• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
BAG3 (HGNC:939) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
BAG cochaperone 3
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
55.47(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.62(Read more about gnomAD pLI score)
LOEUF
0.45(Read more about gnomAD LOEUF score)
Cytoband
10q26.11
Genomic Coordinates
GRCh37/hg19: chr10:121410892-121437331 NCBI Ensembl UCSC
GRCh38/hg38: chr10:119651380-119677819 NCBI Ensembl UCSC
MANE Select Transcript
NM_004281.4 ENST00000369085.8 (Read more about MANE Select)
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:105... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-36739
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
02/12/2015

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 21353195
    Norton et al. (2011) performed whole-genome array and whole-exome sequencing on a multigenerational family affected with familial autosomal dominant dilated cardiomyopathy (DCM) and identified an 8.7 kb deletion including exon 4 present in all 7 family members and absent from 355 controls. Targeted sequencing of exons 2-4 on a cohort of 311 additional DCM patients identified one frameshift, two nonsense, and four missense heterozygous mutations all predicted to result in loss-of-function in 7 unrelated probands; these mutations were also absent from 355 controls. Knockdown studies in zebrafish supported the data. This study has also been reviewed in OMIM (see http://www.omim.org/entry/603883)
  • PUBMED: 25008357
    Franaszczyk et al. (2014) performed direct sequencing of exons and splice sites of BAG3 on a cohort of 90 DCM patients and identified 3 missense mutations, one nonsense mutation, and a 17.9 kb deletion encompassing exons 3-4 in 6 unrelated probands.
  • PUBMED: 21459883
    Villard et al. (2011) performed BAG3 exome sequencing in a cohort of 168 patients with DCM and identified 4 nonsense and two missense mutations in 6 probands. Each mutation was heterozygous and present in all affected relatives of the probands and absent from 347 healthy controls.
HI Evidence Comments:
Heterozygous mutations and intragenic deletions affecting BAG3 have been identified in multiple unrelated patients with dilated cardiomyopathy (DCM). There are some reports of normal echo/ECG in BAG3 mutation carriers, suggestive of incomplete penetrance (see PMID 25008357, 21459883). Of the two families with intragenic BAG3 deletions, all carriers were shown to be affected. Functional studies support some of these findings (see http://www.omim.org/entry/603883 and PMID 21353195, 25008357, 21898660, 21459883). As yet, whole BAG3 deletions have not been reported Additionally, p.P209 mutations have been reported in association with myofibrillar myopathy (see PMID 19085932, 21361913, 25208129).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000010.10) (NC_000010.11)