HSP90B1

Chr 12

heat shock protein 90 beta family member 1

Also known as: ECGP, GP96, GRP94, HEL-S-125m, HEL35, TRA1

NCBI Gene: 7184ENSG00000166598UniProt: P14625

This gene encodes a member of a family of adenosine triphosphate(ATP)-metabolizing molecular chaperones with roles in stabilizing and folding other proteins. The encoded protein is localized to melanosomes and the endoplasmic reticulum. Expression of this protein is associated with a variety of pathogenic states, including tumor formation. There is a microRNA gene located within the 5' exon of this gene. There are pseudogenes for this gene on chromosomes 1 and 15. [provided by RefSeq, Aug 2012]

133
ClinVar variants
8
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HSP90B1
⚡
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
8 Pathogenic / Likely Pathogenic· 81 VUS of 133 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.
0.27LOEUF
pLI 0.997
Z-score 5.29
OE 0.14 (0.07–0.27)
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.
2.12Z-score
OE missense 0.71 (0.65–0.78)
307 obs / 431.1 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.0.14 (0.07–0.27)
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 (0.65–0.78)
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.0.98
0≤1.21.6
LoF obs/exp: 6 / 43.7Missense obs/exp: 307 / 431.1Syn Z: 0.20

ClinVar Variant Classifications

133 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS81
Likely Benign2
Benign1
7
Pathogenic
1
Likely Pathogenic
81
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
76
5
0
81
Likely Benign
0
1
0
1
2
Benign
0
0
0
1
1
Total07713292

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

View in ClinVar →

Protein Context — Lollipop Plot

HSP90B1 · 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
Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.
Zheng ZG et al.·Autophagy
2021
Cholesterol induction in CD8(+) T cell exhaustion in colorectal cancer via the regulation of endoplasmic reticulum-mitochondria contact sites.
Shuwen H et al.·Cancer Immunol Immunother
2023
Single-cell transcriptomic atlas throughout anti-BCMA CAR-T therapy in patients with multiple myeloma.
Xia Y et al.·Front Immunol
2023Cohort
Nanocarriers Targeting Circular RNA ADARB1 Boost Radiosensitivity of Nasopharyngeal Carcinoma through Synergically Promoting Ferroptosis.
Wang D et al.·ACS Nano
2024
Colon cancer exosome-associated HSP90B1 initiates pre-metastatic niche formation in the liver by polarizing M1 macrophage into M2 phenotype.
Li S et al.·Biol Direct
2025
Supplementing sialic acid analogs overcomes radiotherapy resistance in triple-negative breast cancer by exacerbating ER stress.
Yang M et al.·Redox Biol
2025
CCDC134 controls TLR biogenesis through the ER chaperone Gp96.
Bernaleau L et al.·J Exp Med
2025
HSP90B1 regulates autophagy via PI3K/AKT/mTOR signaling, mediating HNSC biological behaviors.
Li C et al.·PeerJ
2024
Toll-like receptor chaperone HSP90B1 and the immune response to Mycobacteria.
Graustein AD et al.·PLoS One
2018
MicroRNA-223 is a novel negative regulator of HSP90B1 in CLL.
Rodríguez-Vicente AE et al.·BMC Cancer
2015
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