HSPA1B
heat shock protein family A (Hsp70) member 1B, the group of TIM23 complex|Heat shock 70kDa proteins
Basic information
Region (hg38): 6:31827738-31830254
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 HSPA1B 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 | 0 | |||||
| missense | 8 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 8 | 0 | 0 |
Variants in HSPA1B
This is a list of pathogenic ClinVar variants found in the HSPA1B region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-31827773-C-T | Chronic obstructive pulmonary disease | association (Aug 04, 2019) | ||
| 6-31828143-A-G | not specified | Uncertain significance (Mar 13, 2023) | ||
| 6-31828204-C-G | not specified | Uncertain significance (Sep 08, 2024) | ||
| 6-31828417-A-G | not specified | Uncertain significance (Apr 08, 2022) | ||
| 6-31829422-C-T | not specified | Likely benign (Aug 21, 2024) | ||
| 6-31829495-C-G | not specified | Uncertain significance (Dec 06, 2021) | ||
| 6-31829604-G-A | not specified | Uncertain significance (Dec 21, 2022) | ||
| 6-31829679-G-A | not specified | Uncertain significance (Feb 28, 2024) | ||
| 6-31829803-G-A | not specified | Uncertain significance (Aug 27, 2024) | ||
| 6-31829805-C-T | not specified | Uncertain significance (Oct 07, 2024) | ||
| 6-31829833-A-C | not specified | Uncertain significance (Jul 07, 2024) | ||
| 6-31829836-G-A | not specified | Uncertain significance (Nov 09, 2023) | ||
| 6-31829850-G-A | not specified | Uncertain significance (Jul 31, 2023) | ||
| 6-31829851-G-A | not specified | Uncertain significance (Dec 05, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HSPA1B | protein_coding | protein_coding | ENST00000375650 | 1 | 2520 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00535 | 0.726 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.11 | 126 | 166 | 0.758 | 0.00000873 | 4167 |
| Missense in Polyphen | 68 | 83.963 | 0.80988 | 2324 | ||
| Synonymous | -0.927 | 87 | 76.7 | 1.13 | 0.00000469 | 1317 |
| Loss of Function | 0.774 | 4 | 6.06 | 0.661 | 2.57e-7 | 168 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| 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. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity 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. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as 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:24012426, PubMed:26865365, PubMed:24318877). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). {ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256, ECO:0000303|PubMed:24012426, 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;Neutrophil degranulation;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;mechanism of gene regulation by peroxisome proliferators via ppara;hypoxia and p53 in the cardiovascular system;chaperones modulate interferon signaling pathway;tumor suppressor arf inhibits ribosomal biogenesis;Regulation of HSF1-mediated heat shock response;HSP90 chaperone cycle for steroid hormone receptors (SHR);Cellular responses to stress;Innate Immune System;Immune System;Cellular responses to external stimuli;Cellular response to heat stress;Direct p53 effectors;FOXM1 transcription factor network
(Consensus)
Haploinsufficiency Scores
- pHI
- 0.611
- hipred
- hipred_score
- ghis
- 0.394
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hspa1b
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs 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);
Gene ontology
- Biological process
- mRNA catabolic process;response to unfolded protein;negative regulation of cell population proliferation;positive regulation of gene expression;regulation of cell death;negative regulation of cell growth;regulation of protein ubiquitination;negative regulation of protein ubiquitination;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of interleukin-8 production;cellular response to oxidative stress;cellular response to heat;cellular response to unfolded protein;protein refolding;negative regulation of apoptotic process;neutrophil degranulation;positive regulation of erythrocyte differentiation;ATP metabolic process;viral entry into host cell;protein stabilization;chaperone cofactor-dependent protein refolding;positive regulation of NF-kappaB transcription factor activity;negative regulation of cell death;cellular heat acclimation;positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway;positive regulation of microtubule nucleation;negative regulation of inclusion body assembly;regulation of cellular response to heat;regulation of mitotic spindle assembly;positive regulation of tumor necrosis factor-mediated signaling pathway;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- Cellular component
- ubiquitin ligase complex;extracellular region;nucleus;nucleoplasm;cytoplasm;mitochondrion;endoplasmic reticulum;centrosome;centriole;cytosol;focal adhesion;COP9 signalosome;inclusion body;aggresome;nuclear speck;vesicle;protein-containing complex;perinuclear region of cytoplasm;extracellular exosome;blood microparticle;ficolin-1-rich granule lumen;ribonucleoprotein complex
- Molecular function
- virus receptor activity;G protein-coupled receptor binding;RNA binding;signaling receptor binding;protein binding;ATP binding;ATPase activity;enzyme binding;heat shock protein binding;ubiquitin protein ligase binding;ATPase activity, coupled;histone deacetylase binding;protein folding chaperone;protein N-terminus binding;unfolded protein binding;misfolded protein binding;C3HC4-type RING finger domain binding