KLF4 Gene (Protein Coding)

Kruppel Like Factor 4

GC09M107484
GIFtS:
45
This gene encodes a protein that belongs to the Kruppel family of transcription factors. The encoded zinc finger protein is required for normal development of the barrier function of skin. The encoded protein is thought to control the G1-to-S transition of the cell cycle following DNA damage by mediating the tumor suppressor gene p53. Mice lacking this gene have a normal appear... See more...

Aliases for KLF4 Gene

Aliases for KLF4 Gene

  • Kruppel Like Factor 4 2 3 5
  • GKLF 2 3 4
  • EZF 2 3 4
  • Epithelial Zinc Finger Protein EZF 3 4
  • Gut-Enriched Krueppel-Like Factor 3 4
  • Kruppel-Like Factor 4 (Gut) 2 3
  • Gut Kruppel-Like Factor 2 3
  • Krueppel-Like Factor 4 3 4
  • Endothelial Kruppel-Like Zinc Finger Protein 3
  • KLF4 5

External Ids for KLF4 Gene

Previous GeneCards Identifiers for KLF4 Gene

  • GC09M101042
  • GC09M101979
  • GC09M103704
  • GC09M105626
  • GC09M107326
  • GC09M109286
  • GC09M110247
  • GC09M079848

Summaries for KLF4 Gene

Entrez Gene Summary for KLF4 Gene

  • This gene encodes a protein that belongs to the Kruppel family of transcription factors. The encoded zinc finger protein is required for normal development of the barrier function of skin. The encoded protein is thought to control the G1-to-S transition of the cell cycle following DNA damage by mediating the tumor suppressor gene p53. Mice lacking this gene have a normal appearance but lose weight rapidly, and die shortly after birth due to fluid evaporation resulting from compromised epidermal barrier function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

GeneCards Summary for KLF4 Gene

KLF4 (Kruppel Like Factor 4) is a Protein Coding gene. Diseases associated with KLF4 include Secretory Meningioma and Skin Squamous Cell Carcinoma. Among its related pathways are Regulation of Wnt-mediated beta catenin signaling and target gene transcription and Preimplantation Embryo. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription factor binding. An important paralog of this gene is KLF2.

UniProtKB/Swiss-Prot Summary for KLF4 Gene

  • Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription.

Gene Wiki entry for KLF4 Gene

Additional gene information for KLF4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KLF4 Gene

Genomics for KLF4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for KLF4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KLF4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KLF4

Top Transcription factor binding sites by QIAGEN in the KLF4 gene promoter:
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alpha isoform 3
  • AP-2alpha isoform 4
  • AP-2alphaA
  • SRF
  • SRF (504 AA)
  • STAT1

Genomic Locations for KLF4 Gene

Genomic Locations for KLF4 Gene
chr9:107,484,852-107,490,482
(GRCh38/hg38)
Size:
5,631 bases
Orientation:
Minus strand
chr9:110,247,133-110,252,763
(GRCh37/hg19)
Size:
5,631 bases
Orientation:
Minus strand

Genomic View for KLF4 Gene

Genes around KLF4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLF4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLF4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for KLF4 Gene

Proteins for KLF4 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for KLF4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43474-KLF4_HUMAN
    Recommended name:
    Krueppel-like factor 4
    Protein Accession:
    O43474
    Secondary Accessions:
    • B2R8S4
    • B3KT79
    • L0R3I6
    • L0R4N5
    • P78338
    • Q5T3J8
    • Q5T3J9
    • Q8N717
    • Q9UNP3

    Protein attributes for KLF4 Gene

    Size:
    513 amino acids
    Molecular mass:
    54671 Da
    Quaternary structure:
    • Interacts with POU5F1/OCT4 and SOX2 (By similarity). Interacts with MUC1 (via the C-terminal domain) (PubMed:17308127). Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a (PubMed:21746878). Interacts with ZNF296 (By similarity). Interacts with GLIS1 (PubMed:21654807).
    SequenceCaution:
    • Sequence=AAB48399.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAC03462.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAD42165.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH29923.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH30811.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=ABG25917.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAG36271.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=EAW59020.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=EAW59021.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Alternative splice isoforms for KLF4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KLF4 Gene

Protein Expression for KLF4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for KLF4 Gene

  • Ubiquitination at Lys32
  • Modification sites at PhosphoSitePlus

Other Protein References for KLF4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for KLF4

No data available for DME Specific Peptides for KLF4 Gene

Domains & Families for KLF4 Gene

Gene Families for KLF4 Gene

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

Protein Domains for KLF4 Gene

InterPro:
Blocks:
  • C2H2-type zinc finger signature
ProtoNet:

Suggested Antigen Peptide Sequences for KLF4 Gene

GenScript: Design optimal peptide antigens:
  • Kruppel-like factor 4 short isoform (F2VTX5_HUMAN)
  • Gut-enriched krueppel-like factor (KLF4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O43474

UniProtKB/Swiss-Prot:

KLF4_HUMAN :
  • the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
  • Belongs to the krueppel C2H2-type zinc-finger protein family.
Domain:
  • the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
Family:
  • Belongs to the krueppel C2H2-type zinc-finger protein family.
genes like me logo Genes that share domains with KLF4: view

Function for KLF4 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for KLF4 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription.
GENATLAS Biochemistry:
Kruppel-like factor 4 (gut),zinc finger protein,mouse EZF and GKLF homolog,nuclear,expressed in select tissues,colon,testis,lung and small intestine,binding DNA fragments,containing the CACCC motif of the beta globin promoter,acting both as a transcriptional activator and repressor

Phenotypes From GWAS Catalog for KLF4 Gene

Gene Ontology (GO) - Molecular Function for KLF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding ISS, IBA --
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IEA --
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IEA,ISA --
GO:0000987 proximal promoter sequence-specific DNA binding IDA 21539536
GO:0001010 RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity IEA,ISS --
genes like me logo Genes that share ontologies with KLF4: view
genes like me logo Genes that share phenotypes with KLF4: view

Animal Models for KLF4 Gene

MGI Knock Outs for KLF4:

Animal Model Products

CRISPR Products

Targeted motifs for KLF4 Gene
HOMER Transcription Factor Regulatory Elements motif KLF4
  • Consensus sequence: GCCACACCCA Submotif: canonical Cell Type: mES GEO ID: GSE11431

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLF4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and Transcription Factor Targets for KLF4 Gene

Localization for KLF4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KLF4 Gene

Nucleus.

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 KLF4 gene
Compartment Confidence
nucleus 5
extracellular 3
cytoskeleton 3
plasma membrane 2
mitochondrion 2
endoplasmic reticulum 2
endosome 2
cytosol 2
lysosome 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

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

Gene Ontology (GO) - Cellular Components for KLF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin IEA --
GO:0000790 nuclear chromatin IDA,ISA --
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IEA --
genes like me logo Genes that share ontologies with KLF4: view

Pathways & Interactions for KLF4 Gene

genes like me logo Genes that share pathways with KLF4: view

SIGNOR curated interactions for KLF4 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for KLF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 20551324
GO:0006351 transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IEA --
GO:0006366 transcription by RNA polymerase II IEA --
GO:0007500 mesodermal cell fate determination TAS 8940147
genes like me logo Genes that share ontologies with KLF4: view

Drugs & Compounds for KLF4 Gene

Products:

  1. Drug

(5) Drugs for KLF4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for KLF4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with KLF4: view

Transcripts for KLF4 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for KLF4 Gene

2 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
6 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 KLF4

Alternative Splicing Database (ASD) splice patterns (SP) for KLF4 Gene

No ASD Table

Relevant External Links for KLF4 Gene

GeneLoc Exon Structure for
KLF4

Expression for KLF4 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KLF4 Gene

mRNA expression in normal human tissues for KLF4 Gene
mRNA expression by GTEx for KLF4 GenemRNA expression by BioGPS for KLF4 Gene

mRNA differential expression in normal tissues according to GTEx for KLF4 Gene

This gene is overexpressed in Skin - Not Sun Exposed (Suprapubic) (x7.2) and Skin - Sun Exposed (Lower leg) (x6.2).

Protein differential expression in normal tissues from HIPED for KLF4 Gene

This gene is overexpressed in Monocytes (48.3) and Placenta (20.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for KLF4 Gene



Protein tissue co-expression partners for KLF4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KLF4

SOURCE GeneReport for Unigene cluster for KLF4 Gene:

Hs.376206

Evidence on tissue expression from TISSUES for KLF4 Gene

  • Nervous system(4.7)
  • Lung(4.6)
  • Liver(4.6)
  • Skin(3.7)
  • Heart(3.5)
  • Muscle(3.4)
  • Bone marrow(3.3)
  • Intestine(3.2)
  • Blood(3.1)
  • Stomach(3.1)
  • Spleen(3)
  • Kidney(2.9)
  • Eye(2.8)
  • Lymph node(2.6)
  • Pancreas(2.6)
  • Thyroid gland(2.4)
  • Adrenal gland(2.3)
  • Bone(2.3)
  • Gall bladder(2.2)
genes like me logo Genes that share expression patterns with KLF4: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for KLF4 Gene

Orthologs for KLF4 Gene

This gene was present in the common ancestor of animals.

Orthologs for KLF4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia KLF4 30 31
  • 99.72 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia KLF4 30 31
  • 91.54 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Klf4 30 17 31
  • 88.52 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Klf4 30
  • 88.35 (n)
Dog
(Canis familiaris)
 Mammalia KLF4 30 31
  • 80.43 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia KLF4 31
  • 75 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia KLF4 31
  • 56 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves KLF4 30 31
  • 70.35 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia KLF4 31
  • 65 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia klf4 30
  • 61.13 (n)
Zebrafish
(Danio rerio)
 Actinopterygii klf4a 30 31
  • 57.35 (n)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta CG9895 32
  • 73 (a)
Worm
(Caenorhabditis elegans)
 Secernentea F56F11.3 32
  • 79 (a)
mua-1 32
  • 65 (a)
F53F8.1 32
  • 56 (a)
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 27 (a)
 OneToMany
Sea Vase
(Ciona intestinalis)
 Ascidiacea Cin.290 30
Species where no ortholog for KLF4 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)
  • 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 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)

Evolution for KLF4 Gene

ENSEMBL:
Gene Tree for KLF4 (if available)
TreeFam:
Gene Tree for KLF4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KLF4: view image

Paralogs for KLF4 Gene

Paralogs for KLF4 Gene

(127) SIMAP similar genes for KLF4 Gene using alignment to 6 proteins:

  • KLF4_HUMAN
  • B7ZBT1_HUMAN
  • B7ZBT2_HUMAN
  • F2VTX5_HUMAN
  • L0R3V2_HUMAN
  • Q5T3J6_HUMAN

Pseudogenes.org Pseudogenes for KLF4 Gene

genes like me logo Genes that share paralogs with KLF4: view

Variants for KLF4 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KLF4 Gene

SNP ID Clinical significance and condition Chr 09 pos Variation AA Info Type
720675 Benign: not provided 107,487,134(-) T/C SYNONYMOUS_VARIANT
725601 Likely Benign: not provided 107,488,934(-) T/C MISSENSE_VARIANT
726083 Benign: not provided 107,487,421(-) G/A SYNONYMOUS_VARIANT
734740 Likely Benign: not provided 107,487,703(-) G/A SYNONYMOUS_VARIANT
748147 Likely Benign: not provided 107,487,335(-) G/C SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for KLF4 Gene

Structural Variations from Database of Genomic Variants (DGV) for KLF4 Gene

Variant ID Type Subtype PubMed ID
nsv825028 CNV gain 20364138

Variation tolerance for KLF4 Gene

Residual Variation Intolerance Score: 43% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.45; 28.39% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KLF4 Gene

Human Gene Mutation Database (HGMD)
KLF4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLF4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KLF4 Gene

Disorders for KLF4 Gene

MalaCards: The human disease database

(28) MalaCards diseases for KLF4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
secretory meningioma
  • meningioma
skin squamous cell carcinoma
  • epidermoid skin carcinoma
cerebral cavernous malformations
  • cam
germ cell and embryonal cancer
  • germ cell and embryonal neoplasm
familial adenomatous polyposis
  • fap
- elite association - COSMIC cancer census association via MalaCards
Search KLF4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for KLF4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with KLF4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KLF4 Gene

Publications for KLF4 Gene

  1. Human EZF, a Krüppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains. (PMID: 9422764) Yet SF … Lee ME (The Journal of biological chemistry 1998) 2 3 4 23
  2. Analysis of KLF transcription factor family gene variants in type 2 diabetes. (PMID: 17688680) Gutiérrez-Aguilar R … Neve B (BMC medical genetics 2007) 3 23 41
  3. KLF4, p21 and context-dependent opposing forces in cancer. (PMID: 16372018) Rowland BD … Peeper DS (Nature reviews. Cancer 2006) 2 3 23
  4. Shaking the family tree: identification of novel and biologically active alternatively spliced isoforms across the KLF family of transcription factors. (PMID: 23134681) Camacho-Vanegas O … Martignetti JA (FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2013) 3 4
  5. Cooperative transcriptional activation by Klf4, Meis2, and Pbx1. (PMID: 21746878) Bjerke GA … Wotton D (Molecular and cellular biology 2011) 3 4

ExternalLinks

View latest publications for KLF4 gene in Mastermind

Products for KLF4 Gene

  • Addgene plasmids for KLF4

Sources for KLF4 Gene