BAG5

Summary

BAG5 (BAG cochaperone 5, HGNC:941) is a protein-coding gene on chromosome 14q32.33, encoding BAG family molecular chaperone regulator 5 (Q9UL15). Co-chaperone for HSP/HSP70 proteins.

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. Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 9529 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiomyopathy, dilated, 2F (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 87 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_001015048

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:941
Approved symbol	BAG5
Name	BAG cochaperone 5
Location	14q32.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166170
Ensembl biotype	protein_coding
OMIM	603885
Entrez	9529

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000299204, ENST00000337322, ENST00000445922, ENST00000925610, ENST00000962375

RefSeq mRNA: 3 — MANE Select: NM_001015048 NM_001015048, NM_001015049, NM_004873

CCDS: CCDS9982

Canonical transcript exons

ENST00000299204 — 2 exons

Exon	Start	End
ENSE00002235357	103556551	103561192
ENSE00002446435	103562616	103562657

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.5371 / max 686.9537, expressed in 1796 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145106	26.6294	1793
145105	1.4336	734
145107	1.4314	958
145104	0.0426	8

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.69	gold quality
male germ cell	CL:0000015	96.99	gold quality
left testis	UBERON:0004533	96.74	gold quality
right testis	UBERON:0004534	96.51	gold quality
upper leg skin	UBERON:0004262	96.02	gold quality
testis	UBERON:0000473	95.31	gold quality
skin of hip	UBERON:0001554	95.30	gold quality
endothelial cell	CL:0000115	94.51	gold quality
caput epididymis	UBERON:0004358	94.31	gold quality
tongue squamous epithelium	UBERON:0006919	93.89	gold quality
gingiva	UBERON:0001828	93.58	gold quality
esophagus squamous epithelium	UBERON:0006920	93.57	gold quality
corpus epididymis	UBERON:0004359	93.52	gold quality
squamous epithelium	UBERON:0006914	93.37	gold quality
gingival epithelium	UBERON:0001949	93.35	gold quality
oviduct epithelium	UBERON:0004804	93.12	gold quality
mammalian vulva	UBERON:0000997	93.01	gold quality
epithelium of esophagus	UBERON:0001976	92.89	gold quality
parietal pleura	UBERON:0002400	92.78	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.73	gold quality
pleura	UBERON:0000977	92.34	gold quality
cauda epididymis	UBERON:0004360	92.30	gold quality
middle temporal gyrus	UBERON:0002771	92.13	gold quality
cranial nerve II	UBERON:0000941	92.11	gold quality
visceral pleura	UBERON:0002401	92.06	gold quality
calcaneal tendon	UBERON:0003701	91.95	gold quality
penis	UBERON:0000989	91.75	gold quality
oral cavity	UBERON:0000167	91.73	gold quality
postcentral gyrus	UBERON:0002581	91.50	gold quality
secondary oocyte	CL:0000655	91.38	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.01
E-MTAB-6058	no	221.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PINK1

miRNA regulators (miRDB)

134 targeting BAG5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 20)

• Bcl-2-associated athanogene 5 (BAG5) is a negative regulator of both Hsp70 and parkin function that sensitizes dopaminergic neurons to injury-induced death. (PMID:15603737)
• We replicated the association of BCL2L11 and CASP9 with non-Hodgkin’s lymphoma risk at the gene and SNP level, and identified novel associations with BCLAF1 and BAG5. (PMID:20855536)
• BAG5 directly interacts with Parkin and stabilizes Parkin via the ubiquitin-mediated proteasomal pathway. (PMID:21131737)
• A novel function for BAG5 as a modulator of CHIP E3 ubiquitin ligase activity with implications for CHIP-mediated regulation of alpha-syn oligomerization. (PMID:21358815)
• Bag5 is overexpressed in prostate cancer and plays a role in endoplamic reticulum-stress induced apoptosis. Furthermore we have identified GRP78/BiP as a novel interaction partner of Bag5. (PMID:23448667)
• BAG5 protects against mitochondrial oxidative damage through regulating PINK1 degradation. (PMID:24475098)
• BAG5 is a binding partners of LRRK2 and part of a complex that promotes clearance of Golgi-derived vesicles through the autophagy-lysosome system. (PMID:24510904)
• This study showed that BAG2 (Bcl-2 associated athanogene family protein 2) and BAG5 (Bcl-2-associated athanogene family protein 5) stabilise pathogenic ataxin3-80Q by inhibiting its ubiquitination. (PMID:25006867)
• BAG5 was found as a expression variability marker in an 8-cell human embryo. (PMID:26288249)
• High BAG5 expression is associated with pancreatic cancer. (PMID:27571739)
• Subsequent BAG5 upregulation ameliorated the tumor-suppressive effects of miR-127-3p overexpression in epithelial ovarian cancer (EOC). In conclusion, miR-127-3p functions as a tumor suppressor in EOC, and its influence on EOC is directly through regulation of BAG5. (PMID:27571744)
• Bcl-2-associated athanogene 5 (BAG5) regulates Parkin-dependent mitophagy and cell death. (PMID:31787745)
• miR-155 inhibits mitophagy through suppression of BAG5, a partner protein of PINK1. (PMID:31948758)
• Signals from the Metastatic Niche Regulate Early and Advanced Ovarian Cancer Metastasis through miR-4454 Downregulation. (PMID:32350057)
• Bcl-2-associated athanogene 5 overexpression attenuates catecholamine-induced vascular endothelial cell apoptosis. (PMID:32583430)
• Stress-induced p53 drives BAG5 cochaperone expression to control alpha-synuclein aggregation in Parkinson’s disease. (PMID:33085644)
• PRMT6 deficiency induces autophagy in hostile microenvironments of hepatocellular carcinoma tumors by regulating BAG5-associated HSC70 stability. (PMID:33186656)
• Circ_0008305-mediated miR-660/BAG5 axis contributes to hepatocellular carcinoma tumorigenesis. (PMID:33481351)
• Implication of BAG5 downregulation in metabolic reprogramming of cisplatin-resistant ovarian cancer cells via mTORC2 signaling pathway. (PMID:34126157)
• Akt Is Controlled by Bag5 through a Monoubiquitination to Polyubiquitination Switch. (PMID:38139359)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bag5	ENSDARG00000017316
mus_musculus	Bag5	ENSMUSG00000049792
rattus_norvegicus	Bag5	ENSRNOG00000058841
drosophila_melanogaster	stv	FBGN0086708

Paralogs (2): BAG3 (ENSG00000151929), BAG4 (ENSG00000156735)

Protein

Protein identifiers

BAG family molecular chaperone regulator 5 — Q9UL15 (reviewed: Q9UL15)

Alternative names: Bcl-2-associated athanogene 5

All UniProt accessions (2): A0A024R6M6, Q9UL15

UniProt curated annotations — full annotation on UniProt →

Function. Co-chaperone for HSP/HSP70 proteins. It functions as a nucleotide-exchange factor promoting the release of ADP from HSP70, thereby activating HSP70-mediated protein refolding. Has an essential role in maintaining proteostasis at junctional membrane complexes (JMC), where it may function as a scaffold between the HSPA8 chaperone and JMC proteins enabling correct, HSPA8-dependent JMC protein folding. Inhibits both auto-ubiquitination of PRKN and ubiquitination of target proteins by PRKN.

Subunit / interactions. Binds to the ATPase domain of HSP/HSP70 chaperones. Binds PRKN. Interacts with HSPA8 and JPH2.

Tissue specificity. Expressed in the heart.

Disease relevance. Cardiomyopathy, dilated, 2F (CMD2F) [MIM:619747] A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2F is an autosomal recessive, early-onset form. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The fifth BAG domain is responsible for the interaction with HSP70 nucleotide-binding domain.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UL15-1	1	yes
Q9UL15-2	2

RefSeq proteins (3): NP_001015048, NP_001015049, NP_004864 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003103	BAG_domain	Domain
IPR036533	BAG_dom_sf	Homologous_superfamily
IPR039773	BAG_chaperone_regulator	Family

Pfam: PF02179

UniProt features (19 total): helix 7, domain 5, sequence variant 3, turn 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3A8Y	X-RAY DIFFRACTION	2.3
2D9D	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL15-F1	90.68	0.72

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-2262752	Cellular responses to stress
R-HSA-3371556	Cellular response to heat stress
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 266 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, MORF_MBD4, MORF_RAB5A, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, MORF_PSMC2, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (9): protein folding (GO:0006457), Golgi organization (GO:0007030), negative regulation of neuron projection development (GO:0010977), negative regulation of protein ubiquitination (GO:0031397), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), protein stabilization (GO:0050821), negative regulation of protein refolding (GO:0061084), regulation of inclusion body assembly (GO:0090083), negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902176)

GO Molecular Function (6): adenyl-nucleotide exchange factor activity (GO:0000774), protein kinase binding (GO:0019901), ubiquitin protein ligase binding (GO:0031625), protein-folding chaperone binding (GO:0051087), ubiquitin ligase inhibitor activity (GO:1990948), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), membrane (GO:0016020), inclusion body (GO:0016234), junctional membrane complex (GO:0030314), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular response to heat stress	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
intracellular membrane-bounded organelle	2
intracellular anatomical structure	2
cellular process	1
protein maturation	1
organelle organization	1
endomembrane system organization	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
regulation of protein stability	1
protein refolding	1
regulation of protein refolding	1
negative regulation of protein folding	1
regulation of cellular component biogenesis	1
regulation of cellular component organization	1
inclusion body assembly	1
intrinsic apoptotic signaling pathway in response to oxidative stress	1
regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1
negative regulation of intrinsic apoptotic signaling pathway	1
ATP binding	1
ADP binding	1
ATPase regulator activity	1
kinase binding	1
ubiquitin-like protein ligase binding	1
protein binding	1
ubiquitin-protein transferase inhibitor activity	1
binding	1
sarcoplasm	1
protein-containing complex	1

Protein interactions and networks

STRING

1338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BAG5	GAK	O14976	912
BAG5	HSPA8	P11142	904
BAG5	BAG2	O95816	903
BAG5	BAG1	Q99933	867
BAG5	RAB29	O14966	851
BAG5	STUB1	Q9UNE7	829
BAG5	HSPA4	P34932	811
BAG5	PRKN	O60260	799
BAG5	PINK1	Q9BXM7	742
BAG5	BCL2	P10415	696
BAG5	PARK7	Q99497	671
BAG5	GPR37	O15354	644
BAG5	LRRK2	Q5S007	603
BAG5	CALM1	P02593	597
BAG5	CALML3	P27482	581

IntAct

275 interactions, top by confidence:

A	B	Type	Score
MAD1L1	BAG5	psi-mi:“MI:0915”(physical association)	0.870
BAG5	MAD1L1	psi-mi:“MI:0915”(physical association)	0.870
BAG5	THAP1	psi-mi:“MI:0915”(physical association)	0.780
THAP1	BAG5	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	BAG5	psi-mi:“MI:0915”(physical association)	0.720
KASH5	BAG5	psi-mi:“MI:0915”(physical association)	0.720
BAG5	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
BAG5	KASH5	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
	TOMM70	psi-mi:“MI:0914”(association)	0.690
GBA2	ILVBL	psi-mi:“MI:0914”(association)	0.640
TP53	BAG2	psi-mi:“MI:0914”(association)	0.640
BANP	BAG5	psi-mi:“MI:0915”(physical association)	0.560
FAM118B	BAG5	psi-mi:“MI:0915”(physical association)	0.560
BAG5	BANP	psi-mi:“MI:0915”(physical association)	0.560
BAG5	FAM118B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (470): BAG5 (Affinity Capture-MS), BAG5 (Two-hybrid), BAG5 (Two-hybrid), BANP (Two-hybrid), THAP1 (Two-hybrid), FAM118B (Two-hybrid), CCDC155 (Two-hybrid), BAG5 (Affinity Capture-MS), MAD1L1 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), ABL2 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), BAG5 (Affinity Capture-MS)

ESM2 similar proteins: A0A2H5Q1B8, A5D8W1, A6NC57, B0CM26, B0VXE6, F6S215, O16844, P07666, P10911, P50748, P82872, P93002, P97357, Q08DB2, Q15573, Q20CR4, Q2TA08, Q2TAW0, Q3B7U2, Q4PSA3, Q4R6I5, Q4R804, Q5F486, Q5M6W3, Q5PPS5, Q5QJC9, Q5S006, Q5S007, Q5SPP5, Q5XIR8, Q5XUN4, Q61037, Q62240, Q641A2, Q6DFV1, Q6Q4D0, Q6ZQ18, Q6ZWQ0, Q6ZWR6, Q86XI2

Diamond homologs: O95429, O95817, Q2TA08, Q5F486, Q5QJC9, Q8CI32, Q8CI61, Q9BLJ6, Q9JLV1, Q9UL15, A1CQG2, A1D3C5, A2QQ28, B0XQ72, B8N7E5, G0S9J5, O00308, O14326, O88382, P39940, P46934, P46935, Q0CCL1, Q19404, Q1L8J7, Q2UBP1, Q4WTF3, Q5BDP1, Q5RBF2, Q62940, Q6I6G8, Q76N89, Q7XZU0, Q8BZZ3, Q8CFI0, Q8K4P8, Q92462, Q96PU5, Q9DBH0, Q9H0M0

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
BAG5	“down-regulates activity”	HSPA1A	binding
BAG5	“down-regulates activity”	HSPA1B	binding
BAG5	“down-regulates activity”	PRKN	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 202 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	8	12.0×	2e-04
PKR-mediated signaling	8	8.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

87 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	73
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1341487	NM_001015048.3(BAG5):c.589C>T (p.Arg197Ter)	Pathogenic
1341489	NM_001015048.3(BAG5):c.18dup (p.His7fs)	Pathogenic
57267	GRCh38/hg38 14q32.2-32.33(chr14:100309382-106855263)x1	Pathogenic
1341488	NM_001015048.3(BAG5):c.1168C>T (p.Arg390Ter)	Likely pathogenic
2499992	NM_001015048.3(BAG5):c.321_322del (p.Lys108fs)	Likely pathogenic
3392557	NM_001015048.3(BAG5):c.407_408del (p.His136fs)	Likely pathogenic

SpliceAI

187 predictions. Top by Δscore:

Variant	Effect	Δscore
14:103562611:CTCA:C	donor_loss	1.0000
14:103562612:TCACC:T	donor_loss	1.0000
14:103562613:CA:C	donor_loss	1.0000
14:103562614:ACC:A	donor_loss	1.0000
14:103562615:C:CG	donor_loss	1.0000
14:103561193:C:CC	acceptor_gain	0.9800
14:103562614:A:AC	donor_gain	0.9800
14:103562615:C:CC	donor_gain	0.9800
14:103561191:CA:C	acceptor_gain	0.9700
14:103562615:CCTGT:C	donor_gain	0.9700
14:103562083:C:A	donor_gain	0.8800
14:103561190:GCA:G	acceptor_gain	0.8700
14:103561191:CAC:C	acceptor_gain	0.8700
14:103561188:AAGCA:A	acceptor_gain	0.8500
14:103561191:CACTA:C	acceptor_loss	0.8000
14:103561192:ACT:A	acceptor_loss	0.8000
14:103561193:C:CA	acceptor_loss	0.8000
14:103561194:T:A	acceptor_loss	0.8000
14:103561202:G:T	acceptor_loss	0.7900
14:103561195:A:C	acceptor_loss	0.7800
14:103561189:AGCA:A	acceptor_gain	0.7700
14:103561204:C:CT	acceptor_loss	0.7700
14:103561205:A:T	acceptor_loss	0.7700
14:103561196:AAAGA:A	acceptor_loss	0.7600
14:103562135:C:A	donor_gain	0.7500
14:103561727:C:A	donor_gain	0.7400
14:103562615:CCT:C	donor_gain	0.7400
14:103561802:C:CT	donor_gain	0.7100
14:103559829:C:CA	donor_gain	0.7000
14:103561197:A:C	acceptor_loss	0.7000

AlphaMissense

2950 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:103561028:A:G	L46P	0.991
14:103559832:A:G	W445R	0.989
14:103559832:A:T	W445R	0.989
14:103559886:C:G	A427P	0.987
14:103559960:A:G	L402P	0.987
14:103561075:G:C	F30L	0.987
14:103561075:G:T	F30L	0.987
14:103561077:A:G	F30L	0.987
14:103559893:C:A	R424S	0.986
14:103559893:C:G	R424S	0.986
14:103560162:C:G	A335P	0.986
14:103560485:A:G	L227P	0.986
14:103560007:A:C	F386L	0.984
14:103560007:A:T	F386L	0.984
14:103560009:A:G	F386L	0.984
14:103560440:C:G	R242P	0.984
14:103560961:C:A	R68S	0.983
14:103560961:C:G	R68S	0.983
14:103561016:A:G	L50P	0.983
14:103560718:C:A	R149S	0.982
14:103560718:C:G	R149S	0.982
14:103560920:A:G	L82S	0.982
14:103559830:C:A	W445C	0.981
14:103559830:C:G	W445C	0.981
14:103559948:A:G	L406P	0.981
14:103560929:A:G	L79P	0.981
14:103561127:A:G	L13P	0.981
14:103559963:A:G	L401P	0.980
14:103560764:A:G	L134P	0.979
14:103560506:A:G	L220P	0.978

dbSNP variants (sampled 300 via entrez): RS1000625251 (14:103562825 G>T), RS1001001538 (14:103556563 G>GTC,GT), RS1001089946 (14:103557196 G>A), RS1001117076 (14:103556862 T>C,G), RS1001521297 (14:103561500 A>G), RS1001915235 (14:103556488 G>A), RS1001967517 (14:103556707 C>T), RS1002009532 (14:103560190 GT>G,GTT), RS1002466942 (14:103562611 C>A), RS1002512895 (14:103563912 A>G), RS1003133421 (14:103559128 C>A,T), RS1003739012 (14:103563650 G>A), RS1004087412 (14:103556671 C>T), RS1004420442 (14:103562406 G>A), RS1004472895 (14:103562239 C>G,T)

Disease associations

OMIM: gene MIM:603885 | disease phenotypes: MIM:619747

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiomyopathy, dilated, 2F	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
cardiomyopathy, dilated, 2F	Moderate	AR

Mondo (2): cardiomyopathy, dilated, 2F (MONDO:0030680), cardiomyopathy (MONDO:0004994)

Orphanet (1): Rare cardiomyopathy (Orphanet:167848)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000969	Edema
HP:0001635	Congestive heart failure
HP:0001644	Dilated cardiomyopathy
HP:0001663	Ventricular fibrillation
HP:0001727	Thromboembolic stroke
HP:0002875	Exertional dyspnea
HP:0003198	Myopathy
HP:0003457	EMG abnormality
HP:0003621	Juvenile onset
HP:0004756	Ventricular tachycardia
HP:0011462	Young adult onset
HP:0011675	Arrhythmia
HP:0012378	Fatigue
HP:0012666	Severely reduced left ventricular ejection fraction
HP:0012764	Orthopnea
HP:0025169	Left ventricular systolic dysfunction
HP:0033534	Increased circulating brain natriuretic peptide concentration
HP:0033755	Increased left ventricular end-diastolic volume
HP:0100578	Lipoatrophy

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002539_23	Schizophrenia	1.000000e-13
GCST004521_135	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_15	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_262	Autism spectrum disorder or schizophrenia	6.000000e-09
GCST005839_36	Depression	3.000000e-09
GCST005951_9	Body mass index	4.000000e-09
GCST007257_14	Broad depression or schizophrenia	9.000000e-16
GCST009600_90	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	5.000000e-13
GCST010703_23	Brain morphology (MOSTest)	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Rotenone	increases degradation, increases response to substance, decreases reaction, decreases response to substance, affects localization (+2 more)	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, decreases reaction, increases abundance	2
aristolochic acid I	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Panobinostat	affects cotreatment, affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Arbutin	decreases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Cisplatin	affects cotreatment, affects expression	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Emodin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression, affects cotreatment	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Menthol	increases expression	1
Piroxicam	decreases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	PHASE3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT00185250	PHASE2	COMPLETED	Betaferon/ Betaseron (Interferon Beta-1b) in Patients With Chronic Viral Cardiomyopathy
NCT00490347	PHASE2	COMPLETED	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Feasibility Trial
NCT00694161	PHASE2	COMPLETED	The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy