HSPA5
heat shock protein family A (Hsp70) member 5, the group of Heat shock 70kDa proteins
Basic information
Region (hg38): 9:125234853-125241382
Previous symbols: [ "GRP78" ]
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 HSPA5 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 | 3 | |||||
| missense | 14 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 14 | 2 | 3 |
Variants in HSPA5
This is a list of pathogenic ClinVar variants found in the HSPA5 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 9-125236601-A-T | not specified | Uncertain significance (Mar 17, 2023) | ||
| 9-125236602-T-A | not specified | Uncertain significance (Feb 12, 2024) | ||
| 9-125236656-A-C | not specified | Uncertain significance (Aug 12, 2024) | ||
| 9-125236713-T-A | not specified | Uncertain significance (Apr 25, 2022) | ||
| 9-125236720-T-C | not specified | Uncertain significance (Apr 19, 2023) | ||
| 9-125236755-T-A | Benign (May 16, 2018) | |||
| 9-125236792-C-T | not specified | Uncertain significance (Feb 05, 2024) | ||
| 9-125236798-A-G | not specified | Uncertain significance (Aug 15, 2023) | ||
| 9-125236819-C-G | not specified | Uncertain significance (Jul 16, 2024) | ||
| 9-125236884-C-A | not specified | Uncertain significance (Sep 23, 2023) | ||
| 9-125236884-C-T | not specified | Uncertain significance (Sep 11, 2024) | ||
| 9-125236885-G-A | not specified | Uncertain significance (Jan 16, 2024) | ||
| 9-125236887-T-C | Benign (Jul 06, 2018) | |||
| 9-125236970-G-A | Benign (Jun 06, 2018) | |||
| 9-125237085-G-A | not specified | Uncertain significance (Nov 11, 2024) | ||
| 9-125238231-G-A | not specified | Uncertain significance (Jan 03, 2024) | ||
| 9-125238239-T-C | not specified | Uncertain significance (Mar 21, 2024) | ||
| 9-125238668-G-A | not specified | Uncertain significance (Feb 27, 2023) | ||
| 9-125238985-A-C | not specified | Uncertain significance (Oct 28, 2023) | ||
| 9-125238999-T-C | not specified | Uncertain significance (Feb 21, 2024) | ||
| 9-125239000-A-G | not specified | Uncertain significance (Feb 21, 2024) | ||
| 9-125239182-T-C | not specified | Uncertain significance (May 31, 2022) | ||
| 9-125240219-C-G | not specified | Uncertain significance (Sep 24, 2024) | ||
| 9-125241010-G-A | Likely benign (Aug 07, 2018) | |||
| 9-125241079-C-T | Likely benign (May 25, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HSPA5 | protein_coding | protein_coding | ENST00000324460 | 8 | 6478 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.773 | 0.227 | 125738 | 0 | 9 | 125747 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.03 | 152 | 370 | 0.411 | 0.0000193 | 4304 |
| Missense in Polyphen | 33 | 154.56 | 0.21351 | 1876 | ||
| Synonymous | -0.888 | 156 | 143 | 1.09 | 0.00000740 | 1323 |
| Loss of Function | 3.61 | 4 | 22.5 | 0.178 | 0.00000118 | 284 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000532 | 0.0000527 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000328 | 0.0000327 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:1550958, PubMed:19538957). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62, to enable the productive insertion of these precursors into SEC61 channel. {ECO:0000250|UniProtKB:G3I8R9, ECO:0000250|UniProtKB:P20029, ECO:0000269|PubMed:1550958, ECO:0000269|PubMed:19538957, ECO:0000269|PubMed:2294010, ECO:0000269|PubMed:23769672, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:28332555, ECO:0000269|PubMed:29719251}.;
- Disease
- DISEASE: Note=Autoantigen in rheumatoid arthritis. {ECO:0000269|PubMed:11160188}.;
- Pathway
- Prion diseases - Homo sapiens (human);Antigen processing and presentation - Homo sapiens (human);Protein export - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Ibuprofen Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Ibuprofen Metabolism Pathway;Morphine Metabolism Pathway;Irinotecan Action Pathway;Morphine Action Pathway;Etoposide Action Pathway;Sorafenib Metabolism Pathway;Acetaminophen Metabolism Pathway;Vitamin A Deficiency;Irinotecan Metabolism Pathway;Etoposide Metabolism Pathway;Retinol Metabolism;Parkin-Ubiquitin Proteasomal System pathway;ATF6 (ATF6-alpha) activates chaperone genes;Apoptosis-related network due to altered Notch3 in ovarian cancer;Photodynamic therapy-induced unfolded protein response;Prion disease pathway;ATF6 (ATF6-alpha) activates chaperones;PERK regulates gene expression;prion pathway;Regulation of HSF1-mediated heat shock response;IRE1alpha activates chaperones;Unfolded Protein Response (UPR);Cellular responses to stress;Metabolism of proteins;Immune System;Adaptive Immune System;Class I MHC mediated antigen processing & presentation;AndrogenReceptor;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Cellular responses to external stimuli;Hemostasis;Cellular response to heat stress;TSH;Antigen Presentation: Folding, assembly and peptide loading of class I MHC
(Consensus)
Recessive Scores
- pRec
- 0.966
Intolerance Scores
- loftool
- 0.187
- rvis_EVS
- -0.25
- rvis_percentile_EVS
- 35.75
Haploinsufficiency Scores
- pHI
- 0.803
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.438
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hspa5
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; hearing/vestibular/ear 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); digestive/alimentary phenotype; neoplasm; 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); normal phenotype; reproductive system 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); respiratory system phenotype; embryo phenotype; renal/urinary system phenotype;
Zebrafish Information Network
- Gene name
- hspa5
- Affected structure
- trunk
- Phenotype tag
- abnormal
- Phenotype quality
- degenerate
Gene ontology
- Biological process
- luteolysis;ER overload response;response to unfolded protein;positive regulation of neuron projection development;cerebellum structural organization;cerebellar Purkinje cell layer development;substantia nigra development;neuron differentiation;positive regulation of cell migration;ubiquitin-dependent ERAD pathway;negative regulation of transforming growth factor beta receptor signaling pathway;endoplasmic reticulum unfolded protein response;positive regulation of protein ubiquitination;cellular response to heat;cellular response to unfolded protein;protein folding in endoplasmic reticulum;maintenance of protein localization in endoplasmic reticulum;cellular response to drug;IRE1-mediated unfolded protein response;PERK-mediated unfolded protein response;ATF6-mediated unfolded protein response;protein refolding;cellular response to glucose starvation;response to cocaine;negative regulation of apoptotic process;chaperone cofactor-dependent protein refolding;neuron apoptotic process;regulation of protein folding in endoplasmic reticulum;cellular response to antibiotic;cellular response to calcium ion;cellular response to manganese ion;cellular response to cAMP;cellular response to interleukin-4;cellular response to gamma radiation;negative regulation of protein homodimerization activity;stress response to metal ion;toxin transport;regulation of ATF6-mediated unfolded protein response;regulation of IRE1-mediated unfolded protein response;negative regulation of IRE1-mediated unfolded protein response;regulation of PERK-mediated unfolded protein response;response to methamphetamine hydrochloride;cellular response to nerve growth factor stimulus;positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
- Cellular component
- nucleus;cytoplasm;mitochondrion;endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum membrane;smooth endoplasmic reticulum;endoplasmic reticulum-Golgi intermediate compartment;cytosol;plasma membrane;focal adhesion;COP9 signalosome;cell surface;membrane;integral component of endoplasmic reticulum membrane;midbody;protein-containing complex;endoplasmic reticulum chaperone complex;melanosome;myelin sheath;intracellular membrane-bounded organelle;extracellular exosome
- Molecular function
- calcium ion binding;protein binding;ATP binding;ATPase activity;enzyme binding;protein domain specific binding;heat shock protein binding;ubiquitin protein ligase binding;ATPase activity, coupled;ribosome binding;protein folding chaperone;cadherin binding;unfolded protein binding;chaperone binding;misfolded protein binding