BAG6
BAG cochaperone 6, the group of BAG6 complex|BAG cochaperones
Basic information
Region (hg38): 6:31639028-31652705
Previous symbols: [ "BAT3" ]
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 BAG6 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 | 7 | |||||
| missense | 35 | 35 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | 2 | |||
| non coding | 0 | |||||
| Total | 0 | 0 | 35 | 4 | 3 |
Variants in BAG6
This is a list of pathogenic ClinVar variants found in the BAG6 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-31639162-T-C | not specified | Uncertain significance (Jan 26, 2023) | ||
| 6-31639172-G-A | not specified | Uncertain significance (Feb 01, 2023) | ||
| 6-31639205-G-A | Isolated unilateral hemispheric cerebellar hypoplasia;Periventricular nodular heterotopia • Cerebellar vermis hypoplasia | Uncertain significance (Feb 18, 2019) | ||
| 6-31639211-G-C | not specified | Uncertain significance (Jun 29, 2022) | ||
| 6-31639219-G-C | not specified | Uncertain significance (Mar 25, 2024) | ||
| 6-31639546-C-T | not specified | Uncertain significance (Dec 16, 2021) | ||
| 6-31639573-C-T | not specified | Uncertain significance (Sep 06, 2022) | ||
| 6-31639591-G-A | not specified | Uncertain significance (Apr 13, 2022) | ||
| 6-31639598-G-A | not specified | Uncertain significance (Oct 12, 2021) | ||
| 6-31639644-C-T | Benign (May 30, 2018) | |||
| 6-31640219-T-C | not specified | Uncertain significance (Jun 09, 2022) | ||
| 6-31640444-G-A | not specified | Uncertain significance (Mar 14, 2023) | ||
| 6-31640679-A-T | not specified | Uncertain significance (Jul 09, 2021) | ||
| 6-31640925-C-T | not specified | Uncertain significance (Jul 05, 2023) | ||
| 6-31640934-C-T | not specified | Uncertain significance (Nov 17, 2022) | ||
| 6-31641108-C-T | not specified | Uncertain significance (Dec 13, 2022) | ||
| 6-31641167-G-C | Likely benign (Feb 01, 2023) | |||
| 6-31641339-C-T | Likely benign (Jul 25, 2018) | |||
| 6-31641777-C-T | not specified | Uncertain significance (Dec 20, 2023) | ||
| 6-31641834-C-A | not specified | Uncertain significance (Oct 05, 2023) | ||
| 6-31642287-G-T | Likely benign (Jul 01, 2022) | |||
| 6-31642363-G-C | not specified | Uncertain significance (Feb 28, 2024) | ||
| 6-31642367-G-A | not specified | Uncertain significance (Dec 01, 2022) | ||
| 6-31643088-G-A | not specified | Uncertain significance (Nov 29, 2023) | ||
| 6-31643903-C-T | Likely benign (Feb 01, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BAG6 | protein_coding | protein_coding | ENST00000375964 | 24 | 13678 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.00000381 | 125740 | 0 | 8 | 125748 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.72 | 485 | 685 | 0.708 | 0.0000409 | 7207 |
| Missense in Polyphen | 213 | 340.23 | 0.62604 | 3706 | ||
| Synonymous | 0.990 | 240 | 260 | 0.922 | 0.0000144 | 2491 |
| Loss of Function | 6.21 | 4 | 52.5 | 0.0761 | 0.00000276 | 539 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000582 | 0.0000582 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000364 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins (PubMed:21636303). Functions as part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, which maintains these client proteins in a soluble state and participates to their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20516149, PubMed:21636303, PubMed:21743475, PubMed:28104892). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20516149, PubMed:20676083, PubMed:28104892, PubMed:25535373). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated by RNF126, an E3 ubiquitin-protein ligase associated with BAG6 and are sorted to the proteasome (PubMed:24981174, PubMed:28104892, PubMed:27193484). SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins (PubMed:23129660, PubMed:25179605, PubMed:27193484). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303). BAG6 is also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, it may participate to the production of antigenic peptides and play a role in antigen presentation in immune response (By similarity). BAG6 is also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. BAG6 may ensure the proper degradation of these proteins and thereby protects the endoplasmic reticulum from protein overload upon stress (PubMed:26565908). By inhibiting the polyubiquitination and subsequent proteasomal degradation of HSPA2 it may also play a role in the assembly of the synaptonemal complex during spermatogenesis (By similarity). Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1 (By similarity). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250|UniProtKB:Q9Z1R2, ECO:0000269|PubMed:20516149, ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21743475, ECO:0000269|PubMed:23129660, ECO:0000269|PubMed:24981174, ECO:0000269|PubMed:25179605, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27193484, ECO:0000269|PubMed:28104892}.; FUNCTION: Released extracellularly via exosomes, it is a ligand of the natural killer/NK cells receptor NCR3 and stimulates NK cells cytotoxicity. It may thereby trigger NK cells cytotoxicity against neighboring tumor cells and immature myeloid dendritic cells (DC). {ECO:0000269|PubMed:18055229, ECO:0000269|PubMed:18852879}.;
Intolerance Scores
- loftool
- rvis_EVS
- -1.39
- rvis_percentile_EVS
- 4.25
Haploinsufficiency Scores
- pHI
- 0.564
- hipred
- Y
- hipred_score
- 0.598
- ghis
- 0.628
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Bag6
- Phenotype
- respiratory 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); 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); renal/urinary system phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- kidney development;immune response-activating cell surface receptor signaling pathway;chromatin organization;ubiquitin-dependent protein catabolic process;apoptotic process;synaptonemal complex assembly;spermatogenesis;brain development;proteasomal protein catabolic process;internal peptidyl-lysine acetylation;natural killer cell activation;cell differentiation;lung development;ubiquitin-dependent ERAD pathway;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;regulation of cell population proliferation;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;negative regulation of apoptotic process;negative regulation of proteolysis;regulation of embryonic development;protein stabilization;endoplasmic reticulum stress-induced pre-emptive quality control;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;ER-associated misfolded protein catabolic process;tail-anchored membrane protein insertion into ER membrane;positive regulation of ERAD pathway;maintenance of unfolded protein involved in ERAD pathway;protein localization to cytosolic proteasome complex involved in ERAD pathway
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol;membrane;intracellular membrane-bounded organelle;extracellular exosome;BAT3 complex
- Molecular function
- signaling receptor binding;protein binding;Hsp70 protein binding;polyubiquitin modification-dependent protein binding;ubiquitin protein ligase binding;ribosome binding;misfolded protein binding;proteasome binding;ubiquitin-specific protease binding