HSP90B1

Chr 12

heat shock protein 90 beta family member 1

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

NCBI Gene: 7184 ENSG00000166598 UniProt: P14625 OMIM: 191175

The protein is an ATP-dependent molecular chaperone localized to the endoplasmic reticulum that regulates protein folding and transport, including folding of Wnt pathway components and Toll-like receptors. Mutations cause autosomal recessive neurodevelopmental disorders with epilepsy and intellectual disability. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.27

Clinical Summary— HSP90B1

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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.

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ClinVar Variants

77 VUS of 121 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.14 (0.07–0.27)

0≤0.351.4

Missense OE?0.71 (0.65–0.78)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 6 / 43.7Missense obs/exp: 307 / 431.1Syn Z: 0.20

ClinVar Variant Classifications

121 submitted variants in ClinVar

ClinVar

Classification Summary

VUS77

Likely Benign2

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	77	0	77
Likely Benign	1	1	2
Benign	0	1	1
Total	78	2	80

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap HSP90B1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →