corneal dystrophy, Meesmann, 2

disease
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Also known as MECD2

Summary

corneal dystrophy, Meesmann, 2 (MONDO:0032904) is a disease caused by KRT3 (GenCC Strong), with 1 cohort gene.

At a glance

  • Causal gene: KRT3 (GenCC Strong)
  • Cohort genes: 1
  • ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namecorneal dystrophy, Meesmann, 2
Mondo IDMONDO:0032904
OMIM618767
DOIDDOID:0080671
UMLSC5231495
MedGen1684798
GARD0025769
Is cancer (heuristic)no

Also known as: MECD2

Data availability: 8 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital regioneye disordercorneal disordercorneal dystrophy › epithelial and subepithelial corneal dystrophy › Meesmann corneal dystrophycorneal dystrophy, Meesmann, 2

Related subtypes (1): corneal dystrophy, Meesmann, 1

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

8 retrieved; paginated sample, class counts are floors:

3 pathogenic, 3 uncertain significance, 2 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
14632NM_057088.3(KRT3):c.1525G>A (p.Glu509Lys)KRT3Pathogeniccriteria provided, single submitter
66748NM_057088.3(KRT3):c.1493A>T (p.Glu498Val)KRT3Pathogenicno assertion criteria provided
66749NM_057088.3(KRT3):c.1508G>C (p.Arg503Pro)KRT3Pathogenicno assertion criteria provided
2628033NM_057088.3(KRT3):c.1527G>T (p.Glu509Asp)KRT3Likely pathogeniccriteria provided, single submitter
1213856NM_057088.3(KRT3):c.1492G>A (p.Glu498Lys)LOC126861527Likely pathogeniccriteria provided, single submitter
3289405NM_057088.3(KRT3):c.836T>C (p.Met279Thr)KRT3Uncertain significancecriteria provided, multiple submitters, no conflicts
3606754NM_057088.3(KRT3):c.332G>A (p.Gly111Asp)KRT3Uncertain significancecriteria provided, multiple submitters, no conflicts
3891526NM_057088.3(KRT3):c.398G>A (p.Gly133Glu)KRT3Uncertain significancecriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
KRT3StrongAutosomal dominantcorneal dystrophy, Meesmann, 14

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
KRT3Orphanet:98954Meesmann corneal dystrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
KRT3HGNC:6440ENSG00000186442P12035Keratin, type II cytoskeletal 3gencc,clinvar

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)
KRT3Other/UnknownnoKeratin_II, IF_conserved, Keratin_2_head

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

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
gingiva1
gingival epithelium1
tendon of biceps brachii1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
KRT335tissue_specificmarkergingiva, gingival epithelium, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
KRT31,241

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
KRT3P1203566.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Formation of the cornified envelope187.8×0.027KRT3
Keratinization155.7×0.027KRT3
Developmental Biology114.5×0.069KRT3

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
intermediate filament cytoskeleton organization1936.2×0.004KRT3
intermediate filament organization1240.7×0.006KRT3
keratinization1234.1×0.006KRT3
epithelial cell differentiation1175.5×0.006KRT3

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
KRT300

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 drug1KRT3

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
KRT30

Clinical trials & evidence

Clinical trials

Clinical trials: 0.