KRT14

keratin 14, the group of Keratins, type I

Basic information

Region (hg38): 17:41582279-41586895

Previous symbols: [ "EBS3", "EBS4" ]

Links

ENSG00000186847NCBI:3861OMIM:148066HGNC:6416Uniprot:P02533AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
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, intermediateAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDental; Dermatologic13149726; 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 ClinVar and linked to the KRT14 gene.

  • 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
24
clinvar
7
clinvar
32
missense
28
clinvar
16
clinvar
99
clinvar
8
clinvar
2
clinvar
153
nonsense
9
clinvar
2
clinvar
2
clinvar
13
start loss
1
1
frameshift
8
clinvar
3
clinvar
7
clinvar
18
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
4
clinvar
6
Total 46 22 114 32 9

Highest pathogenic variant AF is 0.0000886237

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KRT14protein_codingprotein_codingENST00000167586 84643
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0002030.9791256510971257480.000386
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.8352502900.8620.00002013066
Missense in Polyphen6174.7660.815881051
Synonymous-1.341421231.150.00000890934
Loss of Function2.06918.60.4858.24e-7226

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.003290.00292
Ashkenazi Jewish0.0003970.000298
East Asian0.0001630.000163
Finnish0.000.00
European (Non-Finnish)0.0002510.000202
Middle Eastern0.0001630.000163
South Asian0.0006860.000392
Other0.001790.000978

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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