HSP90AB1
heat shock protein 90 alpha family class B member 1, the group of Heat shock 90kDa proteins
Basic information
Region (hg38): 6:44246166-44253888
Previous symbols: [ "HSPC2", "HSPCB" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSP90AB1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | |||||
| missense | 22 | 22 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 22 | 2 | 4 |
Variants in HSP90AB1
This is a list of pathogenic ClinVar variants found in the HSP90AB1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-44248746-C-T | Benign (Aug 30, 2018) | |||
| 6-44249455-A-C | not specified | Uncertain significance (Jun 30, 2023) | ||
| 6-44249473-C-T | not specified | Uncertain significance (Jan 03, 2022) | ||
| 6-44249524-A-G | not specified | Uncertain significance (Apr 13, 2022) | ||
| 6-44249822-C-T | not specified | Uncertain significance (Jun 12, 2023) | ||
| 6-44249823-G-A | not specified | Uncertain significance (May 13, 2024) | ||
| 6-44250304-G-A | not specified | Uncertain significance (Dec 06, 2023) | ||
| 6-44250330-G-A | not specified | Uncertain significance (Jul 14, 2023) | ||
| 6-44250379-A-G | not specified | Uncertain significance (Jan 04, 2024) | ||
| 6-44250426-G-T | not specified | Uncertain significance (Dec 16, 2023) | ||
| 6-44250488-A-G | Benign/Likely benign (Mar 01, 2023) | |||
| 6-44251054-T-G | not specified | Uncertain significance (Apr 27, 2023) | ||
| 6-44251140-G-C | not specified | Uncertain significance (Apr 01, 2024) | ||
| 6-44251758-A-G | not specified | Uncertain significance (Feb 23, 2023) | ||
| 6-44251767-C-T | not specified | Uncertain significance (Apr 15, 2024) | ||
| 6-44251794-C-T | not specified | Uncertain significance (Aug 15, 2023) | ||
| 6-44251812-G-A | not specified | Uncertain significance (Aug 31, 2022) | ||
| 6-44251873-A-G | not specified | Uncertain significance (Jan 22, 2024) | ||
| 6-44251875-T-C | not specified | Uncertain significance (Dec 27, 2023) | ||
| 6-44252053-G-A | not specified | Uncertain significance (May 23, 2023) | ||
| 6-44252077-C-T | not specified | Uncertain significance (Dec 16, 2023) | ||
| 6-44252183-G-C | not specified | Uncertain significance (Jun 24, 2022) | ||
| 6-44252189-G-A | Benign (Apr 24, 2018) | |||
| 6-44252191-A-T | not specified | Uncertain significance (May 23, 2023) | ||
| 6-44253152-C-T | Benign (Dec 31, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HSP90AB1 | protein_coding | protein_coding | ENST00000371554 | 11 | 6797 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000765 | 125741 | 0 | 7 | 125748 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.05 | 289 | 405 | 0.713 | 0.0000229 | 4829 |
| Missense in Polyphen | 72 | 153.97 | 0.46762 | 1905 | ||
| Synonymous | -5.06 | 220 | 143 | 1.54 | 0.00000748 | 1313 |
| Loss of Function | 4.70 | 2 | 29.6 | 0.0677 | 0.00000152 | 401 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000643 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000530 | 0.0000527 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co- chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:27295069, PubMed:26991466). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone that is involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Antigen processing and presentation - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Nuclear Receptors Meta-Pathway;NRF2 pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Developmental Biology;Neutrophil degranulation;Signal Transduction;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;Aryl hydrocarbon receptor signalling;Phase I - Functionalization of compounds;The NLRP3 inflammasome;Inflammasomes;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;HSP90 chaperone cycle for steroid hormone receptors (SHR);Cellular responses to stress;Fcgamma receptor (FCGR) dependent phagocytosis;TCR;Biological oxidations;Innate Immune System;Immune System;Metabolism;Cellular responses to external stimuli;Sema3A PAK dependent Axon repulsion;The role of GTSE1 in G2/M progression after G2 checkpoint;Semaphorin interactions;G2/M Transition;Mitotic G2-G2/M phases;Regulation of actin dynamics for phagocytic cup formation;Cellular response to heat stress;Signaling by Nuclear Receptors;Axon guidance;Cell Cycle;TNFalpha;Cell Cycle, Mitotic;ESR-mediated signaling;Signaling events mediated by VEGFR1 and VEGFR2
(Consensus)
Recessive Scores
- pRec
- 0.268
Intolerance Scores
- loftool
- 0.259
- rvis_EVS
- -1.27
- rvis_percentile_EVS
- 5.24
Haploinsufficiency Scores
- pHI
- 0.175
- hipred
- Y
- hipred_score
- 0.802
- ghis
- 0.656
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hsp90ab1
- Phenotype
- embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Zebrafish Information Network
- Gene name
- hsp90ab1
- Affected structure
- vasculature
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- placenta development;protein folding;xenobiotic metabolic process;response to unfolded protein;telomere maintenance via telomerase;response to salt stress;virion attachment to host cell;central nervous system neuron axonogenesis;establishment of cell polarity;positive regulation of transforming growth factor beta receptor signaling pathway;regulation of protein ubiquitination;positive regulation of protein binding;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of phosphoprotein phosphatase activity;positive regulation of peptidyl-serine phosphorylation;obsolete positive regulation of protein import into nucleus, translocation;cellular response to drug;Fc-gamma receptor signaling pathway involved in phagocytosis;response to cocaine;neutrophil degranulation;negative regulation of neuron apoptotic process;positive regulation of nitric oxide biosynthetic process;positive regulation of cell differentiation;positive regulation of cell size;axon extension;protein stabilization;chaperone-mediated protein complex assembly;negative regulation of protein metabolic process;positive regulation of protein kinase B signaling;positive regulation of telomerase activity;regulation of interferon-gamma-mediated signaling pathway;regulation of type I interferon-mediated signaling pathway;negative regulation of cell cycle arrest;cellular response to interleukin-4;cellular response to organic cyclic compound;positive regulation of protein serine/threonine kinase activity;supramolecular fiber organization;regulation of cellular response to heat;negative regulation of transforming growth factor beta activation;negative regulation of proteasomal protein catabolic process;positive regulation of tau-protein kinase activity;negative regulation of complement-dependent cytotoxicity;regulation of cellular protein localization;positive regulation of cyclin-dependent protein kinase activity;telomerase holoenzyme complex assembly;positive regulation of protein localization to cell surface
- Cellular component
- extracellular region;nucleus;nucleoplasm;cytoplasm;mitochondrion;lysosomal membrane;cytosol;COP9 signalosome;cell surface;membrane;inclusion body;basolateral plasma membrane;apical plasma membrane;brush border membrane;protein-containing complex;aryl hydrocarbon receptor complex;secretory granule lumen;melanosome;neuronal cell body;dendritic growth cone;axonal growth cone;perinuclear region of cytoplasm;extracellular exosome;ficolin-1-rich granule lumen;HSP90-CDC37 chaperone complex;sperm head plasma membrane;ooplasm
- Molecular function
- UTP binding;CTP binding;RNA binding;double-stranded RNA binding;protein binding;ATP binding;GTP binding;sulfonylurea receptor binding;protein kinase regulator activity;kinase binding;protein kinase binding;MHC class II protein complex binding;nitric-oxide synthase regulator activity;TPR domain binding;heat shock protein binding;ubiquitin protein ligase binding;dATP binding;peptide binding;ATPase activity, coupled;identical protein binding;protein homodimerization activity;histone deacetylase binding;ATP-dependent protein binding;ion channel binding;cadherin binding;protein dimerization activity;tau protein binding;unfolded protein binding;DNA polymerase binding;disordered domain specific binding;histone methyltransferase binding