KRT14
keratin 14, the group of Keratins, type I
Basic information
Region (hg38): 17:41582279-41586895
Previous symbols: [ "EBS3", "EBS4" ]
Links
Phenotypes
GenCC
Source:
- Naegeli-Franceschetti-Jadassohn syndrome (Strong), mode of inheritance: AD
- epidermolysis bullosa simplex 1C, localized (Strong), mode of inheritance: AD
- dermatopathia pigmentosa reticularis (Strong), mode of inheritance: AD
- Naegeli-Franceschetti-Jadassohn syndrome (Strong), mode of inheritance: AD
- epidermolysis bullosa simplex 1B, generalized intermediate (Strong), mode of inheritance: AD
- epidermolysis bullosa simplex 1A, generalized severe (Strong), mode of inheritance: AD
- epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive (Strong), mode of inheritance: AR
- epidermolysis bullosa simplex 1A, generalized severe (Definitive), mode of inheritance: AD
- Naegeli-Franceschetti-Jadassohn syndrome (Limited), mode of inheritance: AD
- Naegeli-Franceschetti-Jadassohn syndrome (Supportive), mode of inheritance: AD
- epidermolysis bullosa simplex 1A, generalized severe (Supportive), mode of inheritance: AD
- epidermolysis bullosa simplex 2F, with mottled pigmentation (Supportive), mode of inheritance: AD
- epidermolysis bullosa simplex 1B, generalized intermediate (Supportive), mode of inheritance: AD
- epidermolysis bullosa simplex 1C, localized (Supportive), mode of inheritance: AD
- dermatopathia pigmentosa reticularis (Supportive), mode of inheritance: AD
- epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive (Supportive), mode of inheritance: AR
- epidermolysis bullosa simplex 1B, generalized intermediate (Strong), mode of inheritance: AD
- epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive (Strong), mode of inheritance: AR
- epidermolysis bullosa simplex (Definitive), mode of inheritance: AR
- Naegeli-Franceschetti-Jadassohn syndrome (Definitive), mode of inheritance: AD
- epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Naegeli-Franceschetti-Jadassohn syndrome; Dermatopathia pigmentosa reticularis; Epidermolysis bullosa simplex, Weber-Cockayne type; Epidermolysis bullosa simplex 1, severe; Naegeli-Franceschetti-Jadassohn syndrome; Epidermolysis bullosa simplex, autosomal recessive 1; Epidermolysis bullosa simplex 1A, generalized severe; Epidermolysis bullosa simplex 1B, generalized intermediate; Epidermolysis bullosa simplex 1C, localized; Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive; Epidermolysis bullosa simplex 3, intermediate | AD/AR | General | 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 | Dental; Dermatologic | 13149726; 939040; 1717157; 1303619; 7506606; 7526933; 7682883; 8496458; 7682695; 7525408; 7525407; 16098032; 16960809; 20180888; 20199538; 20301543; 21375516; 21593775; 21623745; 21818518; 21967011; 32017015 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (204 variants)
- Inborn_genetic_diseases (25 variants)
- Epidermolysis_bullosa_simplex_1A,_generalized_severe (17 variants)
- Epidermolysis_bullosa_simplex_1D,_generalized,_intermediate_or_severe,_autosomal_recessive (14 variants)
- KRT14-related_disorder (14 variants)
- Epidermolysis_bullosa_simplex,_Koebner_type (13 variants)
- Epidermolysis_bullosa_simplex_1C,_localized (12 variants)
- Epidermolysis_bullosa_simplex (12 variants)
- Dermatopathia_pigmentosa_reticularis (10 variants)
- Naegeli-Franceschetti-Jadassohn_syndrome (7 variants)
- not_specified (4 variants)
- Skin_fragility_with_non-scarring_blistering (1 variants)
- Palmoplantar_blistering (1 variants)
- Abnormality_of_the_skin (1 variants)
- Epidermolysis_bullosa (1 variants)
- EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
- HP:0000750%3B_HP:0001263 (1 variants)
- Sj�gren-Larsson_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT14 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000526.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 24 | 32 | ||||
| missense | 28 | 16 | 99 | 153 | ||
| nonsense | 13 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 18 | |||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| Total | 46 | 22 | 114 | 32 | 9 |
Highest pathogenic variant AF is 0.0000886237
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KRT14 | protein_coding | protein_coding | ENST00000167586 | 8 | 4643 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000203 | 0.979 | 125651 | 0 | 97 | 125748 | 0.000386 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.835 | 250 | 290 | 0.862 | 0.0000201 | 3066 |
| Missense in Polyphen | 61 | 74.766 | 0.81588 | 1051 | ||
| Synonymous | -1.34 | 142 | 123 | 1.15 | 0.00000890 | 934 |
| Loss of Function | 2.06 | 9 | 18.6 | 0.485 | 8.24e-7 | 226 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00329 | 0.00292 |
| Ashkenazi Jewish | 0.000397 | 0.000298 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000251 | 0.000202 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.000686 | 0.000392 |
| Other | 0.00179 | 0.000978 |
dbNSFP
Source:
- Function
- FUNCTION: The nonhelical tail domain is involved in promoting KRT5-KRT14 filaments to self-organize into large bundles and enhances the mechanical properties involved in resilience of keratin intermediate filaments in vitro. {ECO:0000269|PubMed:11724817}.;
- Disease
- DISEASE: Epidermolysis bullosa simplex, Dowling-Meara type (DM- EBS) [MIM:131760]: A severe form of intraepidermal epidermolysis bullosa characterized by generalized herpetiform blistering, milia formation, dystrophic nails, and mucous membrane involvement. {ECO:0000269|PubMed:10583131, ECO:0000269|PubMed:10730767, ECO:0000269|PubMed:10733662, ECO:0000269|PubMed:10820403, ECO:0000269|PubMed:11710919, ECO:0000269|PubMed:12603865, ECO:0000269|PubMed:12655565, ECO:0000269|PubMed:12707098, ECO:0000269|PubMed:14987259, ECO:0000269|PubMed:16786515, ECO:0000269|PubMed:16882168, ECO:0000269|PubMed:1717157, ECO:0000269|PubMed:7561171, ECO:0000269|PubMed:7688405, ECO:0000269|PubMed:8601736, ECO:0000269|PubMed:9804355, ECO:0000269|PubMed:9989794, ECO:0000269|Ref.31}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa simplex, Weber-Cockayne type (WC- EBS) [MIM:131800]: A form of intraepidermal epidermolysis bullosa characterized by blistering limited to palmar and plantar areas of the skin. {ECO:0000269|PubMed:10733662, ECO:0000269|PubMed:12603865, ECO:0000269|PubMed:12655565, ECO:0000269|PubMed:12707098, ECO:0000269|PubMed:14987259, ECO:0000269|PubMed:16786515, ECO:0000269|PubMed:16882168, ECO:0000269|PubMed:7506097, ECO:0000269|PubMed:7506606, ECO:0000269|PubMed:7561171, ECO:0000269|PubMed:9284105, ECO:0000269|PubMed:9804357, ECO:0000269|PubMed:9989794}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa simplex, Koebner type (K-EBS) [MIM:131900]: A form of intraepidermal epidermolysis bullosa characterized by generalized skin blistering. The phenotype is not fundamentally distinct from the Dowling-Meara type, although it is less severe. {ECO:0000269|PubMed:10733662, ECO:0000269|PubMed:10820403, ECO:0000269|PubMed:11710919, ECO:0000269|PubMed:16786515, ECO:0000269|PubMed:1720261, ECO:0000269|PubMed:7526926, ECO:0000269|PubMed:7682883, ECO:0000269|PubMed:9989794, ECO:0000269|Ref.10, ECO:0000269|Ref.31}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa simplex, autosomal recessive 1 (EBSB1) [MIM:601001]: A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering and cleavage within basal keratinocytes, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. {ECO:0000269|PubMed:7526933}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Naegeli-Franceschetti-Jadassohn syndrome (NFJS) [MIM:161000]: A rare autosomal dominant form of ectodermal dysplasia. The cardinal features are absence of dermatoglyphics (fingerprints), reticular cutaneous hyperpigmentation (starting at about the age of 2 years without a preceding inflammatory stage), palmoplantar keratoderma, hypohidrosis with diminished sweat gland function and discomfort provoked by heat, nail dystrophy, and tooth enamel defects. {ECO:0000269|PubMed:16960809}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dermatopathia pigmentosa reticularis (DPR) [MIM:125595]: A rare ectodermal dysplasia characterized by lifelong persistent reticulate hyperpigmentation, non-cicatricial alopecia, and nail dystrophy. Variable features include adermatoglyphia, hypohidrosis or hyperhidrosis, and palmoplantar hyperkeratosis. {ECO:0000269|PubMed:16960809}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Estrogen signaling pathway - Homo sapiens (human);Corticotropin-releasing hormone signaling pathway;Keratinization;Developmental Biology;Glucocorticoid receptor regulatory network;Validated transcriptional targets of deltaNp63 isoforms
(Consensus)
Intolerance Scores
- loftool
- 0.0518
- rvis_EVS
- -0.07
- rvis_percentile_EVS
- 48.69
Haploinsufficiency Scores
- pHI
- 0.326
- hipred
- Y
- hipred_score
- 0.626
- ghis
- 0.430
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.625
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Krt14
- Phenotype
- neoplasm; pigmentation phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; respiratory system phenotype; immune system phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; digestive/alimentary phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype;
Gene ontology
- Biological process
- aging;epidermis development;response to zinc ion;response to ionizing radiation;keratinization;hemidesmosome assembly;hair cycle;intermediate filament bundle assembly;cornification
- Cellular component
- nucleus;cytoplasm;cytosol;intermediate filament;keratin filament;basal part of cell;extracellular exosome;cell periphery
- Molecular function
- structural constituent of cytoskeleton;protein binding;keratin filament binding