HSP90AB1

Chr 6

heat shock protein 90 alpha family class B member 1

Also known as: D6S182, HSP84, HSP90B, HSPC2, HSPCB

NCBI Gene: 3326ENSG00000096384UniProt: P08238

This gene encodes a member of the heat shock protein 90 family; these proteins are involved in signal transduction, protein folding and degradation and morphological evolution. This gene encodes the constitutive form of the cytosolic 90 kDa heat-shock protein and is thought to play a role in gastric apoptosis and inflammation. Alternative splicing results in multiple transcript variants. Pseudogenes have been identified on multiple chromosomes. [provided by RefSeq, Dec 2012]

69
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HSP90AB1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 52 VUS of 69 total submissions

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.
0.21LOEUF
pLI 0.999
Z-score 4.70
OE 0.07 (0.03–0.21)
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.
2.05Z-score
OE missense 0.71 (0.65–0.79)
289 obs / 405.1 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.0.07 (0.03–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.65–0.79)
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.1.54
0≤1.21.6
LoF obs/exp: 2 / 29.6Missense obs/exp: 289 / 405.1Syn Z: -5.06

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS52
Likely Benign4
Benign4
8
Pathogenic
1
Likely Pathogenic
52
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
51
1
0
52
Likely Benign
0
0
1
3
4
Benign
0
0
0
4
4
Total05111769

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

View in ClinVar →

Protein Context — Lollipop Plot

HSP90AB1 · 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
Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.
Hoshino A et al.·Cell
2020
Identification of immune microenvironment subtypes and signature genes for Alzheimer's disease diagnosis and risk prediction based on explainable machine learning.
Lai Y et al.·Front Immunol
2022
A unifying model for mTORC1-mediated regulation of mRNA translation.
Thoreen CC et al.·Nature
2012Functional
CDK1-SRC Interaction-Dependent Transcriptional Activation of HSP90AB1 Promotes Antitumor Immunity in Hepatocellular Carcinoma.
Zhang YJ et al.·J Proteome Res
2023Meta-analysis
Dehydroepiandrosterone ameliorates primary dysmenorrhea by suppressing the SP1/Hsp90ab1/COX-2 signaling pathway.
Wang D et al.·Bioorg Chem
2025
The N6-methyladenosine reader IGF2BP3 promotes bladder cancer progression through enhancing HSP90AB1 expression.
Chen X et al.·FEBS J
2025
circTP63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway.
Wang D et al.·Sci China Life Sci
2025
HNRNPH1 promotes autophagy to inhibit the development of lung adenocarcinoma via the HSP90AB1/MAP1LC3B axis.
Li R et al.·Respir Res
2025
Ubiquitin-related gene markers predict immunotherapy response and prognosis in patients with epithelial ovarian carcinoma.
Luo D et al.·Sci Rep
2024Cohort
Fei Wei formula attenuates pulmonary fibrosis by inhibiting lactate-driven endothelial mesenchymal transition via its target of HSP90ab1.
Gu JM et al.·Phytomedicine
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Polydatin attenuates LPS-induced acute lung injury in rats via targeting HSP90AB1.
Han L et al.·J Ethnopharmacol
2026
HSP90AB1-Mediated Ubiquitin-Proteasome Degradation of ITGBL1 Promotes Osteosarcoma Progression by Inhibiting Endoplasmic Reticulum Stress-Induced Autophagy.
Wang Z et al.·Adv Sci (Weinh)
2026
Hypoxic Reprogramming of ACOX1-Driven HSP90AB1 Crotonylation Stabilizes Thioredoxin to Orchestrate Redox Homeostasis in Oral Squamous Cell Carcinoma.
Yin X et al.·Research (Wash D C)
2026🔓 Open Access
Alantolactone curbs the malignant progression of bladder cancer partly via the HSP90AB1/LRP5/β-catenin axis.
Zhi L et al.·Mamm Genome
2025
Interaction of circPcmtd1 with HSP90AB1 mediates phosphorylation of AKT to regulate pulmonary arterial hypertension induced by high pulmonary blood flow in rat.
Ye B et al.·Clin Exp Hypertens
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