corneal dystrophy, Meesmann, 1

Summary

corneal dystrophy, Meesmann, 1 (MONDO:0020791) is a disease caused by variants in KRT12 and KRT3, with 2 cohort genes.

At a glance

• Causal genes: KRT12 (GenCC Definitive), KRT3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	corneal dystrophy, Meesmann, 1
Mondo ID	MONDO:0020791
OMIM	122100
DOID	DOID:0080670
UMLS	C5231499
MedGen	1684668
GARD	0025252
Is cancer (heuristic)	no

Also known as: MECD1

Data availability: 15 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › corneal disorder › corneal dystrophy › epithelial and subepithelial corneal dystrophy › Meesmann corneal dystrophy › corneal dystrophy, Meesmann, 1

Related subtypes (1): corneal dystrophy, Meesmann, 2

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:

8 pathogenic, 4 uncertain significance, 2 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
254686	NM_000223.4(KRT12):c.395T>C (p.Leu132Pro)	KRT12	Pathogenic	no assertion criteria provided
7921	NM_000223.4(KRT12):c.404G>C (p.Arg135Thr)	KRT12	Pathogenic	no assertion criteria provided
7922	NM_000223.4(KRT12):c.427G>C (p.Val143Leu)	KRT12	Pathogenic	no assertion criteria provided
7923	NM_000223.4(KRT12):c.403A>G (p.Arg135Gly)	KRT12	Pathogenic	no assertion criteria provided
7924	NM_000223.4(KRT12):c.404G>T (p.Arg135Ile)	KRT12	Pathogenic	no assertion criteria provided
7925	NM_000223.4(KRT12):c.1285T>G (p.Tyr429Asp)	KRT12	Pathogenic	no assertion criteria provided
7926	NM_000223.4(KRT12):c.419T>G (p.Leu140Arg)	KRT12	Pathogenic	no assertion criteria provided
7927	NM_000223.4(KRT12):c.386T>C (p.Met129Thr)	KRT12	Pathogenic	criteria provided, single submitter
2628021	NM_000223.4(KRT12):c.1181T>C (p.Leu394Pro)	KRT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2672273	NM_000223.4(KRT12):c.523G>A (p.Asp175Asn)	KRT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1300203	NM_000223.4(KRT12):c.1148_1159del (p.Gln383_Val387delinsLeu)	KRT12	Uncertain significance	criteria provided, single submitter
1300204	NM_000223.4(KRT12):c.1151T>C (p.Leu384Pro)	KRT12	Uncertain significance	criteria provided, single submitter
2433266	NM_000223.4(KRT12):c.988G>T (p.Glu330Ter)	KRT12	Uncertain significance	criteria provided, single submitter
4292051	NM_000223.4(KRT12):c.559A>G (p.Arg187Gly)	KRT12	Uncertain significance	criteria provided, single submitter
66128	NM_000223.4(KRT12):c.43C>T (p.Pro15Ser)	KRT12	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
KRT12	Definitive	Autosomal dominant	corneal dystrophy, Meesmann, 1	4
KRT3	Strong	Autosomal dominant	corneal dystrophy, Meesmann, 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRT12	Orphanet:98954	Meesmann corneal dystrophy
KRT3	Orphanet:98954	Meesmann corneal dystrophy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KRT12	HGNC:6414	ENSG00000187242	Q99456	Keratin, type I cytoskeletal 12	gencc,clinvar
KRT3	HGNC:6440	ENSG00000186442	P12035	Keratin, type II cytoskeletal 3	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KRT12	Keratin, type I cytoskeletal 12	Involved in corneal epithelium organization, integrity and corneal keratin expression.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KRT12	Other/Unknown	no		Keratin_I, IF_conserved, IF_rod_dom
KRT3	Other/Unknown	no		Keratin_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)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
mucosa of transverse colon	1
primordial germ cell in gonad	1
gingiva	1
gingival epithelium	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRT12	83	tissue_specific	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, mucosa of transverse colon
KRT3	35	tissue_specific	marker	gingiva, gingival epithelium, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT3	1,241
KRT12	876

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRT12	Q99456	74.57
KRT3	P12035	66.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the cornified envelope	2	87.8×	4e-04	KRT12, KRT3
Keratinization	2	55.7×	5e-04	KRT12, KRT3
Developmental Biology	2	14.5×	0.005	KRT12, KRT3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intermediate filament organization	2	240.7×	1e-04	KRT12, KRT3
epithelial cell differentiation	2	175.5×	1e-04	KRT12, KRT3
cornea development in camera-type eye	1	648.1×	0.004	KRT12
intermediate filament cytoskeleton organization	1	468.1×	0.004	KRT3
morphogenesis of an epithelium	1	172.0×	0.008	KRT12
keratinization	1	117.0×	0.010	KRT3
visual perception	1	39.8×	0.025	KRT12

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KRT12	0	0
KRT3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	2	KRT12, KRT3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KRT12	0	—
KRT3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.