KRT5

keratin 5, the group of Keratins, type II

Basic information

Region (hg38): 12:52514575-52520530

Previous symbols: [ "EBS2" ]

Links

ENSG00000186081 ∙ NCBI:3852 ∙ OMIM:148040 ∙ HGNC:6442 ∙ Uniprot:P13647 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epidermolysis bullosa simplex 1A, generalized severe (Strong), mode of inheritance: AD
• epidermolysis bullosa simplex 1B, generalized intermediate (Strong), mode of inheritance: AD
• epidermolysis bullosa simplex 2F, with mottled pigmentation (Strong), mode of inheritance: AD
• epidermolysis bullosa simplex 1C, localized (Strong), mode of inheritance: AD
• Dowling-Degos disease 1 (Moderate), mode of inheritance: AD
• epidermolysis bullosa simplex 1A, generalized severe (Definitive), mode of inheritance: AD
• epidermolysis bullosa simplex 2F, with mottled pigmentation (Strong), mode of inheritance: AD
• epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive (Strong), mode of inheritance: AR
• Dowling-Degos disease (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
• epidermolysis bullosa simplex 2E, with migratory circinate erythema (Supportive), mode of inheritance: AD
• Dowling-Degos disease 1 (Strong), mode of inheritance: AD
• epidermolysis bullosa simplex 2B, generalized intermediate (Strong), mode of inheritance: AD
• epidermolysis bullosa simplex 2d, generalized, intermediate or severe, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
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	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	Dermatologic	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; 32017015

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT5 gene.

• not provided (32 variants)
• Epidermolysis bullosa simplex (17 variants)
• KRT5-related disorder (4 variants)
• Epidermolysis bullosa simplex 1C, localized (3 variants)
• Epidermolysis bullosa simplex with mottled pigmentation (3 variants)
• Epidermolysis bullosa simplex 2C, localized (3 variants)
• Epidermolysis bullosa simplex 2B, generalized intermediate (3 variants)
• Epidermolysis bullosa simplex 2A, generalized severe (2 variants)
• Epidermolysis bullosa simplex 1A, generalized severe (2 variants)
• Dowling-Degos disease 1 (2 variants)
• Epidermolysis bullosa (1 variants)
• Epidermolysis bullosa simplex with migratory circinate erythema (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT5 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	16	14	37
missense	28	22	64	15	6	135
nonsense	3		1			4
start loss	1					1
frameshift	3	1	2			6
inframe indel		1	2	1		4
splice donor/acceptor (+/-2bp)	1		2			3
splice region		1	2	2	1	6
non coding	1		10	4	12	27
Total	37	24	88	36	32

Highest pathogenic variant AF is 0.00000658

Variants in KRT5

This is a list of pathogenic ClinVar variants found in the KRT5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-52514608-T-C		Epidermolysis bullosa simplex	Uncertain significance (Jan 13, 2018)
12-52514619-A-G		Epidermolysis bullosa simplex	Benign (Jan 13, 2018)
12-52514622-A-T		Epidermolysis bullosa simplex	Uncertain significance (Jan 12, 2018)
12-52514671-G-A		Epidermolysis bullosa simplex	Uncertain significance (Jan 12, 2018)
12-52514679-A-G		Epidermolysis bullosa simplex	Benign (Jan 13, 2018)
12-52514689-G-A		Epidermolysis bullosa simplex	Benign (Jan 13, 2018)
12-52514710-A-G		Epidermolysis bullosa simplex	Uncertain significance (Jan 17, 2018)
12-52514757-C-T		Epidermolysis bullosa simplex	Benign (Jan 13, 2018)
12-52514808-T-C		Epidermolysis bullosa simplex	Uncertain significance (Jan 13, 2018)
12-52514883-G-A		Epidermolysis bullosa simplex	Uncertain significance (Jan 13, 2018)
12-52514960-C-T			not provided (-)
12-52514961-C-T		KRT5-related disorder	Uncertain significance (Dec 26, 2023)
12-52514962-G-A		Inborn genetic diseases	Uncertain significance (May 16, 2022)
12-52514979-G-T		Epidermolysis bullosa simplex	Likely benign (Jan 13, 2018)
12-52514985-A-T			not provided (-)
12-52514988-T-C		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
12-52514997-G-A		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
12-52515010-C-T		KRT5-related disorder • Epidermolysis bullosa simplex	Benign (Nov 03, 2023)
12-52515023-G-T			not provided (-)
12-52515032-C-CA			Uncertain significance (Nov 18, 2021)
12-52515038-T-A			Likely benign (Dec 31, 2019)
12-52515039-C-T		Epidermolysis bullosa simplex • Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
12-52515040-G-A		KRT5-related disorder	Conflicting classifications of pathogenicity (Apr 25, 2023)
12-52515064-AG-A		Epidermolysis bullosa simplex with migratory circinate erythema	Pathogenic (Feb 02, 2022)
12-52515065-GC-G		Epidermolysis bullosa simplex with migratory circinate erythema • Epidermolysis bullosa simplex • Epidermolysis bullosa simplex with mottled pigmentation • KRT5-related disorder	Pathogenic (Oct 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT5	protein_coding	protein_coding	ENST00000252242	9	6113

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.642	0.358	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.226	342	354	0.966	0.0000240	3847
Missense in Polyphen		87	106.65	0.81577		1335
Synonymous	-0.884	161	147	1.09	0.00000995	1223
Loss of Function	3.41	4	20.7	0.193	0.00000101	255

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000625	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000171	0.000167
Middle Eastern	0.00	0.00
South Asian	0.0000692	0.0000653
Other	0.00	0.00

dbNSFP

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.
• Pathway: Keratinization;Developmental Biology;EGFR1;Glucocorticoid receptor regulatory network;Validated transcriptional targets of deltaNp63 isoforms (Consensus)

Recessive Scores

• pRec: 0.595

Intolerance Scores

• loftool: 0.0384
• rvis_EVS: 0.12
• rvis_percentile_EVS: 62.19

Haploinsufficiency Scores

• pHI: 0.782
• hipred: Y
• hipred_score: 0.584
• ghis: 0.493

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.929

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Krt5
• Phenotype: craniofacial phenotype; 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary 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)

Gene ontology

• Biological process: cytoskeleton organization;epidermis development;keratinization;hemidesmosome assembly;cornification
• Cellular component: nucleus;cytoplasm;cytosol;intermediate filament;plasma membrane;membrane;keratin filament;extracellular exosome
• Molecular function: structural constituent of cytoskeleton;protein binding;scaffold protein binding