Total early-onset cataract
diseaseOn this page
Also known as cataract, total congenitalcataract, total congenital with posterior sutural opacities in heterozygotesCCT
Summary
Total early-onset cataract (MONDO:0021548) is a disease with 16 cohort genes and 1 clinical trial.
At a glance
- Cohort genes: 16
- Clinical trials: 1
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | total early-onset cataract |
| Mondo ID | MONDO:0021548 |
| Orphanet | 98994 |
| UMLS | C0266539 |
| MedGen | 75616 |
| GARD | 0001159 |
| Is cancer (heuristic) | no |
Also known as: cataract, total congenital · cataract, total congenital with posterior sutural opacities in heterozygotes · CCT
Data availability: 15 GenCC gene-disease records.
Disease family
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 › total early-onset cataract
Related subtypes (28): 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
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: 124 · Orphanet: 48 · 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 |
| CRYBB2 | Definitive | Autosomal dominant | cataract 3 multiple types | 11 |
| EPHA2 | Definitive | Autosomal dominant | cataract 6 multiple types | 10 |
| FYCO1 | Definitive | Autosomal recessive | cataract 18 | 5 |
| GCNT2 | Definitive | Autosomal recessive | cataract 13 with adult I phenotype | 6 |
| GJA8 | Definitive | Autosomal dominant | cataract 1 multiple types | 9 |
| HSF4 | Definitive | Autosomal dominant | cataract 5 multiple types | 7 |
| LIM2 | Definitive | Autosomal recessive | cataract 19 multiple types | 6 |
| MIP | Definitive | Autosomal dominant | cataract 15 multiple types | 10 |
| TNPO1 | Definitive | Autosomal dominant | cataract 15 multiple types | 11 |
| DNMBP | Strong | Autosomal recessive | cataract 48 | 3 |
| LEMD2 | Strong | Autosomal recessive | cataract 46 juvenile-onset | 10 |
| LSS | Strong | Autosomal recessive | cataract 44 | 11 |
| SIPA1L3 | Moderate | Autosomal dominant | cataract 45 | 6 |
| AGK | Supportive | Autosomal dominant | total early-onset cataract | 6 |
| CRYGB | Supportive | Autosomal dominant | early-onset lamellar cataract | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| FYCO1 | Orphanet:98991 | Early-onset nuclear cataract |
| FYCO1 | Orphanet:98994 | Total early-onset cataract |
| LEMD2 | Orphanet:441447 | Early-onset posterior subcapsular cataract |
| LEMD2 | Orphanet:659873 | Wormian bones-micrognathia-abnormal dentition-progeroid syndrome |
| LEMD2 | Orphanet:98994 | Total early-onset cataract |
| AGK | Orphanet:1369 | Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome |
| AGK | Orphanet:98994 | Total early-onset cataract |
| SIPA1L3 | 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 |
| 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 |
| CRYGB | Orphanet:441452 | Early-onset lamellar cataract |
| CRYGB | Orphanet:98988 | Early-onset anterior polar cataract |
| CRYGB | Orphanet:98994 | Total early-onset cataract |
| DNMBP | Orphanet:98994 | Total early-onset 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 |
| GCNT2 | Orphanet:98994 | Total early-onset cataract |
| GJA8 | Orphanet:1377 | Cataract-microcornea syndrome |
| GJA8 | Orphanet:91490 | Isolated congenital sclerocornea |
| GJA8 | Orphanet:98984 | Pulverulent cataract |
| GJA8 | Orphanet:98985 | Early-onset sutural cataract |
| GJA8 | Orphanet:98991 | Early-onset nuclear cataract |
| GJA8 | Orphanet:98994 | Total early-onset cataract |
| HSF4 | Orphanet:441452 | Early-onset lamellar cataract |
| HSF4 | Orphanet:98994 | Total early-onset cataract |
| LIM2 | Orphanet:98994 | Total early-onset cataract |
| LSS | Orphanet:1366 | Autosomal recessive palmoplantar keratoderma and congenital alopecia |
| LSS | Orphanet:2850 | Alopecia-intellectual disability syndrome |
| LSS | Orphanet:55654 | Hypotrichosis simplex |
| LSS | Orphanet:98994 | Total early-onset cataract |
| MIP | Orphanet:441452 | Early-onset lamellar cataract |
| MIP | Orphanet:98985 | Early-onset sutural cataract |
| MIP | Orphanet:98989 | Cerulean cataract |
| MIP | Orphanet:98991 | Early-onset nuclear cataract |
| MIP | Orphanet:98993 | Early-onset posterior polar cataract |
| MIP | Orphanet:98994 | Total early-onset cataract |
Cohort genes → proteins
16 cohort genes, 16 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 16 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| FYCO1 | HGNC:14673 | ENSG00000163820 | Q9BQS8 | FYVE and coiled-coil domain-containing protein 1 | gencc |
| LEMD2 | HGNC:21244 | ENSG00000161904 | Q8NC56 | LEM domain-containing protein 2 | gencc |
| AGK | HGNC:21869 | ENSG00000006530 | Q53H12 | Acylglycerol kinase, mitochondrial | gencc |
| SIPA1L3 | HGNC:23801 | ENSG00000105738 | O60292 | Signal-induced proliferation-associated 1-like protein 3 | gencc |
| CRYAA | HGNC:2388 | ENSG00000160202 | P02489 | Alpha-crystallin A chain | gencc |
| CRYBB2 | HGNC:2398 | ENSG00000244752 | P43320 | Beta-crystallin B2 | gencc |
| CRYGB | HGNC:2409 | ENSG00000182187 | P07316 | Gamma-crystallin B | gencc |
| DNMBP | HGNC:30373 | ENSG00000107554 | Q6XZF7 | Dynamin-binding protein | gencc |
| EPHA2 | HGNC:3386 | ENSG00000142627 | P29317 | Ephrin type-A receptor 2 | gencc |
| GCNT2 | HGNC:4204 | ENSG00000111846 | Q8N0V5 | N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase | gencc |
| GJA8 | HGNC:4281 | ENSG00000121634 | P48165 | Gap junction alpha-8 protein | gencc |
| HSF4 | HGNC:5227 | ENSG00000102878 | Q9ULV5 | Heat shock factor protein 4 | gencc |
| TNPO1 | HGNC:6401 | ENSG00000083312 | Q92973 | Transportin-1 | gencc |
| LIM2 | HGNC:6610 | ENSG00000105370 | P55344 | Lens fiber membrane intrinsic protein | gencc |
| LSS | HGNC:6708 | ENSG00000160285 | P48449 | Lanosterol synthase | gencc |
| MIP | HGNC:7103 | ENSG00000135517 | P30301 | Lens fiber major intrinsic protein | gencc |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| FYCO1 | FYVE and coiled-coil domain-containing protein 1 | May mediate microtubule plus end-directed vesicle transport. |
| LEMD2 | LEM domain-containing protein 2 | Nuclear lamina-associated inner nuclear membrane protein that is involved in nuclear structure organization, maintenance of nuclear envelope (NE) integrity and NE reformation after mitosis. |
| AGK | Acylglycerol kinase, mitochondrial | Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively. |
| SIPA1L3 | Signal-induced proliferation-associated 1-like protein 3 | Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens. |
| CRYAA | Alpha-crystallin A chain | Contributes to the transparency and refractive index of the lens. |
| CRYBB2 | Beta-crystallin B2 | Crystallins are the dominant structural components of the vertebrate eye lens. |
| CRYGB | Gamma-crystallin B | Crystallins are the dominant structural components of the vertebrate eye lens. |
| DNMBP | Dynamin-binding protein | Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. |
| 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. |
| GCNT2 | N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase | Branching enzyme that converts linear into branched poly-N-acetyllactosaminoglycans. |
| GJA8 | Gap junction alpha-8 protein | Structural component of eye lens gap junctions. |
| HSF4 | Heat shock factor protein 4 | Heat-shock transcription factor that specifically binds heat shock promoter elements (HSE). |
| TNPO1 | Transportin-1 | Functions in nuclear protein import as nuclear transport receptor. |
| LIM2 | Lens fiber membrane intrinsic protein | Present in the thicker 16-17 nm junctions of mammalian lens fiber cells, where it may contribute to cell junctional organization. |
| LSS | Lanosterol synthase | Key enzyme in the cholesterol biosynthesis pathway. |
| 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. |
Protein-family classification
Druggable: 4 · Difficult: 3 · Unknown: 9 · Druggable fraction: 0.25
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 | 3.5× | 0.559 |
| Scaffold/PPI | 2 | 2.2× | 0.590 |
| Enzyme (other) | 2 | 1.5× | 0.651 |
| Other/Unknown | 9 | 1.0× | 0.736 |
| Transcription factor | 1 | 0.5× | 0.873 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| FYCO1 | Transcription factor | no | Znf_FYVE, Run_dom, GOLD_dom | |
| LEMD2 | Other/Unknown | no | LEM_dom, LEM/LEM-like_dom_sf, Man1/Src1-like_C | |
| AGK | Kinase | yes | 2.7.1.94 | Diacylglycerol_kinase_cat_dom, NAD/diacylglycerol_kinase_sf, ATP-NAD_kinase_N |
| SIPA1L3 | Scaffold/PPI | no | Rap/Ran_GAP_dom, PDZ, SIPA1L_C | |
| CRYAA | Other/Unknown | no | Alpha-crystallin/sHSP_animal, A-crystallin/Hsp20_dom, Alpha-crystallin_N | |
| CRYBB2 | Other/Unknown | no | Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin | |
| CRYGB | Other/Unknown | no | Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin | |
| DNMBP | Scaffold/PPI | no | DH_dom, GDS_CDC24_CS, SH3_domain | |
| EPHA2 | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom |
| GCNT2 | Enzyme (other) | yes | 2.4.1.150 | Glyco_trans_14 |
| GJA8 | Other/Unknown | no | Connexin, Connexin50_C, Connexin_N | |
| HSF4 | Other/Unknown | no | HSF_DNA-bd, WH-like_DNA-bd_sf, WH_DNA-bd_sf | |
| TNPO1 | Other/Unknown | no | Importin-beta_N, ARM-like, ARM-type_fold | |
| LIM2 | Other/Unknown | no | LMIP, PMP22/EMP/MP20/Claudin, PMP22_EMP_MP20 | |
| LSS | Enzyme (other) | yes | 5.4.99.7 | Terpene_synthase_CS, Terpenoid_cyclase/PrenylTrfase, Squalene_cyclase |
| MIP | Other/Unknown | no | MIP, MIP_CS, Aquaporin-like |
Expression context
Cohort genes with no expression data: 0.
12 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) | 15 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| cerebellar cortex | 3 |
| cerebellar hemisphere | 3 |
| male germ line stem cell (sensu Vertebrata) in testis | 3 |
| primordial germ cell in gonad | 3 |
| skeletal muscle tissue of rectus abdominis | 2 |
| right hemisphere of cerebellum | 2 |
| buccal mucosa cell | 2 |
| right lobe of liver | 2 |
| biceps brachii | 1 |
| skeletal muscle tissue of biceps brachii | 1 |
| adrenal tissue | 1 |
| endometrium epithelium | 1 |
| islet of Langerhans | 1 |
| adult mammalian kidney | 1 |
| liver | 1 |
| gluteal muscle | 1 |
| trabecular bone tissue | 1 |
| triceps brachii | 1 |
| sperm | 1 |
| colonic mucosa | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| FYCO1 | 284 | ubiquitous | marker | skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii |
| LEMD2 | 186 | ubiquitous | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| AGK | 161 | ubiquitous | marker | adrenal tissue, cerebellar hemisphere, cerebellar cortex |
| SIPA1L3 | 257 | ubiquitous | marker | buccal mucosa cell, endometrium epithelium, islet of Langerhans |
| CRYAA | 42 | marker | adult mammalian kidney, right lobe of liver, liver | |
| CRYBB2 | 144 | tissue_specific | yes | triceps brachii, gluteal muscle, trabecular bone tissue |
| CRYGB | 35 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, sperm, skeletal muscle tissue of rectus abdominis |
| DNMBP | 279 | ubiquitous | marker | jejunal mucosa, ileal mucosa, colonic mucosa |
| EPHA2 | 224 | ubiquitous | marker | lower esophagus mucosa, esophagus mucosa, pharyngeal mucosa |
| GCNT2 | 136 | ubiquitous | marker | primordial germ cell in gonad, heart left ventricle, male germ line stem cell (sensu Vertebrata) in testis |
| GJA8 | 17 | tissue_specific | yes | buccal mucosa cell, frontal pole, paraflocculus |
| HSF4 | 186 | tissue_specific | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| TNPO1 | 295 | ubiquitous | marker | corpus epididymis, caput epididymis, cauda epididymis |
| LIM2 | 26 | tissue_specific | marker | primordial germ cell in gonad, lens of camera-type eye, granulocyte |
| LSS | 134 | ubiquitous | marker | mucosa of stomach, C1 segment of cervical spinal cord, skin of leg |
| MIP | 91 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right lobe of liver |
Protein interactions among cohort
Intra-cohort edges: 22.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| EPHA2 | 4,794 |
| TNPO1 | 3,147 |
| MIP | 2,496 |
| AGK | 2,341 |
| LEMD2 | 2,340 |
| FYCO1 | 1,637 |
| LIM2 | 1,593 |
| LSS | 1,562 |
| CRYAA | 1,464 |
| DNMBP | 1,328 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| CRYAA | CRYBB2 | biogrid_interaction, intact, string_interaction |
| CRYAA | CRYGB | string_interaction |
| CRYAA | FYCO1 | string_interaction |
| CRYAA | GJA8 | string_interaction |
| CRYAA | HSF4 | string_interaction |
| CRYAA | LIM2 | string_interaction |
| CRYAA | SIPA1L3 | string_interaction |
| CRYBB2 | GCNT2 | string_interaction |
| CRYBB2 | GJA8 | string_interaction |
| CRYBB2 | HSF4 | string_interaction |
| CRYBB2 | LIM2 | string_interaction |
| CRYGB | GJA8 | string_interaction |
| CRYGB | LIM2 | string_interaction |
| DNMBP | SIPA1L3 | string_interaction |
| GCNT2 | HSF4 | string_interaction |
| GJA8 | HSF4 | string_interaction |
| GJA8 | LIM2 | string_interaction |
| GJA8 | MIP | string_interaction |
| GJA8 | SIPA1L3 | string_interaction |
| HSF4 | LIM2 | string_interaction |
| HSF4 | MIP | string_interaction |
| LIM2 | MIP | string_interaction |
Structural data
PDB: 11 · AlphaFold-only: 5 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| EPHA2 | P29317 | 103 |
| TNPO1 | Q92973 | 21 |
| DNMBP | Q6XZF7 | 7 |
| CRYAA | P02489 | 5 |
| FYCO1 | Q9BQS8 | 3 |
| CRYBB2 | P43320 | 3 |
| CRYGB | P07316 | 2 |
| HSF4 | Q9ULV5 | 2 |
| LSS | P48449 | 2 |
| AGK | Q53H12 | 1 |
| LIM2 | P55344 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| GCNT2 | Q8N0V5 | 91.66 |
| MIP | P30301 | 91.08 |
| LEMD2 | Q8NC56 | 71.49 |
| GJA8 | P48165 | 65.85 |
| SIPA1L3 | O60292 | 56.37 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 44. Enrichment computed across 16 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 |
|---|---|---|---|---|
| Cholesterol biosynthesis | 1 | 142.8× | 0.058 | LSS |
| Passive transport by Aquaporins | 1 | 109.8× | 0.058 | MIP |
| Depolymerization of the Nuclear Lamina | 1 | 95.2× | 0.058 | LEMD2 |
| Lanosterol biosynthesis | 1 | 95.2× | 0.058 | LSS |
| Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 1 | 79.3× | 0.058 | TNPO1 |
| Initiation of Nuclear Envelope (NE) Reformation | 1 | 75.1× | 0.058 | LEMD2 |
| Nuclear Envelope Breakdown | 1 | 57.1× | 0.058 | LEMD2 |
| Postmitotic nuclear pore complex (NPC) reformation | 1 | 51.0× | 0.058 | TNPO1 |
| EPHA-mediated growth cone collapse | 1 | 47.6× | 0.058 | EPHA2 |
| Aquaporin-mediated transport | 1 | 46.0× | 0.058 | MIP |
| Mitotic Prophase | 1 | 46.0× | 0.058 | LEMD2 |
| Sealing of the nuclear envelope (NE) by ESCRT-III | 1 | 43.3× | 0.058 | LEMD2 |
| Glycerophospholipid biosynthesis | 1 | 42.0× | 0.058 | AGK |
| Regulation of cholesterol biosynthesis by SREBP (SREBF) | 1 | 39.6× | 0.058 | LSS |
| Gap junction assembly | 1 | 36.6× | 0.058 | GJA8 |
| Nuclear Envelope (NE) Reassembly | 1 | 36.6× | 0.058 | LEMD2 |
| RHOV GTPase cycle | 1 | 35.7× | 0.058 | EPHA2 |
| RHOU GTPase cycle | 1 | 34.8× | 0.058 | EPHA2 |
| RND1 GTPase cycle | 1 | 33.2× | 0.058 | EPHA2 |
| Activation of gene expression by SREBF (SREBP) | 1 | 32.4× | 0.058 | LSS |
| RND3 GTPase cycle | 1 | 32.4× | 0.058 | EPHA2 |
| RND2 GTPase cycle | 1 | 32.4× | 0.058 | EPHA2 |
| Metabolism of lipids | 2 | 7.9× | 0.058 | AGK, LSS |
| Oncogenic MAPK signaling | 1 | 31.0× | 0.058 | AGK |
| EPH-ephrin mediated repulsion of cells | 1 | 27.4× | 0.063 | EPHA2 |
| Phospholipid metabolism | 1 | 25.0× | 0.064 | AGK |
| Intraflagellar transport | 1 | 25.0× | 0.064 | TNPO1 |
| Signaling by BRAF and RAF1 fusions | 1 | 21.3× | 0.072 | AGK |
| EPH-Ephrin signaling | 1 | 20.7× | 0.072 | EPHA2 |
| RHOG GTPase cycle | 1 | 18.5× | 0.077 | EPHA2 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 16 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 | 6 | 140.4× | 2e-10 | CRYAA, CRYBB2, CRYGB, GJA8, LIM2, MIP |
| lens fiber cell morphogenesis | 3 | 395.0× | 2e-06 | CRYAA, CRYGB, EPHA2 |
| gap junction-mediated intercellular transport | 2 | 351.1× | 5e-04 | GJA8, MIP |
| maintenance of lens transparency | 2 | 263.3× | 6e-04 | GCNT2, MIP |
| visual perception | 4 | 19.9× | 9e-04 | CRYAA, CRYBB2, CRYGB, MIP |
| triterpenoid biosynthetic process | 1 | 1053.2× | 0.015 | LSS |
| notochord cell development | 1 | 1053.2× | 0.015 | EPHA2 |
| multicellular organism development | 1 | 526.6× | 0.023 | GCNT2 |
| axial mesoderm formation | 1 | 526.6× | 0.023 | EPHA2 |
| notochord formation | 1 | 351.1× | 0.026 | EPHA2 |
| negative regulation of intracellular transport | 1 | 351.1× | 0.026 | CRYAA |
| negative regulation of lymphangiogenesis | 1 | 351.1× | 0.026 | EPHA2 |
| cAMP metabolic process | 1 | 263.3× | 0.030 | EPHA2 |
| response to UV-A | 1 | 263.3× | 0.030 | CRYAA |
| heart formation | 1 | 210.7× | 0.031 | LEMD2 |
| pericyte cell differentiation | 1 | 210.7× | 0.031 | EPHA2 |
| regulation of blood vessel endothelial cell migration | 1 | 175.5× | 0.031 | EPHA2 |
| apoptotic process involved in morphogenesis | 1 | 175.5× | 0.031 | CRYAA |
| plus-end-directed vesicle transport along microtubule | 1 | 175.5× | 0.031 | FYCO1 |
| regulation of small GTPase mediated signal transduction | 2 | 18.0× | 0.031 | SIPA1L3, DNMBP |
| blood vessel endothelial cell proliferation involved in sprouting angiogenesis | 1 | 150.5× | 0.031 | EPHA2 |
| nuclear membrane organization | 1 | 150.5× | 0.031 | LEMD2 |
| positive regulation of autophagosome maturation | 1 | 150.5× | 0.031 | FYCO1 |
| negative regulation of chemokine production | 1 | 131.7× | 0.033 | EPHA2 |
| glycerolipid metabolic process | 1 | 131.7× | 0.033 | AGK |
| regulation of lamellipodium assembly | 1 | 117.0× | 0.034 | EPHA2 |
| tubulin complex assembly | 1 | 105.3× | 0.034 | CRYAA |
| homotypic cell-cell adhesion | 1 | 105.3× | 0.034 | MIP |
| lipid phosphorylation | 1 | 105.3× | 0.034 | AGK |
| positive regulation of bicellular tight junction assembly | 1 | 105.3× | 0.034 | EPHA2 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 15
Druggability breadth: 8 of 16 evidence-associated genes (50%) 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 |
| FYCO1 | 0 | 0 |
| LEMD2 | 0 | 0 |
| AGK | 0 | 0 |
| SIPA1L3 | 0 | 0 |
| CRYAA | 0 | 0 |
| CRYBB2 | 0 | 0 |
| CRYGB | 0 | 0 |
| DNMBP | 0 | 0 |
| GCNT2 | 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): 4.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| EPHA2 | 567 | Binding:565, Functional:1, ADMET:1 |
| LSS | 46 | Binding:45, Functional:1 |
| CRYAA | 25 | Binding:25 |
| AGK | 19 | Binding:19 |
| CRYBB2 | 9 | Binding:9 |
| TNPO1 | 7 | Binding:7 |
| DNMBP | 1 | Binding:1 |
| HSF4 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| AGK | 2.7.1.94 | acylglycerol kinase |
| EPHA2 | 2.7.10.1 | receptor protein-tyrosine kinase |
| GCNT2 | 2.4.1.150 | N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase |
| LSS | 5.4.99.7 | Lanosterol synthase |
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: 16; 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 | 2 | AGK, LSS |
| D | Druggable family + AlphaFold only, no drug | 1 | GCNT2 |
| E | Difficult family or no structure, no drug | 12 | FYCO1, LEMD2, SIPA1L3, CRYAA, CRYBB2, CRYGB, DNMBP, GJA8, HSF4, TNPO1 (+2 more) |
Undrugged target profiles
15 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| FYCO1 | 0 | — |
| LEMD2 | 0 | — |
| AGK | 19 | — |
| SIPA1L3 | 0 | — |
| CRYAA | 25 | — |
| CRYBB2 | 9 | — |
| CRYGB | 0 | — |
| DNMBP | 1 | — |
| GCNT2 | 0 | — |
| GJA8 | 0 | — |
| HSF4 | 1 | — |
| TNPO1 | 7 | — |
| LIM2 | 0 | — |
| LSS | 46 | — |
| MIP | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06068348 | Not specified | ACTIVE_NOT_RECRUITING | Liquid Biopsy Collection Study |