HSBP1
protein-codingheat shock factor binding protein 1
Gene summary
The heat-shock response is elicited by exposure of cells to thermal and chemical stress and through the activation of HSFs (heat shock factors) results in the elevated expression of heat-shock induced genes. Heat shock factor binding protein 1 (HSBP1), is a 76-amino-acid protein that binds to heat shock factor 1(HSF1), which is a transcription factor involved in the HS response. During HS response, HSF1 undergoes conformational transition from an inert non-DNA-binding monomer to active functional trimers. HSBP1 is nuclear-localized and interacts with the active trimeric state of HSF1 to negatively regulate HSF1 DNA-binding activity. Overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. When overexpressed in C.elegans HSBP1 has severe effects on survival of the animals after thermal and chemical stress consistent with a role of HSBP1 as a negative regulator of heat shock response. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~100.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HSBP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001537.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 9 | 1 | 10 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 9 | 1 | 0 | 10 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001528.1 | 3 | MANE Select | |
| Ensembl | ENSP00000392896.2 | 3 | MANE Select | |
| Ensembl | ENSP00000458007.1 | 3 | Standard | |
| Ensembl | ENSP00000458007.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hsbp1b | Danio rerio | Structure: head Quality: deformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HSF1 activation
- Attenuation phase
- HSF1-dependent transactivation
- Cellular responses to stress
- Cellular responses to external stimuli
Biological Process
- negative regulation of transcription by RNA polymerase II
- muscle contraction
- endodermal cell differentiation
- cellular heat acclimation
- regulation of cellular response to heat
Molecular Function
- transcription corepressor activity
- protein binding
- identical protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000433866
- Coding exons
- 3
- Length
- 11895
- Individuals with no LoFs
- 124209
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124211
- p
- 0.00000805
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.583 | 28 | 38.1 | 0.734 | 0.00000201 | 500 |
| Missense (PolyPhen) | 6 | 4.4199 | 1.3575 | 85 | ||
| Synonymous | -0.678 | 17 | 13.8 | 1.23 | 7.40e-7 | 124 |
| Loss of Function | 1.14 | 1 | 3.20 | 0.312 | 1.36e-7 | 39 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Negative regulator of the heat shock response. Negatively affects HSF1 DNA-binding activity. May have a role in the suppression of the activation of the stress response during the aging process.;
Recessive Scores
- pRec
- 0.0915
Intolerance Scores
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 59.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.987
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |