TBX5

Summary

TBX5 (T-box transcription factor 5, HGNC:11604) is a protein-coding gene on chromosome 12q24.21, encoding T-box transcription factor TBX5 (Q99593). DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation. It is haploinsufficient (ClinGen: sufficient evidence).

This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is closely linked to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12. The encoded protein may play a role in heart development and specification of limb identity. Mutations in this gene have been associated with Holt-Oram syndrome, a developmental disorder affecting the heart and upper limbs. Several transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 6910 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Holt-Oram syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 154
• Clinical variants (ClinVar): 869 total — 168 pathogenic, 41 likely-pathogenic
• Phenotypes (HPO): 131
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 29 downstream targets (CollecTRI)
• MANE Select transcript: NM_181486

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11604
Approved symbol	TBX5
Name	T-box transcription factor 5
Location	12q24.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000089225
Ensembl biotype	protein_coding
OMIM	601620
Entrez	6910

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000310346, ENST00000349716, ENST00000405440, ENST00000526441, ENST00000552726, ENST00000860921, ENST00000860922, ENST00000860923, ENST00000860924, ENST00000860925, ENST00000860926, ENST00000860927, ENST00000860928, ENST00000945349, ENST00000945350, ENST00000945351

RefSeq mRNA: 3 — MANE Select: NM_181486 NM_000192, NM_080717, NM_181486

CCDS: CCDS9173, CCDS9174

Canonical transcript exons

ENST00000405440 — 9 exons

Exon	Start	End
ENSE00000835004	114366165	114366391
ENSE00001512374	114405628	114406144
ENSE00001582631	114394741	114394893
ENSE00001589877	114385476	114385567
ENSE00002197056	114353911	114356106
ENSE00002278860	114403752	114403936
ENSE00003493097	114399513	114399632
ENSE00003508688	114398573	114398720
ENSE00003522498	114401826	114401920

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 99.00.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0798 / max 217.0615, expressed in 243 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133398	0.2658	87
133399	0.2444	55
133396	0.1223	54
133395	0.0927	48
133400	0.0750	27
133397	0.0665	25
133393	0.0634	24
133391	0.0521	24
133392	0.0362	14
133394	0.0327	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.00	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.22	gold quality
buccal mucosa cell	CL:0002336	97.02	gold quality
right atrium auricular region	UBERON:0006631	96.65	gold quality
cardiac atrium	UBERON:0002081	96.55	gold quality
lower lobe of lung	UBERON:0008949	95.65	gold quality
myocardium	UBERON:0002349	95.40	gold quality
heart right ventricle	UBERON:0002080	91.21	gold quality
left ventricle myocardium	UBERON:0006566	90.93	silver quality
visceral pleura	UBERON:0002401	90.36	gold quality
right lung	UBERON:0002167	89.63	gold quality
heart	UBERON:0000948	88.58	gold quality
heart left ventricle	UBERON:0002084	88.20	gold quality
cardiac ventricle	UBERON:0002082	88.11	gold quality
oocyte	CL:0000023	87.47	gold quality
apex of heart	UBERON:0002098	86.89	gold quality
placenta	UBERON:0001987	86.06	gold quality
upper lobe of lung	UBERON:0008948	85.47	gold quality
upper lobe of left lung	UBERON:0008952	84.77	gold quality
type B pancreatic cell	CL:0000169	84.31	gold quality
olfactory bulb	UBERON:0002264	83.96	gold quality
lung	UBERON:0002048	83.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.48	gold quality
lower esophagus	UBERON:0013473	82.41	gold quality
secondary oocyte	CL:0000655	80.80	gold quality
pleura	UBERON:0000977	79.18	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	78.07	gold quality
mammary duct	UBERON:0001765	77.75	silver quality
right coronary artery	UBERON:0001625	75.96	gold quality
thoracic mammary gland	UBERON:0005200	75.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.17

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

29 targets.

Target	Regulation
ATP2A2	Activation
BMP2
BMP4	Unknown
CDKN2A	Activation
DISC1
FGF10	Activation
GJA5	Activation
HLA-DQB1
ITGA9	Unknown
MMP2
MTA2	Repression
MTSS1	Activation
MYH6	Unknown
MYL2
MYL7
NOTCH1
NPPA	Activation
PDLIM7
SALL4	Unknown
SCN5A	Activation
SHOX2	Unknown
SLIT1
SNCG	Repression
SRF	Unknown
TBX5
TBX6
TH
TPM1
UTS2R

JASPAR motifs

Motif	Name	Family
MA0807.1	TBX5	TBX2-related factors

JASPAR matrix evidence (PMIDs): PMID:12093383

Upstream regulators (CollecTRI, top): KLF2, NKX2-5, NR2F2, PITX2, TBX5

miRNA regulators (miRDB)

97 targeting TBX5, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
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-3163	100.00	77.23	8605
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• large TBX5 deletion in a family with Holt-Oram syndrome (PMID:11748310)
• These results reveal TBX5 as a new regulator of apoptosis and cell growth, suggesting a possible mechanism for Holt-Oram syndrome, and a potential reagent for controlling tumor growth. (PMID:12237100)
• functional analysis of missense mutations associated with Holt-Oram syndrome (PMID:12499378)
• results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5 (PMID:12845333)
• Causes of phenotypic diversity in cardiac embryogenesis in TBX5 mutations. (PMID:12858531)
• TBX5 nuclear localization is mediated by dual cooperative intramolecular signals (PMID:14519429)
• Studies enhance understanding of the structure-function relationship of TBX5 and suggest that truncation mutations of TBX5 could cause Holt-Oram syndrome (HOS) through the loss of its transactivating domain and/or the nuclear localization signal. (PMID:15087119)
• Eight novel TBX5 mutations found in patients with non-Holt-Oram syndrome complex cardiac malformations. (PMID:15221798)
• NKX2.5 inhibits myocyte differentiation and myotube formation, and up-regulates Gata4 and Tbx5 expression (PMID:15653675)
• Novel mutations within the TBX5 gene are associated with Holt-Oram syndrome. (PMID:16917909)
• This study confirms TBX5 genetic testing should be reserved for patients who fulfill the strict phenotypic criteria for Holt-Oram syndrome. (PMID:17534187)
• Tbx18 interacts with Gata4 and Nkx2-5 and competes Tbx5-mediated activation of the cardiac Natriuretic peptide precursor type a-promoter. Tbx18 down-regulates Tbx6-activated Delta-like 1 expression in the somitic mesoderm in vivo (PMID:17584735)
• Tbx5-dependent pathway for the transcriptional control of diastolic function, with potential implications for the pathogenesis of heart failure (PMID:18378906)
• we describe a large atypical Holt-Oram syndrome family with mild skeletal deformations and paroxysmal atrial fibrillation, but few have congenital heart disease. Sequencing of TBX5 revealed a novel mutation, c.373G>A, resulting in p.Gly125Arg. (PMID:18451335)
• The residues 267-448 at the C-terminus of TBX5 are highly homologous to the C-terminus domain of yeast DNA-directed RNA polymerase II largest subunit. (PMID:18701034)
• Fluorescence in situ hybridization did not show major deletions or duplications at chromosome 22q11 as well as the TBX5/TBX3 region at 12q24.1. (PMID:18726671)
• The mutation c.1333delC does not locate within functional domains, but impairs the activation of the downstream target (PMID:18828908)
• TBX5 is associated with the occurrence of ventricular septal defect and may be a predisposing gene to congenital heart disease in Han Chinese (PMID:19187613)
• The results indicates that the down expression of TBX5 might not be caused by mutation and methylation in the 1 200 bp region upstream of gene, and might be regulated by abnormal expression of NKX2-5 gene in heart muscle of CHD. (PMID:19586889)
• complex formation between TBX5 and SC35 (PMID:19648116)
• Data present the crystal structures of the human TBX5 T-box domain in its DNA-unbound form and in complex with a natural DNA target site allowing for the first time the comparison between unbound and DNA-bound forms. (PMID:20450920)
• Novel missense mutations in TBX5 lead to functional haploinsufficiency and result in a reduced transcriptional activation of target genes, which is likely central to the pathogenesis of Holt-Oram syndrome. (PMID:20519243)
• a novel functional tumor suppressor gene TBX5 inactivated by promoter methylation in colon cancer was identified. Detection of methylated TBX5 may serve as a potential biomarker for the prognosis of this malignancy. (PMID:20802524)
• Data show that Tbx4 and Tbx5 harbour conserved and divergent transcriptional regulatory domains that account for their roles in limb development. In particular, both factors share an activator domain and the ability to stimulate limb growth (PMID:20975709)
• This incomplete penetrance has not been described in TBX5-associated Holt-Oram syndrome or in families with clinical Holt-Oram syndrome (PMID:21752519)
• Mutations of TBX5 cause Holt-Oram syndrome, which includes congenital heart disease as a clinical feature. (PMID:22011241)
• This is the first known report of an intragenic duplication of TBX5 and its clinical effects; an atypical HOS phenotype. (PMID:22333898)
• We will introduce several genetic approaches, which have been or are currently being applied to the study of PDA, that have been successful in identifying polymorphisms associated with adult diseases. (PMID:22414880)
• Single-base-pair mutation in the TBX5 enhancer is associated with the isolated congenital heart disease. (PMID:22543974)
• data will not only deepen our understanding of genetic causes of CHD but also provide insight into designing novel personalized therapy for adult patients with CHD by upregulating TBX5 gene expression with different approache (PMID:22901678)
• beta-catenin forms a complex with YAP1 and TBX5, which promotes colon cancer cell survival and contributes to malignant transformation. These observations reveal hitherto unidentified components of the beta-catenin pathway that play key roles in survival of beta-catenin-active cells. (PMID:23245941)
• Our results indicate that rs3825214 conferred a significant risk of lone AF in this Chinese Han population. (PMID:23717681)
• a novel mutation of TBX5 gene in Holt-Oram Syndrome (PMID:24408148)
• Data show that Hdac3 physically interacts with Tbx5 and modulates its acetylation to repress Tbx5-dependent activation of cardiomyocyte lineage-specific genes. (PMID:24565863)
• miR-10a and miR-10b repressed TBX5 expression and decreased TBX5 protein levels by targeting the TBX5 3’-untranslated region in Congenital heart disease patients . (PMID:24714979)
• The TBX5 DNA-binding domain complex was shown to interact with a DNA element from atrial natriuretic factor. (PMID:24817716)
• This is a novel gene implicated in atrial fibrillation (PMID:25124494)
• All Holt-Oram syndrome patients in this study showed cardiac septal anomalies. Half of them showed TBX5 gene mutations. (PMID:25216260)
• Tbx5 knock-down hearts displayed a marked decrease in vascular density and coronary vasculogenesis. (PMID:25245104)
• Two heterozygous mutations in TBX5 were discovered in screening a series of 94 patients with Tetralogy of Fallot. (PMID:25263169)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbx5a	ENSDARG00000024894
mus_musculus	Tbx5	ENSMUSG00000018263
rattus_norvegicus	Tbx5	ENSRNOG00000001399
drosophila_melanogaster	H15	FBGN0016660
drosophila_melanogaster	mid	FBGN0261963
drosophila_melanogaster	ocm	FBGN0266083
caenorhabditis_elegans		WBGENE00003106
caenorhabditis_elegans		WBGENE00004750
caenorhabditis_elegans		WBGENE00006545
caenorhabditis_elegans		WBGENE00006546
caenorhabditis_elegans		WBGENE00006556
caenorhabditis_elegans		WBGENE00006557
caenorhabditis_elegans		WBGENE00006559
caenorhabditis_elegans		WBGENE00044798

Paralogs (16): TBX21 (ENSG00000073861), TBX15 (ENSG00000092607), TBX18 (ENSG00000112837), TBX2 (ENSG00000121068), TBX4 (ENSG00000121075), TBX22 (ENSG00000122145), TBX3 (ENSG00000135111), TBR1 (ENSG00000136535), TBX19 (ENSG00000143178), TBX6 (ENSG00000149922), EOMES (ENSG00000163508), TBXT (ENSG00000164458), TBX20 (ENSG00000164532), TBX10 (ENSG00000167800), MGA (ENSG00000174197), TBX1 (ENSG00000184058)

Protein

Protein identifiers

T-box transcription factor TBX5 — Q99593 (reviewed: Q99593)

All UniProt accessions (1): Q99593

UniProt curated annotations — full annotation on UniProt →

Function. DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation. Binds to the core DNA motif of NPPA promoter.

Subunit / interactions. Monomer. Homodimer (via the T-box); binds DNA as homodimer. Interacts (via the T-box) with NKX2-5 (via the homeobox); this complex binds DNA. Interacts with GATA4. Interacts with KAT2A and KAT2B.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Acetylation at Lys-339 by KAT2A and KAT2B promotes nuclear retention.

Disease relevance. Holt-Oram syndrome (HOS) [MIM:142900] Developmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects. The disease is caused by variants affecting the gene represented in this entry. Defects in TBX5 are associated with susceptibility to heart disorders including dilated cardiomyopathy (DCM) and atrial fibrillation (AF). DCM is characterized by ventricular and impaired systolic function, resulting in heart failure and arrhythmia. Patient are at risk of premature death. AF is a common sustained cardiac rhythm disturbance. AF is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.

Domain organisation. The T-Box domain binds to double-stranded DNA.

Isoforms (3)

UniProt ID	Names	Canonical?
Q99593-1	1, Long	yes
Q99593-2	2, Short
Q99593-3	3

RefSeq proteins (3): NP_000183, NP_542448, NP_852259* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001699	TF_T-box	Family
IPR008967	p53-like_TF_DNA-bd_sf	Homologous_superfamily
IPR018186	TF_T-box_CS	Conserved_site
IPR036960	T-box_sf	Homologous_superfamily
IPR046360	T-box_DNA-bd	Domain

Pfam: PF00907

UniProt features (52 total): strand 14, sequence variant 9, sequence conflict 8, mutagenesis site 5, helix 5, splice variant 3, compositionally biased region 3, region of interest 2, chain 1, DNA-binding region 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2X6U	X-RAY DIFFRACTION	1.9
2X6V	X-RAY DIFFRACTION	2.2
5BQD	X-RAY DIFFRACTION	2.58
4S0H	X-RAY DIFFRACTION	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99593-F1	63.38	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 339

Mutagenesis-validated functional residues (5):

Position	Phenotype
234	does not affect acetylation of the protein.
325	does not affect transcription factor activity.
327	does not affect transcription factor activity.
339	abolishes acetylation of the protein, leading to impaired transcription factor activity. impaired subcellular location.
340	does not affect transcription factor activity.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-2032785	YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-5578768	Physiological factors
R-HSA-9733709	Cardiogenesis
R-HSA-1266738	Developmental Biology
R-HSA-212436	Generic Transcription Pathway
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 647 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, MORF_RAGE, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CELL_MIGRATION_INVOLVED_IN_HEART_DEVELOPMENT, GOBP_BUNDLE_OF_HIS_CELL_TO_PURKINJE_MYOCYTE_COMMUNICATION, MORF_FLT1, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CARDIAC_LEFT_VENTRICLE_MORPHOGENESIS

GO Biological Process (42): cell fate specification (GO:0001708), morphogenesis of an epithelium (GO:0002009), sinoatrial node development (GO:0003163), bundle of His development (GO:0003166), atrioventricular bundle cell differentiation (GO:0003167), atrioventricular valve morphogenesis (GO:0003181), endocardial cushion development (GO:0003197), cardiac left ventricle formation (GO:0003218), ventricular septum development (GO:0003281), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), cell-cell signaling (GO:0007267), pattern specification process (GO:0007389), heart development (GO:0007507), negative regulation of cell population proliferation (GO:0008285), negative regulation of epithelial to mesenchymal transition (GO:0010719), lung development (GO:0030324), embryonic limb morphogenesis (GO:0030326), negative regulation of cell migration (GO:0030336), embryonic forelimb morphogenesis (GO:0035115), forelimb morphogenesis (GO:0035136), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of cardioblast differentiation (GO:0051891), cardiac muscle cell proliferation (GO:0060038), pericardium development (GO:0060039), negative regulation of cardiac muscle cell proliferation (GO:0060044), positive regulation of cardiac muscle cell proliferation (GO:0060045), regulation of atrial cardiac muscle cell membrane depolarization (GO:0060371), atrial septum morphogenesis (GO:0060413), atrioventricular node cell development (GO:0060928), atrioventricular node cell fate commitment (GO:0060929), cell migration involved in coronary vasculogenesis (GO:0060980), positive regulation of secondary heart field cardioblast proliferation (GO:0072513), bundle of His cell to Purkinje myocyte communication by electrical coupling (GO:0086054), positive regulation of cell communication by electrical coupling involved in cardiac conduction (GO:1901846), positive regulation of gap junction assembly (GO:1903598), positive regulation of cardiac conduction (GO:1903781), ventricular cardiac muscle tissue development (GO:0003229), atrial septum development (GO:0003283)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), protein-containing complex (GO:0032991), protein-DNA complex (GO:0032993)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Generic Transcription Pathway	1
Cardiac conduction	1
Developmental Biology	1
RNA Polymerase II Transcription	1
Muscle contraction	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
animal organ development	2
transcription cis-regulatory region binding	2
protein-containing complex	2
cell fate commitment	1
cellular developmental process	1
tissue morphogenesis	1
epithelium development	1
cardiac conduction system development	1
atrial cardiac muscle tissue development	1
His-Purkinje system development	1
ventricular cardiac muscle tissue development	1
bundle of His development	1
His-Purkinje system cell differentiation	1
atrioventricular valve development	1
heart valve morphogenesis	1
heart development	1
mesenchyme development	1
cardiac ventricle formation	1
cardiac left ventricle morphogenesis	1
cardiac ventricle development	1
cardiac septum development	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
cell communication	1
signaling	1
multicellular organism development	1
multicellular organismal process	1
circulatory system development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
negative regulation of multicellular organismal process	1
respiratory tube development	1
respiratory system development	1

Protein interactions and networks

STRING

2068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBX5	NKX2-5	P52952	999
TBX5	GATA4	P43694	998
TBX5	CTNNB1	P35222	990
TBX5	YAP1	P46937	984
TBX5	SMARCD3	Q6STE5	959
TBX5	MEF2C	Q06413	914
TBX5	MYH6	P13533	909
TBX5	HAND2	P61296	885
TBX5	WWTR1	Q9GZV5	856
TBX5	RBM19	Q9Y4C8	848
TBX5	SMARCA4	P51532	835
TBX5	NPPA	P01160	828
TBX5	TNNT2	P45379	812
TBX5	PITX1	P78337	810
TBX5	BANF1	O75531	807

IntAct

26 interactions, top by confidence:

A	B	Type	Score
ZMYND10	TBX5	psi-mi:“MI:0915”(physical association)	0.560
TBX5	BAIAP2	psi-mi:“MI:0915”(physical association)	0.560
TBX5	YAP1	psi-mi:“MI:0915”(physical association)	0.560
	TBX5	psi-mi:“MI:0914”(association)	0.520
TBX5		psi-mi:“MI:0407”(direct interaction)	0.520
TBX5	CTNNB1	psi-mi:“MI:0914”(association)	0.460
TBX5	Wwtr1	psi-mi:“MI:0915”(physical association)	0.400
Gata4	TBX5	psi-mi:“MI:0915”(physical association)	0.400
TBX5	Gata4	psi-mi:“MI:0915”(physical association)	0.400
TBX5	Nkx2-5	psi-mi:“MI:0915”(physical association)	0.400
TBX5	Ctnnb1	psi-mi:“MI:0915”(physical association)	0.400
	TBX5	psi-mi:“MI:0915”(physical association)	0.370
TNFSF4	TBX5	psi-mi:“MI:0915”(physical association)	0.370
YAP1		psi-mi:“MI:0914”(association)	0.350
CTNNB1		psi-mi:“MI:0914”(association)	0.350
ZMYND10	TBX5	psi-mi:“MI:0915”(physical association)	0.000
BAIAP2	TBX5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (156): Wwtr1 (Affinity Capture-Western), TBX5 (Reconstituted Complex), FBXO25 (Reconstituted Complex), GATA4 (Affinity Capture-Western), TBX5 (Affinity Capture-Western), TBX5 (Affinity Capture-Western), TBX5 (Two-hybrid), BAIAP2 (Two-hybrid), NKX2-5 (Affinity Capture-Western), TBX5 (Reconstituted Complex), TBX5 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), SMARCA5 (Affinity Capture-MS), SLC25A5 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A7EPL0, A2RV66, A4QP16, A6QPF4, C4QM85, F4JYG0, O35892, P11836, P13386, P19437, P20490, P41739, P53762, P56645, P70326, P79778, Q01362, Q148B6, Q29131, Q3C1V0, Q3C2E2, Q3SA47, Q3UNB8, Q3V3Q4, Q3YBM2, Q5I2P1, Q5JT82, Q5R8D6, Q5R8E0, Q60HE7, Q68FU0, Q6A058, Q8BVM2, Q8N1N2, Q8NDZ0, Q8QGQ8, Q8WUU8, Q920C4, Q92540, Q96HJ5

Diamond homologs: A1YF56, A2AWL7, D3ZJK7, E1BEA8, O01409, O13161, O15119, O15178, O17212, O43435, O54839, O60806, O70306, O73718, O75333, O95935, O95936, O95947, P20293, P24781, P55965, P56158, P57082, P70323, P70324, P70325, P70326, P70327, P79742, P79777, P79778, P79779, P79944, P80492, P87377, P90971, Q07998, Q13207, Q16650, Q17134

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
TBX5	“up-regulates quantity by expression”	CDKN2A	“transcriptional regulation”
TBX5	“up-regulates quantity by expression”	MTSS1	“transcriptional regulation”
TBX5	“down-regulates quantity by repression”	SNCG	“transcriptional regulation”
TBX5	“down-regulates quantity by repression”	MTA2	“transcriptional regulation”
TBX5	“up-regulates quantity by expression”	FGF10	“transcriptional regulation”
TBX5	“up-regulates quantity by expression”	NPPA	“transcriptional regulation”
NKX2-5	“up-regulates quantity by expression”	TBX5	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	168
Likely pathogenic	41
Uncertain significance	333
Likely benign	203
Benign	56

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012346	NM_181486.4(TBX5):c.652C>T (p.Gln218Ter)	Pathogenic
1030662	NM_181486.4(TBX5):c.337A>T (p.Arg113Ter)	Pathogenic
1032248	NM_181486.4(TBX5):c.362+1G>A	Pathogenic
1062314	NM_181486.4(TBX5):c.252T>A (p.Phe84Leu)	Pathogenic
1068185	NM_181486.4(TBX5):c.511-1G>C	Pathogenic
1071824	NM_181486.4(TBX5):c.383_386dup (p.Met131fs)	Pathogenic
1071999	NM_181486.4(TBX5):c.243-2A>G	Pathogenic
1072954	NM_181486.4(TBX5):c.765T>A (p.Tyr255Ter)	Pathogenic
1075045	NM_181486.4(TBX5):c.341dup (p.Tyr114Ter)	Pathogenic
1076612	NC_000012.11:g.(?114793327)(114793921_?)del	Pathogenic
1175344	NM_181486.4(TBX5):c.262A>T (p.Lys88Ter)	Pathogenic
1299664	NM_181486.4(TBX5):c.166del (p.Val56fs)	Pathogenic
1350538	NM_181486.4(TBX5):c.760G>T (p.Glu254Ter)	Pathogenic
139591	NM_181486.4(TBX5):c.338G>A (p.Arg113Lys)	Pathogenic
1409261	NM_181486.4(TBX5):c.982+1G>A	Pathogenic
1453432	NM_181486.4(TBX5):c.400del (p.Arg134fs)	Pathogenic
1454149	NM_181486.4(TBX5):c.1012del (p.Tyr338fs)	Pathogenic
1454646	NM_181486.4(TBX5):c.1037C>A (p.Ser346Ter)	Pathogenic
1457204	NC_000012.11:g.(?114823261)(114823392_?)del	Pathogenic
1459610	NC_000012.11:g.(?114837390)(114846189_?)del	Pathogenic
1470937	NM_181486.4(TBX5):c.755+1G>T	Pathogenic
148683	GRCh38/hg38 12q24.21(chr12:114390252-114394865)x1	Pathogenic
2016615	NM_181486.4(TBX5):c.853_865del (p.Ser285fs)	Pathogenic
2050129	NM_181486.4(TBX5):c.755+1G>A	Pathogenic
2075482	NM_181486.4(TBX5):c.148-2A>C	Pathogenic
213816	NM_181486.4(TBX5):c.373G>C (p.Gly125Arg)	Pathogenic
213820	NM_181486.4(TBX5):c.142C>T (p.Gln48Ter)	Pathogenic
213827	NM_181486.4(TBX5):c.420_432del (p.Asp140fs)	Pathogenic
213828	NM_181486.4(TBX5):c.421_443delinsCCAGGA (p.Ser141fs)	Pathogenic
213829	NM_181486.4(TBX5):c.468_484del (p.Lys157fs)	Pathogenic

SpliceAI

2149 predictions. Top by Δscore:

Variant	Effect	Δscore
12:114356105:CT:C	acceptor_gain	1.0000
12:114356107:C:CC	acceptor_gain	1.0000
12:114394735:GCTTA:G	donor_loss	1.0000
12:114394736:CTTAC:C	donor_loss	1.0000
12:114394737:TTACC:T	donor_loss	1.0000
12:114394738:TACCT:T	donor_loss	1.0000
12:114394739:A:C	donor_loss	1.0000
12:114394890:TAAT:T	acceptor_gain	1.0000
12:114394892:ATC:A	acceptor_loss	1.0000
12:114394893:TCTAA:T	acceptor_loss	1.0000
12:114394894:C:CC	acceptor_gain	1.0000
12:114394894:CTA:C	acceptor_loss	1.0000
12:114394895:T:C	acceptor_loss	1.0000
12:114398565:GTACT:G	donor_loss	1.0000
12:114398567:ACTC:A	donor_loss	1.0000
12:114398569:TCA:T	donor_loss	1.0000
12:114398570:CA:C	donor_loss	1.0000
12:114398571:A:AC	donor_gain	1.0000
12:114398571:ACATG:A	donor_gain	1.0000
12:114398572:C:CC	donor_gain	1.0000
12:114398572:C:CG	donor_loss	1.0000
12:114398572:CATG:C	donor_gain	1.0000
12:114398572:CATGC:C	donor_gain	1.0000
12:114403746:CCTTA:C	donor_loss	1.0000
12:114403747:CTTA:C	donor_loss	1.0000
12:114403748:TTA:T	donor_loss	1.0000
12:114403749:TACCT:T	donor_loss	1.0000
12:114403750:A:AC	donor_gain	1.0000
12:114403751:C:CC	donor_gain	1.0000
12:114403751:C:CT	donor_loss	1.0000

AlphaMissense

3440 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:114385521:C:G	R237P	1.000
12:114385523:A:C	F236L	1.000
12:114385523:A:T	F236L	1.000
12:114385524:A:C	F236C	1.000
12:114385524:A:G	F236S	1.000
12:114385525:A:C	F236V	1.000
12:114385525:A:G	F236L	1.000
12:114385525:A:T	F236I	1.000
12:114385527:C:A	G235V	1.000
12:114385527:C:T	G235E	1.000
12:114385528:C:G	G235R	1.000
12:114385528:C:T	G235R	1.000
12:114385529:T:A	K234N	1.000
12:114385529:T:G	K234N	1.000
12:114385530:T:A	K234I	1.000
12:114385530:T:G	K234T	1.000
12:114385531:T:C	K234E	1.000
12:114385531:T:G	K234Q	1.000
12:114385533:G:A	A233V	1.000
12:114385533:G:C	A233G	1.000
12:114385533:G:T	A233D	1.000
12:114385534:C:G	A233P	1.000
12:114385534:C:T	A233T	1.000
12:114385535:A:C	F232L	1.000
12:114385535:A:T	F232L	1.000
12:114385536:A:C	F232C	1.000
12:114385536:A:G	F232S	1.000
12:114385537:A:C	F232V	1.000
12:114385537:A:G	F232L	1.000
12:114385537:A:T	F232I	1.000

dbSNP variants (sampled 300 via entrez): RS1000094300 (12:114397125 G>A), RS1000153397 (12:114409075 G>A), RS1000171256 (12:114394459 C>T), RS1000280091 (12:114388940 A>G), RS1000282063 (12:114399844 A>C,G), RS1000294903 (12:114379966 G>A), RS1000371364 (12:114354547 G>A,T), RS1000718979 (12:114389113 A>G), RS1000727838 (12:114372422 A>G), RS1000793070 (12:114404549 C>T), RS1000794733 (12:114380971 C>A,T), RS1000836118 (12:114394169 G>T), RS1000870099 (12:114356467 C>T), RS1000877367 (12:114396755 T>C,G), RS1000932042 (12:114404827 G>A,C)

Disease associations

OMIM: gene MIM:601620 | disease phenotypes: MIM:614823, MIM:142900, MIM:108800, MIM:606215, MIM:194200, MIM:614429, MIM:188100

GenCC curated gene-disease

Disease	Classification	Inheritance
Holt-Oram syndrome	Definitive	Autosomal dominant
heart conduction disease	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Holt-Oram syndrome	Definitive	AD

Mondo (13): aortic valve disease 2 (MONDO:0013902), dilated cardiomyopathy (MONDO:0005021), Holt-Oram syndrome (MONDO:0007732), atrial septal defect 1 (MONDO:0007172), familial atrioventricular septal defect (MONDO:0020290), Wolff-Parkinson-White syndrome (MONDO:0008685), ventricular septal defect (MONDO:0002070), atrial septal defect, ostium secundum type (MONDO:0020434), mitral valve insufficiency (MONDO:1030008), atrial septal defect (MONDO:0006664), blue nevus (MONDO:0006680), thumb deformity (MONDO:0008561), heart conduction disease (MONDO:0000992)

Orphanet (7): Dilated cardiomyopathy (Orphanet:217604), Holt-Oram syndrome (Orphanet:392), Interatrial communication (Orphanet:1478), Atrioventricular septal defect (Orphanet:98722), Atrial septal defect, ostium secundum type (Orphanet:99103), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907), NON RARE IN EUROPE: Ventricular septal defect (Orphanet:1480)

HPO phenotypes

131 total (30 of 131 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000185	Cleft soft palate
HP:0000218	High palate
HP:0000268	Dolichocephaly
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000470	Short neck
HP:0000767	Pectus excavatum
HP:0000772	Abnormal rib morphology
HP:0000774	Narrow chest
HP:0000878	11 pairs of ribs
HP:0000882	Hypoplastic scapulae
HP:0000889	Abnormal clavicle morphology
HP:0000894	Short clavicles
HP:0000912	Sprengel anomaly
HP:0000914	Shield chest
HP:0000954	Single transverse palmar crease
HP:0000960	Sacral dimple
HP:0001159	Syndactyly
HP:0001162	Postaxial hand polydactyly
HP:0001171	Split hand
HP:0001191	Abnormal carpal morphology
HP:0001197	Abnormality of prenatal development or birth
HP:0001199	Triphalangeal thumb
HP:0001233	2-3 finger cutaneous syndactyly
HP:0001245	Small thenar eminence
HP:0001250	Seizure
HP:0001279	Syncope
HP:0001377	Limited elbow extension

GWAS associations

154 associations (top):

Study	Trait	p-value
GCST000396_6	Diastolic blood pressure	4.000000e-08
GCST000561_10	Electrocardiographic traits	3.000000e-13
GCST000561_12	Electrocardiographic traits	3.000000e-12
GCST000561_13	Electrocardiographic traits	1.000000e-07
GCST000562_5	PR interval	3.000000e-17
GCST000872_9	QRS duration	1.000000e-10
GCST000971_4	PR interval	7.000000e-09
GCST001236_19	Blood pressure	4.000000e-06
GCST001489_1	Percent mammographic density	1.000000e-08
GCST001525_31	Visceral fat	3.000000e-06
GCST001621_13	Airflow obstruction	6.000000e-07
GCST001735_8	PR interval	1.000000e-19
GCST001762_576	Obesity-related traits	6.000000e-07
GCST001942_14	Prostate cancer	7.000000e-11
GCST002535_5	PR interval	7.000000e-07
GCST002597_6	Laryngeal squamous cell carcinoma	4.000000e-14
GCST002890_14	Prostate cancer	3.000000e-10
GCST003598_1	QRS duration	2.000000e-15
GCST003598_26	QRS duration	2.000000e-06
GCST003598_30	QRS duration	1.000000e-10
GCST003740_7	Barrett’s esophagus or Esophageal adenocarcinoma	2.000000e-09
GCST004280_3	Diastolic blood pressure	5.000000e-13
GCST004280_72	Diastolic blood pressure	5.000000e-13
GCST004295_8	Atrial fibrillation	2.000000e-15
GCST004297_18	Atrial fibrillation	1.000000e-13
GCST004373_17	Atrial fibrillation	5.000000e-15
GCST004826_12	P wave duration	1.000000e-08
GCST004826_18	P wave duration	2.000000e-18
GCST004826_20	P wave duration	6.000000e-13
GCST004826_9	P wave duration	6.000000e-13

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0005054	QRS complex
EFO:0004462	PR interval
EFO:0004682	QT interval
EFO:0006340	mean arterial pressure
EFO:0003892	pulmonary function measurement
EFO:0004730	hormone measurement
EFO:0005094	P wave duration
EFO:0007702	hip bone mineral density
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0009959	diverticular disease
EFO:0004318	smoking behavior
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0008008	lower urinary tract symptom
EFO:0005686	receptive language perception
EFO:0004327	electrocardiography

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D006344	Heart Septal Defects, Atrial	C14.240.400.560.375; C14.280.400.560.375; C16.131.240.400.560.375
D006345	Heart Septal Defects, Ventricular	C14.240.400.560.540; C14.280.400.560.540; C16.131.240.400.560.540
D008944	Mitral Valve Insufficiency	C14.280.484.461
D018329	Nevus, Blue	C04.557.665.560.615.550
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C535326	Holt-Oram syndrome (supp.)
C536903	Thumb deformity (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1687681 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol F	affects cotreatment, increases methylation	1
terbufos	increases methylation	1
arsenite	increases methylation	1
sodium arsenite	affects methylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression	1
Coal	increases abundance, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Formaldehyde	decreases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Asbestos, Crocidolite	affects expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1687115	Binding	Effect on Tbx5 in HEK293 nuclear extract at 50 uM after 15 mins by EMSA assay	Identification of new GATA4-small molecule inhibitors by structure-based virtual screening. — Bioorg Med Chem

Cellosaurus cell lines

15 cell lines: 11 induced pluripotent stem cell, 4 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1MY	WAe009-A-45	Embryonic stem cell	Female
CVCL_A8L9	SEES3-1V human TBX5, clone1	Embryonic stem cell	Male
CVCL_A8M0	SEES3-1V human TBX5, clone2	Embryonic stem cell	Male
CVCL_A8M1	SEES3-1V human TBX5, clone3	Embryonic stem cell	Male
CVCL_B5EP	DHMi004-A	Induced pluripotent stem cell	Male
CVCL_B5SK	DHMi005-A-1	Induced pluripotent stem cell	Male
CVCL_D0DX	DHMi004-A-1	Induced pluripotent stem cell	Male
CVCL_D0DY	DHMi004-A-2	Induced pluripotent stem cell	Male
CVCL_D0DZ	DHMi004-A-3	Induced pluripotent stem cell	Male
CVCL_D0E0	DHMi005-A-5	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	PHASE1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	PHASE1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	PHASE1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	PHASE1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	PHASE1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	PHASE1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	PHASE1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896	PHASE1	COMPLETED	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338	PHASE1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104	PHASE1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy