GeneBe

HSF1

protein-coding

heat shock transcription factor 1

Gene summary

The product of this gene is a transcription factor that is rapidly induced after temperature stress and binds heat shock promoter elements (HSE). This protein plays a role in the regulation of lifespan. Expression of this gene is repressed by phosphorylation, which promotes binding by heat shock protein 90. [provided by RefSeq, Jul 2017]

MANE transcript

NM_005526.4

Inheritance

—

ClinVar variants

U:77B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr8:144,291,591-144,314,720

External References & Databases

Ensembl (ENSG00000185122)NCBI Gene (3297)OMIM (140580)HGNC:5224GenCCUniProt (Q00613)AlphaFoldClinVar (HSF1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~23.1 kb
Loading mutation effect viewer...

GenCC 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 HSF1 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 70
not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005526.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
2
clinvar
 6
missense
68
clinvar
3
clinvar
 71
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
8
clinvar
 8
Total00776285
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 96 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005526.4RefSeqNP_005517.113MANE Select
ENST00000528838.6EnsemblENSP00000431512.113MANE Select
ENST00000400780.8EnsemblENSP00000383590.513Standard
ENST00000400780.9EnsemblENSP00000383590.513Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
hsf1Danio rerio

Structure: retinal ganglion cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Legionellosis - Homo sapiens (human)
  • HSF1 activation
  • Attenuation phase
  • HSF1-dependent transactivation
  • Regulation of HSF1-mediated heat shock response

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • MAPK cascade
  • embryonic placenta development
  • DNA repair
  • mRNA processing

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

Cellular Component

  • kinetochore
  • condensed chromosome kinetochore
  • euchromatin
  • heterochromatin
  • nucleus

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000528838
Coding exons
13
Length
23106
Individuals with no LoFs
125726
Homozygous LoFs
0
Heterozygous LoFs
10
Defined
125736
p
0.0000398
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.7532933320.8840.00002043433
Missense (PolyPhen)4380.5780.53365927
Synonymous-2.041871551.210.00001101069
Loss of Function3.57422.10.1819.46e-7266

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000540.000053rare
South Asian00.0absent
Other0.000170.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

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}.;

Recessive Scores

pRec
0.165

Intolerance Scores

LoFtool
0.0873
RVIS EVS
-0.87
RVIS percentile EVS
10.8

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.