Heat-shock transcription factors (HSFs) activate heat-shock response genes under conditions of heat or other stresses. HSF4 lacks the carboxyl-terminal hydrophobic repeat which is shared among all vertebrate HSFs and has been suggested to be involved in the negative regulation of DNA binding activity. Two alternatively spliced transcripts encoding distinct isoforms and possessi... See more...

Aliases for HSF4 Gene

Aliases for HSF4 Gene

  • Heat Shock Transcription Factor 4 2 3 4 5
  • Heat Shock Factor Protein 4 3 4
  • HSTF 4 3 4
  • HSF 4 3 4
  • HHSF4 3 4
  • Cataract, Marner 2
  • CTRCT5 3
  • HSF4 5
  • CTM 3

External Ids for HSF4 Gene

Previous HGNC Symbols for HSF4 Gene

  • CTM

Previous GeneCards Identifiers for HSF4 Gene

  • GC16P057891
  • GC16P067576
  • GC16P066932
  • GC16P066974
  • GC16P065756
  • GC16P067197
  • GC16P053070

Summaries for HSF4 Gene

Entrez Gene Summary for HSF4 Gene

  • Heat-shock transcription factors (HSFs) activate heat-shock response genes under conditions of heat or other stresses. HSF4 lacks the carboxyl-terminal hydrophobic repeat which is shared among all vertebrate HSFs and has been suggested to be involved in the negative regulation of DNA binding activity. Two alternatively spliced transcripts encoding distinct isoforms and possessing different transcriptional activity have been described. [provided by RefSeq, Jul 2008]

GeneCards Summary for HSF4 Gene

HSF4 (Heat Shock Transcription Factor 4) is a Protein Coding gene. Diseases associated with HSF4 include Cataract 5, Multiple Types and Cataract 16, Multiple Types. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription corepressor activity. An important paralog of this gene is HSF1.

UniProtKB/Swiss-Prot Summary for HSF4 Gene

Gene Wiki entry for HSF4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HSF4 Gene

Genomics for HSF4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HSF4 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 HSF4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HSF4

Top Transcription factor binding sites by QIAGEN in the HSF4 gene promoter:
  • ATF-2
  • c-Ets-1
  • c-Jun
  • E2F
  • E2F-1
  • p53

Genomic Locations for HSF4 Gene

Latest Assembly
chr16:67,163,761-67,169,945
(GRCh38/hg38)
Size:
6,185 bases
Orientation:
Plus strand

Previous Assembly
chr16:67,197,664-67,203,844
(GRCh37/hg19 by Entrez Gene)
Size:
6,181 bases
Orientation:
Plus strand

chr16:67,197,288-67,203,848
(GRCh37/hg19 by Ensembl)
Size:
6,561 bases
Orientation:
Plus strand

Genomic View for HSF4 Gene

Genes around HSF4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HSF4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HSF4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HSF4 Gene

Proteins for HSF4 Gene

  • Protein details for HSF4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9ULV5-HSF4_HUMAN
    Recommended name:
    Heat shock factor protein 4
    Protein Accession:
    Q9ULV5
    Secondary Accessions:
    • Q99472
    • Q9ULV6

    Protein attributes for HSF4 Gene

    Size:
    492 amino acids
    Molecular mass:
    53011 Da
    Quaternary structure:
    • Homotrimer (By similarity). Exhibits constitutive DNA binding and forms trimers even in the absence of stress (By similarity). Interacts with ALKBH4, DUSP26, MAPK1, MAPK2, MAPK8 and MAP kinase p38 (PubMed:16581800, PubMed:23145062).

    Three dimensional structures from OCA and Proteopedia for HSF4 Gene

    Alternative splice isoforms for HSF4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HSF4 Gene

Post-translational modifications for HSF4 Gene

  • Phosphorylated mainly on serine residues. Phosphorylation on Ser-298 promotes sumoylation on Lys-293.
  • Isoform HSF4B is constitutively sumoylated. Sumoylation represses the transcriptional activity and is promoted by phosphorylation on Ser-298. HSFA is not sumoylated.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for HSF4 Gene

Domains & Families for HSF4 Gene

Gene Families for HSF4 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for HSF4 Gene

InterPro:
Blocks:
  • Heat shock factor (HSF)-type DNA-binding domain
ProtoNet:

Suggested Antigen Peptide Sequences for HSF4 Gene

GenScript: Design optimal peptide antigens:
  • Heat shock transcription factor 4 (HSF4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9ULV5

UniProtKB/Swiss-Prot:

HSF4_HUMAN :
  • Belongs to the HSF family.
Family:
  • Belongs to the HSF family.
genes like me logo Genes that share domains with HSF4: view

Function for HSF4 Gene

Molecular function for HSF4 Gene

UniProtKB/Swiss-Prot Function:
DNA-binding protein that specifically binds heat shock promoter elements (HSE).
UniProtKB/Swiss-Prot Function:
[Isoform HSF4A]: Transcriptional repressor.
UniProtKB/Swiss-Prot Function:
[Isoform HSF4B]: Transcriptional activator.
GENATLAS Biochemistry:
heat shock transcription factor 4,preferentially expressed in heart,brain,skeletal muscle,pancreas,potential repressor of genes for HS proteins and molecular chaperones with two alternatively spliced isoform HSF4a,HSF4b,the former acting as an inhibitor,the latter as an activator of tissue specific heat shock gene expression

Phenotypes From GWAS Catalog for HSF4 Gene

Gene Ontology (GO) - Molecular Function for HSF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 8972228
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IDA,ISA --
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IEA,IBA 21873635
GO:0005515 protein binding IPI --
genes like me logo Genes that share ontologies with HSF4: view
genes like me logo Genes that share phenotypes with HSF4: view

Human Phenotype Ontology for HSF4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HSF4 Gene

MGI Knock Outs for HSF4:
  • Hsf4 Hsf4<tm1b(KOMP)Wtsi>
  • Hsf4 Hsf4<tm1Anak>
  • Hsf4 Hsf4<tm1Miv>
  • Hsf4 Hsf4<tm1Xyk>

miRNA for HSF4 Gene

miRTarBase miRNAs that target HSF4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HSF4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for HSF4 Gene

Localization for HSF4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HSF4 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 HSF4 gene
Compartment Confidence
nucleus 5
plasma membrane 2
cytosol 2
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

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

Gene Ontology (GO) - Cellular Components for HSF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin IDA,ISA --
GO:0005634 nucleus IEA,IBA 21873635
GO:0016607 nuclear speck IDA --
GO:0042025 host cell nucleus IEA --
genes like me logo Genes that share ontologies with HSF4: view

Pathways & Interactions for HSF4 Gene

PathCards logo

SuperPathways for HSF4 Gene

No Data Available

SIGNOR curated interactions for HSF4 Gene

Activates:

Gene Ontology (GO) - Biological Process for HSF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 8972228
GO:0001654 eye development IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007601 visual perception IEA --
genes like me logo Genes that share ontologies with HSF4: view

No data available for Pathways by source for HSF4 Gene

Drugs & Compounds for HSF4 Gene

No Compound Related Data Available

Transcripts for HSF4 Gene

mRNA/cDNA for HSF4 Gene

4 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
25 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HSF4

Alternative Splicing Database (ASD) splice patterns (SP) for HSF4 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b · 12c ^ 13a · 13b · 13c
SP1: - - - -
SP2: - - - -
SP3: - - -
SP4:
SP5:
SP6:
SP7: -

Relevant External Links for HSF4 Gene

GeneLoc Exon Structure for
HSF4

Expression for HSF4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HSF4 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HSF4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HSF4

SOURCE GeneReport for Unigene cluster for HSF4 Gene:

Hs.512156

mRNA Expression by UniProt/SwissProt for HSF4 Gene:

Q9ULV5-HSF4_HUMAN
Tissue specificity: Expressed in heart, skeletal muscle, eye and brain, and at much lower levels in some other tissues.

Evidence on tissue expression from TISSUES for HSF4 Gene

  • Heart(4.4)
  • Kidney(3.5)
  • Nervous system(3.3)
  • Skin(2.3)
  • Eye(2.1)
  • Muscle(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HSF4 Gene

Germ Layers:
  • ectoderm
Systems:
  • nervous
Regions:
Head and neck:
  • brain
  • cranial nerve
  • eye
  • head
General:
  • peripheral nervous system
genes like me logo Genes that share expression patterns with HSF4: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Protein tissue co-expression partners for HSF4 Gene

Orthologs for HSF4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for HSF4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HSF4 30 31
  • 99.46 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia HSF4 30 31
  • 91.45 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HSF4 30 31
  • 89.71 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Hsf4 30 17 31
  • 86.19 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 49 (a)
ManyToMany
-- 31
  • 27 (a)
ManyToMany
Oppossum
(Monodelphis domestica)
Mammalia HSF4 31
  • 49 (a)
OneToOne
Chicken
(Gallus gallus)
Aves HSF4 31
  • 44 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia HSF4 31
  • 55 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii hsf4 31
  • 46 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Hsf 31 32
  • 19 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea Y53C10A.12 32
  • 40 (a)
hsf-1 31
  • 18 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HSF1 31
  • 12 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 24 (a)
OneToMany
Species where no ortholog for HSF4 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)
  • 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)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for HSF4 Gene

ENSEMBL:
Gene Tree for HSF4 (if available)
TreeFam:
Gene Tree for HSF4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HSF4: view image

Paralogs for HSF4 Gene

Paralogs for HSF4 Gene

(2) SIMAP similar genes for HSF4 Gene using alignment to 13 proteins:

  • HSF4_HUMAN
  • E5RG51_HUMAN
  • E5RHY0_HUMAN
  • E5RJV4_HUMAN
  • E5RK26_HUMAN
  • E7EWW4_HUMAN
  • H0YAR7_HUMAN
  • H0YAU2_HUMAN
  • H0YBG9_HUMAN
  • H0YBS6_HUMAN
  • H0YBT7_HUMAN
  • H0YC14_HUMAN
  • H0YC39_HUMAN
genes like me logo Genes that share paralogs with HSF4: view

Variants for HSF4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HSF4 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
884526 Uncertain Significance: Cataract 5 multiple types 67,163,415(+) A/C
NM_018378.3(FBXL8):c.720A>C (p.Glu240Asp)
MISSENSE
884592 Benign: Cataract 5 multiple types 67,165,833(+) G/A
NM_001374675.1(HSF4):c.347G>A (p.Arg116His)
MISSENSE
884593 Uncertain Significance: Cataract 5 multiple types 67,165,986(+) A/T
NM_001374675.1(HSF4):c.401A>T (p.Glu134Val)
MISSENSE
884594 Likely Benign: Cataract 5 multiple types 67,166,344(+) G/A
NM_001374675.1(HSF4):c.510G>A (p.Glu170=)
SYNONYMOUS
885460 Uncertain Significance: Cataract 5 multiple types 67,163,476(+) G/C
NM_018378.3(FBXL8):c.781G>C (p.Ala261Pro)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HSF4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for HSF4 Gene

Variant ID Type Subtype PubMed ID
nsv1160429 CNV deletion 26073780
nsv522852 CNV gain 19592680
nsv524363 CNV loss 19592680
nsv827707 CNV loss 20364138
nsv952044 CNV deletion 24416366

Variation tolerance for HSF4 Gene

Residual Variation Intolerance Score: 48.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.03; 21.05% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HSF4 Gene

Human Gene Mutation Database (HGMD)
HSF4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HSF4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HSF4 Gene

Disorders for HSF4 Gene

MalaCards: The human disease database

(11) MalaCards diseases for HSF4 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search HSF4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HSF4_HUMAN
  • Cataract 5, multiple types (CTRCT5) [MIM:116800]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT5 includes infantile, lamellar, zonular, nuclear, anterior polar, stellate, and Marner-type cataracts, among others. Finger malformation is observed in some kindreds. {ECO:0000269 PubMed:12089525, ECO:0000269 PubMed:16876512}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for HSF4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HSF4: view

No data available for Genatlas for HSF4 Gene

Publications for HSF4 Gene

  1. Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract. (PMID: 12089525) Bu L … Kong X (Nature genetics 2002) 2 3 4 74
  2. The mammalian HSF4 gene generates both an activator and a repressor of heat shock genes by alternative splicing. (PMID: 10488131) Tanabe M … Nakai A (The Journal of biological chemistry 1999) 2 3 4 23
  3. HSF4, a new member of the human heat shock factor family which lacks properties of a transcriptional activator. (PMID: 8972228) Nakai A … Nagata K (Molecular and cellular biology 1997) 2 3 4 23
  4. Novel HSF4 mutation causes congenital total white cataract in a Chinese family. (PMID: 16876512) Ke T … Liu M (American journal of ophthalmology 2006) 3 4 23
  5. Human ALKBH4 interacts with proteins associated with transcription. (PMID: 23145062) Bjørnstad LG … Falnes PØ (PloS one 2012) 3 4

Products for HSF4 Gene

Sources for HSF4 Gene