HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
BAG5
BAG cochaperone 5
Chromosome 14 Β· 14q32.33
NCBI Gene: 9529Ensembl: ENSG00000166170.13HGNC: HGNC:941UniProt: A0A024R6M6
131PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytosolmembranemitochondrioninclusion bodycardiomyopathy, dilated, 2Ffamilial isolated dilated cardiomyopathyschizophreniamajor depressive disorder
✦AI Summary

BAG5 (BAG cochaperone 5) functions as a co-chaperone that regulates HSP70 family proteins through nucleotide exchange factor activity, promoting ADP release and activating HSP70-mediated protein folding 1. Unlike other BAG family members with single BAG domains, BAG5 contains five BAG domains that enable its diverse cellular functions 2. BAG5 plays critical roles in male fertility by forming complexes with HSPA8 to promote proper folding of sperm head-tail coupling apparatus proteins including SPATA6, MYO5A, and dynein proteins 1. In spermatogenesis, BAG5 interacts with testis-specific HSPA2 to regulate transcription of transition proteins and maintain chr14 condensation 3. BAG5 also regulates cardiac function at junctional membrane complexes, where loss-of-function mutations cause dilated cardiomyopathy through disrupted calcium handling and JMC protein stability 4. Additionally, BAG5 modulates cellular signaling by controlling Akt stability through switching monoubiquitination to polyubiquitination 5 and protects against mitochondrial oxidative damage by stabilizing PINK1 6. Clinical significance includes associations with male infertility, dilated cardiomyopathy requiring heart transplantation, and potential roles in Parkinson's disease and non-small cell lung cancer 47.

Sources cited
1
BAG5 functions as nucleotide exchange factor for HSP70 proteins and regulates sperm head-tail coupling apparatus assembly
PMID: 38454159
2
BAG5 has five BAG domains unlike other BAG family members with single domains
PMID: 37903258
3
BAG5 interacts with HSPA2 in spermatogenesis and regulates transition protein transcription
PMID: 39992433
4
Loss-of-function BAG5 mutations cause dilated cardiomyopathy through disrupted junctional membrane complexes
PMID: 35044787
5
BAG5 regulates Akt stability by switching monoubiquitination to polyubiquitination
PMID: 38139359
6
BAG5 protects against mitochondrial oxidative damage by stabilizing PINK1
PMID: 24475098
7
BAG5 has potential oncogenic roles in non-small cell lung cancer
PMID: 40787462
Disease Associationsβ“˜21
cardiomyopathy, dilated, 2FOpen Targets
0.61Moderate
familial isolated dilated cardiomyopathyOpen Targets
0.38Weak
schizophreniaOpen Targets
0.36Weak
major depressive disorderOpen Targets
0.35Weak
attention deficit hyperactivity disorderOpen Targets
0.34Weak
obsessive-compulsive disorderOpen Targets
0.32Weak
bipolar disorderOpen Targets
0.28Weak
intelligenceOpen Targets
0.27Weak
hearing lossOpen Targets
0.27Weak
autism spectrum disorderOpen Targets
0.26Weak
cardiomyopathyOpen Targets
0.26Weak
major depressive episodeOpen Targets
0.25Weak
obesityOpen Targets
0.25Weak
genetic disorderOpen Targets
0.19Weak
anorexia nervosaOpen Targets
0.13Weak
Tourette syndromeOpen Targets
0.13Weak
neoplasmOpen Targets
0.09Suggestive
Parkinson diseaseOpen Targets
0.09Suggestive
hypertrophic cardiomyopathyOpen Targets
0.08Suggestive
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.07Suggestive
Cardiomyopathy, dilated, 2FUniProt
Pathogenic Variants5
NM_001015048.3(BAG5):c.1168C>T (p.Arg390Ter)Likely pathogenic
Cardiomyopathy, dilated, 2F
β˜…β˜†β˜†β˜†2025β†’ Residue 390
NM_001015048.3(BAG5):c.407_408del (p.His136fs)Likely pathogenic
Cardiomyopathy, dilated, 2F
β˜…β˜†β˜†β˜†2024β†’ Residue 136
NM_001015048.3(BAG5):c.18dup (p.His7fs)Pathogenic
Cardiomyopathy, dilated, 2F
β˜†β˜†β˜†β˜†2023β†’ Residue 7
NM_001015048.3(BAG5):c.589C>T (p.Arg197Ter)Pathogenic
Cardiomyopathy, dilated, 2F
β˜†β˜†β˜†β˜†2022β†’ Residue 197
NM_001015048.3(BAG5):c.321_322del (p.Lys108fs)Likely pathogenic
Cardiomyopathy
β˜†β˜†β˜†β˜†β†’ Residue 108
View on ClinVar β†—
Related Genes
BAG3Protein interaction100%HSPH1Protein interaction99%TP53Protein interaction97%PINK1Protein interaction96%PRKNProtein interaction95%BAG1Protein interaction92%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
65%
Heart
44%
Lung
28%
Liver
22%
Ovary
19%
Gene Interaction Network
Click a node to explore
BAG5BAG3HSPH1TP53PINK1PRKNBAG1
PROTEIN STRUCTURE
Preparing viewer…
PDB3A8Y Β· 2.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.04LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.74 [0.54–1.04]
RankingsWhere BAG5 stands among ~20K protein-coding genes
  • #3,548of 20,598
    Most Researched131 Β· top quartile
  • #3,506of 5,498
    Most Pathogenic Variants5
  • #10,358of 17,882
    Most Constrained (LOEUF)1.04
Genes detectedBAG5
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
BAG5 regulates HSPA8-mediated protein folding required for sperm head-tail coupling apparatus assembly.
PMID: 38454159
EMBO Rep Β· 2024
1.00
2
Human proteins curing yeast prions.
PMID: 37903258
Proc Natl Acad Sci U S A Β· 2023
0.90
3
Male germ cells with Bag5 deficiency show reduced spermiogenesis and exchange of basic nuclear proteins.
PMID: 39992433
Cell Mol Life Sci Β· 2025
0.80
4
Akt Is Controlled by Bag5 through a Monoubiquitination to Polyubiquitination Switch.
PMID: 38139359
Int J Mol Sci Β· 2023
0.70
5
Loss-of-function mutations in the co-chaperone protein BAG5 cause dilated cardiomyopathy requiring heart transplantation.
PMID: 35044787
Sci Transl Med Β· 2022
0.60