BAG1
protein-codingBAG cochaperone 1, the group of BAG cochaperones
Gene summary
The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. Multiple protein isoforms are encoded by this mRNA through the use of a non-AUG (CUG) initiation codon, and three alternative downstream AUG initiation codons. A related pseudogene has been defined on chromosome X. [provided by RefSeq, Feb 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.9 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 BAG1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004323.6. 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 | 0 | |||||
| missense | 48 | 3 | 1 | 52 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 51 | 3 | 1 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004314.6 | 7 | MANE Select | |
| Ensembl | ENSP00000489189.2 | 7 | MANE Select | |
| RefSeq | NP_001165886.1 | 7 | Standard | |
| RefSeq | NP_001336215.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Androgen receptor signaling pathway
- Regulation of HSF1-mediated heat shock response
- Cellular responses to stress
- AndrogenReceptor
Biological Process
- apoptotic process
- cell surface receptor signaling pathway
- negative regulation of apoptotic process
- regulation of catalytic activity
- chaperone cofactor-dependent protein refolding
Molecular Function
- adenyl-nucleotide exchange factor activity
- protein binding
- ubiquitin protein ligase binding
- chaperone binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000472232
- Coding exons
- 7
- Length
- 16944
- Individuals with no LoFs
- 125627
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 121
- Defined
- 125748
- p
- 0.000481
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.521 | 198 | 178 | 1.11 | 0.00000847 | 2215 |
| Missense (PolyPhen) | 36 | 43.398 | 0.82953 | 594 | ||
| Synonymous | -0.0410 | 72 | 71.6 | 1.01 | 0.00000351 | 696 |
| Loss of Function | 1.11 | 10 | 14.6 | 0.685 | 6.20e-7 | 187 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00022 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0.00031 | 0.00028 | rare |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.0028 | 0.0028 | notable |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
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:27474739, PubMed:9873016, PubMed:24318877). Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity (PubMed:12724406). Markedly increases the anti-cell death function of BCL2 induced by various stimuli (PubMed:9305631). {ECO:0000269|PubMed:12724406, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:9305631, ECO:0000269|PubMed:9873016}.;
Recessive Scores
- pRec
- 0.435
Intolerance Scores
- LoFtool
- 0.260
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.01
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.959
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |