GeneBe

KRT5

protein-coding

keratin 5, 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. This type II cytokeratin is specifically expressed in the basal layer of the epidermis with family member KRT14. Mutations in these genes have been associated with a complex of diseases termed epidermolysis bullosa simplex. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

Previous symbols:
  • EBS2

MANE transcript

NM_000424.4

Inheritance

AD, AR

ClinVar variants

P:105U:196B:68

Top phenotype

Epidermolysis bullosa simplex, recessive 1; Epidermolysis bullosa simplex 2, severe; Epidermolysis bullosa simplex 2A, generalized severe; Epidermolysis bullosa simplex 2B, generalized intermediate; Epidermolysis bullosa simplex 2C, localized; Epidermolysis bullosa simplex 2D, generalized, intermediate or severe, autosomal recessive; Epidermolysis bullosa simplex 2E, with migratory circinate erythema; Epidermolysis bullosa simplex 2F, with mottled pigmentation; Dowling-Degos disease 1; Epidermolysis bullosa simplex 3, intermediate; Epidermolysis bullosa simplex 4, intermediate; Epidermolysis bullosa simplex, Weber-Cockayne type;

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr12:52,514,575-52,520,530

External References & Databases

Ensembl (ENSG00000186081)NCBI Gene (3852)OMIM (148040)HGNC:6442GenCCUniProt (P13647)AlphaFoldClinVar (KRT5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~6.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epidermolysis bullosa simplex 2F, with mottled pigmentationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007556

Submitter: Orphanet

epidermolysis bullosa simplex 1C, localizedSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007551

Submitter: Genomics England PanelApp

epidermolysis bullosa simplex 2d, generalized, intermediate or severe, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030535

Submitter: Ambry Genetics

epidermolysis bullosaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0006541

Submitter: PanelApp Australia

Dowling-Degos disease 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024534

Submitter: Labcorp Genetics (formerly Invitae)

epidermolysis bullosa simplex 2B, generalized intermediateSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030525

Submitter: Labcorp Genetics (formerly Invitae)

Dowling-Degos disease 1MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0024534

Submitter: Ambry Genetics

epidermolysis bullosaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0006541

Submitter: PanelApp Australia

Dowling-Degos diseaseSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008371

Submitter: Orphanet

epidermolysis bullosa simplex 1A, generalized severeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007550

Submitter: Ambry Genetics

epidermolysis bullosa simplex 1A, generalized severeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007550

Submitter: Genomics England PanelApp

epidermolysis bullosa simplex 2F, with mottled pigmentationDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007556

Submitter: G2P

epidermolysis bullosa simplex 2F, with mottled pigmentationSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007556

Submitter: Genomics England PanelApp

epidermolysis bullosa simplex 2d, generalized, intermediate or severe, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030535

Submitter: Labcorp Genetics (formerly Invitae)

epidermolysis bullosa simplex 1A, generalized severeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007550

Submitter: Orphanet

epidermolysis bullosa simplex 2E, with migratory circinate erythemaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012258

Submitter: Orphanet

epidermolysis bullosa simplex 1C, localizedSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007551

Submitter: Orphanet

epidermolysis bullosa simplex 1B, generalized intermediateSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007554

Submitter: Genomics England PanelApp

Dowling-Degos diseaseDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008371

Submitter: G2P

epidermolysis bullosa simplex 1B, generalized intermediateSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007554

Submitter: Orphanet

Clinical Genomic Database (CGD)

Epidermolysis bullosa simplex, recessive 1; Epidermolysis bullosa simplex 2, severe; Epidermolysis bullosa simplex 2A, generalized severe; Epidermolysis bullosa simplex 2B, generalized intermediate; Epidermolysis bullosa simplex 2C, localized; Epidermolysis bullosa simplex 2D, generalized, intermediate or severe, autosomal recessive; Epidermolysis bullosa simplex 2E, with migratory circinate erythema; Epidermolysis bullosa simplex 2F, with mottled pigmentation; Dowling-Degos disease 1; Epidermolysis bullosa simplex 3, intermediate; Epidermolysis bullosa simplex 4, intermediate; Epidermolysis bullosa simplex, Weber-Cockayne type;AD/AR

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

Refs: 11973334; 19991630; 13171638; 3188604; 1718160; 1372711; 7688477; 7686424; 7682695; 7520042; 7537780; 7534039; 8799157; 9129237; 10234505; 10730767; 11167681; 11407989; 12925204; 15324323; 16098032; 16465624; 20923750; 21144712 ; 21375516; 21569119; 22005030; 22583733; 22639907; 22747925; 31302245; 31312705; 32017015Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT5 variants in ClinVar

21 Conditions Cataloged
not providedTotal: 257
Inborn genetic diseasesTotal: 87
Epidermolysis bullosa simplexTotal: 66
KRT5-related disorderTotal: 55
not specifiedTotal: 23
Epidermolysis bullosa simplex 2B, generalized intermediateTotal: 20
Epidermolysis bullosa simplex 2C, localizedTotal: 17
Epidermolysis bullosa simplex 2A, generalized severeTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000424.4. 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.

EffectPLPVUSLBBSum
synonymous
14
clinvar
32
clinvar
7
clinvar
 53
missense
39
clinvar
40
clinvar
171
clinvar
27
clinvar
2
clinvar
 279
nonsense
7
clinvar
3
clinvar
2
clinvar
 12
start loss
1
clinvar
1
clinvar
 2
frameshift
7
clinvar
2
clinvar
5
clinvar
 14
splice donor/acceptor (+/-2bp)
3
clinvar
3
clinvar
3
clinvar
 9
Total5748196599369

Highest pathogenic variant AF is 0.000023941708

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000424.4RefSeqNP_000415.29MANE Select
ENST00000252242.9EnsemblENSP00000252242.49MANE Select
ENST00000546577.1EnsemblENSP00000449651.11Standard
ENST00000548409.5EnsemblENSP00000448767.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Keratinization
  • Developmental Biology
  • EGFR1
  • Glucocorticoid receptor regulatory network
  • Validated transcriptional targets of deltaNp63 isoforms

Biological Process

  • cytoskeleton organization
  • epidermis development
  • keratinization
  • hemidesmosome assembly
  • cornification

Molecular Function

  • structural constituent of cytoskeleton
  • protein binding
  • scaffold protein binding

Cellular Component

  • nucleus
  • cytoplasm
  • cytosol
  • intermediate filament
  • plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000252242
Coding exons
9
Length
6113
Individuals with no LoFs
125726
Homozygous LoFs
0
Heterozygous LoFs
22
Defined
125748
p
0.0000875
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.2263423540.9660.00002403847
Missense (PolyPhen)87106.650.815771335
Synonymous-0.8841611471.090.000009951223
Loss of Function3.41420.70.1930.00000101255

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000630.000062rare
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.000170.00017rare
South Asian0.0000690.000065rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Disease
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:11973334}. Note=The disease is caused by mutations affecting the gene represented in this entry.; 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:10730767, ECO:0000269|PubMed:12655565, ECO:0000269|PubMed:1372711, ECO:0000269|PubMed:16786515, ECO:0000269|PubMed:16882168, ECO:0000269|PubMed:21623745, ECO:0000269|PubMed:8757772, ECO:0000269|PubMed:9036937, ECO:0000269|PubMed:9406827, ECO:0000269|PubMed:9989794, ECO:0000269|Ref.17}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa simplex, with migratory circinate erythema (EBSMCE) [MIM:609352]: A form of intraepidermal epidermolysis bullosa characterized by unusual migratory circinate erythema. Skin lesions appear from birth primarily on the hands, feet, and legs but spare nails, ocular epithelia and mucosae. Lesions heal with brown pigmentation but no scarring. Electron microscopy findings are distinct from those seen in the DM-EBS, with no evidence of tonofilament clumping. 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:10782015, ECO:0000269|PubMed:12655565, ECO:0000269|PubMed:12707098, ECO:0000269|PubMed:14723728, ECO:0000269|PubMed:15140024, ECO:0000269|PubMed:15347343, ECO:0000269|PubMed:16786515, ECO:0000269|PubMed:16882168, ECO:0000269|PubMed:21623745, ECO:0000269|PubMed:7506097, ECO:0000269|PubMed:7520042, ECO:0000269|PubMed:7688477, ECO:0000269|PubMed:8595431, ECO:0000269|PubMed:8807337, ECO:0000269|PubMed:9804357}. 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:11407988, ECO:0000269|PubMed:16882168, ECO:0000269|PubMed:21623745, ECO:0000269|PubMed:7534039, ECO:0000269|PubMed:7686424, ECO:0000269|PubMed:9740251, ECO:0000269|PubMed:9989794}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa simplex, with mottled pigmentation (MP-EBS) [MIM:131960]: A form of intraepidermal epidermolysis bullosa characterized by blistering at acral sites and 'mottled' pigmentation of the trunk and proximal extremities with hyper- and hypopigmentation macules. {ECO:0000269|PubMed:10494094, ECO:0000269|PubMed:16882168, ECO:0000269|PubMed:21623745, ECO:0000269|PubMed:8799157}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dowling-Degos disease 1 (DDD1) [MIM:179850]: An autosomal dominant genodermatosis. Affected individuals develop a postpubertal reticulate hyperpigmentation that is progressive and disfiguring, and small hyperkeratotic dark brown papules that affect mainly the flexures and great skin folds. Patients usually show no abnormalities of the hair or nails. {ECO:0000269|PubMed:16465624}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.595

Intolerance Scores

LoFtool
0.0384
RVIS EVS
0.12
RVIS percentile EVS
62.19

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.929

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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