HSF4: Heat Shock Transcription Factor 4
A key regulator of heat shock protein expression and lens development, associated with cataract formation.
Gene Information Card
| Symbol | HSF4 |
|---|---|
| Full Name | Heat Shock Transcription Factor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 3299 ncbi.nlm.nih.gov/gene/3299 |
| Ensembl ID | ENSG00000103168 |
| UniProt ID | Q9ULV5 |
| OMIM ID | 602438 |
| HGNC ID | 5237 |
| Aliases | CTM, HSF4b |
Description
HSF4 (Heat Shock Transcription Factor 4) encodes a member of the heat shock transcription factor family that regulates the expression of heat shock proteins (HSPs) and other stress-responsive genes. HSF4 is essential for normal lens development and maintenance, and mutations in this gene are associated with autosomal dominant and recessive forms of cataract. The protein lacks the classical heat shock element-binding domain found in other HSFs and exhibits both activator and repressor functions depending on the cellular context.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cataract, autosomal dominant (CTM) | Mutations in HSF4 disrupt lens fiber cell differentiation and HSP expression, leading to opacification. | OMIM #602438; ClinVar |
| Cataract, autosomal recessive | Loss-of-function mutations impair HSF4 transcriptional activity, causing congenital cataract. | OMIM #602438; ClinVar |
| Marner-type cataract | Specific missense mutations (e.g., p.Arg116His) alter DNA-binding and transactivation. | OMIM #116800; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lens | 12.5 | High |
| Heart | 4.2 | Medium |
| Skeletal Muscle | 3.8 | Medium |
| Brain | 2.1 | Low |
| Liver | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 5.0 | Moderate expression |
| HeLa | 3.2 | Low expression |
| HepG2 | 2.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.347G>A (p.Arg116His) | Missense | Rare | Dominant negative; reduces DNA-binding and transactivation |
| c.595C>T (p.Arg199Trp) | Missense | Rare | Loss of function; associated with recessive cataract |
| c.1327C>T (p.Arg443*) | Nonsense | Very rare | Truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg443*) lead to truncated protein with no transcriptional activity, causing recessive cataract.
Gain of Function (GOF)
Not reported for HSF4.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg116His) produce a protein that interferes with wild-type HSF4 function, causing dominant cataract.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cellular response to heat stress (Reactome: R-HSA-3371556)
• HSF1-dependent transactivation (Reactome: R-HSA-3371571)
Protein Summary
HSF4 is a 493-amino acid transcription factor with a DNA-binding domain (DBD) and a leucine zipper (LZ) domain. It lacks the classical heat shock element (HSE) binding domain found in HSF1 and HSF2. HSF4 forms homotrimers and binds to heat shock elements in the promoters of target genes, including HSP27, HSP70, and alphaB-crystallin. It is constitutively expressed in the lens and plays a critical role in lens fiber cell differentiation. Mutations in HSF4 cause cataract by impairing its transcriptional activity and disrupting the expression of protective heat shock proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HSF4 Knockout HEK293 Cell Line | EDJ-KQ4944 | Human | 3299 | Details Get a Quote |
| HSF4 Knockout A-549 Cell Line | EDJ-KQ27801 | Human | 3299 | Details Get a Quote |
| HSF4 Knockout HCT 116 Cell Line | EDJ-KQ27802 | Human | 3299 | Details Get a Quote |
| HSF4 Knockout HeLa Cell Line | EDJ-KQ27803 | Human | 3299 | Details Get a Quote |
