Cornea plana 2

disease
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Also known as CNA2cornea plana caused by mutation in KERAcornea plana type 2KERA cornea plana

Summary

Cornea plana 2 (MONDO:0009014) is a disease caused by KERA (GenCC Strong), with 1 cohort gene.

At a glance

  • Causal gene: KERA (GenCC Strong)
  • Cohort genes: 1
  • ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namecornea plana 2
Mondo IDMONDO:0009014
MeSHC565677
OMIM217300
UMLSC1857574
MedGen346616
GARD0018050
Is cancer (heuristic)no

Also known as: CNA2 · cornea plana 2 · cornea plana caused by mutation in KERA · cornea plana type 2 · KERA cornea plana

Data availability: 15 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital regioneye disordercorneal disordercornea planacornea plana 2

Related subtypes (1): cornea plana 1, autosomal dominant

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

15 retrieved; paginated sample, class counts are floors:

6 pathogenic, 4 likely pathogenic, 3 uncertain significance, 1 benign, 1 conflicting classifications of pathogenicity

ClinVarVariant (HGVS)GeneClassificationReview
225521NM_007035.4(KERA):c.320T>G (p.Ile107Arg)KERAPathogenicno assertion criteria provided
56550NM_007035.4(KERA):c.835C>T (p.Arg279Ter)KERAPathogeniccriteria provided, multiple submitters, no conflicts
6519NM_007035.4(KERA):c.740A>G (p.Asn247Ser)KERAPathogeniccriteria provided, multiple submitters, no conflicts
6520NM_007035.4(KERA):c.520C>T (p.Gln174Ter)KERAPathogenicno assertion criteria provided
6521NM_007035.4(KERA):c.644C>A (p.Thr215Lys)KERAPathogenicno assertion criteria provided
6522NM_007035.4(KERA):c.937C>T (p.Arg313Ter)KERAPathogeniccriteria provided, single submitter
3779786NM_007035.4(KERA):c.242A>G (p.Asn81Ser)KERALikely pathogeniccriteria provided, single submitter
4087749NM_007035.4(KERA):c.38_41del (p.Leu12_Phe13insTer)KERALikely pathogeniccriteria provided, single submitter
4531440NM_007035.4(KERA):c.528C>G (p.Asn176Lys)KERALikely pathogeniccriteria provided, single submitter
56549NM_007035.4(KERA):c.391A>G (p.Asn131Asp)KERALikely pathogenicno assertion criteria provided
56548NM_007035.4(KERA):c.1026del (p.Cys343fs)KERAConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1687461NM_007035.4(KERA):c.623C>G (p.Pro208Arg)KERAUncertain significancecriteria provided, single submitter
2628327NM_007035.4(KERA):c.331G>A (p.Gly111Arg)KERAUncertain significancecriteria provided, single submitter
2628328NM_007035.4(KERA):c.229T>C (p.Tyr77His)KERAUncertain significancecriteria provided, single submitter
1174695NM_007035.4(KERA):c.69G>A (p.Val23=)KERABenigncriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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.

GeneClassificationInheritanceDiseaseRecords
KERADefinitiveAutosomal recessivecornea plana5

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
KERAOrphanet:53691Congenital cornea plana

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
KERAHGNC:6309ENSG00000139330O60938Keratocangencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
KERAKeratocanMay be important in developing and maintaining corneal transparency and for the structure of the stromal matrix.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Other/Unknown11.8×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
KERAOther/UnknownnoLRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

TissueCohort genes
calcaneal tendon1
male germ line stem cell (sensu Vertebrata) in testis1
tendon1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
KERA85tissue_specificyescalcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
KERA1,184

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
KERAO6093887.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Defective CHST6 causes MCDC111427.5×0.003KERA
Defective ST3GAL3 causes MCT12 and EIEE1511427.5×0.003KERA
Defective B4GALT1 causes B4GALT1-CDG (CDG-2d)11427.5×0.003KERA
Diseases associated with glycosaminoglycan metabolism1761.3×0.004KERA
Keratan sulfate degradation1713.8×0.004KERA
Keratan sulfate/keratin metabolism1496.5×0.004KERA
Keratan sulfate biosynthesis1380.7×0.005KERA
Glycosaminoglycan metabolism1219.6×0.007KERA
Diseases of glycosylation1131.3×0.011KERA
Metabolism of carbohydrates and carbohydrate derivatives1120.2×0.011KERA
Diseases of metabolism180.4×0.015KERA
Disease113.1×0.083KERA
Metabolism111.6×0.086KERA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
cornea development in camera-type eye11296.3×0.002KERA
visual perception179.5×0.013KERA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
KERA00

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1KERA

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
KERA0

Clinical trials & evidence

Clinical trials

Clinical trials: 0.