KRT6A
protein-codingkeratin 6A, the group of Keratins, type II
Gene summary
The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. As many as six of this type II cytokeratin (KRT6) have been identified; the multiplicity of the genes is attributed to successive gene duplication events. The genes are expressed with family members KRT16 and/or KRT17 in the filiform papillae of the tongue, the stratified epithelial lining of oral mucosa and esophagus, the outer root sheath of hair follicles, and the glandular epithelia. This KRT6 gene in particular encodes the most abundant isoform. Mutations in these genes have been associated with pachyonychia congenita. In addition, peptides from the C-terminal region of the protein have antimicrobial activity against bacterial pathogens. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Oct 2014]
- KRT6C
- KRT6D
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014324
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0014324
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0016471
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0014324
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Dermatologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KRT6A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005554.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 40 | 8 | 48 | |||
| missense | 13 | 8 | 135 | 16 | 10 | 182 |
| nonsense | 1 | 2 | 3 | |||
| start loss | 0 | |||||
| frameshift | 2 | 2 | 4 | |||
| splice donor/acceptor (+/-2bp) | 4 | 4 | 8 | |||
| Total | 13 | 15 | 143 | 56 | 18 | 245 |
Highest pathogenic variant AF is 0.0000068158047
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005545.1 | 9 | MANE Select | |
| Ensembl | ENSP00000369317.3 | 9 | MANE Select | |
| Ensembl | ENSP00000811066.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ectoderm Differentiation
- Keratinization
- Developmental Biology
- EGFR1
Biological Process
- negative regulation of cytolysis by symbiont of host cells
- morphogenesis of an epithelium
- cytoskeleton organization
- positive regulation of cell population proliferation
- cell differentiation
Molecular Function
- structural constituent of cytoskeleton
- protein binding
Cellular Component
- nucleus
- cytosol
- membrane
- keratin filament
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000330722
- Coding exons
- 9
- Length
- 6084
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125748
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.948 | 367 | 319 | 1.15 | 0.0000203 | 3663 |
| Missense (PolyPhen) | 119 | 101.99 | 1.1668 | 1396 | ||
| Synonymous | -3.34 | 183 | 134 | 1.37 | 0.00000852 | 1165 |
| Loss of Function | 2.09 | 10 | 20.1 | 0.497 | 8.97e-7 | 261 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Epidermis-specific type I keratin involved in wound healing. Involved in the activation of follicular keratinocytes after wounding, while it does not play a major role in keratinocyte proliferation or migration. Participates in the regulation of epithelial migration by inhibiting the activity of SRC during wound repair. {ECO:0000250|UniProtKB:P50446}.;
Recessive Scores
- pRec
- 0.273
Intolerance Scores
- LoFtool
- 0.0244
- RVIS EVS
- 0.71
- RVIS percentile EVS
- 85.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.920
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |