HSP90AA1
heat shock protein 90 alpha family class A member 1, the group of Heat shock 90kDa proteins
Basic information
Region (hg38): 14:102080742-102139699
Previous symbols: [ "HSPC1", "HSPCA" ]
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 HSP90AA1 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 | 4 | |||||
| missense | 22 | 22 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 1 | |||||
| Total | 0 | 0 | 22 | 3 | 2 |
Variants in HSP90AA1
This is a list of pathogenic ClinVar variants found in the HSP90AA1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-102081732-G-A | not specified | Uncertain significance (Apr 09, 2024) | ||
| 14-102081792-C-T | not specified | Uncertain significance (Jun 27, 2022) | ||
| 14-102082104-G-T | Benign (Mar 29, 2018) | |||
| 14-102082121-T-C | Benign/Likely benign (Apr 01, 2022) | |||
| 14-102082283-G-C | not specified | Uncertain significance (Apr 19, 2023) | ||
| 14-102082285-C-T | not specified | Uncertain significance (Apr 09, 2024) | ||
| 14-102083098-T-C | not specified | Uncertain significance (Nov 25, 2024) | ||
| 14-102083224-A-G | not specified | Uncertain significance (Oct 12, 2021) | ||
| 14-102083261-G-A | not specified | Uncertain significance (Nov 10, 2022) | ||
| 14-102083276-A-C | not specified | Uncertain significance (Jan 26, 2022) | ||
| 14-102083560-A-G | not specified | Uncertain significance (Sep 01, 2021) | ||
| 14-102083606-A-C | not specified | Uncertain significance (Aug 16, 2021) | ||
| 14-102083632-G-A | not specified | Uncertain significance (Apr 11, 2023) | ||
| 14-102083784-T-C | Benign (Jun 15, 2018) | |||
| 14-102083847-C-T | Benign (Mar 29, 2018) | |||
| 14-102083857-G-C | not specified | Uncertain significance (Sep 03, 2024) | ||
| 14-102083906-A-C | not specified | Uncertain significance (Dec 28, 2022) | ||
| 14-102084823-ATCT-A | Hepatocellular carcinoma | Pathogenic (Jun 15, 2021) | ||
| 14-102084917-C-T | not specified | Uncertain significance (Jun 02, 2023) | ||
| 14-102084920-C-T | not specified | Uncertain significance (Dec 15, 2023) | ||
| 14-102084922-T-C | not specified | Uncertain significance (Nov 12, 2021) | ||
| 14-102084974-C-T | not specified | Uncertain significance (Dec 07, 2023) | ||
| 14-102085359-C-T | not specified | Uncertain significance (Jan 08, 2024) | ||
| 14-102085795-G-A | Likely benign (Apr 01, 2023) | |||
| 14-102085833-T-C | not specified | Uncertain significance (Apr 13, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HSP90AA1 | protein_coding | protein_coding | ENST00000334701 | 12 | 58962 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.860 | 0.140 | 125715 | 0 | 33 | 125748 | 0.000131 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.04 | 384 | 446 | 0.862 | 0.0000230 | 5668 |
| Missense in Polyphen | 42 | 76.86 | 0.54645 | 1039 | ||
| Synonymous | -8.62 | 303 | 163 | 1.86 | 0.00000881 | 1544 |
| Loss of Function | 4.60 | 7 | 37.3 | 0.188 | 0.00000194 | 503 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000301 | 0.000300 |
| Ashkenazi Jewish | 0.000299 | 0.000298 |
| East Asian | 0.000218 | 0.000217 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000133 | 0.000132 |
| Middle Eastern | 0.000218 | 0.000217 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000163 | 0.000163 |
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 which is essential for its chaperone 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:11274138, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). 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 (PubMed:29127155). 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 (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues(PubMed:25973397). 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 (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1- mediated inhibition of TGF-beta signaling via inhibition of STUB1- mediated SMAD3 ubiquitination and degradation (PubMed:24613385). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, 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);Glucocorticoid Pathway (Peripheral Tissue), Pharmacodynamics;Prednisolone Metabolism Pathway;Prednisolone Action Pathway;Nucleotide-binding Oligomerization Domain (NOD) pathway;TNF alpha Signaling Pathway;Corticotropin-releasing hormone signaling pathway;Aryl Hydrocarbon Receptor;EBV LMP1 signaling;Aryl Hydrocarbon Receptor Pathway;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;NRF2 pathway;Photodynamic therapy-induced AP-1 survival signaling.;VEGFA-VEGFR2 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Interleukin-4 and 13 signaling;PI3K-Akt Signaling Pathway;Developmental Biology;Neutrophil degranulation;Disease;Signal Transduction;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;ahr signal transduction pathway;mechanism of gene regulation by peroxisome proliferators via ppara;hypoxia-inducible factor in the cardivascular system;hypoxia and p53 in the cardiovascular system;Vesicle-mediated transport;tumor suppressor arf inhibits ribosomal biogenesis;akt signaling pathway;corticosteroids and cardioprotection;ion channels and their functional role in vascular endothelium;vegf hypoxia and angiogenesis;VEGFA-VEGFR2 Pathway;Metabolism of nitric oxide;vRNP Assembly;Influenza Viral RNA Transcription and Replication;HSP90 chaperone cycle for steroid hormone receptors (SHR);Cellular responses to stress;Influenza Life Cycle;Influenza Infection;Fcgamma receptor (FCGR) dependent phagocytosis;Infectious disease;eNOS activation;eNOS activation and regulation;Innate Immune System;Immune System;Metabolism;Hypoxic and oxygen homeostasis regulation of HIF-1-alpha;Fibroblast growth factor-1;AndrogenReceptor;actions of nitric oxide in the heart;Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation;Metabolism of cofactors;Metabolism of vitamins and cofactors;Downregulation of ERBB2 signaling;Cellular responses to external stimuli;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Signaling events mediated by HDAC Class II;Glucocorticoid receptor regulatory network;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;Sema3A PAK dependent Axon repulsion;The role of GTSE1 in G2/M progression after G2 checkpoint;AURKA Activation by TPX2;Semaphorin interactions;G2/M Transition;Mitotic G2-G2/M phases;IL2;Regulation of actin dynamics for phagocytic cup formation;Cellular response to heat stress;Signaling by Nuclear Receptors;Class I PI3K signaling events;Signaling by EGFRvIII in Cancer;Signaling by EGFR in Cancer;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;Signaling by VEGF;Axon guidance;M Phase;Signaling by ERBB2;Cell Cycle;IL6;TNFalpha;Integrin-linked kinase signaling;Constitutive Signaling by EGFRvIII;Binding and Uptake of Ligands by Scavenger Receptors;Signaling by Receptor Tyrosine Kinases;Cell Cycle, Mitotic;Scavenging by Class F Receptors;Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants;Signaling by Ligand-Responsive EGFR Variants in Cancer;Anchoring of the basal body to the plasma membrane;ESR-mediated signaling;Diseases of signal transduction;Validated targets of C-MYC transcriptional activation;Regulation of Telomerase;IL2 signaling events mediated by PI3K;Regulation of Androgen receptor activity;Class I PI3K signaling events mediated by Akt;ErbB receptor signaling network;Signaling events mediated by VEGFR1 and VEGFR2;Integrins in angiogenesis;LKB1 signaling events;VEGFR1 specific signals;VEGFR2 mediated vascular permeability;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Intolerance Scores
- loftool
- 0.567
- rvis_EVS
- -1.02
- rvis_percentile_EVS
- 8.14
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.731
- ghis
- 0.508
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.890
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hsp90aa1
- Phenotype
- craniofacial phenotype; cellular phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; limbs/digits/tail phenotype; immune system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; 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
- hsp90aa1.1
- Affected structure
- fast muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- disorganized
Gene ontology
- Biological process
- G2/M transition of mitotic cell cycle;positive regulation of protein phosphorylation;mitochondrial transport;receptor-mediated endocytosis;response to unfolded protein;telomere maintenance via telomerase;signal transduction;response to heat;response to cold;regulation of G2/M transition of mitotic cell cycle;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;central nervous system neuron axonogenesis;establishment of cell polarity;regulation of protein ubiquitination;positive regulation of protein polymerization;positive regulation of peptidyl-serine phosphorylation;cellular response to heat;Fc-gamma receptor signaling pathway involved in phagocytosis;ERBB2 signaling pathway;protein refolding;regulation of protein complex assembly;neutrophil degranulation;protein unfolding;protein insertion into mitochondrial outer membrane;positive regulation of nitric oxide biosynthetic process;response to antibiotic;vascular endothelial growth factor receptor signaling pathway;axon extension;protein stabilization;regulation of nitric-oxide synthase activity;chaperone-mediated protein complex assembly;cofactor metabolic process;positive regulation of protein kinase B signaling;positive regulation of telomerase activity;chaperone-mediated autophagy;ciliary basal body-plasma membrane docking;regulation of cellular response to heat;positive regulation of tau-protein kinase activity;positive regulation of cellular protein catabolic process;regulation of cellular protein localization;telomerase holoenzyme complex assembly
- Cellular component
- extracellular region;nucleus;nucleoplasm;cytoplasm;cytosol;plasma membrane;cell surface;membrane;protein-containing complex;secretory granule lumen;melanosome;neuronal cell body;lysosomal lumen;myelin sheath;dendritic growth cone;axonal growth cone;perinuclear region of cytoplasm;extracellular exosome;endocytic vesicle lumen;ficolin-1-rich granule lumen
- Molecular function
- nucleotide binding;RNA binding;protein tyrosine kinase activity;protein binding;ATP binding;ATPase activity;MHC class II protein complex binding;nitric-oxide synthase regulator activity;TPR domain binding;ubiquitin protein ligase binding;ATPase activity, coupled;identical protein binding;protein homodimerization activity;histone deacetylase binding;tau protein binding;GTPase binding;unfolded protein binding;DNA polymerase binding;scaffold protein binding;disordered domain specific binding;protein tyrosine kinase binding