Corneal dystrophy
diseaseOn this page
Also known as corneal dystrophy (disease)
Summary
Corneal dystrophy (MONDO:0018102) is a disease (an umbrella term covering 13 Mondo subtypes) with 10 cohort genes (21 GWAS associations across 5 studies) and 20 clinical trials.
At a glance
- Prevalence: Unknown (Worldwide)
- Umbrella term: 13 Mondo subtypes
- Cohort genes: 10
- GWAS associations: 21
- ClinVar variants: 304
- Clinical trials: 20
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Point prevalence | >1 / 1000 | 110 | United States | Not yet validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | corneal dystrophy |
| Mondo ID | MONDO:0018102 |
| MeSH | D003317 |
| Orphanet | 34533 |
| DOID | DOID:2566 |
| ICD-11 | 1291475891 |
| NCIT | C34513 |
| SNOMED CT | 5587004 |
| UMLS | C0010036 |
| MedGen | 3619 |
| GARD | 0027867 |
| MedDRA | 10011005 |
| Is cancer (heuristic) | no |
Also known as: corneal dystrophy · corneal dystrophy (disease)
Data availability: 304 ClinVar variants · 21 GWAS associations (5 studies) · 1 GenCC gene-disease record · 1 HPO phenotype.
Disease family
An umbrella term covering 13 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › corneal disorder › corneal dystrophy
Related subtypes (23): cornea plana, pseudopterygium, corneal deposit, Bowman’s membrane folds or rupture, corneal degeneration, corneal staphyloma, corneal argyrosis, corneal ectasia, keratopathy, keratitis, corneal edema, brittle cornea syndrome, megalocornea, X-linked corneal dermoid, Peters anomaly, pellucid marginal degeneration, keratoconus, sclerocornea, cornea neoplasm, Arnold stickler bourne syndrome, limbal stem cell deficiency, thygeson superficial punctate keratopathy, Terrien marginal degeneration
Subtypes (13): epithelial and subepithelial corneal dystrophy, epithelial-stromal TGFBI dystrophy, corneal endothelial dystrophy, Finnish type amyloidosis, autosomal dominant keratitis, macular dystrophy, fenestrated sheen type, band keratopathy, superficial corneal dystrophy, stromal corneal dystrophy, posterior corneal dystrophy, Chandler syndrome, Judge Misch wright syndrome, corneal dystrophy, punctiform and polychromatic pre-descemet
Genetics & variants
GWAS landscape
21 GWAS associations across 5 studies. Top hits map to 8 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs11659764 | 1e-323 | TCF4 - LINC01415 | T | 1.3 |
| rs72932713 | 1e-323 | TCF4 | T | 1.2 |
| rs10873768 | 6e-30 | COL24A1 - LINC02795 | T | 0.27 |
| rs1200108 | 2e-29 | LINC00970, LINC00970 | G | 0.21 |
| rs80095409 | 3e-19 | LAMB1 | G | 0.55 |
| rs4075897 | 1e-15 | RXRA - COL5A1 | G | 0.16 |
| rs79742895 | 3e-14 | KANK4 | T | 0.35 |
| chr2:69392619 | 6e-14 | T | 0.14 | |
| rs5013914 | 2e-13 | ANTXR1 | A | 0.14 |
| rs533213012 | 3e-13 | LINC02392 - LINC02822 | G | 4.66 |
| chr8:124300658 | 1e-11 | G | 0.16 | |
| rs146163259 | 1e-11 | CHRNB1 | T | 3.32 |
| rs567221527 | 3e-11 | GDPD5 | G | 2.2 |
| rs543597577 | 5e-11 | RPS4XP20 - RPS4XP21 | C | 2.02 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90475864 | Verma A | 2024 | 5,946 | 441,092 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90475863 | Verma A | 2024 | 636 | 120,755 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90480063 | Verma A | 2024 | 636 | 120,755 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90476530 | Verma A | 2024 | 253 | 59,432 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90435980 | Zhou W | 2018 | 212 | 397,761 | Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 1 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 2 |
| Tier 4: intronic/intergenic | 11 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 6 |
| low_freq (0.01-0.05) | 4 |
| rare (<0.01) | 4 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 7 |
| regulatory_region_variant | 2 |
| unknown | 2 |
| intergenic_variant | 2 |
| missense_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs11659764 | 18 | 55668281 | T>A,G | 0.045 | intron_variant | TCF4 - LINC01415 | 1e-323 | Tier 4: intronic/intergenic |
| rs72932713 | 18 | 55519680 | T>C | 0.041 | intron_variant | TCF4 | 1e-323 | Tier 4: intronic/intergenic |
| rs10873768 | 1 | 86247838 | T>A,G | 0.205 | regulatory_region_variant | COL24A1 - LINC02795 | 6e-30 | Tier 3: regulatory |
| rs1200108 | 1 | 169088731 | G>A | 0.346 | intron_variant | LINC00970, LINC00970 | 2e-29 | Tier 4: intronic/intergenic |
| rs80095409 | 7 | 107959766 | G>A,C | 0.012 | missense_variant | LAMB1 | 3e-19 | Tier 1: coding |
| rs4075897 | 9 | 134625181 | G>C,T | 0.32 | regulatory_region_variant | RXRA - COL5A1 | 1e-15 | Tier 3: regulatory |
| rs79742895 | 1 | 62317189 | T>C | 0.033 | intron_variant | KANK4 | 3e-14 | Tier 4: intronic/intergenic |
| chr2:69392619 | 0.452 | 6e-14 | Tier 4: intronic/intergenic | |||||
| rs5013914 | 2 | 69162023 | A>C,G,T | 0.484 | intron_variant | ANTXR1 | 2e-13 | Tier 4: intronic/intergenic |
| rs533213012 | 12 | 90400110 | G>A | 0 | intergenic_variant | LINC02392 - LINC02822 | 3e-13 | Tier 4: intronic/intergenic |
| chr8:124300658 | 0.217 | 1e-11 | Tier 4: intronic/intergenic | |||||
| rs146163259 | 17 | 7453769 | T>C | 0 | intron_variant | CHRNB1 | 1e-11 | Tier 4: intronic/intergenic |
| rs567221527 | 11 | 75499978 | G>C | 0.001 | intron_variant | GDPD5 | 3e-11 | Tier 4: intronic/intergenic |
| rs543597577 | 19 | 34067319 | C>A,T | 0.002 | intergenic_variant | RPS4XP20 - RPS4XP21 | 5e-11 | Tier 4: intronic/intergenic |
ClinVar germline variants
304 retrieved; paginated sample, class counts are floors:
150 uncertain significance, 81 conflicting classifications of pathogenicity, 38 benign, 17 benign/likely benign, 7 pathogenic, 5 likely benign, 4 pathogenic/likely pathogenic, 2 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 208978 | NM_000494.4(COL17A1):c.3156C>T (p.Gly1052=) | COL17A1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 489403 | NM_024915.4(GRHL2):c.20+544G>T | GRHL2 | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 489405 | NM_024915.4(GRHL2):c.20+133del | GRHL2 | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 1306 | NM_001174089.2(SLC4A11):c.1343G>A (p.Gly448Asp) | SLC4A11 | Pathogenic | criteria provided, single submitter |
| 1312 | NM_001174089.2(SLC4A11):c.425_432del (p.Arg142fs) | SLC4A11 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 7866 | NM_000358.3(TGFBI):c.1663C>T (p.Arg555Trp) | TGFBI | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 7868 | NM_000358.3(TGFBI):c.370C>T (p.Arg124Cys) | TGFBI | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 7871 | NM_000358.3(TGFBI):c.1501C>A (p.Pro501Thr) | TGFBI | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1691711 | NM_001174096.2(ZEB1):c.1093dup (p.Ile365fs) | ZEB1 | Pathogenic/Likely pathogenic | criteria provided, single submitter |
| 2571620 | NM_001174096.2(ZEB1):c.1586_1595del (p.Asp529fs) | ZEB1 | Pathogenic | criteria provided, single submitter |
| 437319 | NM_001174096.2(ZEB1):c.1579dup (p.Val527fs) | ZEB1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 489404 | NM_024915.4(GRHL2):c.20+257del | GRHL2 | Likely pathogenic | no assertion criteria provided |
| 2138323 | NM_001174089.2(SLC4A11):c.2363G>A (p.Arg788His) | SLC4A11 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 166980 | NM_207352.4(CYP4V2):c.*4T>C | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 193951 | NM_207352.4(CYP4V2):c.1446G>A (p.Ser482=) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 348296 | NM_207352.4(CYP4V2):c.24C>T (p.Leu8=) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 348298 | NM_207352.4(CYP4V2):c.282C>T (p.Val94=) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 348307 | NM_207352.4(CYP4V2):c.736C>G (p.Leu246Val) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 348312 | NM_207352.4(CYP4V2):c.1338C>G (p.Pro446=) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 348333 | NM_207352.4(CYP4V2):c.*1027C>T | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 348355 | NM_207352.4(CYP4V2):c.*1737A>G | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 39259 | NM_207352.4(CYP4V2):c.237G>T (p.Glu79Asp) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 39264 | NM_207352.4(CYP4V2):c.367A>G (p.Met123Val) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 493404 | NM_207352.4(CYP4V2):c.610G>A (p.Ala204Thr) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 497287 | NM_207352.4(CYP4V2):c.1328G>A (p.Arg443Gln) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 782095 | NM_207352.4(CYP4V2):c.99G>A (p.Leu33=) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 899608 | NM_207352.4(CYP4V2):c.1344T>C (p.Asn448=) | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 899863 | NM_207352.4(CYP4V2):c.*2166C>G | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 900596 | NM_207352.4(CYP4V2):c.674+14T>C | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 900663 | NM_207352.4(CYP4V2):c.1091-15A>G | CYP4V2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 2 · Orphanet: 23 · 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 |
|---|---|---|---|---|
| SPARCL1 | Limited | Autosomal dominant | stromal corneal dystrophy | 2 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SPARCL1 | Orphanet:101068 | Congenital stromal corneal dystrophy |
| ZEB1 | Orphanet:98973 | Posterior polymorphous corneal dystrophy |
| ZEB1 | Orphanet:98974 | Fuchs endothelial corneal dystrophy |
| TGFBI | Orphanet:98956 | Epithelial basement membrane dystrophy |
| TGFBI | Orphanet:98960 | Thiel-Behnke corneal dystrophy |
| TGFBI | Orphanet:98961 | Reis-Bücklers corneal dystrophy |
| TGFBI | Orphanet:98962 | Granular corneal dystrophy type I |
| TGFBI | Orphanet:98963 | Granular corneal dystrophy type II |
| TGFBI | Orphanet:98964 | Lattice corneal dystrophy type I |
| SLC4A11 | Orphanet:1490 | Corneal dystrophy-perceptive deafness syndrome |
| SLC4A11 | Orphanet:293603 | Congenital hereditary endothelial dystrophy type II |
| SLC4A11 | Orphanet:98974 | Fuchs endothelial corneal dystrophy |
| COL17A1 | Orphanet:251393 | Localized junctional epidermolysis bullosa |
| COL17A1 | Orphanet:293381 | Epithelial recurrent erosion dystrophy |
| COL17A1 | Orphanet:79402 | Intermediate generalized junctional epidermolysis bullosa |
| COL17A1 | Orphanet:79406 | Late-onset junctional epidermolysis bullosa |
| CYP4V2 | Orphanet:41751 | Bietti crystalline dystrophy |
| GRHL2 | Orphanet:423454 | Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome |
| GRHL2 | Orphanet:90635 | Rare autosomal dominant non-syndromic sensorineural deafness type DFNA |
| GRHL2 | Orphanet:98973 | Posterior polymorphous corneal dystrophy |
| UBIAD1 | Orphanet:98967 | Schnyder corneal dystrophy |
| ITPA | Orphanet:457375 | ITPA-related lethal infantile neurological disorder with cataract and cardiac involvement |
| KLKB1 | Orphanet:749 | Congenital prekallikrein deficiency |
Cohort genes → proteins
10 cohort genes, 10 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 10 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SPARCL1 | HGNC:11220 | ENSG00000152583 | Q14515 | SPARC-like protein 1 | gencc |
| ZEB1 | HGNC:11642 | ENSG00000148516 | P37275 | Zinc finger E-box-binding homeobox 1 | clinvar |
| TGFBI | HGNC:11771 | ENSG00000120708 | Q15582 | Transforming growth factor-beta-induced protein ig-h3 | clinvar |
| SLC4A11 | HGNC:16438 | ENSG00000088836 | Q8NBS3 | Solute carrier family 4 member 11 | clinvar |
| COL17A1 | HGNC:2194 | ENSG00000065618 | Q9UMD9 | Collagen alpha-1(XVII) chain | clinvar |
| CYP4V2 | HGNC:23198 | ENSG00000145476 | Q6ZWL3 | Cytochrome P450 4V2 | clinvar |
| GRHL2 | HGNC:2799 | ENSG00000083307 | Q6ISB3 | Grainyhead-like protein 2 homolog | clinvar |
| UBIAD1 | HGNC:30791 | ENSG00000120942 | Q9Y5Z9 | UbiA prenyltransferase domain-containing protein 1 | clinvar |
| ITPA | HGNC:6176 | ENSG00000125877 | Q9BY32 | Inosine triphosphate pyrophosphatase | clinvar |
| KLKB1 | HGNC:6371 | ENSG00000164344 | P03952 | Plasma kallikrein | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| ZEB1 | Zinc finger E-box-binding homeobox 1 | Acts as a transcriptional repressor. |
| TGFBI | Transforming growth factor-beta-induced protein ig-h3 | Plays a role in cell adhesion. |
| SLC4A11 | Solute carrier family 4 member 11 | Multifunctional transporter with an impact in cell morphology and differentiation. |
| COL17A1 | Collagen alpha-1(XVII) chain | May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane. |
| CYP4V2 | Cytochrome P450 4V2 | A cytochrome P450 monooxygenase involved in fatty acid metabolism in the eye. |
| GRHL2 | Grainyhead-like protein 2 homolog | Transcription factor playing an important role in primary neurulation and in epithelial development. |
| UBIAD1 | UbiA prenyltransferase domain-containing protein 1 | Prenyltransferase that mediates the formation of menaquinone-4 (MK-4) and coenzyme Q10. |
| ITPA | Inosine triphosphate pyrophosphatase | Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2’-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP) and xanthosine 5’-triphosphate (XTP) to the… |
| KLKB1 | Plasma kallikrein | Participates in the surface-dependent activation of blood coagulation. |
Protein-family classification
Druggable: 3 · Difficult: 2 · Unknown: 5 · Druggable fraction: 0.3
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 |
|---|---|---|---|
| Protease | 1 | 3.7× | 0.461 |
| Enzyme (other) | 2 | 2.4× | 0.461 |
| Transcription factor | 2 | 1.6× | 0.461 |
| Other/Unknown | 5 | 0.9× | 0.756 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SPARCL1 | Other/Unknown | no | Osteonectin_CS, EF_hand_dom, Kazal_dom | |
| ZEB1 | Transcription factor | no | HD, Di19_Zn-bd, Homeodomain-like_sf | |
| TGFBI | Other/Unknown | no | FAS1_domain, EMI_domain, TGFBI/POSTN | |
| SLC4A11 | Other/Unknown | no | HCO3_transpt_euk, HCO3_transpt-like_TM_dom, PTrfase/Anion_transptr | |
| COL17A1 | Other/Unknown | no | Collagen, Collagen_superfamily | |
| CYP4V2 | Enzyme (other) | yes | 1.14.14.79 | Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS |
| GRHL2 | Transcription factor | no | CP2, TF_CP2-like, GRHL1/CP2_C | |
| UBIAD1 | Other/Unknown | no | UbiA_prenyltransferase, UBIAD1, UbiA_sf | |
| ITPA | Enzyme (other) | yes | 3.6.1.66 | RdgB/HAM1, ITPase, ITPase-like_fam |
| KLKB1 | Protease | yes | 3.4.21.34 | Apple, Trypsin_dom, Peptidase_S1A |
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) | 0 |
| broad (>20) | 10 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| metanephros cortex | 2 |
| liver | 2 |
| blood vessel layer | 1 |
| middle temporal gyrus | 1 |
| postcentral gyrus | 1 |
| calcaneal tendon | 1 |
| colonic epithelium | 1 |
| tendon | 1 |
| amniotic fluid | 1 |
| pericardium | 1 |
| synovial joint | 1 |
| nasal cavity epithelium | 1 |
| olfactory segment of nasal mucosa | 1 |
| skin of abdomen | 1 |
| skin of leg | 1 |
| zone of skin | 1 |
| ileal mucosa | 1 |
| kidney epithelium | 1 |
| buccal mucosa cell | 1 |
| cervix squamous epithelium | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SPARCL1 | 303 | broad | marker | middle temporal gyrus, blood vessel layer, postcentral gyrus |
| ZEB1 | 287 | ubiquitous | marker | calcaneal tendon, colonic epithelium, tendon |
| TGFBI | 278 | ubiquitous | marker | amniotic fluid, synovial joint, pericardium |
| SLC4A11 | 197 | broad | marker | nasal cavity epithelium, olfactory segment of nasal mucosa, metanephros cortex |
| COL17A1 | 182 | broad | marker | skin of abdomen, skin of leg, zone of skin |
| CYP4V2 | 254 | ubiquitous | marker | kidney epithelium, ileal mucosa, liver |
| GRHL2 | 200 | broad | marker | buccal mucosa cell, oviduct epithelium, cervix squamous epithelium |
| UBIAD1 | 232 | ubiquitous | marker | gastrocnemius, muscle of leg, hindlimb stylopod muscle |
| ITPA | 274 | ubiquitous | marker | right lobe of thyroid gland, left lobe of thyroid gland, metanephros cortex |
| KLKB1 | 196 | tissue_specific | yes | right lobe of liver, liver, primordial germ cell in gonad |
Protein interactions among cohort
Intra-cohort edges: 4.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ZEB1 | 4,171 |
| TGFBI | 2,988 |
| ITPA | 2,856 |
| SPARCL1 | 2,354 |
| CYP4V2 | 1,867 |
| COL17A1 | 1,769 |
| UBIAD1 | 1,655 |
| KLKB1 | 1,537 |
| GRHL2 | 1,365 |
| SLC4A11 | 846 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| GRHL2 | ZEB1 | string_interaction |
| SLC4A11 | TGFBI | string_interaction |
| SLC4A11 | UBIAD1 | string_interaction |
| SLC4A11 | ZEB1 | string_interaction |
Structural data
PDB: 8 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| KLKB1 | P03952 | 22 |
| TGFBI | Q15582 | 10 |
| SLC4A11 | Q8NBS3 | 4 |
| ITPA | Q9BY32 | 4 |
| SPARCL1 | Q14515 | 1 |
| ZEB1 | P37275 | 1 |
| COL17A1 | Q9UMD9 | 1 |
| GRHL2 | Q6ISB3 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| CYP4V2 | Q6ZWL3 | 91.05 |
| UBIAD1 | Q9Y5Z9 | 90.21 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 37. Enrichment computed across 10 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 |
|---|---|---|---|---|
| Metabolism of vitamin K | 1 | 475.8× | 0.021 | UBIAD1 |
| R-HSA-9651496 | 1 | 475.8× | 0.021 | KLKB1 |
| Defective factor XII causes hereditary angioedema | 1 | 356.9× | 0.021 | KLKB1 |
| Defective SERPING1 causes hereditary angioedema | 1 | 356.9× | 0.021 | KLKB1 |
| Diseases of hemostasis | 1 | 356.9× | 0.021 | KLKB1 |
| R-HSA-140837 | 1 | 178.4× | 0.024 | KLKB1 |
| Nucleotide catabolism | 1 | 158.6× | 0.024 | ITPA |
| Regulation of FXIIa and plasma kallikrein activity | 1 | 142.8× | 0.024 | KLKB1 |
| FXIIa, PKa-dependent activation of coagulation pathway | 1 | 142.8× | 0.024 | KLKB1 |
| Type I hemidesmosome assembly | 1 | 129.8× | 0.024 | COL17A1 |
| Purine catabolism | 1 | 129.8× | 0.024 | ITPA |
| Ribavirin ADME | 1 | 129.8× | 0.024 | ITPA |
| R-HSA-140877 | 1 | 119.0× | 0.024 | KLKB1 |
| Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition | 1 | 109.8× | 0.024 | ZEB1 |
| The canonical retinoid cycle in rods (twilight vision) | 1 | 64.9× | 0.038 | CYP4V2 |
| Endogenous sterols | 1 | 49.2× | 0.047 | CYP4V2 |
| Activation of Matrix Metalloproteinases | 1 | 38.6× | 0.054 | KLKB1 |
| Metabolism of nucleotides | 1 | 37.6× | 0.054 | ITPA |
| Collagen chain trimerization | 1 | 32.4× | 0.059 | COL17A1 |
| Drug ADME | 1 | 28.6× | 0.064 | ITPA |
| Assembly of collagen fibrils and other multimeric structures | 1 | 25.0× | 0.069 | COL17A1 |
| Collagen degradation | 1 | 22.0× | 0.071 | COL17A1 |
| FXIIa activates plasma kallikrein-kinin system | 1 | 21.6× | 0.071 | KLKB1 |
| Collagen biosynthesis and modifying enzymes | 1 | 21.3× | 0.071 | COL17A1 |
| Negative Regulation of CDH1 Gene Transcription | 1 | 15.0× | 0.094 | ZEB1 |
| Degradation of the extracellular matrix | 1 | 14.7× | 0.094 | KLKB1 |
| Interleukin-4 and Interleukin-13 signaling | 1 | 12.9× | 0.098 | ZEB1 |
| Amyloid fiber formation | 1 | 12.9× | 0.098 | TGFBI |
| Post-translational protein phosphorylation | 1 | 12.5× | 0.098 | SPARCL1 |
| Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 1 | 10.9× | 0.106 | COL17A1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| ITP catabolic process | 1 | 1685.2× | 0.007 | ITPA |
| deoxyribonucleoside triphosphate catabolic process | 1 | 1685.2× | 0.007 | ITPA |
| menaquinone biosynthetic process | 1 | 1685.2× | 0.007 | UBIAD1 |
| regulation of mesenchymal cell proliferation | 1 | 1685.2× | 0.007 | ZEB1 |
| vitamin K biosynthetic process | 1 | 1685.2× | 0.007 | UBIAD1 |
| borate transport | 1 | 1685.2× | 0.007 | SLC4A11 |
| epithelium migration | 1 | 1685.2× | 0.007 | GRHL2 |
| Factor XII activation | 1 | 561.7× | 0.015 | KLKB1 |
| fluid transport | 1 | 561.7× | 0.015 | SLC4A11 |
| epithelial cell morphogenesis involved in placental branching | 1 | 561.7× | 0.015 | GRHL2 |
| anterior neural tube closure | 1 | 421.3× | 0.015 | GRHL2 |
| regulation of mesenchymal stem cell differentiation | 1 | 421.3× | 0.015 | SLC4A11 |
| nucleoside triphosphate catabolic process | 1 | 337.0× | 0.015 | ITPA |
| negative regulation of endothelial cell differentiation | 1 | 337.0× | 0.015 | ZEB1 |
| regulation of smooth muscle cell differentiation | 1 | 337.0× | 0.015 | ZEB1 |
| positive regulation of fibrinolysis | 1 | 337.0× | 0.015 | KLKB1 |
| fatty acid omega-oxidation | 1 | 280.9× | 0.016 | CYP4V2 |
| hemidesmosome assembly | 1 | 240.7× | 0.016 | COL17A1 |
| regulation of T cell differentiation in thymus | 1 | 240.7× | 0.016 | ZEB1 |
| semicircular canal morphogenesis | 1 | 240.7× | 0.016 | ZEB1 |
| monoatomic ion homeostasis | 1 | 240.7× | 0.016 | SLC4A11 |
| vitamin K metabolic process | 1 | 210.7× | 0.017 | UBIAD1 |
| lung lobe morphogenesis | 1 | 210.7× | 0.017 | GRHL2 |
| cardiac ventricle morphogenesis | 1 | 187.2× | 0.018 | GRHL2 |
| lung epithelial cell differentiation | 1 | 187.2× | 0.018 | GRHL2 |
| cell junction assembly | 1 | 168.5× | 0.019 | GRHL2 |
| monoatomic anion transport | 1 | 140.4× | 0.020 | SLC4A11 |
| cellular hypotonic response | 1 | 140.4× | 0.020 | SLC4A11 |
| visual perception | 2 | 15.9× | 0.020 | TGFBI, CYP4V2 |
| plasminogen activation | 1 | 129.6× | 0.021 | KLKB1 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 9
Druggability breadth: 3 of 10 evidence-associated genes (30%) 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 |
|---|---|
| KLKB1 | BEROTRALSTAT |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| KLKB1 | 10 | 4 |
| SPARCL1 | 0 | 0 |
| ZEB1 | 0 | 0 |
| TGFBI | 0 | 0 |
| SLC4A11 | 0 | 0 |
| COL17A1 | 0 | 0 |
| CYP4V2 | 0 | 0 |
| GRHL2 | 0 | 0 |
| UBIAD1 | 0 | 0 |
| ITPA | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| BEROTRALSTAT | 4 | KLKB1 |
| DAREXABAN | 3 | KLKB1 |
| MILVEXIAN | 3 | KLKB1 |
| AVORALSTAT | 3 | KLKB1 |
| SEBETRALSTAT | 3 | KLKB1 |
| GABEXATE | 3 | KLKB1 |
| LETAXABAN | 2 | KLKB1 |
| GW813893 | 2 | KLKB1 |
| FENIRALSTAT | 2 | KLKB1 |
| BMS-962212 | 1 | KLKB1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| KLKB1 | 300 | Binding:283, ADMET:17 |
| ITPA | 8 | Binding:8 |
| TGFBI | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| CYP4V2 | 1.14.14.79 | docosahexaenoic acid omega-hydroxylase |
| ITPA | 3.6.1.66, 3.6.1.9 | XTP/dITP diphosphatase, nucleotide diphosphatase |
| KLKB1 | 3.4.21.34 | plasma kallikrein |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| KLKB1 | 300 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
10 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) |
|---|---|---|
| BEROTRALSTAT | 4 | KLKB1 |
| DAREXABAN | 3 | KLKB1 |
| MILVEXIAN | 3 | KLKB1 |
| AVORALSTAT | 3 | KLKB1 |
| SEBETRALSTAT | 3 | KLKB1 |
| GABEXATE | 3 | KLKB1 |
| LETAXABAN | 2 | KLKB1 |
| GW813893 | 2 | KLKB1 |
| FENIRALSTAT | 2 | KLKB1 |
| BMS-962212 | 1 | KLKB1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | KLKB1 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | ITPA |
| D | Druggable family + AlphaFold only, no drug | 1 | CYP4V2 |
| E | Difficult family or no structure, no drug | 7 | SPARCL1, ZEB1, TGFBI, SLC4A11, COL17A1, GRHL2, UBIAD1 |
Undrugged target profiles
9 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| SPARCL1 | 0 | — |
| ZEB1 | 0 | — |
| TGFBI | 1 | — |
| SLC4A11 | 0 | — |
| COL17A1 | 0 | — |
| CYP4V2 | 0 | — |
| GRHL2 | 0 | — |
| UBIAD1 | 0 | — |
| ITPA | 8 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 20.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 17 |
| PHASE1/PHASE2 | 1 |
| PHASE2 | 1 |
| EARLY_PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04484402 | PHASE1/PHASE2 | COMPLETED | Treatment of Patients With Inflammatory-dystrophic Diseases of the Cornea Using Autologous Stem Cells |
| NCT05279157 | PHASE2 | COMPLETED | Autologous Adipose-Derived Adult Stem Cell Implantation for Corneal Diseases (ADASCs-CT-CD) |
| NCT02932852 | EARLY_PHASE1 | UNKNOWN | Autologous Adipose-Derived Adult Stem Cell Transplantation for Corneal Diseases |
| NCT03504800 | Not specified | RECRUITING | OCT in Diagnosis of Irregular Corneas |
| NCT04129021 | Not specified | RECRUITING | High Resolution, High-speed Multimodal Ophthalmic Imaging |
| NCT05742321 | Not specified | RECRUITING | Analysis of the Genotype/Phenotype Relationship in the Fuchs’ Corneal Endothelial Dystrophy in France |
| NCT06491615 | Not specified | RECRUITING | National Ophthalmic Genotyping and Phenotyping Network (eyeGENE (Registered Trademark)), Stage 3 - Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases |
| NCT06844123 | Not specified | RECRUITING | Microsurgical Robot-assisted Corneal Transplant |
| NCT06881771 | Not specified | RECRUITING | FECD-TRACE: Fuchs’ Endothelial Corneal Dystrophy TRAjectory and Correlation With Genotype in the United Kingdom |
| NCT01084850 | Not specified | UNKNOWN | Corneal Endothelium Morphology and Central Thickness in Type II Diabetes Mellitus and Normal Subjects |
| NCT02173847 | Not specified | COMPLETED | Laser Assisted Procedures in Penetrating Keratoplasty |
| NCT02736877 | Not specified | UNKNOWN | Corneal Transplantation Guided by OCT RESCAN |
| NCT02746055 | Not specified | UNKNOWN | Study of the Prevalence of TGFBI Corneal Dystrophies |
| NCT03461991 | Not specified | COMPLETED | Correlation Between In-vivo Anatomy of Corneal Dystrophies as Assessed by High- Resolution Optical Coherence Tomography (OCT) Measurement and Histological Examination |
| NCT04164407 | Not specified | UNKNOWN | Keratoconus, Corneal Diseases and Transplant Registry |
| NCT04384094 | Not specified | UNKNOWN | Defining the Operating Parameters for a Rebound-esthesiometer |
| NCT04424550 | Not specified | COMPLETED | Comparative Results After DSAEK, UT-DSAEK and DMEK for Fuchs Endothelial Corneal Dystophy |
| NCT05891106 | Not specified | COMPLETED | AONDA Therapeutic Indication Study I |
| NCT05927740 | Not specified | COMPLETED | The Efficacy of Hyperemesis Gravidarum on Macular Thickness, Corneal Thickness and Intraocular Pressure in Pregnancy |
| NCT05956535 | Not specified | COMPLETED | Air Optix® Night and Day® Aqua Therapeutic Wear |