HSPA1A

Chr 6

heat shock protein family A (Hsp70) member 1A

Also known as: HEL-S-103, HSP70, HSP70-1, HSP70-1A, HSP70-2, HSP70.1, HSP70.2, HSP70I

NCBI Gene: 3303ENSG00000204389UniProt: P0DMV8

This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq, Jul 2008]

43
ClinVar variants
7
Pathogenic / LP
0.03
pLI score
2
Active trials
Clinical Summary— HSPA1A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 33 VUS of 43 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.29LOEUF
pLI 0.030
Z-score 1.12
OE 0.50 (0.23–1.29)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.43Z-score
OE missense 0.69 (0.59–0.81)
116 obs / 168.1 exp
Tolerant

Mild missense constraint

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.0.50 (0.23–1.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.59–0.81)
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.1.03
0≤1.21.6
LoF obs/exp: 3 / 6.0Missense obs/exp: 116 / 168.1Syn Z: -0.22

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS33
Likely Benign1
Benign2
5
Pathogenic
2
Likely Pathogenic
33
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
2
0
2
VUS
0
29
4
0
33
Likely Benign
0
0
1
0
1
Benign
0
0
2
0
2
Total02914043

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

View in ClinVar →

Protein Context — Lollipop Plot

HSPA1A · 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
Integrating single-nucleus sequence profiling to reveal the transcriptional dynamics of Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
Fan LY et al.·J Transl Med
2023
Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma.
Rindler K et al.·Mol Cancer
2021
SPP1(high) macrophage-induced T-cell stress promotes colon cancer liver metastasis through SPP1/CD44/PI3K/AKT signaling.
Ding D et al.·J Immunother Cancer
2025
HSPA1A Protects Cells from Thermal Stress by Impeding ESCRT-0-Mediated Autophagic Flux in Epidermal Thermoresistance.
Wu S et al.·J Invest Dermatol
2021Review
Re-examining HSPC1 inhibitors.
Lee SL et al.·Cell Stress Chaperones
2017
Up-regulation of HSPA1A and HSPA1B in the blood of tophi patients and its clinical significance.
Li Y et al.·Acta Biochim Pol
2022Cohort
Single-nucleus transcriptomics reveals a distinct microglial state and increased MSR1-mediated phagocytosis as common features across dementia subtypes.
Chia SY et al.·Genome Med
2025
Comprehensive multiplexed autoantibody profiling of patients with advanced urothelial cancer.
Ravi P et al.·J Immunother Cancer
2024Cohort
lncRNA IGFL2-AS1 mediates NSCLC chemoresistance via YBX1-induced HSPA1A/RAP1 activation.
Dong H et al.·Cell Mol Biol Lett
2025
Single-Cell RNA Sequencing Reveals the Immune Landscape of Granulomatous Mastitis.
Zhou Y et al.·Inflammation
2025
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
Healthy

Effect of Transcranial Alternative Current Stimulation at Alpha Frequency (α-tACS) on Stressed Healthy Subjects

RECRUITING
NCT06229002Phase NAHôpital le VinatierStarted 2024-01-24
Transcranial alternative current stimulation (tACS) at alpha frequencySham stimulation
Advanced Lung Non-Small Cell CarcinomaLocally Advanced Lung Non-Small Cell CarcinomaStage III Lung Cancer AJCC v8

Minnelide and Osimertinib for the Treatment of Advanced EGFR Mutated Non-Small Cell Lung Cancer

ACTIVE NOT RECRUITING
NCT05166616Phase PHASE1City of Hope Medical CenterStarted 2022-03-07
BiopsyOsimertinibTriptolide Analog

External Resources

Links to major genomics databases and tools