HSF2

Chr 6

heat shock transcription factor 2

Also known as: HSF 2, HSTF 2

NCBI Gene: 3298ENSG00000025156UniProt: Q03933

The protein encoded by this gene belongs to the HSF family of transcription factors that bind specifically to the heat-shock promoter element and activate transcription. Heat shock transcription factors activate heat-shock response genes under conditions of heat or other stresses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

0
ClinVar variants
0
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HSF2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.32LOEUF
pLI 0.975
Z-score 4.30
OE 0.14 (0.07–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.07Z-score
OE missense 0.65 (0.57–0.73)
179 obs / 275.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.14 (0.07–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.57–0.73)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 4 / 29.0Missense obs/exp: 179 / 275.6Syn Z: -0.76

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HSF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HSF2 drives breast cancer progression by acting as a stage-specific switch between proliferation and invasion.
Pessa JC et al.·Sci Adv
2025
Establishment and validation of exhausted CD8+ T cell feature as a prognostic model of HCC.
Shi J et al.·Front Immunol
2023Functional
Heat-shock factor 2 is a suppressor of prostate cancer invasion.
Björk JK et al.·Oncogene
2016
SUMOylation is not a prerequisite for HSF1's role in stress protection and transactivation.
Bardelcik M et al.·Sci Rep
2025
Cerebellar injury induced by cadmium via disrupting the heat-shock response.
Bi SS et al.·Environ Sci Pollut Res Int
2023
New genes involved in Angelman syndrome-like: Expanding the genetic spectrum.
Aguilera C et al.·PLoS One
2021
PRC1 associates with the hsp70i promoter and interacts with HSF2 during mitosis.
Murphy LA et al.·Exp Cell Res
2008
HSP90 Family Members, Their Regulators and Ischemic Stroke Risk: A Comprehensive Molecular-Genetics and Bioinformatics Analysis.
Kobzeva K et al.·Front Biosci (Schol Ed)
2024
Analysis of IL12B gene variants in inflammatory bowel disease.
Glas J et al.·PLoS One
2012
Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure.
Cannarella R et al.·Asian J Androl
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools