BAG4
protein-codingBAG cochaperone 4, the group of BAG cochaperones
Gene summary
The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that functions through interactions with a variety of cell apoptosis and growth related proteins including BCL-2, Raf-protein kinase, steroid hormone receptors, growth factor receptors and members of the heat shock protein 70 kDa family. This protein contains a BAG domain near the C-terminus, which could bind and inhibit the chaperone activity of Hsc70/Hsp70. This protein was found to be associated with the death domain of tumor necrosis factor receptor type 1 (TNF-R1) and death receptor-3 (DR3), and thereby negatively regulates downstream cell death signaling. The regulatory role of this protein in cell death was demonstrated in epithelial cells which undergo apoptosis while integrin mediated matrix contacts are lost. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BAG4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004874.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 67 | 2 | 69 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 69 | 2 | 0 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004865.1 | 5 | MANE Select | |
| Ensembl | ENSP00000287322.4 | 5 | MANE Select | |
| RefSeq | NP_001191807.1 | 4 | Standard | |
| Ensembl | ENSP00000393298.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TNF signaling pathway - Homo sapiens (human)
- Oxidative Damage
- Disease
- Signal Transduction
- tnfr1 signaling pathway
Biological Process
- protein folding
- positive regulation of fibroblast migration
- positive regulation of actin filament polymerization
- positive regulation of peptidyl-serine phosphorylation
- tumor necrosis factor-mediated signaling pathway
Molecular Function
- adenyl-nucleotide exchange factor activity
- RNA binding
- protein binding
- ubiquitin protein ligase binding
- chaperone binding
Cellular Component
- nucleus
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000287322
- Coding exons
- 5
- Length
- 36769
- Individuals with no LoFs
- 125605
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 143
- Defined
- 125748
- p
- 0.000569
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.105 | 258 | 253 | 1.02 | 0.0000129 | 2880 |
| Missense (PolyPhen) | 60 | 71.285 | 0.84169 | 920 | ||
| Synonymous | 1.62 | 77 | 97.3 | 0.791 | 0.00000507 | 953 |
| Loss of Function | 2.47 | 10 | 22.7 | 0.440 | 0.00000107 | 263 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00027 | 0.00026 | rare |
| Ashkenazi Jewish | 0.010 | 0.010 | notable |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release (By similarity). Prevents constitutive TNFRSF1A signaling. Negative regulator of PRKN translocation to damaged mitochondria. {ECO:0000250, ECO:0000269|PubMed:24270810}.;
Recessive Scores
- pRec
- 0.153
Intolerance Scores
- LoFtool
- 0.396
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.01
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |