KRT12
Chr 17ADkeratin 12
Also known as: K12, MECD1
KRT12 encodes the type I intermediate filament chain keratin 12, expressed in corneal epithelia. Mutations in this gene lead to Meesmann corneal dystrophy. [provided by RefSeq, Jul 2008]
Primary Disease Associations & Inheritance
Meesmann corneal dystrophy 1MIM #122100
AD
UniProtCorneal dystrophy, Meesmann 1
Clinical Summary— KRT12
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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
17 Pathogenic / Likely Pathogenic· 56 VUS of 98 total submissions
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.32LOEUF
pLI 0.000
Z-score 0.35
OE 0.92 (0.66–1.32)
Highly tolerant — LoF variants common in population
Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.57Z-score
OE missense 0.91 (0.82–1.00)
266 obs / 293.5 exp
Mild missense constraint
Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.92 (0.66–1.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.82–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 22 / 23.8Missense obs/exp: 266 / 293.5Syn Z: 1.36
ClinVar Variant Classifications
98 submitted variants in ClinVar
Classification Summary
Pathogenic15
Likely Pathogenic2
VUS56
Likely Benign10
Benign10
Conflicting5
15
Pathogenic
2
Likely Pathogenic
56
VUS
10
Likely Benign
10
Benign
5
Conflicting
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 8 | 7 | 0 | 15 |
Likely Pathogenic | 0 | 2 | 0 | 0 | 2 |
VUS | 2 | 50 | 4 | 0 | 56 |
Likely Benign | 0 | 5 | 1 | 4 | 10 |
Benign | 0 | 6 | 1 | 3 | 10 |
Conflicting | — | 5 | |||
| Total | 2 | 71 | 13 | 7 | 98 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KRT12 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
KRT12-related Meesmann corneal dystrophy
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
KERATIN 12, TYPE I; KRT12
MIM #601687 · *
Autosomal dominant
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healing.
Li Y et al.·Stem Cell Res Ther
2024
Identification of presumed pathogenic KRT3 and KRT12 gene mutations associated with Meesmann corneal dystrophy.
Chen JL et al.·Mol Vis
2015Case report
Mutation analysis of TGFBI and KRT12 in a case of concomitant keratoconus and granular corneal dystrophy.
Du X et al.·Graefes Arch Clin Exp Ophthalmol
2017
Meesmann Corneal Dystrophy with Epithelial Basement Membrane Abnormalities: Clinical and Genetic Analysis of Two Families with Novel and Known Mutations in KRT3 and KRT12.
Charoenrook V et al.·Int J Mol Sci
2026
Epithelial Cell-Derived Extracellular Vesicles Trigger the Differentiation of Two Epithelial Cell Lines.
Ramos T et al.·Int J Mol Sci
2022
A novel mutation in KRT12 associated with Meesmann's epithelial corneal dystrophy.
Irvine AD et al.·Br J Ophthalmol
2002
[Analysis of mutation in KRT12 gene in a Chinese family with Meesmann's corneal dystrophy].
Wang LJ et al.·Zhonghua Yan Ke Za Zhi
2007
FoxC1 activates limbal epithelial stem cells following corneal epithelial debridement.
Yang W et al.·Exp Eye Res
2023
Transforming growth factor beta receptor 2 (Tgfbr2) deficiency in keratocytes results in corneal ectasia.
Wang YC et al.·Ocul Surf
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Identification of a Novel Missense KRT12 Mutation in a Vietnamese Family with Meesmann Corneal Dystrophy.
Dong PN et al.·Case Rep Ophthalmol
2020Open Access
In vivo histology and p.L132V mutation in KRT12 gene in Japanese patients with Meesmann corneal dystrophy.
Nishino T et al.·Jpn J Ophthalmol
2019Cohort
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
A Keratin 12 Expression-Based Analysis of Stem-Precursor Cells and Differentiation in the Limbal-Corneal Epithelium Using Single-Cell RNA-Seq Data
Wolosin JM·Biology (Basel)
2024
Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?
Latta L et al.·Biomolecules
2021
Single nuclei transcriptomics of the in situ human limbal stem cell niche
Davidson KC et al.·Sci Rep
2024
Identification of pathogenic variants in six Chinese families with keratoconus of autosomal dominant inheritance: pathogenicity analysis and variable phenotype
Huang X et al.·Int Ophthalmol
2025
MYEOV Is a Novel Marker of Differentiated Corneal Epithelium.
Fukuda Y et al.·Invest Ophthalmol Vis Sci
2025
Topical mutant allele-specific siRNA delivery for treatment of Meesmann epithelial corneal dystrophy and elucidation of disease biomarkers.
McLain A et al.·J Control Release
2025
A novel variant in the keratin 12 gene in a four-generation Chinese family with high myopia.
Lin Q et al.·Eye (Lond)
2024
Induction of Corneal Epithelial Differentiation of Induced Pluripotent and Orbital Fat-Derived Stem Cells Seeded on Decellularized Human Corneas.
da Mata Martins TM et al.·Stem Cell Rev Rep
2022
Top 8 full-text resultsSearch PubTator3 ↗
External Resources
Links to major genomics databases and tools