Early-onset non-syndromic cataract
diseaseOn this page
Summary
Early-onset non-syndromic cataract (MONDO:0011060) is a disease (an umbrella term covering 29 Mondo subtypes) with 9 cohort genes.
At a glance
- Umbrella term: 29 Mondo subtypes
- Cohort genes: 9
- ClinVar variants: 7
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | early-onset non-syndromic cataract |
| Mondo ID | MONDO:0011060 |
| OMIM | 601371 |
| Orphanet | 91492 |
| ICD-11 | 1080602978 |
| UMLS | C1832423 |
| MedGen | 371326 |
| GARD | 0016801 |
| Is cancer (heuristic) | no |
Data availability: 7 ClinVar variants · 3 GenCC gene-disease records.
Disease family
An umbrella term covering 29 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › lens disorder › cataract › early-onset non-syndromic cataract
Related subtypes (28): immature cataract, diabetic cataract, mature cataract, tetanic cataract, myotonic cataract, senile cataract, diabetes mellitus type 2 associated cataract, cataract 4 multiple types, cataract 29, cataract 1 multiple types, cataract 3 multiple types, cataract 9 multiple types, cataract 28, cataract 18, cataract 12 multiple types, cataract 34 multiple types, cataract 36, bhaskar jagannathan syndrome, autosomal dominant cataract, craniostenosis cataract, Kozlowski Rafinski Klicharska syndrome, cataract 49, cataract 48, hypermature cataract, nuclear cataract, cortical cataract, cataract 2, multiple types, cataract 50 with or without glaucoma
Subtypes (29): cataract 32 multiple types, cataract 8 multiple types, cataract 42, cataract 20 multiple types, cataract 6 multiple types, cataract 13 with adult I phenotype, cataract 5 multiple types, cataract 46 juvenile-onset, cataract 40, cataract 10 multiple types, cataract 14 multiple types, pulverulent cataract, cataract 31 multiple types, cataract 26 multiple types, cataract 22 multiple types, cataract 21 multiple types, cataract 23, cataract 11 multiple types, cataract 33, cataract 17 multiple types, cataract 38, cataract 39 multiple types, cataract 15 multiple types, cataract 19 multiple types, cataract 43, cataract 44, cataract 45, early-onset partial cataract, total early-onset cataract
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
7 retrieved; paginated sample, class counts are floors:
3 pathogenic, 2 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 4796486 | NM_001887.4(CRYBB1):c.576-637_587del | CRYBA4 | Pathogenic | criteria provided, single submitter |
| 4796487 | NM_001886.3(CRYBA4):c.220T>C (p.Tyr74His) | CRYBA4 | Pathogenic | criteria provided, single submitter |
| 2574672 | NM_001353214.3(DYM):c.916C>T (p.Gln306Ter) | DYM | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 215406 | NM_006005.3(WFS1):c.1243_1245del (p.Val415del) | WFS1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 4796489 | NM_001395002.1(MAP4K4):c.298C>T (p.Gln100Ter) | MAP4K4 | Likely pathogenic | criteria provided, single submitter |
| 4796490 | NM_020989.4(CRYGC):c.419G>C (p.Arg140Pro) | CRYGC | Uncertain significance | criteria provided, single submitter |
| 1305889 | NM_021954.4(GJA3):c.161G>A (p.Cys54Tyr) | GJA3 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 28 · Orphanet: 24 · 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 |
|---|---|---|---|---|
| BFSP2 | Definitive | Autosomal dominant | cataract 12 multiple types | 9 |
| CRYBB3 | Definitive | Autosomal recessive | cataract 22 multiple types | 9 |
| EPHA2 | Definitive | Autosomal dominant | cataract 6 multiple types | 10 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| BFSP2 | Orphanet:441452 | Early-onset lamellar cataract |
| BFSP2 | Orphanet:98984 | Pulverulent cataract |
| BFSP2 | Orphanet:98985 | Early-onset sutural cataract |
| CRYBB3 | Orphanet:98988 | Early-onset anterior polar cataract |
| CRYBB3 | Orphanet:98991 | Early-onset nuclear cataract |
| EPHA2 | Orphanet:441447 | Early-onset posterior subcapsular cataract |
| EPHA2 | Orphanet:98991 | Early-onset nuclear cataract |
| EPHA2 | Orphanet:98993 | Early-onset posterior polar cataract |
| EPHA2 | Orphanet:98994 | Total early-onset cataract |
| WFS1 | Orphanet:3463 | Wolfram syndrome |
| WFS1 | Orphanet:411590 | Wolfram-like syndrome |
| WFS1 | Orphanet:90635 | Rare autosomal dominant non-syndromic sensorineural deafness type DFNA |
| WFS1 | Orphanet:98991 | Early-onset nuclear cataract |
| DYM | Orphanet:178355 | Smith-McCort dysplasia |
| DYM | Orphanet:239 | Dyggve-Melchior-Clausen disease |
| CRYBA4 | Orphanet:1377 | Cataract-microcornea syndrome |
| CRYBA4 | Orphanet:441452 | Early-onset lamellar cataract |
| CRYGC | Orphanet:1377 | Cataract-microcornea syndrome |
| CRYGC | Orphanet:441452 | Early-onset lamellar cataract |
| CRYGC | Orphanet:98984 | Pulverulent cataract |
| CRYGC | Orphanet:98991 | Early-onset nuclear cataract |
| GJA3 | Orphanet:98984 | Pulverulent cataract |
| GJA3 | Orphanet:98991 | Early-onset nuclear cataract |
| GJA3 | Orphanet:98993 | Early-onset posterior polar cataract |
Cohort genes → proteins
9 cohort genes, 9 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 9 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| BFSP2 | HGNC:1041 | ENSG00000170819 | Q13515 | Phakinin | gencc |
| CRYBB3 | HGNC:2400 | ENSG00000100053 | P26998 | Beta-crystallin B3 | gencc |
| EPHA2 | HGNC:3386 | ENSG00000142627 | P29317 | Ephrin type-A receptor 2 | gencc |
| WFS1 | HGNC:12762 | ENSG00000109501 | O76024 | Wolframin | clinvar |
| DYM | HGNC:21317 | ENSG00000141627 | Q7RTS9 | Dymeclin | clinvar |
| CRYBA4 | HGNC:2396 | ENSG00000196431 | P53673 | Beta-crystallin A4 | clinvar |
| CRYGC | HGNC:2410 | ENSG00000163254 | P07315 | Gamma-crystallin C | clinvar |
| GJA3 | HGNC:4277 | ENSG00000121743 | Q9Y6H8 | Gap junction alpha-3 protein | clinvar |
| MAP4K4 | HGNC:6866 | ENSG00000071054 | O95819 | Mitogen-activated protein kinase kinase kinase kinase 4 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| BFSP2 | Phakinin | Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA. |
| CRYBB3 | Beta-crystallin B3 | Crystallins are the dominant structural components of the vertebrate eye lens. |
| EPHA2 | Ephrin type-A receptor 2 | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. |
| WFS1 | Wolframin | Participates in the regulation of cellular Ca(2+) homeostasis, at least partly, by modulating the filling state of the endoplasmic reticulum Ca(2+) store. |
| DYM | Dymeclin | Necessary for correct organization of Golgi apparatus. |
| CRYBA4 | Beta-crystallin A4 | Crystallins are the dominant structural components of the vertebrate eye lens. |
| CRYGC | Gamma-crystallin C | Crystallins are the dominant structural components of the vertebrate eye lens. |
| GJA3 | Gap junction alpha-3 protein | Structural component of lens fiber gap junctions. |
| MAP4K4 | Mitogen-activated protein kinase kinase kinase kinase 4 | Serine/threonine kinase that plays a role in the response to environmental stress and cytokines such as TNF. |
Protein-family classification
Druggable: 2 · Difficult: 0 · Unknown: 7 · Druggable fraction: 0.22
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 | 6.2× | 0.079 |
| Other/Unknown | 7 | 1.4× | 0.161 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| BFSP2 | Other/Unknown | no | Keratin_I, IF_rod_dom | |
| CRYBB3 | Other/Unknown | no | Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin | |
| EPHA2 | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom |
| WFS1 | Other/Unknown | no | TPR-like_helical_dom_sf, Wolframin, Wolframin_fam | |
| DYM | Other/Unknown | no | Dymeclin | |
| CRYBA4 | Other/Unknown | no | Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin | |
| CRYGC | Other/Unknown | no | Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin | |
| GJA3 | Other/Unknown | no | Connexin, Connexin46, Connexin_N | |
| MAP4K4 | Kinase | yes | Prot_kinase_dom, CNH_dom, Ser/Thr_kinase_AS |
Expression context
Cohort genes with no expression data: 0.
5 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) | 1 |
| broad (>20) | 8 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 4 |
| primordial germ cell in gonad | 3 |
| ganglionic eminence | 2 |
| lens of camera-type eye | 1 |
| buccal mucosa cell | 1 |
| mucosa of transverse colon | 1 |
| esophagus mucosa | 1 |
| lower esophagus mucosa | 1 |
| pharyngeal mucosa | 1 |
| body of uterus | 1 |
| left ovary | 1 |
| right ovary | 1 |
| bone marrow cell | 1 |
| embryo | 1 |
| frontal pole | 1 |
| testis | 1 |
| heart right ventricle | 1 |
| left ventricle myocardium | 1 |
| myocardium | 1 |
| C1 segment of cervical spinal cord | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| BFSP2 | 111 | tissue_specific | yes | lens of camera-type eye, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad |
| CRYBB3 | 145 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, mucosa of transverse colon |
| EPHA2 | 224 | ubiquitous | marker | lower esophagus mucosa, esophagus mucosa, pharyngeal mucosa |
| WFS1 | 280 | ubiquitous | marker | right ovary, left ovary, body of uterus |
| DYM | 254 | ubiquitous | marker | bone marrow cell, embryo, ganglionic eminence |
| CRYBA4 | 72 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, frontal pole |
| CRYGC | 15 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, testis |
| GJA3 | 75 | broad | yes | left ventricle myocardium, heart right ventricle, myocardium |
| MAP4K4 | 295 | ubiquitous | marker | C1 segment of cervical spinal cord, cortical plate, ganglionic eminence |
Protein interactions among cohort
Intra-cohort edges: 7.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| EPHA2 | 4,794 |
| WFS1 | 3,409 |
| CRYGC | 2,111 |
| MAP4K4 | 1,975 |
| CRYBB3 | 1,718 |
| DYM | 1,298 |
| BFSP2 | 1,203 |
| CRYBA4 | 601 |
| GJA3 | 449 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| BFSP2 | CRYBA4 | string_interaction |
| BFSP2 | CRYBB3 | string_interaction |
| BFSP2 | CRYGC | string_interaction |
| BFSP2 | GJA3 | string_interaction |
| CRYBA4 | GJA3 | string_interaction |
| CRYBB3 | GJA3 | string_interaction |
| CRYGC | GJA3 | string_interaction |
Structural data
PDB: 5 · AlphaFold-only: 4 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| EPHA2 | P29317 | 103 |
| MAP4K4 | O95819 | 18 |
| CRYBB3 | P26998 | 1 |
| CRYBA4 | P53673 | 1 |
| CRYGC | P07315 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| DYM | Q7RTS9 | 87.91 |
| BFSP2 | Q13515 | 78.15 |
| WFS1 | O76024 | 73.85 |
| GJA3 | Q9Y6H8 | 69.53 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 9 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Attenuation phase | 1 | 81.6× | 0.046 | CRYBA4 |
| HSF1 activation | 1 | 76.1× | 0.046 | CRYBA4 |
| EPHA-mediated growth cone collapse | 1 | 76.1× | 0.046 | EPHA2 |
| HSF1-dependent transactivation | 1 | 63.4× | 0.046 | CRYBA4 |
| Gap junction assembly | 1 | 58.6× | 0.046 | GJA3 |
| RHOV GTPase cycle | 1 | 57.1× | 0.046 | EPHA2 |
| RHOU GTPase cycle | 1 | 55.7× | 0.046 | EPHA2 |
| RND1 GTPase cycle | 1 | 53.1× | 0.046 | EPHA2 |
| RND3 GTPase cycle | 1 | 51.9× | 0.046 | EPHA2 |
| RND2 GTPase cycle | 1 | 51.9× | 0.046 | EPHA2 |
| EPH-ephrin mediated repulsion of cells | 1 | 43.9× | 0.046 | EPHA2 |
| XBP1(S) activates chaperone genes | 1 | 43.1× | 0.046 | WFS1 |
| EPH-Ephrin signaling | 1 | 33.1× | 0.054 | EPHA2 |
| RHOG GTPase cycle | 1 | 29.7× | 0.054 | EPHA2 |
| Regulation of HSF1-mediated heat shock response | 1 | 27.9× | 0.054 | CRYBA4 |
| Cellular Senescence | 1 | 27.5× | 0.054 | MAP4K4 |
| RAC2 GTPase cycle | 1 | 25.4× | 0.055 | EPHA2 |
| RAC3 GTPase cycle | 1 | 23.8× | 0.055 | EPHA2 |
| Post-translational protein phosphorylation | 1 | 20.0× | 0.062 | WFS1 |
| Oxidative Stress Induced Senescence | 1 | 18.1× | 0.065 | MAP4K4 |
| Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) | 1 | 17.3× | 0.065 | WFS1 |
| RAC1 GTPase cycle | 1 | 12.2× | 0.086 | EPHA2 |
| Cellular responses to stress | 1 | 7.4× | 0.134 | MAP4K4 |
| Cellular responses to stimuli | 1 | 6.3× | 0.149 | MAP4K4 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 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 | 53.0× | 3e-08 | BFSP2, WFS1, CRYBA4, CRYBB3, CRYGC, GJA3 |
| lens development in camera-type eye | 3 | 124.8× | 7e-05 | CRYBA4, CRYBB3, CRYGC |
| notochord cell development | 1 | 1872.4× | 0.017 | EPHA2 |
| axial mesoderm formation | 1 | 936.2× | 0.019 | EPHA2 |
| negative regulation of ATF6-mediated unfolded protein response | 1 | 936.2× | 0.019 | WFS1 |
| notochord formation | 1 | 624.1× | 0.019 | EPHA2 |
| positive regulation of ARF protein signal transduction | 1 | 624.1× | 0.019 | MAP4K4 |
| negative regulation of lymphangiogenesis | 1 | 624.1× | 0.019 | EPHA2 |
| positive regulation of growth | 1 | 468.1× | 0.020 | WFS1 |
| cAMP metabolic process | 1 | 468.1× | 0.020 | EPHA2 |
| pericyte cell differentiation | 1 | 374.5× | 0.020 | EPHA2 |
| regulation of blood vessel endothelial cell migration | 1 | 312.1× | 0.020 | EPHA2 |
| gap junction-mediated intercellular transport | 1 | 312.1× | 0.020 | GJA3 |
| blood vessel endothelial cell proliferation involved in sprouting angiogenesis | 1 | 267.5× | 0.020 | EPHA2 |
| negative regulation of response to endoplasmic reticulum stress | 1 | 267.5× | 0.020 | WFS1 |
| negative regulation of chemokine production | 1 | 234.1× | 0.020 | EPHA2 |
| lens fiber cell development | 1 | 234.1× | 0.020 | BFSP2 |
| lens fiber cell morphogenesis | 1 | 234.1× | 0.020 | EPHA2 |
| negative regulation of type B pancreatic cell apoptotic process | 1 | 234.1× | 0.020 | WFS1 |
| regulation of lamellipodium assembly | 1 | 208.1× | 0.020 | EPHA2 |
| olfactory behavior | 1 | 208.1× | 0.020 | WFS1 |
| positive regulation of focal adhesion disassembly | 1 | 208.1× | 0.020 | MAP4K4 |
| positive regulation of bicellular tight junction assembly | 1 | 187.2× | 0.022 | EPHA2 |
| ER overload response | 1 | 170.2× | 0.022 | WFS1 |
| mammary gland epithelial cell proliferation | 1 | 170.2× | 0.022 | EPHA2 |
| branching involved in mammary gland duct morphogenesis | 1 | 156.0× | 0.022 | EPHA2 |
| response to growth factor | 1 | 156.0× | 0.022 | EPHA2 |
| negative regulation of cell adhesion mediated by integrin | 1 | 144.0× | 0.022 | EPHA2 |
| positive regulation of keratinocyte migration | 1 | 144.0× | 0.022 | MAP4K4 |
| nervous system process | 1 | 133.8× | 0.023 | WFS1 |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 7
Druggability breadth: 4 of 9 evidence-associated genes (44%) 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 |
|---|---|
| EPHA2 | PONATINIB |
| MAP4K4 | PONATINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| MAP4K4 | 62 | 4 |
| EPHA2 | 50 | 4 |
| BFSP2 | 0 | 0 |
| CRYBB3 | 0 | 0 |
| WFS1 | 0 | 0 |
| DYM | 0 | 0 |
| CRYBA4 | 0 | 0 |
| CRYGC | 0 | 0 |
| GJA3 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| PONATINIB | 4 | EPHA2, MAP4K4 |
| FEDRATINIB | 4 | EPHA2 |
| TIVOZANIB | 4 | EPHA2 |
| SORAFENIB | 4 | EPHA2, MAP4K4 |
| DASATINIB ANHYDROUS | 4 | EPHA2 |
| REGORAFENIB | 4 | EPHA2 |
| CABOZANTINIB | 4 | EPHA2 |
| VANDETANIB | 4 | EPHA2, MAP4K4 |
| NILOTINIB | 4 | EPHA2 |
| BOSUTINIB | 4 | EPHA2, MAP4K4 |
| TOVORAFENIB | 4 | EPHA2 |
| NINTEDANIB | 4 | EPHA2, MAP4K4 |
| DASATINIB | 4 | EPHA2, MAP4K4 |
| CRIZOTINIB | 4 | EPHA2 |
| AXITINIB | 4 | MAP4K4 |
| NERATINIB | 4 | MAP4K4 |
| PALBOCICLIB | 4 | MAP4K4 |
| ENTRECTINIB | 4 | MAP4K4 |
| PACRITINIB | 4 | MAP4K4 |
| ABEMACICLIB | 4 | MAP4K4 |
| GILTERITINIB | 4 | MAP4K4 |
| PAZOPANIB | 4 | MAP4K4 |
| SUNITINIB | 4 | MAP4K4 |
| QUIZARTINIB | 4 | MAP4K4 |
| MIDOSTAURIN | 4 | MAP4K4 |
| GEFITINIB | 4 | MAP4K4 |
| SARACATINIB | 3 | EPHA2, MAP4K4 |
| LINIFANIB | 3 | EPHA2 |
| TESEVATINIB | 3 | EPHA2, MAP4K4 |
| ALVOCIDIB | 3 | EPHA2 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| EPHA2 | 567 | Binding:565, Functional:1, ADMET:1 |
| MAP4K4 | 407 | Binding:400, ADMET:5, Functional:1, Toxicity:1 |
| CRYGC | 9 | Binding:9 |
| WFS1 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| EPHA2 | 2.7.10.1 | receptor protein-tyrosine kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| EPHA2 | 567 |
| MAP4K4 | 407 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 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) |
|---|---|---|
| PONATINIB | 4 | EPHA2, MAP4K4 |
| FEDRATINIB | 4 | EPHA2 |
| TIVOZANIB | 4 | EPHA2 |
| SORAFENIB | 4 | EPHA2, MAP4K4 |
| DASATINIB ANHYDROUS | 4 | EPHA2 |
| REGORAFENIB | 4 | EPHA2 |
| CABOZANTINIB | 4 | EPHA2 |
| VANDETANIB | 4 | EPHA2, MAP4K4 |
| NILOTINIB | 4 | EPHA2 |
| BOSUTINIB | 4 | EPHA2, MAP4K4 |
| TOVORAFENIB | 4 | EPHA2 |
| NINTEDANIB | 4 | EPHA2, MAP4K4 |
| DASATINIB | 4 | EPHA2, MAP4K4 |
| CRIZOTINIB | 4 | EPHA2 |
| AXITINIB | 4 | MAP4K4 |
| NERATINIB | 4 | MAP4K4 |
| PALBOCICLIB | 4 | MAP4K4 |
| ENTRECTINIB | 4 | MAP4K4 |
| PACRITINIB | 4 | MAP4K4 |
| ABEMACICLIB | 4 | MAP4K4 |
| GILTERITINIB | 4 | MAP4K4 |
| PAZOPANIB | 4 | MAP4K4 |
| SUNITINIB | 4 | MAP4K4 |
| QUIZARTINIB | 4 | MAP4K4 |
| MIDOSTAURIN | 4 | MAP4K4 |
| GEFITINIB | 4 | MAP4K4 |
| SARACATINIB | 3 | EPHA2, MAP4K4 |
| LINIFANIB | 3 | EPHA2 |
| TESEVATINIB | 3 | EPHA2, MAP4K4 |
| ALVOCIDIB | 3 | EPHA2 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | EPHA2, MAP4K4 |
| 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 | 7 | BFSP2, CRYBB3, WFS1, DYM, CRYBA4, CRYGC, GJA3 |
Undrugged target profiles
7 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| BFSP2 | 0 | — |
| CRYBB3 | 0 | — |
| WFS1 | 1 | — |
| DYM | 0 | — |
| CRYBA4 | 0 | — |
| CRYGC | 9 | — |
| GJA3 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.