HSPA1B

Chr 6

heat shock protein family A (Hsp70) member 1B

Also known as: HSP70-1, HSP70-1B, HSP70-2, HSP70.1, HSP70.2, HSP72, HSPA1, HSX70

NCBI Gene: 3304ENSG00000204388UniProt: P0DMV9

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]

40
ClinVar variants
7
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— HSPA1B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 27 VUS of 40 total submissions

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.
1.48LOEUF
pLI 0.005
Z-score 0.77
OE 0.66 (0.32–1.48)
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.
1.11Z-score
OE missense 0.76 (0.66–0.88)
126 obs / 166.2 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.0.66 (0.32–1.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.66–0.88)
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.1.13
0≤1.21.6
LoF obs/exp: 4 / 6.1Missense obs/exp: 126 / 166.2Syn Z: -0.93

ClinVar Variant Classifications

40 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS27
Likely Benign4
Benign2
5
Pathogenic
2
Likely Pathogenic
27
VUS
4
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
23
4
0
27
Likely Benign
0
2
2
0
4
Benign
0
0
2
0
2
Total02515040

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

View in ClinVar →

Protein Context — Lollipop Plot

HSPA1B · 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
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
Diagnostic and Prognostic Risk Assessment of Heat Shock Protein HSPA1B rs2763979 Gene Variant in Asthma.
Faisal S et al.·Genes (Basel)
2022
Up-regulation of HSPA1A and HSPA1B in the blood of tophi patients and its clinical significance.
Li Y et al.·Acta Biochim Pol
2022Cohort
Next Generation Sequencing of Genotype Variants and Genetic Association between Heat Shock Proteins HSPA1B Single Nucleotide Polymorphism at the g.31829044 Locus and Heat Tolerance: A Pilot Quasi-Experimental Study.
Alele FO et al.·Biomolecules
2022
Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations and interfere with outcome after major injury.
Schröder O et al.·Crit Care Med
2003
Deciphering chondrocyte diversity in diabetic osteoarthritis through single-cell transcriptomics.
Qin W et al.·Comput Biol Chem
2025
Multi-omics profiling reveals an immunosuppressive plasma cell subset within tertiary lymphoid structures in cervical cancer.
Huang Q et al.·Cancer Immunol Immunother
2025
Polymorphisms of heat shock protein-70 (HSPA1B and HSPA1L loci) do not influence infection or outcome risk in critically ill surgical patients.
Bowers DJ et al.·Shock
2006Cohort
Association of HSPA1B Polymorphisms with Paranoid Schizophrenia in a Polish Population.
Kowalczyk M et al.·Neuromolecular Med
2020
Polymorphisms of heat shock protein 70 gene (HSPA1A, HSPA1B and HSPA1L) and schizophrenia.
Pae CU et al.·Neurosci Res
2005
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Overexpression of Hspa1b in the mouse hippocampus may be associated with major depressive disorder.
Zhao X et al.·Behav Brain Funct
2025🔓 Open AccessFunctional
HSPA1B Regulates the Expression of Blood Pressure Related Genes in Human Umbilical Vein Endothelial Cells (HUVECs) and Its Mechanism.
Zhong L et al.·Tohoku J Exp Med
2025Functional
The Endothelial Cell-Related Genes EIF1 and HSPA1B Contribute to the Pathogenesis of Alzheimer's Disease by Modulating Peripheral Immunoinflammatory Responses.
Gu Y et al.·Brain Sci
2025🔓 Open Access
N6-methyladenosine (m6A) modification regulates HSPA1A and HSPA1B expression in Müller cells under high glucose stress.
Yang H et al.·Exp Eye Res
2025
Exosomes derived from TREM-2 knocked-out macrophages alleviated renal fibrosis via HSPa1b/AKT pathway.
Xiao Z et al.·Am J Physiol Renal Physiol
2025
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