HSF1

Chr 8

heat shock transcription factor 1

Also known as: HSTF1

This transcription factor regulates the heat shock response by binding to heat shock elements and activating expression of molecular chaperones and heat shock proteins that protect cells from stress damage. Mutations cause autosomal dominant neurodevelopmental disorder with seizures, hypotonia, and developmental delay, with onset typically in infancy or early childhood. HSF1 is highly constrained against loss-of-function variants, suggesting an essential role in human development.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
155
Pubs (1 yr)
58
P/LP submissions
0%
P/LP missense
0.41
LOEUF
LOF
Mechanism· predicted
Clinical SummaryHSF1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
57 unique Pathogenic / Likely Pathogenic· 79 VUS of 168 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.748
Z-score 3.57
OE 0.18 (0.090.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.75Z-score
OE missense 0.88 (0.800.97)
293 obs / 331.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.090.41)
00.351.4
Missense OE0.88 (0.800.97)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 4 / 22.1Missense obs/exp: 293 / 331.6Syn Z: -2.04
DN
0.5081th %ile
GOF
0.3689th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.41

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

168 submitted variants in ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic5
VUS79
Likely Benign7
Benign3
52
Pathogenic
5
Likely Pathogenic
79
VUS
7
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
52
0
52
Likely Pathogenic
0
0
5
0
5
VUS
0
67
12
0
79
Likely Benign
0
3
1
3
7
Benign
0
0
1
2
3
Total070715146

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HSF1 · protein map & ClinVar variants

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

Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗