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 differentiated layers of the mucosal and esophageal e... See more...

Aliases for KRT4 Gene

Aliases for KRT4 Gene

  • Keratin 4 2 3 5
  • Keratin, Type II Cytoskeletal 4 2 3 4
  • CYK4 2 3 4
  • K4 2 3 4
  • Type-II Keratin Kb4 3 4
  • Cytokeratin 4 2 3
  • CK-4 3 4
  • CK4 2 3
  • Keratin 4, Type II 3
  • Cytokeratin-4 4
  • Keratin-4 4
  • WSN1 3
  • KRT4 5

External Ids for KRT4 Gene

Previous HGNC Symbols for KRT4 Gene

  • CYK4

Previous GeneCards Identifiers for KRT4 Gene

  • GC12M053448
  • GC12P053657
  • GC12M052627
  • GC12M051486
  • GC12M053200
  • GC12M050244

Summaries for KRT4 Gene

Entrez Gene Summary for KRT4 Gene

  • 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 differentiated layers of the mucosal and esophageal epithelia with family member KRT13. Mutations in these genes have been associated with White Sponge Nevus, characterized by oral, esophageal, and anal leukoplakia. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

GeneCards Summary for KRT4 Gene

KRT4 (Keratin 4) is a Protein Coding gene. Diseases associated with KRT4 include White Sponge Nevus 1 and Leukoplakia. Among its related pathways are Cytoskeleton remodeling Neurofilaments and Developmental Biology. Gene Ontology (GO) annotations related to this gene include structural molecule activity. An important paralog of this gene is KRT5.

Gene Wiki entry for KRT4 Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KRT4 Gene

Genomics for KRT4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KRT4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J052814 Promoter/Enhancer 0.9 EPDnew Ensembl 600.7 -0.3 -341 0.9 FOXA1 REST SP1 CTBP1 PKNOX1 SIN3A ESR1 GATA3 MNT BCL3 KRT4 lnc-KRT79-1 KRT79 lnc-KRT18-5
GH12J052515 Promoter/Enhancer 1.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 9.7 +293.1 293072 11.4 CREB1 ZBTB33 JUND ZIC2 SCRT2 MNT ESR1 CTBP1 NR3C1 FOS KRT5 HSALNG0091190 lnc-KRT6A-1 KRT6A KRT6C KRT71 KRT74 KRT84 KRT2 KRT4
GH12J052609 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE dbSUPER 10.2 +203.1 203115 17.2 FOXA1 ZIC2 SCRT2 MGA ESR1 E2F5 USF1 ESRRA GABPA NFYB KRT73-AS1 KRT72 KRT2 KRT1 KRT74 KRT71 KRT78 KRT4 KRT79 KRT76
GH12J052968 Enhancer 1.5 Ensembl ENCODE CraniofacialAtlas dbSUPER 9.1 -159.2 -159212 9 CEBPG CREB1 GATAD2A CTCF ZBTB33 YBX1 PRDM10 IKZF1 NFKBIZ ZNF692 KRT18 SOAT2 EIF4B AAAS ZNF740 TARBP2 KRT79 KRT82 KRT71 ENSG00000257808
GH12J052859 Enhancer 1.2 FANTOM5 Ensembl ENCODE dbSUPER 10.9 -46.1 -46085 3.2 CEBPG FOXA1 RFX1 ZNF600 SCRT2 CEBPB BMI1 CTBP1 CHD1 ZNF217 KRT79 KRT4 KRT76 KRT1 KRT2 KRT83 KRT71 KRT6A RARG KRT5
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KRT4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KRT4

Top Transcription factor binding sites by QIAGEN in the KRT4 gene promoter:
  • E47
  • FOXD3
  • HNF-4alpha1
  • p300
  • PPAR-alpha
  • RFX1
  • STAT3
  • Tal-1beta
  • YY1
  • Zic1

Genomic Locations for KRT4 Gene

Genomic Locations for KRT4 Gene
chr12:52,806,549-52,814,116
(GRCh38/hg38)
Size:
7,568 bases
Orientation:
Minus strand
chr12:53,200,327-53,208,335
(GRCh37/hg19)
Size:
8,009 bases
Orientation:
Minus strand

Genomic View for KRT4 Gene

Genes around KRT4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KRT4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KRT4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KRT4 Gene

Proteins for KRT4 Gene

  • Protein details for KRT4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P19013-K2C4_HUMAN
    Recommended name:
    Keratin, type II cytoskeletal 4
    Protein Accession:
    P19013
    Secondary Accessions:
    • B4DRS2
    • F8VS64
    • Q6GTR8
    • Q96LA7
    • Q9BTL1

    Protein attributes for KRT4 Gene

    Size:
    520 amino acids
    Molecular mass:
    56144 Da
    Quaternary structure:
    • Heterotetramer of two type I and two type II keratins. Keratin-4 is generally associated with keratin-13.
    Miscellaneous:
    • There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).

neXtProt entry for KRT4 Gene

Post-translational modifications for KRT4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for KRT4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for KRT4 Gene

Domains & Families for KRT4 Gene

Gene Families for KRT4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for KRT4 Gene

InterPro:
Blocks:
  • Intermediate filament protein
  • Type I keratin signature
  • Type II keratin signature
ProtoNet:

Suggested Antigen Peptide Sequences for KRT4 Gene

GenScript: Design optimal peptide antigens:
  • Type-II keratin Kb4 (K2C4_HUMAN)
  • KRT4 protein (Q6PIN2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P19013

UniProtKB/Swiss-Prot:

K2C4_HUMAN :
  • Belongs to the intermediate filament family.
Family:
  • Belongs to the intermediate filament family.
genes like me logo Genes that share domains with KRT4: view

Function for KRT4 Gene

Molecular function for KRT4 Gene

GENATLAS Biochemistry:
keratin 4,type II,non cornifying mucosal epithelia (buccal,nasal,esophageal,anogenital)

Phenotypes From GWAS Catalog for KRT4 Gene

Gene Ontology (GO) - Molecular Function for KRT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 17709412
genes like me logo Genes that share ontologies with KRT4: view
genes like me logo Genes that share phenotypes with KRT4: view

Human Phenotype Ontology for KRT4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for KRT4 Gene

MGI Knock Outs for KRT4:

Animal Model Products

CRISPR Products

miRNA for KRT4 Gene

miRTarBase miRNAs that target KRT4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KRT4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for KRT4 Gene

Localization for KRT4 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KRT4 gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Intermediate filaments (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for KRT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus HDA 21630459
GO:0005829 cytosol TAS --
GO:0005882 intermediate filament NAS 2452170
GO:0009986 cell surface IDA 17709412
GO:0045095 keratin filament IDA 21371075
genes like me logo Genes that share ontologies with KRT4: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for KRT4 Gene

Pathways & Interactions for KRT4 Gene

PathCards logo

SuperPathways for KRT4 Gene

SuperPathway Contained pathways
1 Cytoskeletal Signaling
2 Developmental Biology
3 Keratinization
4 Cytoskeleton remodeling Neurofilaments
.32
genes like me logo Genes that share pathways with KRT4: view

Pathways by source for KRT4 Gene

2 Reactome pathways for KRT4 Gene
1 GeneGo (Thomson Reuters) pathway for KRT4 Gene
  • Cytoskeleton remodeling Keratin filaments
1 Cell Signaling Technology pathway for KRT4 Gene

SIGNOR curated interactions for KRT4 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for KRT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007010 cytoskeleton organization NAS 2452170
GO:0030855 epithelial cell differentiation IEA,ISS --
GO:0031424 keratinization TAS --
GO:0050680 negative regulation of epithelial cell proliferation IEA,ISS --
GO:0070268 cornification TAS --
genes like me logo Genes that share ontologies with KRT4: view

Drugs & Compounds for KRT4 Gene

(3) Drugs for KRT4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for KRT4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with KRT4: view

Transcripts for KRT4 Gene

mRNA/cDNA for KRT4 Gene

1 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KRT4

Alternative Splicing Database (ASD) splice patterns (SP) for KRT4 Gene

ExUns: 1 ^ 2a · 2b ^ 3a · 3b · 3c ^ 4a · 4b · 4c ^ 5a · 5b · 5c ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10
SP1: - -
SP2: - - -
SP3: - - - - -
SP4: - - -
SP5: -
SP6:

Relevant External Links for KRT4 Gene

GeneLoc Exon Structure for
KRT4

Expression for KRT4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KRT4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KRT4 Gene

This gene is overexpressed in Esophagus - Mucosa (x38.5), Minor Salivary Gland (x7.6), and Vagina (x4.4).

Protein differential expression in normal tissues from HIPED for KRT4 Gene

This gene is overexpressed in Saliva (48.6), Esophagus (9.6), and Urine (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for KRT4 Gene



Protein tissue co-expression partners for KRT4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KRT4

SOURCE GeneReport for Unigene cluster for KRT4 Gene:

Hs.654610

mRNA Expression by UniProt/SwissProt for KRT4 Gene:

P19013-K2C4_HUMAN
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 level). Expressed widely in the exocervix and esophageal epithelium, with lowest levels detected in the basal cell layer.

Evidence on tissue expression from TISSUES for KRT4 Gene

  • Nervous system(4.5)
  • Lung(3.3)
  • Heart(2.9)
  • Blood(2.9)
  • Eye(2.9)
  • Kidney(2.9)
  • Intestine(2.8)
  • Skin(2.7)
  • Liver(2.4)
  • Pancreas(2.3)
  • Muscle(2.2)
  • Adrenal gland(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for KRT4 Gene

Germ Layers:
  • ectoderm
  • endoderm
Systems:
  • digestive
  • integumentary
  • respiratory
Regions:
Head and neck:
  • head
  • mouth
  • nose
  • pharynx
Thorax:
  • esophagus
Pelvis:
  • rectum
  • vagina
General:
  • skin
genes like me logo Genes that share expression patterns with KRT4: view

Orthologs for KRT4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for KRT4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KRT4 30 31
  • 98.46 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia KRT4 30 31
  • 86.01 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia KRT4 30
  • 85.26 (n)
KRT71 31
  • 76 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Krt4 30 17 31
  • 83.05 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Krt4 30
  • 81.97 (n)
Oppossum
(Monodelphis domestica)
Mammalia KRT4 31
  • 74 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 73 (a)
ManyToMany
Chicken
(Gallus gallus)
Aves KRT4 30
  • 70.63 (n)
-- 31
  • 61 (a)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 55 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100489468 30
  • 61.86 (n)
Species where no ortholog for KRT4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for KRT4 Gene

ENSEMBL:
Gene Tree for KRT4 (if available)
TreeFam:
Gene Tree for KRT4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KRT4: view image

Paralogs for KRT4 Gene

(54) SIMAP similar genes for KRT4 Gene using alignment to 5 proteins:

  • K2C4_HUMAN
  • F5H8K9_HUMAN
  • F8VX05_HUMAN
  • F8VZR6_HUMAN
  • Q6PIN2_HUMAN
genes like me logo Genes that share paralogs with KRT4: view

Variants for KRT4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for KRT4 Gene

K2C4_HUMAN-P19013
Three alleles of K4 are known: K4A1, K4A2 and K4B (displayed here).

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KRT4 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
743163 Likely Benign: not provided 52,813,903(-) G/C SYNONYMOUS_VARIANT
768551 Benign: not provided 52,813,799(-) C/CCACCAAAGCCACC INFRAME_INSERTION
778637 Benign/Likely Benign: White sponge nevus 1; not provided 52,807,672(-) G/A MISSENSE_VARIANT
881137 Uncertain Significance: White sponge nevus 1 52,806,573(-) A/C THREE_PRIME_UTR_VARIANT
881185 Uncertain Significance: White sponge nevus 1 52,808,347(-) G/C MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for KRT4 Gene

Structural Variations from Database of Genomic Variants (DGV) for KRT4 Gene

Variant ID Type Subtype PubMed ID
esv3629524 CNV gain 21293372
nsv1048816 CNV gain 25217958
nsv470293 CNV loss 18288195
nsv832416 CNV loss 17160897
nsv976623 CNV duplication 23825009

Variation tolerance for KRT4 Gene

Residual Variation Intolerance Score: 94.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.92; 91.92% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KRT4 Gene

Human Gene Mutation Database (HGMD)
KRT4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KRT4

SNP Genotyping and Copy Number Assay Products

Disorders for KRT4 Gene

MalaCards: The human disease database

(17) MalaCards diseases for KRT4 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search KRT4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

K2C4_HUMAN
  • 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.
genes like me logo Genes that share disorders with KRT4: view

No data available for Genatlas for KRT4 Gene

Publications for KRT4 Gene

  1. A glutamine insertion in the 1A alpha helical domain of the keratin 4 gene in a familial case of white sponge nevus. (PMID: 10652003) Terrinoni A … Melino G (The Journal of investigative dermatology 2000) 3 4 23
  2. Allelic variations of human keratins K4 and K5 provide polymorphic markers within the type II keratin gene cluster on chromosome 12. (PMID: 7684424) Wanner R … Mischke D (The Journal of investigative dermatology 1993) 3 4 23
  3. Comparative analysis of the expression of cytokeratins (1, 10, 14, 16, 4), involucrin, filaggrin and e-cadherin in plane warts and epidermodysplasia verruciformis plane wart-type lesions. (PMID: 19515043) Barcelos AC … Sotto MN (Journal of cutaneous pathology 2009) 3 23
  4. The surface protein Srr-1 of Streptococcus agalactiae binds human keratin 4 and promotes adherence to epithelial HEp-2 cells. (PMID: 17709412) Samen U … Borges F (Infection and immunity 2007) 3 23
  5. New consensus nomenclature for mammalian keratins. (PMID: 16831889) Schweizer J … Wright MW (The Journal of cell biology 2006) 2 3

Products for KRT4 Gene

Sources for KRT4 Gene