GeneBe

KRT14

protein-coding

keratin 14, the group of Keratins, type I

Gene summary

This gene encodes a member of the keratin family, the most diverse group of intermediate filaments. This gene product, a type I keratin, is usually found as a heterotetramer with two keratin 5 molecules, a type II keratin. Together they form the cytoskeleton of epithelial cells. Mutations in the genes for these keratins are associated with epidermolysis bullosa simplex. At least one pseudogene has been identified at 17p12-p11. [provided by RefSeq, Jul 2008]

Previous symbols:
  • EBS3
  • EBS4

MANE transcript

NM_000526.5

Inheritance

AD, AR

ClinVar variants

P:81U:140B:45

Top phenotype

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

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr17:41,582,279-41,586,895

External References & Databases

Ensembl (ENSG00000186847)NCBI Gene (3861)OMIM (148066)HGNC:6416GenCCUniProt (P02533)AlphaFoldClinVar (KRT14)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~4.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

dermatopathia pigmentosa reticularisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007445

Submitter: Genomics England PanelApp

Naegeli-Franceschetti-Jadassohn syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008059

Submitter: Genomics England PanelApp

epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010976

Submitter: Genomics England PanelApp

epidermolysis bullosa simplexDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017610

Submitter: G2P

Naegeli-Franceschetti-Jadassohn syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008059

Submitter: G2P

epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010976

Submitter: Labcorp Genetics (formerly Invitae)

epidermolysis bullosa simplex 1B, generalized intermediateSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007554

Submitter: Labcorp Genetics (formerly Invitae)

epidermolysis bullosaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0006541

Submitter: PanelApp Australia

epidermolysis bullosa simplex 1B, generalized intermediateSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007554

Submitter: Genomics England PanelApp

epidermolysis bullosa simplex 1A, generalized severeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007550

Submitter: Genomics England PanelApp

epidermolysis bullosa simplex 1C, localizedSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007551

Submitter: Orphanet

epidermolysis bullosa simplex 2F, with mottled pigmentationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007556

Submitter: Orphanet

Naegeli-Franceschetti-Jadassohn syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008059

Submitter: Orphanet

epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessiveDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010976

Submitter: Ambry Genetics

dermatopathia pigmentosa reticularisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007445

Submitter: PanelApp Australia

Naegeli-Franceschetti-Jadassohn syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008059

Submitter: PanelApp Australia

Naegeli-Franceschetti-Jadassohn syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008059

Submitter: Ambry Genetics

epidermolysis bullosa simplex 1A, generalized severeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007550

Submitter: Ambry Genetics

epidermolysis bullosa simplex 1C, localizedSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007551

Submitter: Genomics England PanelApp

epidermolysis bullosaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0006541

Submitter: PanelApp Australia

epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010976

Submitter: Orphanet

epidermolysis bullosa simplex 1A, generalized severeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007550

Submitter: Orphanet

Naegeli-Franceschetti-Jadassohn syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008059

Submitter: Labcorp Genetics (formerly Invitae)

dermatopathia pigmentosa reticularisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007445

Submitter: Orphanet

epidermolysis bullosa simplex 1B, generalized intermediateSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007554

Submitter: Orphanet

Clinical Genomic Database (CGD)

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/AR

Manifestation: Dental; 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

Refs: 13149726; 939040; 1717157; 1303619; 7506606; 7526933; 7682883; 8496458; 7682695; 7525408; 7525407; 16098032; 16960809; 20180888; 20199538; 20301543; 21375516; 21593775; 21623745; 21818518; 21967011; 32017015Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT14 variants in ClinVar

18 Conditions Cataloged
not providedTotal: 230
KRT14-related disorderTotal: 38
Inborn genetic diseasesTotal: 33
Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessiveTotal: 20
Epidermolysis bullosa simplex 1A, generalized severeTotal: 19
Epidermolysis bullosa simplex 1C, localizedTotal: 16
Epidermolysis bullosa simplex, Koebner typeTotal: 15
Epidermolysis bullosa simplexTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000526.5. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
30
clinvar
5
clinvar
 37
missense
26
clinvar
24
clinvar
118
clinvar
8
clinvar
2
clinvar
 178
nonsense
8
clinvar
5
clinvar
4
clinvar
 17
start loss
1
clinvar
 1
frameshift
10
clinvar
6
clinvar
7
clinvar
 23
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
8
clinvar
 10
Total4536140387266

Highest pathogenic variant AF is 0.000088623696

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000526.5RefSeqNP_000517.38MANE Select
ENST00000167586.7EnsemblENSP00000167586.68MANE Select
ENST00001101343.1EnsemblENSP00000771149.12Standard
ENST00001101344.1EnsemblENSP00000771150.18Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Estrogen signaling pathway - Homo sapiens (human)
  • Corticotropin-releasing hormone signaling pathway
  • Keratinization
  • Developmental Biology
  • Glucocorticoid receptor regulatory network

Biological Process

  • aging
  • epidermis development
  • response to zinc ion
  • response to ionizing radiation
  • keratinization

Molecular Function

  • structural constituent of cytoskeleton
  • protein binding
  • keratin filament binding

Cellular Component

  • nucleus
  • cytoplasm
  • cytosol
  • intermediate filament
  • keratin filament

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000167586
Coding exons
8
Length
4643
Individuals with no LoFs
125651
Homozygous LoFs
0
Heterozygous LoFs
97
Defined
125748
p
0.000386
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.8352502900.8620.00002013066
Missense (PolyPhen)6174.7660.815881051
Synonymous-1.341421231.150.00000890934
Loss of Function2.06918.60.4858.24e-7226

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000920.00055rare
Latino/Admixed American0.00240.0012notable
Ashkenazi Jewish0.000400.00030rare
East Asian0.000160.00016rare
Finnish00.0absent
European (Non-Finnish)0.000250.00020rare
South Asian0.000690.00039rare
Other0.00180.00098notable

dbNSFP Gene Annotations

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.;

Intolerance Scores

LoFtool
0.0518
RVIS EVS
-0.07
RVIS percentile EVS
48.69

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.625

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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