KRT14

keratin 14, the group of Keratins, type I

Basic information

Region (hg38): 17:41582279-41586895

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

Links

ENSG00000186847 ∙ NCBI:3861 ∙ OMIM:148066 ∙ HGNC:6416 ∙ Uniprot:P02533 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the KRT14 gene.

• not provided (31 variants)
• Epidermolysis bullosa simplex (12 variants)
• Epidermolysis bullosa simplex 1A, generalized severe (5 variants)
• Epidermolysis bullosa simplex, Koebner type (3 variants)
• Epidermolysis bullosa simplex 1C, localized (2 variants)
• Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive (2 variants)
• KRT14-related disorder (2 variants)
• Dermatopathia pigmentosa reticularis (1 variants)
• Sjögren-Larsson syndrome (1 variants)
• Abnormality of the skin (1 variants)
• Palmoplantar blistering;Skin fragility with non-scarring blistering (1 variants)
• Epidermolysis bullosa simplex 1A, generalized severe;Epidermolysis bullosa simplex, Koebner type (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.

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				22	11	33
missense	23	11	50	6	4	94
nonsense	5	1				6
start loss						0
frameshift	5	3				8
inframe indel	1	2	2	2		7
splice donor/acceptor (+/-2bp)	1		2			3
splice region	1		1			2
non coding				7	6	13
Total	35	17	54	37	21

Highest pathogenic variant AF is 0.0000131

Variants in KRT14

This is a list of pathogenic ClinVar variants found in the KRT14 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-41582448-C-T		Inborn genetic diseases	Uncertain significance (Oct 16, 2023)
17-41582456-C-G		Inborn genetic diseases	Uncertain significance (Jun 27, 2023)
17-41582493-T-C		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
17-41582500-C-T			Benign (Jan 24, 2024)
17-41582501-C-G		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
17-41582508-C-T		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
17-41582518-G-A			Uncertain significance (Dec 03, 2022)
17-41582518-G-T		Inborn genetic diseases	Uncertain significance (Sep 15, 2021)
17-41582545-T-C		not specified	Benign (Jan 29, 2024)
17-41583081-A-G			Likely benign (Jul 02, 2022)
17-41583086-G-T			Uncertain significance (Sep 01, 2022)
17-41583111-G-A		Inborn genetic diseases	Uncertain significance (Mar 18, 2023)
17-41583141-C-T			Uncertain significance (Mar 18, 2022)
17-41583159-A-G			Benign (Jan 29, 2024)
17-41583199-T-TG			Benign (Mar 03, 2015)
17-41583206-G-C			Benign (Mar 03, 2015)
17-41583216-G-A			Likely benign (Aug 16, 2022)
17-41583223-G-A			Likely benign (Nov 14, 2023)
17-41583230-C-G		Epidermolysis bullosa simplex	Pathogenic (Oct 12, 2009)
17-41583245-C-T		Epidermolysis bullosa simplex 1C, localized	Pathogenic (Apr 01, 2000)
17-41583246-G-A		not specified	Likely benign (Sep 17, 2015)
17-41583248-C-T		KRT14-related disorder	Uncertain significance (Jul 24, 2024)
17-41583249-CTCCAGCAGGCGGCGGTAG-C		Epidermolysis bullosa simplex 1A, generalized severe	Pathogenic (Nov 09, 2021)
17-41583253-A-T		Epidermolysis bullosa simplex 1A, generalized severe	Pathogenic (Apr 01, 2000)
17-41583257-G-C			not provided (-)

GnomAD

Source: gnomAD

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: 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

	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