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Atlas / Disease / Amblyopia

Amblyopia

disease
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Also known as amblyopia (disease)

Summary

Amblyopia (MONDO:0001020) is a disease with 8 cohort genes (22 GWAS associations across 14 studies) and 156 clinical trials. Top therapeutic interventions include atropine, carbidopa anhydrous, and levodopa.

At a glance

  • Cohort genes: 8
  • GWAS associations: 22
  • ClinVar variants: 10
  • Clinical trials: 156

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameamblyopia
Mondo IDMONDO:0001020
MeSHD000550
DOIDDOID:10376
NCITC118764
SNOMED CT387742006
UMLSC0002418
MedGen8009
Is cancer (heuristic)no

Also known as: amblyopia · amblyopia (disease)

Data availability: 10 ClinVar variants · 22 GWAS associations (14 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › perceptual disorders › vision disorder › amblyopia

Related subtypes (6): visual agnosia, binocular vision disease, color vision disorder, visual pathway disorder, blindness (disorder), Alice in Wonderland syndrome

Subtypes (3): suppression amblyopia, ametropic amblyopia, disuse amblyopia

Genetics & variants

GWAS landscape

22 GWAS associations across 14 studies. Top hits map to 10 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
chr17:796068201e-31T0.22
rs98957412e-28NPLOC4A0.2
rs1165120631e-12MLIP, MLIP-AS1T0.91
rs1219181662e-11OCA2C0.61
rs1405941773e-11CARTPT - MAP1BA1.35
rs109109372e-07CACNA1EC1.71
rs1443966603e-07RPS15AP14 - EXTL2P1?
rs729220854e-07DYNLT5 - INSL5G1.63
rs1505790854e-07AIFM1P1 - MALRD1C3.26
rs1164506889e-07HLA-DQA2 - MIR3135BG1.84
rs134340701e-06ZPLD1 - RNU6-461PC1.75
rs1927567102e-06AIFM1P1 - MALRD1T3.24
rs1169319122e-06BCKDHBT3.35
rs104150813e-06ZNF675G1.54
rs780110353e-06PARP8 - LINC02106A2.47
rs1494072654e-06TLR4 - TPT1P9G2.66
rs1114867315e-06CAMK1DA2.68
rs178040476e-06LINC01713 - BMP2T1.8
rs617458887e-06CNGB1T3.08
rs94795617e-06RNA5SP224 - RNA5SP225G1.83
rs109650268e-06MIR31HGC1.42

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90475884Verma A20246,367441,123Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90044331Jiang L20213,694451,960A generalized linear mixed model association tool for biobank-scale data.
GCST90079346Backman JD20212,9302,167Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083332Backman JD20212,9302,167Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90079345Backman JD20211,9653,132Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083331Backman JD20211,9653,132Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90477698Verma A20241,038120,085Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480079Verma A20241,038120,085Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079918Backman JD2021794386,946Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083904Backman JD2021794386,946Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding2
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic19

MAF distribution

BucketVariants
common (>=0.05)16
low_freq (0.01-0.05)0
rare (<0.01)3
unknown2

Functional consequences

ConsequenceCount
intergenic_variant10
intron_variant8
missense_variant2
unknown1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
chr17:796068200.3751e-31Tier 4: intronic/intergenic
rs98957411781636805A>C,G0.314intron_variantNPLOC42e-28Tier 4: intronic/intergenic
rs116512063654021160T>C0.003intron_variantMLIP, MLIP-AS11e-12Tier 4: intronic/intergenic
rs1219181661527985101C>G,T0.006missense_variantOCA22e-11Tier 1: coding
rs140594177571864740A>C0.005intergenic_variantCARTPT - MAP1B3e-11Tier 4: intronic/intergenic
rs109109371181428088T>C0.05intergenic_variantCACNA1E2e-07Tier 4: intronic/intergenic
rs1443966602175807282T>C,G0.05intron_variantRPS15AP14 - EXTL2P13e-07Tier 4: intronic/intergenic
rs72922085166795937T>A,C,G0.05intergenic_variantDYNLT5 - INSL54e-07Tier 4: intronic/intergenic
rs1505790851019032587A>C0.05intergenic_variantAIFM1P1 - MALRD14e-07Tier 4: intronic/intergenic
rs116450688632748350intergenic_variantHLA-DQA2 - MIR3135B9e-07Tier 4: intronic/intergenic
rs134340703102705418T>C0.05intergenic_variantZPLD1 - RNU6-461P1e-06Tier 4: intronic/intergenic
rs1927567101018920520G>Tintron_variantAIFM1P1 - MALRD12e-06Tier 4: intronic/intergenic
rs116931912680136830A>T0.05intron_variantBCKDHB2e-06Tier 4: intronic/intergenic
rs104150811923578711A>G,T0.05intergenic_variantZNF6753e-06Tier 4: intronic/intergenic
rs78011035550881621G>A,T0.05intergenic_variantPARP8 - LINC021063e-06Tier 4: intronic/intergenic
rs1494072659117983668A>G0.05intron_variantTLR4 - TPT1P94e-06Tier 4: intronic/intergenic
rs1114867311012440371G>A0.05intron_variantCAMK1D5e-06Tier 4: intronic/intergenic
rs17804047206745480C>T0.05intergenic_variantLINC01713 - BMP26e-06Tier 4: intronic/intergenic
rs617458881657959937C>T0.05missense_variantCNGB17e-06Tier 1: coding
rs94795616153229012A>G0.05intergenic_variantRNA5SP224 - RNA5SP2257e-06Tier 4: intronic/intergenic
rs10965026921485850C>G,T0.05intron_variantMIR31HG8e-06Tier 4: intronic/intergenic

ClinVar germline variants

10 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 conflicting classifications of pathogenicity, 2 uncertain significance, 1 likely pathogenic, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVarVariant (HGVS)GeneClassificationReview
374004NM_001256789.3(CACNA1F):c.694A>T (p.Lys232Ter)CACNA1FPathogeniccriteria provided, single submitter
374024NM_000153.4(GALC):c.850G>A (p.Gly284Ser)GALCPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
523459NM_001372066.1(TFAP2A):c.1043_1044del (p.Lys348fs)TFAP2APathogeniccriteria provided, multiple submitters, no conflicts
2120NM_207346.3(TSEN54):c.919G>T (p.Ala307Ser)TSEN54Pathogeniccriteria provided, multiple submitters, no conflicts
374023NM_000153.4(GALC):c.196G>A (p.Ala66Thr)GALCLikely pathogeniccriteria provided, single submitter
977143NM_003482.4(KMT2D):c.10624C>G (p.Leu3542Val)KMT2DConflicting classifications of pathogenicitycriteria provided, conflicting classifications
48425NM_206933.4(USH2A):c.14027A>G (p.Gln4676Arg)USH2AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
523282GRCh37/hg19 6p24.1-23(chr6:12536624-13968949)RNF182Uncertain significancecriteria provided, single submitter
523398NM_001379110.1(SLC9A6):c.1190C>A (p.Ala397Glu)SLC9A6Uncertain significancecriteria provided, single submitter
48481NM_206933.4(USH2A):c.1966G>A (p.Asp656Asn)USH2ALikely benignreviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SLC9A6Orphanet:85278Christianson syndrome
TFAP2AOrphanet:1297Branchio-oculo-facial syndrome
USH2AOrphanet:231178Usher syndrome type 2
USH2AOrphanet:791Retinitis pigmentosa
CACNA1FOrphanet:178333Åland Islands eye disease
CACNA1FOrphanet:1872Cone rod dystrophy
CACNA1FOrphanet:714070Incomplete congenital stationary night blindness, Schubert-Bornschein type
TSEN54Orphanet:166063Pontocerebellar hypoplasia type 4
TSEN54Orphanet:2524Pontocerebellar hypoplasia type 2
GALCOrphanet:206436Infantile Krabbe disease
GALCOrphanet:206443Late-infantile/juvenile Krabbe disease
GALCOrphanet:206448Adult Krabbe disease
KMT2DOrphanet:2322Kabuki syndrome
KMT2DOrphanet:589856Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence8

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SLC9A6HGNC:11079ENSG00000198689Q92581Sodium/hydrogen exchanger 6clinvar
TFAP2AHGNC:11742ENSG00000137203P05549Transcription factor AP-2-alphaclinvar
USH2AHGNC:12601ENSG00000042781O75445Usherinclinvar
CACNA1FHGNC:1393ENSG00000102001O60840Voltage-dependent L-type calcium channel subunit alpha-1Fclinvar
TSEN54HGNC:27561ENSG00000182173Q7Z6J9tRNA-splicing endonuclease subunit Sen54clinvar
RNF182HGNC:28522ENSG00000180537Q8N6D2E3 ubiquitin-protein ligase RNF182clinvar
GALCHGNC:4115ENSG00000054983P54803Galactocerebrosidaseclinvar
KMT2DHGNC:7133ENSG00000167548O14686Histone-lysine N-methyltransferase 2Dclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SLC9A6Sodium/hydrogen exchanger 6Endosomal Na(+), K(+)/H(+) antiporter.
TFAP2ATranscription factor AP-2-alphaSequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
USH2AUsherinInvolved in hearing and vision as member of the USH2 complex.
CACNA1FVoltage-dependent L-type calcium channel subunit alpha-1FVoltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
TSEN54tRNA-splicing endonuclease subunit Sen54Non-catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA.
RNF182E3 ubiquitin-protein ligase RNF182E3 ubiquitin-protein ligase that mediates the ubiquitination of ATP6V0C and targets it to degradation via the ubiquitin-proteasome pathway.
GALCGalactocerebrosidaseHydrolyzes the galactose ester bonds of glycolipids such as galactosylceramide and galactosylsphingosine.
KMT2DHistone-lysine N-methyltransferase 2DHistone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).

Protein-family classification

Druggable: 4 · Difficult: 3 · Unknown: 1 · Druggable fraction: 0.5

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.

FamilyGenesFoldFDR
Ion channel113.9×0.174
Transcription factor33.1×0.174
Enzyme (other)23.0×0.232
Antibody/Immunoglobulin13.6×0.304
Other/Unknown10.2×0.999

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SLC9A6Other/UnknownnoNHE-6/7/9, NaH_exchanger, Cation/H_exchanger_TM
TFAP2ATranscription factornoTF_AP2, TF_AP2_alpha_N, TF_AP2_C
USH2AAntibody/ImmunoglobulinyesLaminin_G, LE_dom, FN3_dom
CACNA1FIon channelyesVDCCAlpha1, VDCC_L_a1su, Ion_trans_dom
TSEN54Enzyme (other)yes4.6.1.16tRNA_splic_suSen54_N, tRNA_splic_suSen54
RNF182Transcription factornoZnf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
GALCEnzyme (other)yes3.2.1.46Glyco_hydro_59, Aldolase_TIM, GH_hydrolase_sf
KMT2DTranscription factornoSET_dom, Znf_RING, Znf_PHD

Expression context

Cohort genes with no expression data: 0.

6 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)8
unknown0

Top tissues across cohort

TissueCohort genes
buccal mucosa cell2
granulocyte2
lateral nuclear group of thalamus1
middle temporal gyrus1
pons1
gingiva1
gingival epithelium1
upper leg skin1
male germ line stem cell (sensu Vertebrata) in testis1
right lobe of liver1
parotid gland1
right hemisphere of cerebellum1
cerebellar hemisphere1
right uterine tube1
cortical plate1
endothelial cell1
ganglionic eminence1
adrenal tissue1
bronchial epithelial cell1
jejunal mucosa1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SLC9A6286ubiquitousyeslateral nuclear group of thalamus, middle temporal gyrus, pons
TFAP2A220ubiquitousmarkerupper leg skin, gingival epithelium, gingiva
USH2A30tissue_specificmarkermale germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, buccal mucosa cell
CACNA1F143tissue_specificmarkerparotid gland, granulocyte, right hemisphere of cerebellum
TSEN54232ubiquitousmarkergranulocyte, right uterine tube, cerebellar hemisphere
RNF182192broadyesendothelial cell, cortical plate, ganglionic eminence
GALC295ubiquitousmarkeradrenal tissue, bronchial epithelial cell, jejunal mucosa
KMT2D272ubiquitousmarkerbuccal mucosa cell, medial globus pallidus, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
KMT2D3,223
TFAP2A2,734
USH2A2,332
SLC9A61,867
CACNA1F1,616
GALC1,154
TSEN541,085
RNF182508

Structural data

PDB: 3 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
KMT2DO1468611
TSEN54Q7Z6J95
TFAP2AP055493

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
GALCP5480394.56
RNF182Q8N6D270.67
SLC9A6Q9258170.61
CACNA1FO6084067.46
USH2AO75445

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 54. Enrichment computed across 8 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.

PathwayCohort genesFoldFDRSample cohort genes
Defective SLC9A6 causes X-linked, syndromic mental retardation,, Christianson type (MRXSCH)11903.3×0.028SLC9A6
TFAP2 (AP-2) family regulates transcription of other transcription factors1475.8×0.028TFAP2A
TFAP2 (AP-2) family regulates transcription of cell cycle factors1380.7×0.028TFAP2A
TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation1380.7×0.028TFAP2A
Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome1380.7×0.028KMT2D
Sodium/Proton exchangers1211.5×0.038SLC9A6
Negative regulation of activity of TFAP2 (AP-2) family transcription factors1190.3×0.038TFAP2A
Activation of the TFAP2 (AP-2) family of transcription factors1158.6×0.038TFAP2A
Positive Regulation of CDH1 Gene Transcription1158.6×0.038TFAP2A
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors1126.9×0.039TFAP2A
Developmental Lineage of Mammary Stem Cells1126.9×0.039TFAP2A
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors1105.7×0.039TFAP2A
Specification of the neural plate border1105.7×0.039TFAP2A
SUMOylation of transcription factors195.2×0.040TFAP2A
Activation of HOX genes during differentiation173.2×0.049KMT2D
tRNA processing159.5×0.056TSEN54
Glycosphingolipid catabolism148.8×0.062GALC
Formation of WDR5-containing histone-modifying complexes144.3×0.062KMT2D
Regulation of MITF-M-dependent genes involved in pigmentation144.3×0.062TFAP2A
Gastrulation143.3×0.062TFAP2A
Deactivation of the beta-catenin transactivating complex138.8×0.063KMT2D
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes135.9×0.063KMT2D
SLC transporter disorders134.0×0.063SLC9A6
tRNA processing in the nucleus132.8×0.063TSEN54
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes132.8×0.063KMT2D
RNA Polymerase II Transcription27.5×0.063TFAP2A, KMT2D
MITF-M-dependent gene expression130.2×0.065TFAP2A
PKMTs methylate histone lysines126.8×0.070KMT2D
Epigenetic regulation by WDR5-containing histone modifying complexes125.7×0.070KMT2D
Transcriptional regulation by RUNX1124.4×0.070KMT2D

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
optic cup structural organization12106.5×0.013TFAP2A
beta-catenin-TCF complex assembly12106.5×0.013KMT2D
optic vesicle morphogenesis11053.2×0.013TFAP2A
galactosylceramide catabolic process11053.2×0.013GALC
oculomotor nerve formation11053.2×0.013TFAP2A
tRNA-type intron splice site recognition and cleavage1702.2×0.013TSEN54
positive regulation of tooth mineralization1702.2×0.013TFAP2A
oocyte growth1526.6×0.014KMT2D
maintenance of animal organ identity1421.3×0.014USH2A
inner ear receptor cell differentiation1421.3×0.014USH2A
negative regulation of voltage-gated calcium channel activity1421.3×0.014CACNA1F
sensory perception of sound225.2×0.014TFAP2A, USH2A
trigeminal nerve development1300.9×0.016TFAP2A
cellular response to iron ion1300.9×0.016TFAP2A
hair cell differentiation1263.3×0.017USH2A
sensory perception of light stimulus1234.1×0.017USH2A
visual perception219.9×0.017USH2A, CACNA1F
dendrite extension1210.7×0.017SLC9A6
glycosphingolipid catabolic process1191.5×0.018GALC
tRNA splicing, via endonucleolytic cleavage and ligation1175.5×0.019TSEN54
obsolete negative regulation of transcription by competitive promoter binding1162.0×0.019TFAP2A
positive regulation of intracellular estrogen receptor signaling pathway1150.5×0.019KMT2D
inner ear auditory receptor cell differentiation1150.5×0.019USH2A
eyelid development in camera-type eye1131.7×0.021TFAP2A
negative regulation of reactive oxygen species metabolic process1117.0×0.022TFAP2A
retina layer formation181.0×0.029TFAP2A
detection of light stimulus involved in visual perception181.0×0.029CACNA1F
sodium ion import across plasma membrane178.0×0.029SLC9A6
regulation of intracellular pH175.2×0.029SLC9A6
bone morphogenesis175.2×0.029TFAP2A

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
AtropinePhase 3 (in late-stage trials)
LevodopaPhase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 7

Druggability breadth: 3 of 8 evidence-associated genes (38%) 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.

SymbolExample approved molecule
CACNA1FBEPRIDIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
CACNA1F484
SLC9A600
TFAP2A00
USH2A00
TSEN5400
RNF18200
GALC00
KMT2D00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
BEPRIDIL4CACNA1F
IMIPRAMINE4CACNA1F
HALOFANTRINE4CACNA1F
DROPERIDOL4CACNA1F
SAQUINAVIR4CACNA1F
DULOXETINE4CACNA1F
DIAZEPAM4CACNA1F
SERTINDOLE4CACNA1F
QUINIDINE4CACNA1F
LAMIVUDINE4CACNA1F
PIMOZIDE4CACNA1F
PHENYTOIN4CACNA1F
TERFENADINE4CACNA1F
CISAPRIDE4CACNA1F
SOLIFENACIN4CACNA1F
NIFEDIPINE4CACNA1F
DILTIAZEM4CACNA1F
NILOTINIB4CACNA1F
ASTEMIZOLE4CACNA1F
TERODILINE4CACNA1F
CLOZAPINE4CACNA1F
MIBEFRADIL4CACNA1F
DOFETILIDE4CACNA1F
THIORIDAZINE4CACNA1F
PAROXETINE4CACNA1F
DONEPEZIL4CACNA1F
IBUTILIDE4CACNA1F
SUNITINIB4CACNA1F
HALOPERIDOL4CACNA1F
DASATINIB4CACNA1F

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
CACNA1F221Binding:135, Functional:79, Toxicity:5, ADMET:2
KMT2D11Binding:11
GALC3Binding:2, Functional:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
TSEN544.6.1.16tRNA-intron lyase
GALC3.2.1.46galactosylceramidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
CACNA1F221

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

29 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.

CompoundMax phaseCohort target (bioactivity)
BEPRIDIL4CACNA1F
IMIPRAMINE4CACNA1F
HALOFANTRINE4CACNA1F
DROPERIDOL4CACNA1F
SAQUINAVIR4CACNA1F
DULOXETINE4CACNA1F
DIAZEPAM4CACNA1F
SERTINDOLE4CACNA1F
QUINIDINE4CACNA1F
LAMIVUDINE4CACNA1F
PIMOZIDE4CACNA1F
PHENYTOIN4CACNA1F
TERFENADINE4CACNA1F
CISAPRIDE4CACNA1F
SOLIFENACIN4CACNA1F
NIFEDIPINE4CACNA1F
DILTIAZEM4CACNA1F
NILOTINIB4CACNA1F
ASTEMIZOLE4CACNA1F
TERODILINE4CACNA1F
CLOZAPINE4CACNA1F
MIBEFRADIL4CACNA1F
DOFETILIDE4CACNA1F
THIORIDAZINE4CACNA1F
PAROXETINE4CACNA1F
IBUTILIDE4CACNA1F
SUNITINIB4CACNA1F
HALOPERIDOL4CACNA1F
DASATINIB4CACNA1F

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CACNA1F
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1TSEN54
DDruggable family + AlphaFold only, no drug2USH2A, GALC
EDifficult family or no structure, no drug4SLC9A6, TFAP2A, RNF182, KMT2D

Undrugged target profiles

7 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
SLC9A60—
TFAP2A0—
USH2A0—
TSEN540—
RNF1820—
GALC3—
KMT2D11—

Clinical trials & evidence

Clinical trials

Clinical trials: 156.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified120
PHASE320
PHASE1/PHASE25
PHASE15
PHASE24
PHASE42

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00094614PHASE4COMPLETEDTrial Comparing Daily Atropine Versus Weekend Atropine
NCT03109314PHASE4COMPLETEDCombining Donepezil With Perceptual Learning in Normal and Amblyopic Human The Effect of Donepezil on Perceptual Learning in Adult Amblyopia
NCT04378790PHASE3RECRUITINGA Randomized Trial to Evaluate Sequential vs Simultaneous Patching
NCT06380517PHASE3RECRUITINGDichoptic Treatment for Amblyopia in Children 4 to 7 Years of Age
NCT06524882PHASE3RECRUITINGDichoptic Treatment for Amblyopia in Children 8 to 12 Years of Age
NCT00000170PHASE3COMPLETEDOcclusion Versus Pharmacologic Therapy for Moderate Amblyopia
NCT00001864PHASE3COMPLETEDAmblyopia (Lazy Eye) Treatment Study
NCT00038753PHASE3UNKNOWNVision In Preschoolers Study (VIP Study)
NCT00091923PHASE3COMPLETEDTrial to Evaluate 2 Hours of Daily Patching for Amblyopia in Children
NCT00094679PHASE3COMPLETEDTrial Comparing Part-time Versus Minimal-time Patching for Moderate Amblyopia
NCT00094692PHASE3COMPLETEDAn Evaluation of Treatment of Amblyopia in Children 7 To <18 Years Old
NCT00094744PHASE3COMPLETEDTrial Comparing Part-time Versus Full-time Patching for Severe Amblyopia
NCT00131729PHASE3COMPLETEDElectronic Recording of Compliance With Occlusion Therapy for Amblyopia
NCT00315198PHASE3COMPLETEDTrial Comparing Near Versus Distance Activities While Patching for Amblyopia in Children 3 to <7 Years Old
NCT00315302PHASE3COMPLETEDTrial Comparing Atropine to Atropine Plus a Plano Lens for the Sound Eye for Amblyopia in Children 3 to <7 Years Old
NCT00315328PHASE3COMPLETEDTrial Comparing Patching Versus Atropine for Amblyopia in 7 to < 13 Year Olds
NCT00506675PHASE3TERMINATEDCombined Patching-Atropine for Residual Amblyopia
NCT00525174PHASE3COMPLETEDFull-time Bangerter Filters Versus Part-time Daily Patching for Moderate Amblyopia in Children
NCT00587171PHASE3TERMINATEDTrial Comparing Patching With Active Vision Therapy to Patching With Control Vision Therapy as Treatment for Amblyopia
NCT00944710PHASE3COMPLETEDAugmenting Atropine Treatment for Amblyopia in Children 3 to < 8 Years Old
NCT00945100PHASE3COMPLETEDIncreasing Patching for Amblyopia in Children 3 to < 8 Years Old
NCT01190813PHASE3COMPLETEDLevodopa for the Treatment of Residual Amblyopia
NCT07226141PHASE1/PHASE2NOT_YET_RECRUITINGValproate for the Treatment of Residual Amblyopia
NCT07554131PHASE2NOT_YET_RECRUITINGEvaluation of Echothiophate in Pediatric Patients With Refractory Amblyopia
NCT00789672PHASE2COMPLETEDPilot Study to Evaluate Levodopa as Treatment for Residual Amblyopia
NCT00815581PHASE1/PHASE2COMPLETEDComparison of Photorefraction With Cycloautorefraction and Cycloretinoscopy at Emam Hosein Medical Centre in 2008-2009
NCT00970554PHASE1/PHASE2COMPLETEDEffectiveness of Telescopic Magnification in the Treatment of Amblyopia
NCT01308307PHASE2COMPLETEDIs Non-cycloplegic Photorefraction Applicable for Screening Refractive Risk Factors of Amblyopia?
NCT01702727PHASE2COMPLETEDI-BiT - Evaluation of a Novel Binocular Treatment System (I-BiTTM) in Children With Amblyopia
NCT02594358PHASE1/PHASE2WITHDRAWNCaffeine in Amblyopia Study
NCT03402789PHASE1/PHASE2WITHDRAWNDocosahexaenoic Acid (DHA) Supplementation in Amblyopia
NCT00097162PHASE1COMPLETEDVisual Cortex Stimulation in Patients With Amblyopia
NCT00274664PHASE1COMPLETEDPatching for Lazy Eye: Trial to Evaluate Daily Patching Amounts
NCT01584076PHASE1COMPLETEDTreatment of Residual Amblyopia With Donepezil
NCT02246556PHASE1TERMINATEDDichoptic Virtual Reality Therapy for Amblyopia in Adults
NCT04784390PHASE1TERMINATEDProof of Concept Study of Binocular Videogames Versus Patching for Amblyopia
NCT02365090Not specifiedACTIVE_NOT_RECRUITINGBinocular iPad Sub-Study
NCT03288948Not specifiedRECRUITINGBinocular Amblyopia Treatment
NCT03655912Not specifiedRECRUITINGBinocular Visual Therapy and Video Games for Amblyopia Treatment.
NCT04310241Not specifiedRECRUITINGVisual Function Abnormalities in Strabismus and Amblyopia and Response to Therapy

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
ATROPINE48
CARBIDOPA ANHYDROUS46
LEVODOPA42
VALPROIC ACID42
CAFFEINE41
DONEPEZIL41
ECHOTHIOPHATE IODIDE41
DOCONEXENT31
CHEMBL455743308
CHEMBL35104202
CHEMBL443941301
PARAXANTHINE01

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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This page pulls from 70 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot