BAG3
BAG cochaperone 3, the group of BAG cochaperones
Basic information
Region (hg38): 10:119651380-119677819
Links
Phenotypes
GenCC
Source:
- familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
- myofibrillar myopathy 6 (Supportive), mode of inheritance: AD
- myofibrillar myopathy 6 (Strong), mode of inheritance: AD
- dilated cardiomyopathy 1HH (Definitive), mode of inheritance: AD
- myofibrillar myopathy 6 (Strong), mode of inheritance: AD
- dilated cardiomyopathy 1HH (Strong), mode of inheritance: AD
- myofibrillar myopathy (Definitive), mode of inheritance: AD
- dilated cardiomyopathy (Definitive), mode of inheritance: AD
- myofibrillar myopathy (Definitive), mode of inheritance: AD
- distal hereditary motor neuropathy (Limited), mode of inheritance: AD
- Charcot-Marie-tooth disease, axonal, type 2JJ (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cardiomyopathy, dilated, 1HH; Myopathy, myofibrillar 6 | AD | Cardiovascular | In Dilated cardiomyopathy, surveillance (eg, with echocardiogram and electocardiogram) may allow early detection and management of manifestations, which may be beneficial; In Myofibrillar myopathy, individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary individuals with severe forms of cardiomyopathy; Heart transplant has been described | Cardiovascular; Musculoskeletal; Neurologic | 16936253; 19085932; 20301672; 21898660; 21256014; 21353195; 21361913; 21459883; 25208129; 28754666; 31853710; 37907725 |
ClinVar
This is a list of variants' phenotypes submitted to
- Dilated_cardiomyopathy_1HH (1017 variants)
- Myofibrillar_myopathy_6 (1007 variants)
- Cardiovascular_phenotype (454 variants)
- not_provided (296 variants)
- not_specified (118 variants)
- BAG3-related_disorder (31 variants)
- Cardiomyopathy (23 variants)
- Primary_dilated_cardiomyopathy (21 variants)
- Primary_familial_dilated_cardiomyopathy (6 variants)
- Dilated_Cardiomyopathy,_Dominant (5 variants)
- Myofibrillar_Myopathy,_Dominant (5 variants)
- Long_QT_syndrome (3 variants)
- Primary_familial_hypertrophic_cardiomyopathy (3 variants)
- Atrial_fibrillation (2 variants)
- Hypertrophic_cardiomyopathy (2 variants)
- Myocarditis (2 variants)
- Premature_ventricular_contraction (1 variants)
- Peripheral_neuropathy (1 variants)
- Left_ventricular_noncompaction_1 (1 variants)
- Myofibrillar_myopathy (1 variants)
- Abnormality_of_the_musculature (1 variants)
- Elevated_circulating_creatine_kinase_concentration (1 variants)
- See_cases (1 variants)
- Familial_isolated_arrhythmogenic_right_ventricular_dysplasia (1 variants)
- Neuronopathy,_distal_hereditary_motor,_autosomal_dominant_15 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BAG3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004281.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 274 | 284 | ||||
| missense | 622 | 69 | 702 | |||
| nonsense | 36 | 19 | 60 | |||
| start loss | 2 | 2 | ||||
| frameshift | 52 | 25 | 14 | 91 | ||
| splice donor/acceptor (+/-2bp) | 5 | |||||
| Total | 92 | 52 | 646 | 343 | 11 |
Highest pathogenic variant AF is 0.000006594566
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BAG3 | protein_coding | protein_coding | ENST00000369085 | 4 | 26450 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.617 | 0.383 | 125743 | 0 | 5 | 125748 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.736 | 376 | 338 | 1.11 | 0.0000201 | 3675 |
| Missense in Polyphen | 113 | 102.62 | 1.1012 | 1022 | ||
| Synonymous | -0.128 | 144 | 142 | 1.01 | 0.00000903 | 1258 |
| Loss of Function | 3.37 | 4 | 20.5 | 0.195 | 0.00000133 | 198 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000702 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000264 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70 (PubMed:9873016, PubMed:27474739). Has anti-apoptotic activity (PubMed:10597216). Plays a role in the HSF1 nucleocytoplasmic transport (PubMed:26159920). {ECO:0000269|PubMed:10597216, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:26159920, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:9873016}.;
- Disease
- DISEASE: Myopathy, myofibrillar, 6 (MFM6) [MIM:612954]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM6 is characterized by early- onset of severe, progressive, diffuse muscle weakness associated with cardiomyopathy, severe respiratory insufficiency during adolescence, and a rigid spine in some patients. {ECO:0000269|PubMed:19085932, ECO:0000269|PubMed:21361913, ECO:0000269|PubMed:21898660}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1HH (CMD1HH) [MIM:613881]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:21353195, ECO:0000269|PubMed:21459883, ECO:0000269|PubMed:21898660}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Busulfan Pathway, Pharmacodynamics;Apoptosis Modulation and Signaling;Regulation of HSF1-mediated heat shock response;Cellular responses to stress;Cellular responses to external stimuli;Cellular response to heat stress
(Consensus)
Recessive Scores
- pRec
- 0.211
Intolerance Scores
- loftool
- 0.127
- rvis_EVS
- 0.11
- rvis_percentile_EVS
- 62.14
Haploinsufficiency Scores
- pHI
- 0.591
- hipred
- Y
- hipred_score
- 0.734
- ghis
- 0.460
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.441
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Bag3
- Phenotype
- 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; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary 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); hematopoietic 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); immune system phenotype;
Zebrafish Information Network
- Gene name
- bag3
- Affected structure
- slow muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- broken
Gene ontology
- Biological process
- autophagosome assembly;protein folding;brain development;extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of striated muscle cell apoptotic process;spinal cord development;cellular response to heat;cellular response to unfolded protein;positive regulation of protein import into nucleus;negative regulation of apoptotic process;muscle cell cellular homeostasis;positive regulation of protein export from nucleus;regulation of catalytic activity;protein stabilization;chaperone-mediated autophagy;aggresome assembly;cellular response to mechanical stimulus;chaperone-mediated protein transport;extrinsic apoptotic signaling pathway in absence of ligand;negative regulation of transcription from RNA polymerase II promoter in response to stress;protein transport along microtubule;regulation of cellular response to heat;negative regulation of protein targeting to mitochondrion;positive regulation of aggrephagy
- Cellular component
- stress fiber;nucleus;cytoplasm;cytosol;plasma membrane;aggresome;Z disc;neuron projection;chaperone complex
- Molecular function
- adenyl-nucleotide exchange factor activity;protein binding;protein transporter activity;protein-containing complex binding;cadherin binding;dynein intermediate chain binding;chaperone binding