Early-onset nuclear cataract
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Summary
Early-onset nuclear cataract (MONDO:0020376) is a disease with 19 cohort genes.
At a glance
- Cohort genes: 19
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | early-onset nuclear cataract |
| Mondo ID | MONDO:0020376 |
| MeSH | C563333 |
| Orphanet | 98991 |
| UMLS | C5681644 |
| MedGen | 1842550 |
| GARD | 0016887 |
| MedDRA | 10007759, 10057735 |
| Is cancer (heuristic) | no |
Data availability: 18 GenCC gene-disease records.
Disease family
An umbrella term covering 4 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 › early-onset partial cataract › early-onset zonular cataract › early-onset nuclear cataract
Related subtypes (2): cataract 16 multiple types, early-onset sutural cataract
Subtypes (4): cataract 41, cataract 27, cataract 35, autosomal recessive nonsyndromic congenital nuclear 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
No tiered GWAS variants or ClinVar records for this disease.
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 172 · Orphanet: 70 · 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 |
|---|---|---|---|---|
| CRYAA | Definitive | Autosomal recessive | cataract 9 multiple types | 8 |
| CRYBA1 | Definitive | Autosomal dominant | cataract 10 multiple types | 7 |
| CRYBB1 | Definitive | Autosomal dominant | cataract 17 multiple types | 8 |
| CRYBB2 | Definitive | Autosomal dominant | cataract 3 multiple types | 11 |
| CRYBB3 | Definitive | Autosomal recessive | cataract 22 multiple types | 9 |
| CRYGC | Definitive | Autosomal dominant | cataract 2, multiple types | 7 |
| CRYGD | Definitive | Autosomal dominant | cataract 4 multiple types | 9 |
| EPHA2 | Definitive | Autosomal dominant | cataract 6 multiple types | 10 |
| FYCO1 | Definitive | Autosomal recessive | cataract 18 | 5 |
| GJA3 | Definitive | Autosomal dominant | cataract 14 multiple types | 6 |
| GJA8 | Definitive | Autosomal dominant | cataract 1 multiple types | 9 |
| MIP | Definitive | Autosomal dominant | cataract 15 multiple types | 10 |
| TNPO1 | Definitive | Autosomal dominant | cataract 15 multiple types | 11 |
| BFSP1 | Strong | Autosomal dominant | cataract 33 | 8 |
| CRYAB | Strong | Autosomal dominant | cataract 16 multiple types | 16 |
| CRYBA2 | Strong | Autosomal dominant | cataract 42 | 5 |
| UNC45B | Strong | Autosomal dominant | cataract 43 | 8 |
| WFS1 | Strong | Autosomal dominant | cataract 41 | 19 |
| NHS | Supportive | Autosomal dominant | early-onset nuclear cataract | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| BFSP1 | Orphanet:98991 | Early-onset nuclear 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 |
| UNC45B | Orphanet:441447 | Early-onset posterior subcapsular cataract |
| UNC45B | Orphanet:98991 | Early-onset nuclear cataract |
| FYCO1 | Orphanet:98991 | Early-onset nuclear cataract |
| FYCO1 | Orphanet:98994 | Total early-onset cataract |
| CRYAA | Orphanet:1377 | Cataract-microcornea syndrome |
| CRYAA | Orphanet:441452 | Early-onset lamellar cataract |
| CRYAA | Orphanet:98988 | Early-onset anterior polar cataract |
| CRYAA | Orphanet:98991 | Early-onset nuclear cataract |
| CRYAA | Orphanet:98994 | Total early-onset cataract |
| CRYAB | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| CRYAB | Orphanet:280553 | Fatal infantile hypertonic myofibrillar myopathy |
| CRYAB | Orphanet:399058 | Alpha-B crystallin-related late-onset myopathy |
| CRYAB | Orphanet:441452 | Early-onset lamellar cataract |
| CRYAB | Orphanet:98991 | Early-onset nuclear cataract |
| CRYAB | Orphanet:98993 | Early-onset posterior polar cataract |
| CRYBA1 | Orphanet:441452 | Early-onset lamellar cataract |
| CRYBA1 | Orphanet:98985 | Early-onset sutural cataract |
| CRYBA1 | Orphanet:98991 | Early-onset nuclear cataract |
| CRYBA1 | Orphanet:98993 | Early-onset posterior polar cataract |
| CRYBA2 | Orphanet:98988 | Early-onset anterior polar cataract |
| CRYBA2 | Orphanet:98991 | Early-onset nuclear cataract |
| CRYBB1 | Orphanet:1377 | Cataract-microcornea syndrome |
| CRYBB1 | Orphanet:98984 | Pulverulent cataract |
| CRYBB1 | Orphanet:98991 | Early-onset nuclear cataract |
| CRYBB2 | Orphanet:1377 | Cataract-microcornea syndrome |
| CRYBB2 | Orphanet:441447 | Early-onset posterior subcapsular cataract |
| CRYBB2 | Orphanet:98984 | Pulverulent cataract |
| CRYBB2 | Orphanet:98985 | Early-onset sutural cataract |
| CRYBB2 | Orphanet:98989 | Cerulean cataract |
| CRYBB2 | Orphanet:98991 | Early-onset nuclear cataract |
| CRYBB2 | Orphanet:98994 | Total early-onset cataract |
| CRYBB3 | Orphanet:98988 | Early-onset anterior polar cataract |
| CRYBB3 | Orphanet:98991 | Early-onset nuclear 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 |
| CRYGD | Orphanet:1377 | Cataract-microcornea syndrome |
| CRYGD | Orphanet:441452 | Early-onset lamellar cataract |
| CRYGD | Orphanet:98984 | Pulverulent cataract |
| CRYGD | Orphanet:98989 | Cerulean cataract |
| CRYGD | Orphanet:98990 | Coralliform cataract |
| CRYGD | Orphanet:98991 | Early-onset nuclear cataract |
| EPHA2 | Orphanet:441447 | Early-onset posterior subcapsular cataract |
| EPHA2 | Orphanet:98991 | Early-onset nuclear cataract |
Cohort genes → proteins
19 cohort genes, 19 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 19 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| BFSP1 | HGNC:1040 | ENSG00000125864 | Q12934 | Filensin | gencc |
| WFS1 | HGNC:12762 | ENSG00000109501 | O76024 | Wolframin | gencc |
| UNC45B | HGNC:14304 | ENSG00000141161 | Q8IWX7 | Protein unc-45 homolog B | gencc |
| FYCO1 | HGNC:14673 | ENSG00000163820 | Q9BQS8 | FYVE and coiled-coil domain-containing protein 1 | gencc |
| CRYAA | HGNC:2388 | ENSG00000160202 | P02489 | Alpha-crystallin A chain | gencc |
| CRYAB | HGNC:2389 | ENSG00000109846 | P02511 | Alpha-crystallin B chain | gencc |
| CRYBA1 | HGNC:2394 | ENSG00000108255 | P05813 | Beta-crystallin A3 | gencc |
| CRYBA2 | HGNC:2395 | ENSG00000163499 | P53672 | Beta-crystallin A2 | gencc |
| CRYBB1 | HGNC:2397 | ENSG00000100122 | P53674 | Beta-crystallin B1 | gencc |
| CRYBB2 | HGNC:2398 | ENSG00000244752 | P43320 | Beta-crystallin B2 | gencc |
| CRYBB3 | HGNC:2400 | ENSG00000100053 | P26998 | Beta-crystallin B3 | gencc |
| CRYGC | HGNC:2410 | ENSG00000163254 | P07315 | Gamma-crystallin C | gencc |
| CRYGD | HGNC:2411 | ENSG00000118231 | P07320 | Gamma-crystallin D | gencc |
| EPHA2 | HGNC:3386 | ENSG00000142627 | P29317 | Ephrin type-A receptor 2 | gencc |
| GJA3 | HGNC:4277 | ENSG00000121743 | Q9Y6H8 | Gap junction alpha-3 protein | gencc |
| GJA8 | HGNC:4281 | ENSG00000121634 | P48165 | Gap junction alpha-8 protein | gencc |
| TNPO1 | HGNC:6401 | ENSG00000083312 | Q92973 | Transportin-1 | gencc |
| MIP | HGNC:7103 | ENSG00000135517 | P30301 | Lens fiber major intrinsic protein | gencc |
| NHS | HGNC:7820 | ENSG00000188158 | Q6T4R5 | Actin remodeling regulator NHS | gencc |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| BFSP1 | Filensin | Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA. |
| 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. |
| UNC45B | Protein unc-45 homolog B | Acts as a co-chaperone for HSP90 and is required for proper folding of the myosin motor domain. |
| FYCO1 | FYVE and coiled-coil domain-containing protein 1 | May mediate microtubule plus end-directed vesicle transport. |
| CRYAA | Alpha-crystallin A chain | Contributes to the transparency and refractive index of the lens. |
| CRYAB | Alpha-crystallin B chain | May contribute to the transparency and refractive index of the lens. |
| CRYBA1 | Beta-crystallin A3 | Crystallins are the dominant structural components of the vertebrate eye lens. |
| CRYBA2 | Beta-crystallin A2 | Crystallins are the dominant structural components of the vertebrate eye lens. |
| CRYBB1 | Beta-crystallin B1 | Crystallins are the dominant structural components of the vertebrate eye lens. |
| CRYBB2 | Beta-crystallin B2 | Crystallins are the dominant structural components of the vertebrate eye lens. |
| CRYBB3 | Beta-crystallin B3 | 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. |
| CRYGD | Gamma-crystallin D | 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. |
| GJA3 | Gap junction alpha-3 protein | Structural component of lens fiber gap junctions. |
| GJA8 | Gap junction alpha-8 protein | Structural component of eye lens gap junctions. |
| TNPO1 | Transportin-1 | Functions in nuclear protein import as nuclear transport receptor. |
| MIP | Lens fiber major intrinsic protein | Aquaporins form homotetrameric transmembrane channels, with each monomer independently mediating water transport across the plasma membrane along its osmotic gradient. |
| NHS | Actin remodeling regulator NHS | May function in cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. |
Protein-family classification
Druggable: 1 · Difficult: 1 · Unknown: 17 · Druggable fraction: 0.05
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 | 17 | 1.6× | 0.006 |
| Kinase | 1 | 1.5× | 0.754 |
| Transcription factor | 1 | 0.4× | 0.914 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| BFSP1 | Other/Unknown | no | IF_rod_dom, BFSP1 | |
| WFS1 | Other/Unknown | no | TPR-like_helical_dom_sf, Wolframin, Wolframin_fam | |
| UNC45B | Other/Unknown | no | Armadillo, ARM-like, TPR-like_helical_dom_sf | |
| FYCO1 | Transcription factor | no | Znf_FYVE, Run_dom, GOLD_dom | |
| CRYAA | Other/Unknown | no | Alpha-crystallin/sHSP_animal, A-crystallin/Hsp20_dom, Alpha-crystallin_N | |
| CRYAB | Other/Unknown | no | Alpha-crystallin/sHSP_animal, A-crystallin/Hsp20_dom, Alpha-crystallin_N | |
| CRYBA1 | Other/Unknown | no | Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin | |
| CRYBA2 | Other/Unknown | no | Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin | |
| CRYBB1 | Other/Unknown | no | Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin | |
| CRYBB2 | Other/Unknown | no | Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin | |
| CRYBB3 | 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 | |
| CRYGD | 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 |
| GJA3 | Other/Unknown | no | Connexin, Connexin46, Connexin_N | |
| GJA8 | Other/Unknown | no | Connexin, Connexin50_C, Connexin_N | |
| TNPO1 | Other/Unknown | no | Importin-beta_N, ARM-like, ARM-type_fold | |
| MIP | Other/Unknown | no | MIP, MIP_CS, Aquaporin-like | |
| NHS | Other/Unknown | no | NHS-like |
Expression context
Cohort genes with no expression data: 0.
9 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) | 2 |
| broad (>20) | 17 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 7 |
| primordial germ cell in gonad | 7 |
| left ventricle myocardium | 3 |
| buccal mucosa cell | 3 |
| right lobe of liver | 2 |
| tendon of biceps brachii | 1 |
| body of uterus | 1 |
| left ovary | 1 |
| right ovary | 1 |
| cardiac muscle of right atrium | 1 |
| tibialis anterior | 1 |
| biceps brachii | 1 |
| skeletal muscle tissue of biceps brachii | 1 |
| skeletal muscle tissue of rectus abdominis | 1 |
| adult mammalian kidney | 1 |
| liver | 1 |
| cardiac ventricle | 1 |
| middle frontal gyrus | 1 |
| lens of camera-type eye | 1 |
| islet of Langerhans | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| BFSP1 | 176 | broad | yes | tendon of biceps brachii, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis |
| WFS1 | 280 | ubiquitous | marker | right ovary, left ovary, body of uterus |
| UNC45B | 111 | tissue_specific | yes | left ventricle myocardium, cardiac muscle of right atrium, tibialis anterior |
| FYCO1 | 284 | ubiquitous | marker | skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii |
| CRYAA | 42 | marker | adult mammalian kidney, right lobe of liver, liver | |
| CRYAB | 289 | ubiquitous | marker | middle frontal gyrus, left ventricle myocardium, cardiac ventricle |
| CRYBA1 | 138 | tissue_specific | yes | lens of camera-type eye, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis |
| CRYBA2 | 128 | tissue_specific | marker | islet of Langerhans, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis |
| CRYBB1 | 154 | broad | yes | primordial germ cell in gonad, prefrontal cortex, Brodmann (1909) area 10 |
| CRYBB2 | 144 | tissue_specific | yes | triceps brachii, gluteal muscle, trabecular bone tissue |
| CRYBB3 | 145 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, mucosa of transverse colon |
| CRYGC | 15 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, testis |
| CRYGD | 60 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, ventricular zone |
| EPHA2 | 224 | ubiquitous | marker | lower esophagus mucosa, esophagus mucosa, pharyngeal mucosa |
| GJA3 | 75 | broad | yes | left ventricle myocardium, heart right ventricle, myocardium |
| GJA8 | 17 | tissue_specific | yes | buccal mucosa cell, frontal pole, paraflocculus |
| TNPO1 | 295 | ubiquitous | marker | corpus epididymis, caput epididymis, cauda epididymis |
| MIP | 91 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right lobe of liver |
| NHS | 214 | ubiquitous | marker | oviduct epithelium, buccal mucosa cell, endothelial cell |
Protein interactions among cohort
Intra-cohort edges: 57.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| EPHA2 | 4,794 |
| WFS1 | 3,409 |
| CRYAB | 3,368 |
| TNPO1 | 3,147 |
| MIP | 2,496 |
| CRYGC | 2,111 |
| CRYBB3 | 1,718 |
| FYCO1 | 1,637 |
| CRYBB1 | 1,508 |
| CRYAA | 1,464 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| BFSP1 | CRYAA | string_interaction |
| BFSP1 | CRYBA1 | string_interaction |
| BFSP1 | CRYBA2 | string_interaction |
| BFSP1 | CRYBB1 | string_interaction |
| BFSP1 | CRYBB2 | string_interaction |
| BFSP1 | CRYBB3 | string_interaction |
| BFSP1 | CRYGD | string_interaction |
| BFSP1 | GJA3 | string_interaction |
| BFSP1 | GJA8 | string_interaction |
| BFSP1 | MIP | string_interaction |
| CRYAA | CRYAB | biogrid_interaction, intact |
| CRYAA | CRYBA1 | biogrid_interaction, string_interaction |
| CRYAA | CRYBA2 | string_interaction |
| CRYAA | CRYBB1 | string_interaction |
| CRYAA | CRYBB2 | biogrid_interaction, intact, string_interaction |
| CRYAA | CRYBB3 | intact, string_interaction |
| CRYAA | CRYGC | biogrid_interaction, intact, string_interaction |
| CRYAA | CRYGD | biogrid_interaction, string_interaction |
| CRYAA | FYCO1 | string_interaction |
| CRYAA | GJA3 | string_interaction |
| CRYAA | GJA8 | string_interaction |
| CRYAB | CRYBA1 | string_interaction |
| CRYAB | CRYBA2 | string_interaction |
| CRYAB | CRYBB1 | string_interaction |
| CRYAB | CRYBB2 | biogrid_interaction, intact, string_interaction |
| CRYAB | CRYBB3 | string_interaction |
| CRYAB | CRYGC | biogrid_interaction, intact |
| CRYAB | CRYGD | biogrid_interaction, string_interaction |
| CRYAB | GJA8 | string_interaction |
| CRYBA1 | CRYBB1 | biogrid_interaction, intact |
| CRYBA1 | CRYBB2 | biogrid_interaction, intact |
| CRYBA1 | CRYBB3 | biogrid_interaction, intact |
| CRYBA1 | GJA3 | string_interaction |
| CRYBA1 | GJA8 | string_interaction |
| CRYBA2 | CRYBB1 | intact |
| CRYBA2 | CRYBB2 | intact |
| CRYBA2 | GJA3 | string_interaction |
| CRYBA2 | GJA8 | string_interaction |
| CRYBB1 | CRYBB3 | intact |
| CRYBB1 | FYCO1 | string_interaction |
| CRYBB1 | GJA3 | string_interaction |
| CRYBB1 | GJA8 | string_interaction |
| CRYBB1 | MIP | string_interaction |
| CRYBB2 | CRYGC | biogrid_interaction, intact |
| CRYBB2 | GJA3 | string_interaction |
| CRYBB2 | GJA8 | string_interaction |
| CRYBB3 | GJA3 | string_interaction |
| CRYBB3 | GJA8 | string_interaction |
| CRYGC | CRYGD | biogrid_interaction |
| CRYGC | GJA3 | string_interaction |
Structural data
PDB: 10 · AlphaFold-only: 9 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| EPHA2 | P29317 | 103 |
| CRYAB | P02511 | 21 |
| TNPO1 | Q92973 | 21 |
| CRYGD | P07320 | 16 |
| CRYAA | P02489 | 5 |
| FYCO1 | Q9BQS8 | 3 |
| CRYBB2 | P43320 | 3 |
| CRYBB1 | P53674 | 1 |
| CRYBB3 | P26998 | 1 |
| CRYGC | P07315 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| CRYBA2 | P53672 | 93.12 |
| MIP | P30301 | 91.08 |
| UNC45B | Q8IWX7 | 88.38 |
| CRYBA1 | P05813 | 88.27 |
| WFS1 | O76024 | 73.85 |
| GJA3 | Q9Y6H8 | 69.53 |
| GJA8 | P48165 | 65.85 |
| BFSP1 | Q12934 | 64.66 |
| NHS | Q6T4R5 | 43.65 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 19 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Gap junction assembly | 2 | 73.2× | 0.007 | GJA3, GJA8 |
| RAC2 GTPase cycle | 2 | 31.7× | 0.015 | EPHA2, NHS |
| RAC3 GTPase cycle | 2 | 29.7× | 0.015 | EPHA2, NHS |
| RAC1 GTPase cycle | 2 | 15.3× | 0.040 | EPHA2, NHS |
| Passive transport by Aquaporins | 1 | 109.8× | 0.042 | MIP |
| Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 1 | 79.3× | 0.047 | TNPO1 |
| Postmitotic nuclear pore complex (NPC) reformation | 1 | 51.0× | 0.047 | TNPO1 |
| EPHA-mediated growth cone collapse | 1 | 47.6× | 0.047 | EPHA2 |
| Aquaporin-mediated transport | 1 | 46.0× | 0.047 | MIP |
| HSF1-dependent transactivation | 1 | 39.6× | 0.047 | CRYAB |
| RHOV GTPase cycle | 1 | 35.7× | 0.047 | EPHA2 |
| RHOU GTPase cycle | 1 | 34.8× | 0.047 | EPHA2 |
| RND1 GTPase cycle | 1 | 33.2× | 0.047 | EPHA2 |
| RND3 GTPase cycle | 1 | 32.4× | 0.047 | EPHA2 |
| RND2 GTPase cycle | 1 | 32.4× | 0.047 | EPHA2 |
| EPH-ephrin mediated repulsion of cells | 1 | 27.4× | 0.049 | EPHA2 |
| XBP1(S) activates chaperone genes | 1 | 26.9× | 0.049 | WFS1 |
| Intraflagellar transport | 1 | 25.0× | 0.050 | TNPO1 |
| EPH-Ephrin signaling | 1 | 20.7× | 0.057 | EPHA2 |
| RHOG GTPase cycle | 1 | 18.5× | 0.061 | EPHA2 |
| Post-translational protein phosphorylation | 1 | 12.5× | 0.084 | WFS1 |
| Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) | 1 | 10.8× | 0.093 | WFS1 |
| Transport of small molecules | 1 | 3.1× | 0.277 | MIP |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| lens development in camera-type eye | 13 | 256.2× | 2e-28 | UNC45B, CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBB1, CRYBB2, CRYBB3 (+5 more) |
| visual perception | 11 | 46.0× | 4e-15 | WFS1, CRYAA, CRYBA1, CRYBA2, CRYBB1, CRYBB2, CRYBB3, CRYGC (+3 more) |
| gap junction-mediated intercellular transport | 3 | 443.5× | 1e-06 | GJA3, GJA8, MIP |
| negative regulation of intracellular transport | 2 | 591.3× | 1e-04 | CRYAA, CRYAB |
| apoptotic process involved in morphogenesis | 2 | 295.6× | 4e-04 | CRYAA, CRYAB |
| lens fiber cell morphogenesis | 2 | 221.7× | 7e-04 | CRYAA, EPHA2 |
| tubulin complex assembly | 2 | 177.4× | 9e-04 | CRYAA, CRYAB |
| protein refolding | 2 | 65.7× | 0.006 | CRYAA, CRYAB |
| response to hydrogen peroxide | 2 | 49.3× | 0.010 | CRYAA, CRYAB |
| response to heat | 2 | 44.4× | 0.011 | CRYAA, CRYAB |
| microtubule polymerization or depolymerization | 1 | 887.0× | 0.012 | CRYAB |
| notochord cell development | 1 | 887.0× | 0.012 | EPHA2 |
| axial mesoderm formation | 1 | 443.5× | 0.020 | EPHA2 |
| negative regulation of ATF6-mediated unfolded protein response | 1 | 443.5× | 0.020 | WFS1 |
| protein stabilization | 3 | 10.6× | 0.022 | WFS1, CRYAA, CRYAB |
| notochord formation | 1 | 295.6× | 0.024 | EPHA2 |
| negative regulation of lymphangiogenesis | 1 | 295.6× | 0.024 | EPHA2 |
| positive regulation of growth | 1 | 221.7× | 0.028 | WFS1 |
| cAMP metabolic process | 1 | 221.7× | 0.028 | EPHA2 |
| response to UV-A | 1 | 221.7× | 0.028 | CRYAA |
| pericyte cell differentiation | 1 | 177.4× | 0.032 | EPHA2 |
| muscle organ development | 2 | 17.6× | 0.032 | UNC45B, CRYAB |
| regulation of programmed cell death | 1 | 147.8× | 0.033 | CRYAB |
| regulation of blood vessel endothelial cell migration | 1 | 147.8× | 0.033 | EPHA2 |
| plus-end-directed vesicle transport along microtubule | 1 | 147.8× | 0.033 | FYCO1 |
| blood vessel endothelial cell proliferation involved in sprouting angiogenesis | 1 | 126.7× | 0.035 | EPHA2 |
| positive regulation of autophagosome maturation | 1 | 126.7× | 0.035 | FYCO1 |
| negative regulation of response to endoplasmic reticulum stress | 1 | 126.7× | 0.035 | WFS1 |
| negative regulation of chemokine production | 1 | 110.9× | 0.035 | EPHA2 |
| maintenance of lens transparency | 1 | 110.9× | 0.035 | MIP |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 18
Druggability breadth: 8 of 19 evidence-associated genes (42%) 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 |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| EPHA2 | 50 | 4 |
| BFSP1 | 0 | 0 |
| WFS1 | 0 | 0 |
| UNC45B | 0 | 0 |
| FYCO1 | 0 | 0 |
| CRYAA | 0 | 0 |
| CRYAB | 0 | 0 |
| CRYBA1 | 0 | 0 |
| CRYBA2 | 0 | 0 |
| CRYBB1 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| PONATINIB | 4 | EPHA2 |
| FEDRATINIB | 4 | EPHA2 |
| TIVOZANIB | 4 | EPHA2 |
| SORAFENIB | 4 | EPHA2 |
| DASATINIB ANHYDROUS | 4 | EPHA2 |
| REGORAFENIB | 4 | EPHA2 |
| CABOZANTINIB | 4 | EPHA2 |
| VANDETANIB | 4 | EPHA2 |
| NILOTINIB | 4 | EPHA2 |
| BOSUTINIB | 4 | EPHA2 |
| TOVORAFENIB | 4 | EPHA2 |
| NINTEDANIB | 4 | EPHA2 |
| DASATINIB | 4 | EPHA2 |
| CRIZOTINIB | 4 | EPHA2 |
| SARACATINIB | 3 | EPHA2 |
| LINIFANIB | 3 | EPHA2 |
| TESEVATINIB | 3 | EPHA2 |
| ALVOCIDIB | 3 | EPHA2 |
| ALISERTIB | 3 | EPHA2 |
| LESTAURTINIB | 3 | EPHA2 |
| DORAMAPIMOD | 2 | EPHA2 |
| NEFLAMAPIMOD | 2 | EPHA2 |
| FORETINIB | 2 | EPHA2 |
| ILORASERTIB | 2 | EPHA2 |
| CEP-32496 | 2 | EPHA2 |
| BAFETINIB | 2 | EPHA2 |
| SAPITINIB | 2 | EPHA2 |
| OSI-632 | 2 | EPHA2 |
| GOLVATINIB | 2 | EPHA2 |
| PEXMETINIB | 2 | 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 |
| CRYAA | 25 | Binding:25 |
| CRYAB | 13 | Binding:13 |
| CRYBB2 | 9 | Binding:9 |
| CRYGC | 9 | Binding:9 |
| CRYGD | 9 | Binding:9 |
| TNPO1 | 7 | Binding:7 |
| 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 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 19; 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 |
| FEDRATINIB | 4 | EPHA2 |
| TIVOZANIB | 4 | EPHA2 |
| SORAFENIB | 4 | EPHA2 |
| DASATINIB ANHYDROUS | 4 | EPHA2 |
| REGORAFENIB | 4 | EPHA2 |
| CABOZANTINIB | 4 | EPHA2 |
| VANDETANIB | 4 | EPHA2 |
| NILOTINIB | 4 | EPHA2 |
| BOSUTINIB | 4 | EPHA2 |
| TOVORAFENIB | 4 | EPHA2 |
| NINTEDANIB | 4 | EPHA2 |
| DASATINIB | 4 | EPHA2 |
| CRIZOTINIB | 4 | EPHA2 |
| SARACATINIB | 3 | EPHA2 |
| LINIFANIB | 3 | EPHA2 |
| TESEVATINIB | 3 | EPHA2 |
| ALVOCIDIB | 3 | EPHA2 |
| ALISERTIB | 3 | EPHA2 |
| LESTAURTINIB | 3 | EPHA2 |
| DORAMAPIMOD | 2 | EPHA2 |
| NEFLAMAPIMOD | 2 | EPHA2 |
| FORETINIB | 2 | EPHA2 |
| ILORASERTIB | 2 | EPHA2 |
| CEP-32496 | 2 | EPHA2 |
| BAFETINIB | 2 | EPHA2 |
| SAPITINIB | 2 | EPHA2 |
| OSI-632 | 2 | EPHA2 |
| GOLVATINIB | 2 | EPHA2 |
| PEXMETINIB | 2 | EPHA2 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | EPHA2 |
| 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 | 18 | BFSP1, WFS1, UNC45B, FYCO1, CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBB1, CRYBB2 (+8 more) |
Undrugged target profiles
18 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| BFSP1 | 0 | — |
| WFS1 | 1 | — |
| UNC45B | 0 | — |
| FYCO1 | 0 | — |
| CRYAA | 25 | — |
| CRYAB | 13 | — |
| CRYBA1 | 0 | — |
| CRYBA2 | 0 | — |
| CRYBB1 | 0 | — |
| CRYBB2 | 9 | — |
| CRYBB3 | 0 | — |
| CRYGC | 9 | — |
| CRYGD | 9 | — |
| GJA3 | 0 | — |
| GJA8 | 0 | — |
| TNPO1 | 7 | — |
| MIP | 0 | — |
| NHS | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.