BAG3 - dismech genes

Normal function · from ai-gene-review (O95817, commit 79fe13b38970) · AI-generated, not KB evidence

BAG3 is a human BAG-family HSP70 co-chaperone and modular adaptor that links HSP70/HSC70 to small heat shock proteins such as HSPB8, promotes HSP70 nucleotide exchange/client release, and routes damaged or aggregation-prone proteins through chaperone-assisted selective autophagy, aggresome targeting, and muscle Z-disc proteostasis. It also has non-core stress-response roles in HSF1 nucleocytoplasmic shuttling and apoptosis modulation.

HSP70 nucleotide-exchange co-chaperone activity: BAG3 uses its BAG domain to bind HSP70/HSC70 nucleotide-binding domains and promote ADP release/client release in protein-folding chaperone cycles.

molecular function: adenyl-nucleotide exchange factor activity · directly involved in: protein folding · locations: cytosol

Modular chaperone adaptor/scaffold activity: BAG3 links HSP70/HSC70 with small heat shock proteins including HSPB8 and HSPB1/HSP27, coordinating client handling by ATP-dependent and ATP-independent chaperones.

molecular function: protein-macromolecule adaptor activity · directly involved in: protein folding · locations: cytosol · in complex: protein folding chaperone complex

Chaperone-assisted selective autophagy and aggrephagy: BAG3-HSP70-HSPB8 complexes route damaged or aggregation-prone clients to aggresomes and autophagic degradation with dynein, STUB1/CHIP, p62/SQSTM1, and LC3-linked machinery.

molecular function: protein-macromolecule adaptor activity · directly involved in: protein transport along microtubule; aggresome assembly; positive regulation of aggrephagy · locations: cytosol; aggresome

Striated muscle Z-disc proteostasis and mechanotransduction: BAG3-containing CASA machinery senses mechanically damaged filamin and other Z-disc components, supports autophagosome formation, and maintains muscle cell homeostasis under mechanical stress.

molecular function: protein-macromolecule adaptor activity · directly involved in: muscle cell cellular homeostasis; autophagosome assembly · locations: Z disc; cytosol

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Charcot-Marie-Tooth disease, axonal, type 2JJ	causative germline gain of function	mechanism: BAG3 IPV Motif Variant
Dilated Cardiomyopathy 1HH	causative	mechanism: BAG3 Loss-of-Function Variant
Distal Hereditary Motor Neuronopathy, Autosomal Dominant	causative	mechanism: Motor Neuron and Distal Axon Gene Defect subtype: dHMN-BAG3 scoped to subtype: dHMN-BAG3
Myofibrillar Myopathy	causative de novo	mechanism: Z-Disc and Chaperone Protein Variant subtype: MFM6 scoped to subtype: MFM6
Dilated Cardiomyopathy	untyped Pathogenic Variants	mechanism: Sarcomeric and Cytoskeletal Dysfunction

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
dilated cardiomyopathy 1HH MONDO:0013479	AD	Definitive 2026-03-04	Dilated Cardiomyopathy 1HH causative

Mechanism modules · computed from kb/

cardiomyopathy_maladaptive_remodeling via Dilated Cardiomyopathy 1HH