KRT4

keratin 4, the group of Keratins, type II

Basic information

Region (hg38): 12:52806549-52814116

Previous symbols: [ "CYK4" ]

Links

ENSG00000170477 ∙ NCBI:3851 ∙ OMIM:123940 ∙ HGNC:6441 ∙ Uniprot:P19013 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• white sponge nevus 1 (Strong), mode of inheritance: AD
• white sponge nevus 1 (Moderate), mode of inheritance: AD
• hereditary mucosal leukokeratosis (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
White sponge nevus 1	AD	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	7493030; 10652003; 12828738

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT4 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			5	10	10	25
missense			39	8	10	57
nonsense				2		2
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)			1			1
splice region			2		2	4
non coding			6	2	20	28
Total	0	0	51	23	40

Variants in KRT4

This is a list of pathogenic ClinVar variants found in the KRT4 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-52806573-A-C		White sponge nevus 1	Uncertain significance (Jan 12, 2018)
12-52806664-C-T		White sponge nevus 1	Uncertain significance (Jan 13, 2018)
12-52806780-C-T		White sponge nevus 1	Uncertain significance (Jan 12, 2018)
12-52806800-T-C		White sponge nevus 1	Benign (Nov 12, 2018)
12-52806802-C-T		White sponge nevus 1	Benign (Jan 12, 2018)
12-52806936-G-A		White sponge nevus 1	Benign (Jan 12, 2018)
12-52806943-G-T		White sponge nevus 1	Uncertain significance (Jan 13, 2018)
12-52806988-A-T		White sponge nevus 1	Benign (Jan 13, 2018)
12-52807001-G-A		White sponge nevus 1	Benign (Jan 13, 2018)
12-52807039-A-T		White sponge nevus 1	Benign (Jan 13, 2018)
12-52807091-G-A		Inborn genetic diseases	Uncertain significance (Sep 26, 2022)
12-52807101-T-C		Inborn genetic diseases	Uncertain significance (May 03, 2023)
12-52807120-G-T		White sponge nevus 1	Benign (Jan 13, 2018)
12-52807137-C-G		White sponge nevus 1 • Inborn genetic diseases	Conflicting classifications of pathogenicity (May 25, 2022)
12-52807139-A-G		White sponge nevus 1 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 05, 2024)
12-52807165-G-T		White sponge nevus 1	Uncertain significance (Jan 13, 2018)
12-52807191-C-T		White sponge nevus 1	Uncertain significance (Jan 13, 2018)
12-52807202-C-A		KRT4-related disorder	Uncertain significance (Mar 11, 2024)
12-52807213-G-A		White sponge nevus 1	Benign (Jan 13, 2018)
12-52807215-T-A		White sponge nevus 1	Uncertain significance (Jan 12, 2018)
12-52807246-C-T		White sponge nevus 1	Likely benign (Jan 12, 2018)
12-52807344-G-A		White sponge nevus 1	Benign (May 12, 2021)
12-52807382-T-G		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
12-52807396-G-A		White sponge nevus 1	Uncertain significance (Jan 13, 2018)
12-52807629-T-A		White sponge nevus 1	Likely benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT4	protein_coding	protein_coding	ENST00000551956	9	8003

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.50e-10	0.620	125548	0	200	125748	0.000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.456	314	292	1.08	0.0000180	3414
Missense in Polyphen		114	108.35	1.0521		1341
Synonymous	-1.10	135	120	1.13	0.00000783	1019
Loss of Function	1.33	18	25.2	0.715	0.00000157	262

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000360	0.000357
Ashkenazi Jewish	0.00	0.00
East Asian	0.000943	0.000925
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000297	0.000290
Middle Eastern	0.000943	0.000925
South Asian	0.00441	0.00435
Other	0.000663	0.000652

dbNSFP

Source: dbNSFP

• Disease: DISEASE: White sponge nevus 1 (WSN1) [MIM:193900]: A rare disorder characterized by the presence of soft, white, and spongy plaques in the oral mucosa. The characteristic histopathologic features are epithelial thickening, parakeratosis, and vacuolization of the suprabasal layer of oral epithelial keratinocytes. Less frequently the mucous membranes of the nose, esophagus, genitalia and rectum are involved. {ECO:0000269|PubMed:10652003, ECO:0000269|PubMed:12828738}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Keratinization;Developmental Biology (Consensus)

Recessive Scores

• pRec: 0.219

Intolerance Scores

• loftool: 0.261
• rvis_EVS: 0.34
• rvis_percentile_EVS: 73.68

Haploinsufficiency Scores

• pHI: 0.330
• hipred: N
• hipred_score: 0.422
• ghis: 0.399

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.643

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Krt4
• Phenotype: growth/size/body region 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); craniofacial phenotype; pigmentation 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); vision/eye phenotype; digestive/alimentary phenotype

Gene ontology

• Biological process: cytoskeleton organization;epithelial cell differentiation;keratinization;negative regulation of epithelial cell proliferation;cornification
• Cellular component: nucleus;cytosol;intermediate filament;cell surface;keratin filament;intermediate filament cytoskeleton
• Molecular function: structural molecule activity;protein binding