric acid cycle (TCA cycle) | 1 | 70.5× | 0.047 | ACO2 |
| Laminin interactions | 1 | 63.4× | 0.048 | COL4A5 |
| Inactivation, recovery and regulation of the phototransduction cascade | 1 | 52.9× | 0.049 | GUCA1A |
| Visual phototransduction | 1 | 43.3× | 0.049 | ABCA4 |
| Collagen chain trimerization | 1 | 43.3× | 0.049 | COL4A5 |
| Signaling by PDGF | 1 | 42.3× | 0.049 | COL4A5 |
| NCAM1 interactions | 1 | 41.4× | 0.049 | COL4A5 |
| Transport of small molecules | 2 | 8.4× | 0.049 | BEST1, ABCA4 |
| Developmental Lineage of Pancreatic Ductal Cells | 1 | 38.1× | 0.051 | PROM1 |
| Assembly of collagen fibrils and other multimeric structures | 1 | 33.4× | 0.054 | COL4A5 |
| Protein localization | 1 | 31.7× | 0.054 | ACO2 |
| Collagen degradation | 1 | 29.3× | 0.054 | COL4A5 |
| Collagen biosynthesis and modifying enzymes | 1 | 28.4× | 0.054 | COL4A5 |
| Mitochondrial protein import | 1 | 28.0× | 0.054 | ACO2 |
| Non-integrin membrane-ECM interactions | 1 | 25.7× | 0.056 | COL4A5 |
| ECM proteoglycans | 1 | 25.0× | 0.056 | COL4A5 |
| Stimuli-sensing channels | 1 | 22.7× | 0.058 | BEST1 |
| Integrin cell surface interactions | 1 | 22.4× | 0.058 | COL4A5 |
| ABC-family protein mediated transport | 1 | 20.2× | 0.062 | ABCA4 |
| Mitochondrial protein degradation | 1 | 19.0× | 0.063 | ACO2 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| visual perception | 6 | 39.8× | 2e-07 | BEST1, ABCA4, GUCA1A, IMPG1, PDE6C, PRPH2 |
| photoreceptor cell maintenance | 3 | 89.6× | 1e-04 | ABCA4, MAK, PROM1 |
| phototransduction, visible light | 2 | 216.1× | 7e-04 | ABCA4, PDE6C |
| detection of light stimulus involved in visual perception | 2 | 108.0× | 0.002 | BEST1, PRPH2 |
| response to low light intensity stimulus | 1 | 1404.3× | 0.007 | PRPH2 |
| positive regulation of guanylate cyclase activity | 1 | 1404.3× | 0.007 | GUCA1A |
| gamma-aminobutyric acid secretion, neurotransmission | 1 | 702.2× | 0.010 | BEST1 |
| glomerular parietal epithelial cell differentiation | 1 | 702.2× | 0.010 | PROM1 |
| negative regulation of non-motile cilium assembly | 1 | 702.2× | 0.010 | MAK |
| phospholipid transfer to membrane | 1 | 468.1× | 0.012 | ABCA4 |
| positive regulation of nephron tubule epithelial cell differentiation | 1 | 468.1× | 0.012 | PROM1 |
| citrate metabolic process | 1 | 351.1× | 0.014 | ACO2 |
| camera-type eye photoreceptor cell differentiation | 1 | 280.9× | 0.017 | PROM1 |
| obsolete positive regulation of cGMP-mediated signaling | 1 | 200.6× | 0.022 | GUCA1A |
| transepithelial chloride transport | 1 | 156.0× | 0.024 | BEST1 |
| retina morphogenesis in camera-type eye | 1 | 156.0× | 0.024 | PROM1 |
| glutamate secretion | 1 | 140.4× | 0.025 | BEST1 |
| retinal cone cell development | 1 | 117.0× | 0.027 | PDE6C |
| podocyte differentiation | 1 | 117.0× | 0.027 | PROM1 |
| collagen-activated tyrosine kinase receptor signaling pathway | 1 | 108.0× | 0.028 | COL4A5 |
| photoreceptor cell outer segment organization | 1 | 87.8× | 0.031 | PRPH2 |
| protein heterooligomerization | 1 | 87.8× | 0.031 | PRPH2 |
| sphingolipid metabolic process | 1 | 82.6× | 0.032 | CERKL |
| retinal metabolic process | 1 | 78.0× | 0.032 | ABCA4 |
| regulation of calcium ion transport | 1 | 66.9× | 0.036 | BEST1 |
| protein complex oligomerization | 1 | 56.2× | 0.041 | BEST1 |
| retina layer formation | 1 | 54.0× | 0.041 | PROM1 |
| phospholipid translocation | 1 | 52.0× | 0.042 | ABCA4 |
| negative regulation of cAMP/PKA signal transduction | 1 | 50.1× | 0.042 | PDE6C |
| intraciliary transport | 1 | 46.8× | 0.042 | MAK |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 10
Druggability breadth: 3 of 12 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| PDE6C | VARDENAFIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| MAK | 7 | 3 |
| PDE6C | 6 | 4 |
| ACO2 | 0 | 0 |
| BEST1 | 0 | 0 |
| CERKL | 0 | 0 |
| COL4A5 | 0 | 0 |
| ABCA4 | 0 | 0 |
| UBAP1L | 0 | 0 |
| GUCA1A | 0 | 0 |
| IMPG1 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| VARDENAFIL | 4 | PDE6C |
| SILDENAFIL | 4 | PDE6C |
| TADALAFIL | 4 | PDE6C |
| DIPYRIDAMOLE | 4 | PDE6C |
| ALVOCIDIB | 3 | MAK |
| LESTAURTINIB | 3 | MAK |
| FORETINIB | 2 | MAK |
| RG-547 | 2 | MAK |
| AT-7519 | 2 | MAK |
| ZAPRINAST | 2 | PDE6C |
| TBA-7371 | 2 | PDE6C |
| BMS-387032 | 1 | MAK |
| AST-487 | 1 | MAK |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PDE6C | 103 | Binding:97, ADMET:6 |
| MAK | 94 | Binding:94 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| ACO2 | 4.2.1.3 | aconitate hydratase |
| MAK | 2.7.11.22 | cyclin-dependent kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| PDE6C | 103 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
13 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| VARDENAFIL | 4 | PDE6C |
| SILDENAFIL | 4 | PDE6C |
| TADALAFIL | 4 | PDE6C |
| DIPYRIDAMOLE | 4 | PDE6C |
| ALVOCIDIB | 3 | MAK |
| LESTAURTINIB | 3 | MAK |
| FORETINIB | 2 | MAK |
| RG-547 | 2 | MAK |
| AT-7519 | 2 | MAK |
| ZAPRINAST | 2 | PDE6C |
| TBA-7371 | 2 | PDE6C |
| BMS-387032 | 1 | MAK |
| AST-487 | 1 | MAK |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | PDE6C |
| B | Phased (≥1) drug, not yet approved | 1 | MAK |
| C | Druggable family + PDB, no drug | 1 | ABCA4 |
| D | Druggable family + AlphaFold only, no drug | 2 | ACO2, CERKL |
| E | Difficult family or no structure, no drug | 7 | BEST1, COL4A5, UBAP1L, GUCA1A, IMPG1, PROM1, PRPH2 |
Undrugged target profiles
10 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| ACO2 | 0 | — |
| BEST1 | 0 | — |
| CERKL | 0 | — |
| COL4A5 | 0 | — |
| ABCA4 | 0 | — |
| UBAP1L | 0 | — |
| GUCA1A | 0 | — |
| IMPG1 | 0 | — |
| PROM1 | 0 | — |
| PRPH2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.