KRT4 (keratin 4)

Gene

• Entrez ID: 3851
• Gene name: Keratin 4
• Gene symbol: KRT4
• Synonyms (NCBI Gene): CK-4, CK4, CYK4, K4, WSN1
• Chromosome: 12
• Chromosome location: 12q13.13
• 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 ep

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587776844	TTG>-	Pathogenic	Coding sequence variant, inframe deletion
rs587776845	->TGT	Pathogenic	Coding sequence variant, inframe indel

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017456	hsa-miR-335-5p	Microarray	18185580
MIRT029264	hsa-miR-26b-5p	Microarray	19088304
MIRT2027576	hsa-miR-1252	CLIP-seq
MIRT2027577	hsa-miR-3616-5p	CLIP-seq
MIRT2027578	hsa-miR-3647-5p	CLIP-seq
MIRT2027579	hsa-miR-4795-5p	CLIP-seq
MIRT2027580	hsa-miR-573	CLIP-seq
MIRT2258888	hsa-miR-2114	CLIP-seq
MIRT2258889	hsa-miR-339-5p	CLIP-seq
MIRT2438265	hsa-miR-3117-5p	CLIP-seq
MIRT2438266	hsa-miR-4659a-3p	CLIP-seq
MIRT2438267	hsa-miR-4659b-3p	CLIP-seq
MIRT2438268	hsa-miR-483-3p	CLIP-seq
MIRT2438269	hsa-miR-942	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ELF3	Repression	10773884

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	17709412, 22458338, 25416956, 29892012, 30021884, 31391242, 31515488, 32296183, 33961781
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005882	Component	Intermediate filament	IEA
GO:0005882	Component	Intermediate filament	NAS	2452170
GO:0007010	Process	Cytoskeleton organization	IMP	21371075
GO:0007010	Process	Cytoskeleton organization	NAS	2452170
GO:0009986	Component	Cell surface	IDA	17709412
GO:0030280	Function	Structural constituent of skin epidermis	IBA
GO:0030855	Process	Epithelial cell differentiation	IEA
GO:0030855	Process	Epithelial cell differentiation	ISS
GO:0031424	Process	Keratinization	IBA
GO:0045095	Component	Keratin filament	IBA
GO:0045095	Component	Keratin filament	IDA	21371075
GO:0045095	Component	Keratin filament	IEA
GO:0045109	Process	Intermediate filament organization	IBA
GO:0045111	Component	Intermediate filament cytoskeleton	IDA	21371075
GO:0050680	Process	Negative regulation of epithelial cell proliferation	IEA
GO:0050680	Process	Negative regulation of epithelial cell proliferation	ISS

Other IDs

• MIM: 123940
• HGNC: 6441
• e!Ensembl: ENSG00000170477

Protein

• UniProt ID: P19013
• Protein name: Keratin, type II cytoskeletal 4 (Cytokeratin-4) (CK-4) (Keratin-4) (K4) (Type-II keratin Kb4)
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16208	Keratin_2_head	14 → 147	Keratin type II head	Family
  PF00038	Filament	150 → 463	Intermediate filament protein	Coiled-coil

• Tissue specificity: TISSUE SPECIFICITY: Detected in the suprabasal layer of the stratified epithelium of the esophagus, exocervix, vagina, mouth and lingual mucosa, and in cells and cell clusters in the mucosa and serous gland ducts of the esophageal submucosa (at protein le
• Sequence:

  MIARQQCVRGGPRGFSCGSAIVGGGKRGAFSSVSMSGGAGRCSSGGFGSRSLYNLRGNKS
  ISMSVAGSRQGACFGGAGGFGTGGFGGGFGGSFSGKGGPGFPVCPAGGIQEVTINQSLLT
  PLHVEIDPEIQKVRTEEREQIKLLNNKFASFIDKVQFLEQQNKVLETKWNLLQQQTTTTS
  SKNLEPLFETYLSVLRKQLDTLGNDKGRLQSELKTMQDSVEDFKTKYEEEINKRTAAEND
  FVVLKKDVDAAYLNKVELEAKVDSLNDEINFLKVLYDAELSQMQTHVSDTSVVLSMDNNR
  NLDLDSIIAEVRAQYEEIAQRSKAEAEALYQTKVQQLQISVDQHGDNLKNTKSEIAELNR
  MIQRLRAEIENIKKQCQTLQVSVADAEQRGENALKDAHSKRVELEAALQQAKEELARMLR
  EYQELMSVKLALDIEIATYRKLLEGEEYRMSGECQSAVSISVVSGSTSTGGISGGLGSGS
  GFGLSSGFGSGSGSGFGFGGSVSGSSSSKIISTTTLNKRR

• Sequence length: 520

Pathways

Reactome:

Keratinization
Formation of the cornified envelope

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
White sponge nevus 1	Pathogenic	rs587776844, rs587776845, rs62642055	RCV000018420 RCV000018421 RCV000018422	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CONTACT DERMATITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORNEAL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DERMATITIS, CONTACT	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KRT4-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
WHITE SPONGE NEVUS	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	12680208		★☆☆☆☆ Found in Text Mining only
Barrett Esophagus	Barrett esophagus	Pubtator	35328735	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	12679910	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	21897749, 9930073	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	24051697	Inhibit	★☆☆☆☆ Found in Text Mining only
Cholesteatoma	Cholesteatoma	Pubtator	25093596	Associate	★☆☆☆☆ Found in Text Mining only
Contact Dermatitis	Dermatitis	CTD_human_DG	25724174		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Eosinophilic Esophagitis	Eosinophilia	Pubtator	28104354	Inhibit	★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophageal neoplasm	Pubtator	10802067	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	17187659, 21498718	Associate	★☆☆☆☆ Found in Text Mining only
Intraepithelial Neoplasia	Intraepithelial Neoplasia	BEFREE	21371075		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	30480765	Associate	★☆☆☆☆ Found in Text Mining only
Leukokeratosis, Hereditary Mucosal	Leukokeratosis	BEFREE	10652003, 12828738, 18992023, 23182699, 29047160, 29738605, 31473371, 9727004		★☆☆☆☆ Found in Text Mining only
Leukokeratosis, Hereditary Mucosal	Leukokeratosis	ORPHANET_DG	10652003, 12828738, 23182699		★☆☆☆☆ Found in Text Mining only
Leukokeratosis, Hereditary Mucosal	Leukokeratosis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Leukoplakia	Leukoplakia	BEFREE	15975524		★☆☆☆☆ Found in Text Mining only
Leukoplakia, Oral	Leukoplakia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	31515263		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	22032772	Associate	★☆☆☆☆ Found in Text Mining only
Mesothelioma	Mesothelioma	Pubtator	2414994	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31515263		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	35163645	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	1372155	Associate	★☆☆☆☆ Found in Text Mining only
Pterygium	Pterygium	BEFREE	19956562		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	15975524, 21371075		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	14647409, 21498718		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	18254958, 19835631, 37092360, 37185487	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	12778082	Associate	★☆☆☆☆ Found in Text Mining only
Waisman syndrome	Waisman syndrome	BEFREE	10652003, 18992023, 23182699, 26021387, 29476668, 29738605		★☆☆☆☆ Found in Text Mining only
White sponge nevus	White Sponge Nevus	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
WHITE SPONGE NEVUS 1	White Sponge Nevus	UNIPROT_DG	10652003, 12828738		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
WHITE SPONGE NEVUS 1	White Sponge Nevus	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)