HSPA8
heat shock protein family A (Hsp70) member 8, the group of Heat shock 70kDa proteins|Spliceosomal P complex|Spliceosomal C complex
Basic information
Region (hg38): 11:123057488-123063230
Previous symbols: [ "HSPA10" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (5 variants)
- not provided (4 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPA8 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 | 5 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 5 | 0 | 4 |
Variants in HSPA8
This is a list of pathogenic ClinVar variants found in the HSPA8 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 11-123057801-A-T | not specified | Uncertain significance (Jan 26, 2023) | ||
| 11-123057829-C-T | not specified | Uncertain significance (Dec 05, 2023) | ||
| 11-123058770-T-C | not specified | Uncertain significance (Sep 14, 2022) | ||
| 11-123059519-T-C | Benign (Jul 11, 2018) | |||
| 11-123059588-G-A | Benign (May 14, 2018) | |||
| 11-123059751-C-T | not specified | Uncertain significance (Nov 15, 2021) | ||
| 11-123059806-G-A | not specified | Uncertain significance (Nov 29, 2021) | ||
| 11-123060258-T-C | not specified | Uncertain significance (Mar 29, 2022) | ||
| 11-123060629-T-C | Benign (Dec 31, 2019) | |||
| 11-123060671-G-C | Benign (Jun 01, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HSPA8 | protein_coding | protein_coding | ENST00000534624 | 8 | 5742 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.00137 | 125740 | 0 | 7 | 125747 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.46 | 119 | 356 | 0.335 | 0.0000177 | 4258 |
| Missense in Polyphen | 25 | 119.64 | 0.20896 | 1612 | ||
| Synonymous | -7.09 | 222 | 122 | 1.82 | 0.00000582 | 1279 |
| Loss of Function | 4.31 | 1 | 23.6 | 0.0424 | 0.00000126 | 291 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000629 | 0.0000615 |
| Ashkenazi Jewish | 0.0000993 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000472 | 0.0000462 |
| European (Non-Finnish) | 0.0000528 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J- domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP- bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24318877, PubMed:27474739, PubMed:24121476, PubMed:26865365). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Participates in the ER- associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). {ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}.;
- Pathway
- Antigen processing and presentation - Homo sapiens (human);Legionellosis - Homo sapiens (human);Endocytosis - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Influenza A - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Spliceosome - Homo sapiens (human);Measles - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Parkin-Ubiquitin Proteasomal System pathway;MAPK Signaling Pathway;Interleukin-4 and 13 signaling;Exercise-induced Circadian Regulation;Developmental Biology;Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;Neutrophil degranulation;trans-Golgi Network Vesicle Budding;Attenuation phase;HSF1-dependent transactivation;Vesicle-mediated transport;Membrane Trafficking;Regulation of HSF1-mediated heat shock response;HSP90 chaperone cycle for steroid hormone receptors (SHR);Cellular responses to stress;Post-translational protein modification;Metabolism of proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Metabolism of RNA;Innate Immune System;Immune System;mRNA Splicing - Major Pathway;Neuronal System;AndrogenReceptor;Cellular responses to external stimuli;Clathrin-mediated endocytosis;TGF_beta_Receptor;CHL1 interactions;Cellular response to heat stress;GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;C-MYB transcription factor network;L1CAM interactions;Transmission across Chemical Synapses;Axon guidance;Protein methylation;Regulation of mRNA stability by proteins that bind AU-rich elements;mRNA Splicing;Regulation of nuclear SMAD2/3 signaling;Processing of Capped Intron-Containing Pre-mRNA
(Consensus)
Recessive Scores
- pRec
- 0.927
Intolerance Scores
- loftool
- 0.0958
- rvis_EVS
- -0.82
- rvis_percentile_EVS
- 11.68
Haploinsufficiency Scores
- pHI
- 1.00
- hipred
- Y
- hipred_score
- 0.793
- ghis
- 0.611
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.964
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hspa8
- Phenotype
Zebrafish Information Network
- Gene name
- hspa8
- Affected structure
- ceratohyal cartilage
- Phenotype tag
- abnormal
- Phenotype quality
- deformed
Gene ontology
- Biological process
- mRNA splicing, via spliceosome;protein folding;response to unfolded protein;axo-dendritic transport;cellular response to starvation;viral process;vesicle-mediated transport;cytokine-mediated signaling pathway;regulation of protein stability;cellular response to heat;cellular response to unfolded protein;protein refolding;regulation of protein complex assembly;neutrophil degranulation;regulation of mRNA stability;positive regulation by host of viral genome replication;negative regulation of transcription, DNA-templated;ATP metabolic process;positive regulation of mRNA splicing, via spliceosome;chaperone cofactor-dependent protein refolding;regulation of cell cycle;membrane organization;regulation of protein complex stability;chaperone-mediated autophagy;late endosomal microautophagy;protein targeting to lysosome involved in chaperone-mediated autophagy;chaperone-mediated protein transport involved in chaperone-mediated autophagy;clathrin coat disassembly;regulation of postsynapse organization;regulation of cellular response to heat;negative regulation of supramolecular fiber organization;regulation of protein import;chaperone-mediated autophagy translocation complex disassembly;slow axonal transport
- Cellular component
- ubiquitin ligase complex;Prp19 complex;extracellular region;extracellular space;nucleus;nucleoplasm;spliceosomal complex;nucleolus;cytoplasm;lysosome;lysosomal membrane;late endosome;autophagosome;cytosol;plasma membrane;focal adhesion;membrane;axon;dendrite;secretory granule lumen;melanosome;terminal bouton;lysosomal lumen;myelin sheath;perinuclear region of cytoplasm;clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane;extracellular exosome;blood microparticle;lumenal side of lysosomal membrane;photoreceptor ribbon synapse;glycinergic synapse;glutamatergic synapse;presynaptic cytosol;postsynaptic cytosol;postsynaptic specialization membrane;chaperone complex;ficolin-1-rich granule lumen;ribonucleoprotein complex
- Molecular function
- G protein-coupled receptor binding;phosphatidylserine binding;RNA binding;protein binding;ATP binding;ATPase activity;enzyme binding;MHC class II protein complex binding;protein binding, bridging;heat shock protein binding;ubiquitin protein ligase binding;ATPase activity, coupled;protein folding chaperone;cadherin binding;unfolded protein binding;chaperone binding;misfolded protein binding;C3HC4-type RING finger domain binding;clathrin-uncoating ATPase activity