HSP90B1

protein-coding

heat shock protein 90 beta family member 1, the group of MicroRNA protein coding host genes|Heat shock 90kDa proteins

Gene summary

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]

Previous symbols:

TRA1

MANE transcript

NM_003299.3

Inheritance

—

ClinVar variants

U:98B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr12:103,930,107-103,953,931

External References & Databases

Ensembl (ENSG00000166598)

Transcript & Mutation Effects

hg38 • Region Span ~23.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSP90B1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 78

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003299.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	1 clinvar	1 clinvar	6
missense			80 clinvar	1 clinvar		81
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			13 clinvar			13
Total	0	0	98	2	1	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003299.3	RefSeq	NP_003290.1	18	MANE Select
ENST00000299767.10	Ensembl	ENSP00000299767.4	18	MANE Select
ENST00000549334.5	Ensembl	ENSP00000446748.1	2	Standard
ENST00000550595.2	Ensembl	ENSP00000450215.2	18	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
hsp90b1	Danio rerio	Structure: muscle cell Quality: disorganized abnormal

Gene / Model

Organism

Observed Phenotype

hsp90b1

Danio rerio

Structure: muscle cell

Quality: disorganized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Thyroid hormone synthesis - Homo sapiens (human)
Protein processing in endoplasmic reticulum - Homo sapiens (human)
Prostate cancer - Homo sapiens (human)
Estrogen signaling pathway - Homo sapiens (human)

Biological Process

response to hypoxia
toll-like receptor signaling pathway
receptor-mediated endocytosis
protein transport
cytokine-mediated signaling pathway

Molecular Function

RNA binding
calcium ion binding
protein binding
ATP binding
protein phosphatase binding

Cellular Component

extracellular region
nucleus
endoplasmic reticulum
endoplasmic reticulum lumen
endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299767
Coding exons: 18
Length: 23539
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125747
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.12	307	431	0.712	0.0000226	5333
Missense (PolyPhen)		88	173.48	0.50725		2132
Synonymous	0.195	152	155	0.980	0.00000873	1437
Loss of Function	5.29	6	43.7	0.137	0.00000226	553

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00024	0.00022	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000065	0.000062	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Molecular chaperone that functions in the processing and transport of secreted proteins. When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in endoplasmic reticulum associated degradation (ERAD). Has ATPase activity. {ECO:0000250, ECO:0000269|PubMed:18264092}.;

Recessive Scores

pRec: 0.429

Intolerance Scores

LoFtool: 0.297
RVIS EVS: -0.36
RVIS percentile EVS: 29.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.941

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium