KRT9
Chr 17ADkeratin 9
Also known as: CK-9, EPPK, K9
This gene encodes the type I keratin 9, an intermediate filament chain expressed only in the terminally differentiated epidermis of palms and soles. Mutations in this gene cause epidermolytic palmoplantar keratoderma. [provided by RefSeq, Jul 2008]
Primary Disease Associations & Inheritance
Palmoplantar keratoderma, epidermolytic, 1MIM #144200
AD
Clinical Summary— KRT9
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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
24 Pathogenic / Likely Pathogenic· 131 VUS of 233 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.
0.92LOEUF
pLI 0.000
Z-score 1.84
OE 0.58 (0.38–0.92)
Typical tolerance to LoF variation
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.
0.20Z-score
OE missense 0.97 (0.89–1.06)
338 obs / 348.4 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.0.58 (0.38–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.89–1.06)
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.1.03
0≤1.21.6
LoF obs/exp: 13 / 22.4Missense obs/exp: 338 / 348.4Syn Z: -0.29
ClinVar Variant Classifications
233 submitted variants in ClinVar
Classification Summary
Pathogenic17
Likely Pathogenic7
VUS131
Likely Benign35
Benign24
Conflicting19
17
Pathogenic
7
Likely Pathogenic
131
VUS
35
Likely Benign
24
Benign
19
Conflicting
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 10 | 7 | 0 | 17 |
Likely Pathogenic | 0 | 7 | 0 | 0 | 7 |
VUS | 1 | 104 | 22 | 4 | 131 |
Likely Benign | 0 | 7 | 6 | 22 | 35 |
Benign | 0 | 1 | 17 | 6 | 24 |
Conflicting | — | 19 | |||
| Total | 1 | 129 | 52 | 32 | 233 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KRT9 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
KRT9-related palmoplantar keratoderma Vorner-Unna-Thost (epidermolytic)
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
KERATIN 9, TYPE I; KRT9
MIM #607606 · *
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
Exome sequencing identifies a KRT9 pathogenic variant in a Chinese pedigree with epidermolytic palmoplantar keratoderma.
Li C et al.·Mol Genet Genomic Med
2019Case report
Clinical and Genetic Findings in Patients With Palmoplantar Keratoderma.
Gram SB et al.·JAMA Dermatol
2025Cohort
Identification of a KRT9 gene variant and preimplantation genetic diagnosis in a Chinese family with KRT9-palmoplantar epidermal differentiation disorder.
Lin D et al.·Hereditas
2025
Analysis of the KRT9 gene in a Mexican family with epidermolytic palmoplantar keratoderma.
Lopez-Valdez J et al.·Pediatr Dermatol
2013
Salivary annexin A1: A candidate biomarker for periodontitis.
Casarin RCV et al.·J Clin Periodontol
2023
Hereditary palmoplantar keratoderma - phenotypes and mutations in 64 patients.
Harjama L et al.·J Eur Acad Dermatol Venereol
2021Cohort
The most common mutation of KRT9, c.C487T (p.R163W), in epidermolytic palmoplantar keratoderma in two large Chinese pedigrees.
Liu WT et al.·Anat Rec (Hoboken)
2012
Protein expression of prognostic genes in primary melanoma and benign nevi.
Gambichler T et al.·J Cancer Res Clin Oncol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
KRT9 is required for GBP5 suppression of human respiratory syncytial virus.
Qu X et al.·J Virol
2025Open Access
A missense mutation (rs209302038) of KRT9 gene associated with heat stress in Chinese cattle.
Yang X et al.·Anim Biotechnol
2023
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
KRT9 hotspot mutation disrupts keratin organization and impairs Nrf2-mediated oxidative stress regulation.
Cao Y et al.·J Invest Dermatol
2025
An in-frame 18 bp deletion in linker domain L1 of KRT9 identified in a Japanese patient with epidermolytic palmoplantar keratoderma.
Omi M et al.·J Dermatol
2023
Under Pressure: A unique mechanoresponsive mechanism of body site-specific keratin regulation in palmoplantar epidermis.
Steiner SN et al.·bioRxiv
2025Functional
Cohen syndrome combined with novel KRT9 gene mutation leading to epidermolytic palmoplantar keratoderma: A rare case report.
Shu Y et al.·Asian J Surg
2023Case report
Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: A systematic review Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: a systematic review
Rezaeeyan H et al.·Immun Inflamm Dis
2023Review
Top 5 full-text resultsSearch PubTator3 ↗
External Resources
Links to major genomics databases and tools