HSF1
heat shock transcription factor 1
Basic information
Region (hg38): 8:144291591-144314720
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSF1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | |||||
| missense | 36 | 37 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 36 | 3 | 2 |
Variants in HSF1
This is a list of pathogenic ClinVar variants found in the HSF1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-144291796-C-G | not specified | Uncertain significance (Jul 30, 2024) | ||
| 8-144291829-C-A | Benign (Jul 26, 2018) | |||
| 8-144291851-G-A | not specified | Uncertain significance (Mar 25, 2022) | ||
| 8-144291861-T-C | not specified | Uncertain significance (Jan 30, 2024) | ||
| 8-144308917-C-A | not specified | Uncertain significance (Dec 17, 2024) | ||
| 8-144308973-A-G | not specified | Uncertain significance (Aug 14, 2024) | ||
| 8-144308988-C-T | not specified | Uncertain significance (Jan 23, 2025) | ||
| 8-144309545-G-A | not specified | Uncertain significance (Feb 16, 2023) | ||
| 8-144309584-T-G | not specified | Uncertain significance (Aug 08, 2023) | ||
| 8-144309837-C-T | Benign (Dec 13, 2017) | |||
| 8-144309869-T-C | not specified | Uncertain significance (Jan 04, 2024) | ||
| 8-144309886-G-A | not specified | Uncertain significance (Nov 29, 2021) | ||
| 8-144309889-A-G | not specified | Uncertain significance (Dec 18, 2023) | ||
| 8-144311202-G-A | not specified | Uncertain significance (Nov 10, 2021) | ||
| 8-144311241-G-A | not specified | Uncertain significance (Jan 21, 2025) | ||
| 8-144311555-G-T | not specified | Uncertain significance (Jun 01, 2023) | ||
| 8-144311589-G-A | Likely benign (Jul 26, 2018) | |||
| 8-144311721-A-G | not specified | Likely benign (Jan 23, 2023) | ||
| 8-144311727-A-G | not specified | Uncertain significance (Sep 16, 2021) | ||
| 8-144311988-C-T | not specified | Uncertain significance (Jan 21, 2025) | ||
| 8-144312007-C-T | not specified | Uncertain significance (Feb 01, 2025) | ||
| 8-144312013-C-T | not specified | Uncertain significance (Mar 07, 2024) | ||
| 8-144312028-G-A | not specified | Uncertain significance (Feb 11, 2022) | ||
| 8-144312038-G-T | not specified | Uncertain significance (Mar 16, 2022) | ||
| 8-144312048-G-A | not specified | Uncertain significance (Apr 12, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HSF1 | protein_coding | protein_coding | ENST00000528838 | 13 | 23106 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.748 | 0.252 | 125726 | 0 | 10 | 125736 | 0.0000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.753 | 293 | 332 | 0.884 | 0.0000204 | 3433 |
| Missense in Polyphen | 43 | 80.578 | 0.53365 | 927 | ||
| Synonymous | -2.04 | 187 | 155 | 1.21 | 0.0000110 | 1069 |
| Loss of Function | 3.57 | 4 | 22.1 | 0.181 | 9.46e-7 | 266 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000909 | 0.0000908 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000540 | 0.0000527 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000166 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Function as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones heat shock proteins (HSPs) that protect cells from cellular insults' damage (PubMed:1871105, PubMed:11447121, PubMed:1986252, PubMed:7760831, PubMed:7623826, PubMed:8946918, PubMed:8940068, PubMed:9341107, PubMed:9121459, PubMed:9727490, PubMed:9499401, PubMed:9535852, PubMed:12659875, PubMed:12917326, PubMed:15016915, PubMed:25963659, PubMed:26754925). In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form (PubMed:9727490, PubMed:11583998, PubMed:16278218). Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes (PubMed:1871105, PubMed:1986252, PubMed:8455624, PubMed:7935471, PubMed:7623826, PubMed:8940068, PubMed:9727490, PubMed:9499401, PubMed:10359787, PubMed:11583998, PubMed:12659875, PubMed:16278218, PubMed:25963659, PubMed:26754925). Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form (PubMed:11583998, PubMed:16278218). Binds to inverted 5'-NGAAN-3' pentamer DNA sequences (PubMed:1986252, PubMed:26727489). Binds to chromatin at heat shock gene promoters (PubMed:25963659). Plays also several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells (PubMed:9341107). Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner (PubMed:14707147). Plays a role in nuclear export of stress-induced HSP70 mRNA (PubMed:17897941). Plays a role in the regulation of mitotic progression (PubMed:18794143). Plays also a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage- dependent manner (PubMed:26359349). Involved in stress-induced cancer cell proliferation in a IER5-dependent manner (PubMed:26754925). {ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11583998, ECO:0000269|PubMed:12659875, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:1871105, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:1986252, ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:26727489, ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7760831, ECO:0000269|PubMed:7935471, ECO:0000269|PubMed:8455624, ECO:0000269|PubMed:8940068, ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9341107, ECO:0000269|PubMed:9499401, ECO:0000269|PubMed:9535852, ECO:0000269|PubMed:9727490}.;
- Pathway
- Legionellosis - Homo sapiens (human);HSF1 activation;Attenuation phase;HSF1-dependent transactivation;Regulation of HSF1-mediated heat shock response;Cellular responses to stress;p73 transcription factor network;Cellular responses to external stimuli;Cellular response to heat stress
(Consensus)
Recessive Scores
- pRec
- 0.165
Intolerance Scores
- loftool
- 0.0873
- rvis_EVS
- -0.87
- rvis_percentile_EVS
- 10.8
Haploinsufficiency Scores
- pHI
- 0.115
- hipred
- Y
- hipred_score
- 0.570
- ghis
- 0.588
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hsf1
- Phenotype
- cellular phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; pigmentation phenotype;
Zebrafish Information Network
- Gene name
- hsf1
- Affected structure
- retinal ganglion cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;MAPK cascade;embryonic placenta development;DNA repair;mRNA processing;defense response;female meiotic nuclear division;spermatogenesis;positive regulation of cell population proliferation;negative regulation of cell population proliferation;mRNA transcription;negative regulation of cardiac muscle cell apoptotic process;response to activity;negative regulation of tumor necrosis factor production;response to testosterone;cellular response to heat;cellular response to unfolded protein;cellular protein-containing complex assembly;cellular response to potassium ion;positive regulation of multicellular organism growth;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;regulation of protein heterodimerization activity;positive regulation of mitotic cell cycle;positive regulation of transcription by RNA polymerase II;mRNA transport;protein homooligomerization;embryonic process involved in female pregnancy;positive regulation of transcription from RNA polymerase II promoter in response to heat stress;protein homotrimerization;cellular response to hydrogen peroxide;cellular response to lipopolysaccharide;cellular response to cadmium ion;cellular response to copper ion;cellular response to estradiol stimulus;cellular response to gamma radiation;cellular response to diamide;negative regulation of inclusion body assembly;positive regulation of inclusion body assembly;positive regulation of cold-induced thermogenesis;regulation of cellular response to heat;positive regulation of mRNA polyadenylation;negative regulation of neuron death;positive regulation of apoptotic DNA fragmentation;cellular response to sodium arsenite;cellular response to angiotensin;positive regulation of microtubule binding;cellular response to nitroglycerin;cellular response to L-glutamine;response to hypobaric hypoxia;response to psychosocial stress;negative regulation of double-strand break repair via nonhomologous end joining
- Cellular component
- kinetochore;condensed chromosome kinetochore;euchromatin;heterochromatin;nucleus;nucleoplasm;cytoplasm;centrosome;cytosol;PML body;pronucleus;perinuclear region of cytoplasm;nuclear stress granule;mitotic spindle pole;ribonucleoprotein complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;protein kinase binding;heat shock protein binding;chromatin DNA binding;identical protein binding;sequence-specific DNA binding;protein self-association;protein heterodimerization activity;Hsp90 protein binding;translation elongation factor binding;STAT family protein binding;sequence-specific single stranded DNA binding;promoter-specific chromatin binding