SMAD7

Summary

SMAD7 (SMAD family member 7, HGNC:6773) is a protein-coding gene on chromosome 18q21.1, encoding SMAD family member 7 (O15105). Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access.

The protein encoded by this gene is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. Upon binding, this complex translocates to the cytoplasm, where it interacts with TGF-beta receptor type-1 (TGFBR1), leading to the degradation of both the encoded protein and TGFBR1. Expression of this gene is induced by TGFBR1. Variations in this gene are a cause of susceptibility to colorectal cancer type 3 (CRCS3). Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4092 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 50
• Clinical variants (ClinVar): 52 total
• Phenotypes (HPO): 1
• Transcription factor: yes — 71 downstream targets (CollecTRI)
• MANE Select transcript: NM_005904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6773
Approved symbol	SMAD7
Name	SMAD family member 7
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101665
Ensembl biotype	protein_coding
OMIM	602932
Entrez	4092

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000262158, ENST00000545051, ENST00000585986, ENST00000586093, ENST00000587336, ENST00000588190, ENST00000589634, ENST00000591805, ENST00000911789, ENST00000951831

RefSeq mRNA: 4 — MANE Select: NM_005904 NM_001190821, NM_001190822, NM_001190823, NM_005904

CCDS: CCDS11936, CCDS54186, CCDS59317

Canonical transcript exons

ENST00000262158 — 4 exons

Exon	Start	End
ENSE00001243787	48919853	48921910
ENSE00001243795	48949812	48950965
ENSE00003472239	48942481	48942555
ENSE00003518942	48948384	48948437

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 96.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.7864 / max 668.6443, expressed in 1767 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171888	24.4398	1753
171887	2.8969	1221
171879	0.6025	203
171886	0.2534	88
171881	0.2001	78
171880	0.1834	87
171882	0.1268	29
171883	0.0835	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	96.68	gold quality
tibial artery	UBERON:0007610	96.67	gold quality
aorta	UBERON:0000947	95.77	gold quality
saphenous vein	UBERON:0007318	95.71	gold quality
descending thoracic aorta	UBERON:0002345	95.56	gold quality
right atrium auricular region	UBERON:0006631	95.55	gold quality
cardiac atrium	UBERON:0002081	95.41	gold quality
ascending aorta	UBERON:0001496	94.80	gold quality
thoracic aorta	UBERON:0001515	94.64	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.15	gold quality
right lung	UBERON:0002167	93.65	gold quality
left coronary artery	UBERON:0001626	93.27	gold quality
right coronary artery	UBERON:0001625	93.02	gold quality
coronary artery	UBERON:0001621	92.87	gold quality
vena cava	UBERON:0004087	92.37	gold quality
cartilage tissue	UBERON:0002418	91.39	gold quality
right lobe of thyroid gland	UBERON:0001119	91.33	gold quality
left lobe of thyroid gland	UBERON:0001120	90.66	gold quality
omental fat pad	UBERON:0010414	90.58	gold quality
peritoneum	UBERON:0002358	90.53	gold quality
upper lobe of left lung	UBERON:0008952	90.45	gold quality
upper lobe of lung	UBERON:0008948	89.89	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.83	gold quality
metanephros cortex	UBERON:0010533	89.72	gold quality
thyroid gland	UBERON:0002046	89.66	gold quality
heart	UBERON:0000948	88.92	gold quality
gall bladder	UBERON:0002110	88.77	gold quality
islet of Langerhans	UBERON:0000006	88.34	gold quality
endocervix	UBERON:0000458	88.27	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	189.28
E-GEOD-135922	yes	22.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

71 targets.

Target	Regulation
ACTA2
ACTG2	Unknown
ACVR1B
ADAM2
APC
BCL2L11	Unknown
BMP4
CASP8	Unknown
CAT
CCN2	Repression
CD79A
CDH2	Repression
CDK1	Repression
CDKN1A	Repression
CDKN2B	Repression
CEL
CHRD	Activation
COL1A1	Repression
COL1A2	Repression
COL3A1	Repression
COL5A2	Repression
COL6A2	Repression
COL6A3	Repression
CTNNB1	Activation
CYP17A1
E2F1	Repression
FN1	Unknown
FSHB	Unknown
GAST	Unknown
HAMP	Unknown

Upstream regulators (CollecTRI, top): AP1, BMP6, EP300, ETV1, FOS, GGCX, GRHL3, HAMP, HDAC1, HDAC3, JUN, KDM5B, KLF10, KLF11, KLF13, MECOM, MTA1, MYC, NFKB, NR0B2, NR2C2, OLIG1, OVOL2, PRMT5, RELA, SKI, SKIL, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD7, SP1, TBL1XR1, TFE3, YY1, ZNF165

miRNA regulators (miRDB)

118 targeting SMAD7, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-5696	99.98	72.36	4487

Literature-anchored findings (GeneRIF, showing 40)

• plasma membrane localization of Smad7 by Smurf1 requires the C2 domain of Smurf1 and is essential for the inhibitory effect of Smad7 in the transforming growth factor-beta signaling pathway (PMID:12151385)
• Smad7 is activated in injured podocytes in vitro and in human glomerular disease and participates in negative control of TGF-beta/Smad signaling in addition to its pro-apoptotic activity. (PMID:12397035)
• Smad6 and Smad7 regulate thrombomodulin-dependent activation of protein C (PMID:12407115)
• CRM1-dependent nuclear export of Smurf1 is essential for the negative regulation of TGF-beta signaling by Smad7. (PMID:12519765)
• Smad7 may act as a scaffolding protein and facilitate TAK1- and MKK3-mediated activation of p38 (PMID:12589052)
• attenuation of transforming growth factor-beta signaling by activating Smad7 transcription may proceed not only through TGF-beta receptor-regulated Smad proteins but also an independent pathway involving transcription factor ER81 and TAK1 protein kinase (PMID:12947087)
• Smad7 was overexpressed in ARO anaplastic cell line, the most malignant follicular thyroid carcinoma. (PMID:12952364)
• GADD34-PP1c recruited by Smad7 inhibits TGFbeta-induced cell cycle arrest. (PMID:14718519)
• Smad7 and Smurf1 have roles in regulation of TGF-beta signaling in scleroderma fibroblasts (PMID:14722617)
• In Helicobacter pylori-infected gastric mucosa, interferon-gamma induces expression of Smad7, which then prevents endogenous TGF-beta 1 from down-regulating ongoing tissue-damaging Th1 response. (PMID:14988821)
• Jab1/CSN5 as an adapter that targets Smad7 for degradation, thus releasing Smad7-mediated suppression of TGF-beta1 signaling. (PMID:14993265)
• Overexpression of SMAD7 inhibited the activity of the proliferation-specific promoters for the keratin 14 and cdc2 genes and reduced the expression of the mRNA for the proliferation-specific genes cdc2 and E2F1. (PMID:15023526)
• tetradecanoylphorbol-13-acetate down-regulates Smad6 expression presumably via PKCmu-ERK-dependent pathway and up-regulates Smad7 expression via PKCmu-dependent mechanism(s) which need no MAPK and NF-kappaB activation (PMID:15033458)
• Enhanced expression of the TGF-beta signaling inhibitor Smad7 may present one of the novel mechanisms of TGF-beta resistance in human gastric carcinomas. (PMID:15033661)
• novel role for Smad7 in TGF-beta-dependent activation of Rho GTPases (PMID:15075243)
• Smad7 is repressed by ski (PMID:15128733)
• dual signaling pathways involving TGF-beta1, an antiapoptotic pathway mediated by the Smad pathway involving p21, and an apoptosis-permissive pathway mediated in part by p38 MAPK. (PMID:15132952)
• WWP1 negatively regulates TGF-beta signaling in cooperation with Smad7. (PMID:15221015)
• identified target genes regulated by Smad7 in primitive hematopoietic cells that may control process of modulating the cell fate decisions of primary multipotent human repopulating cells (PMID:15498852)
• The regulation in chondrocytes of Smad6 and Smad7 expression by IL-1beta suggests a potentially important role of IL-1beta signaling in chondrocytes, via indirect influencing of the bone morphogenetic protein/TGFbeta signaling cascade. (PMID:15529348)
• induction of Smad7 gene expression by UV irradiation is mediated via induction of the transcription factor AP-1 in human skin fibroblasts (PMID:15579469)
• Abeta1-42 may play an important role in the negative regulation of TGF-beta1-induced MMP-2 production via Smad7 expression (PMID:15632190)
• Smad7 appears to be upregulated in endometrial cancers compared to normal endometrium. (PMID:15661223)
• Physical association of Smad7 and beta-catenin was found to be important for TGF-beta-induced apoptosis. (PMID:15684397)
• expression of Smad7 is crucial for 2-ME-induced apoptosis in human prostate cancer cells (PMID:15708859)
• Smad6 and Smad7 expression affects the progression of early lesions of esophageal SCC and indicates a poor prognosis. (PMID:15736400)
• autocrine TGF-beta/Smad signaling is involved in contractility and matrix gene expression of fibroblasts from normal and hypertrophic scars; Smad7 inhibits these processes and may exert beneficial effects on excessive scar formation (PMID:15788410)
• UV-induced down-regulation of TbetaRII and the concerted over-expression of Smad7 may trigger the inhibition of the TGF-beta-induced phosphorylation of Smad2. (PMID:15811425)
• Smad7 acts to functionally inactivate RB and de-repress E2F without blocking the activation of TbetaRI and the nuclear translocation of Smad2/3, allowing TGF-beta1 to exert effects in a cancer cell that is resistant to TGF-beta1-mediated growth inhibition (PMID:15811853)
• the degradation of Smad7 is regulated by the balance between acetylation, deacetylation and ubiquitination (PMID:15831498)
• In mature human B cells, BMP-6 inhibited cell growth, and rapidly induced phosphorylation of Smad8. (PMID:15877825)
• SMAD7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis. (PMID:15922743)
• Various cellular functions implicated in melanoma development may be under control of autocrine TGF-beta and may be inhibited by Smad7 expression (PMID:16007121)
• TGF-beta1 and bleomycin intracellular signaling through autocrine regulation of Smad 3 binding to the proximal promoter of the Smad 7 gene (PMID:16187293)
• TGF-beta is involved in the physiological loss of gastric epithelial cells by activating apoptosis mediated by Smad7, Bim, and caspase-9 (PMID:16260615)
• Smad7 is not transcriptionally regulated in gut but its increase in inflammatory bowel disease is due to posttranscriptional acetylation and stabilization by p300, which prevents Smad7 ubiquitination and degradation in the proteasome (PMID:16285943)
• TGFbeta-mediated phosphorylation of IkappaB-alpha and NF-kappaB nuclear translocation and DNA binding activity are inhibited by Smad7 (PMID:16288847)
• SnoN also seems to regulate negatively the TGF-beta-responsive smad7 gene by binding and repressing its promoter in a similar way to Ski (PMID:16442497)
• Axin and Arkadia cooperate with each other in promoting Smad7 ubiquitination. (PMID:16601693)
• analysis of the WW domain recognition motif for the interaction of Smad7 and the E3 ubiquitin ligase Smurf2 (PMID:16641086)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	smad7	ENSDARG00000016858
mus_musculus	Smad7	ENSMUSG00000025880
rattus_norvegicus	Smad7	ENSRNOG00000018359
drosophila_melanogaster	Dad	FBGN0020493
caenorhabditis_elegans		WBGENE00000910
caenorhabditis_elegans	tag-68	WBGENE00006445

Paralogs (7): SMAD5 (ENSG00000113658), SMAD9 (ENSG00000120693), SMAD6 (ENSG00000137834), SMAD4 (ENSG00000141646), SMAD3 (ENSG00000166949), SMAD1 (ENSG00000170365), SMAD2 (ENSG00000175387)

Protein

Protein identifiers

SMAD family member 7 — O15105 (reviewed: O15105)

Alternative names: Mothers against decapentaplegic homolog 7, Mothers against decapentaplegic homolog 8

All UniProt accessions (2): O15105, K7EKF0

UniProt curated annotations — full annotation on UniProt →

Function. Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.

Subunit / interactions. Interacts with WWP1. Interacts with COPS5. Interacts with NEDD4L. Interacts with STAMBP. Interacts with RNF111, AXIN1 and AXIN2. Interacts with PPP1R15A. Interacts (via MH2 domain) with EP300. Interacts with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7 recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates its degradation. Interacts with PDPK1 (via PH domain). Interacts with TSC22D1/TSC-22; the interaction requires TGF-beta and the interaction is inhibited by TGFBR1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitous with higher expression in the lung and vascular endothelium.

Post-translational modifications. Phosphorylation on Ser-249 does not affect its stability, nuclear localization or inhibitory function in TGFB signaling; however it affects its ability to regulate transcription. Phosphorylated by PDPK1. Ubiquitinated by WWP1. Polyubiquitinated by RNF111, which is enhanced by AXIN1 and promotes proteasomal degradation. In response to TGF-beta, ubiquitinated by SMURF1; which promotes its degradation. Acetylation prevents ubiquitination and degradation mediated by SMURF1.

Disease relevance. Colorectal cancer 3 (CRCS3) [MIM:612229] A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Induction. By TGFB1.

Similarity. Belongs to the dwarfin/SMAD family.

Isoforms (3)

UniProt ID	Names	Canonical?
O15105-1	1	yes
O15105-2	2
O15105-3	3

RefSeq proteins (3): NP_001177750, NP_001177751, NP_005895* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001132	SMAD_dom	Domain
IPR003619	MAD_homology1_Dwarfin-type	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR013019	MAD_homology_MH1	Domain
IPR013790	SMAD/Dwarfins	Family
IPR017855	SMAD-like_dom_sf	Homologous_superfamily
IPR036578	SMAD_MH1_sf	Homologous_superfamily

Pfam: PF03165, PF03166

UniProt features (26 total): mutagenesis site 5, binding site 4, modified residue 3, domain 2, cross-link 2, splice variant 2, strand 2, region of interest 2, chain 1, sequence conflict 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2DJY	SOLUTION NMR
2KXQ	SOLUTION NMR
2LTV	SOLUTION NMR
2LTW	SOLUTION NMR
2LTX	SOLUTION NMR
2LTY	SOLUTION NMR
2LTZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15105-F1	75.08	0.52

Functional residue map

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

Ligand- & substrate-binding residues (4): 197; 125; 180; 192

Post-translational modifications (5): 64, 70, 249, 64, 70

Mutagenesis-validated functional residues (5):

Position	Phenotype
64	loss of acetylation, and of smurf1-dependent degradation; when associated with a-70.
70	loss of acetylation, and of smurf1-dependent degradation; when associated with a-64.
207–211	diminishes interaction with smurf2.
211	diminishes interaction with smurf2 and reduces inhibition of tgf-beta signaling.
409–426	90% reduction in tgf-beta receptor binding.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP
R-HSA-2173788	Downregulation of TGF-beta receptor signaling
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-5689603	UCH proteinases
R-HSA-5689880	Ub-specific processing proteases
R-HSA-877300	Interferon gamma signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-212436	Generic Transcription Pathway
R-HSA-2173789	TGF-beta receptor signaling activates SMADs
R-HSA-2173793	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006936	Signaling by TGFB family members
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 645 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, PID_HDAC_CLASSI_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION

GO Biological Process (41): negative regulation of transcription by RNA polymerase II (GO:0000122), ureteric bud development (GO:0001657), negative regulation of T cell cytokine production (GO:0002725), regulation of transcription by RNA polymerase II (GO:0006357), transforming growth factor beta receptor signaling pathway (GO:0007179), anatomical structure morphogenesis (GO:0009653), regulation of epithelial to mesenchymal transition (GO:0010717), negative regulation of epithelial to mesenchymal transition (GO:0010719), obsolete negative regulation of transcription by competitive promoter binding (GO:0010944), cell differentiation (GO:0030154), negative regulation of ossification (GO:0030279), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of BMP signaling pathway (GO:0030514), protein-containing complex localization (GO:0031503), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), negative regulation of activin receptor signaling pathway (GO:0032926), protein-containing complex disassembly (GO:0032984), adherens junction assembly (GO:0034333), response to laminar fluid shear stress (GO:0034616), artery morphogenesis (GO:0048844), protein stabilization (GO:0050821), ventricular cardiac muscle tissue morphogenesis (GO:0055010), regulation of cardiac muscle contraction (GO:0055117), regulation of ventricular cardiac muscle cell membrane depolarization (GO:0060373), negative regulation of SMAD protein signal transduction (GO:0060392), SMAD protein signal transduction (GO:0060395), ventricular septum morphogenesis (GO:0060412), negative regulation of chondrocyte proliferation (GO:1902731), positive regulation of chondrocyte hypertrophy (GO:1903043), beta-catenin destruction complex disassembly (GO:1904886), cellular response to leukemia inhibitory factor (GO:1990830), positive regulation of cell-cell adhesion mediated by cadherin (GO:2000049), negative regulation of T-helper 17 type immune response (GO:2000317), negative regulation of T-helper 17 cell differentiation (GO:2000320), regulation of DNA-templated transcription (GO:0006355), regulation of gene expression (GO:0010468), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), negative regulation of cell differentiation (GO:0045596), cellular response to growth factor stimulus (GO:0071363)

GO Molecular Function (11): transcription corepressor activity (GO:0003714), collagen binding (GO:0005518), beta-catenin binding (GO:0008013), ubiquitin protein ligase binding (GO:0031625), type I transforming growth factor beta receptor binding (GO:0034713), metal ion binding (GO:0046872), I-SMAD binding (GO:0070411), activin receptor binding (GO:0070697), transcription regulator inhibitor activity (GO:0140416), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (13): chromatin (GO:0000785), fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), ciliary basal body (GO:0036064), heteromeric SMAD protein complex (GO:0071144), transcription regulator complex (GO:0005667), adherens junction (GO:0005912)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Signaling by TGFB family members	2
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	2
Deubiquitination	2
Signaling by TGF-beta Receptor Complex	2
TGF-beta receptor signaling activates SMADs	1
Interferon Signaling	1
Immune System	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Post-translational protein modification	1
Metabolism of proteins	1
Gene expression (Transcription)	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	3
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
epithelial to mesenchymal transition	2
negative regulation of multicellular organismal process	2
microtubule organizing center	2
regulation of transcription by RNA polymerase II	1
mesonephric tubule development	1
T cell cytokine production	1
negative regulation of T cell mediated immunity	1
negative regulation of cytokine production involved in immune response	1
regulation of T cell cytokine production	1
regulation of DNA-templated transcription	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
developmental process	1
anatomical structure development	1
regulation of cell differentiation	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
cellular developmental process	1
ossification	1
regulation of ossification	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
macromolecule localization	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
activin receptor signaling pathway	1
regulation of activin receptor signaling pathway	1
cellular component disassembly	1

Protein interactions and networks

STRING

2864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMAD7	TGFBR1	P36897	998
SMAD7	SMURF2	Q9HAU4	998
SMAD7	SMURF1	Q9HCE7	996
SMAD7	UCHL5	Q9Y5K5	982
SMAD7	TGFB1	P01137	978
SMAD7	RNF111	Q6ZNA4	924
SMAD7	TAB2	Q9NYJ8	916
SMAD7	WWP1	Q9H0M0	895
SMAD7	CTNNB1	P35222	887
SMAD7	TGFB2	P08112	885
SMAD7	TAB3	Q8N5C8	863
SMAD7	PPP1R15A	O75807	856
SMAD7	TGFBR2	P37173	855
SMAD7	SKIL	P12756	850
SMAD7	AXIN1	O15169	847
SMAD7	STRAP	Q9Y3F4	847

IntAct

80 interactions, top by confidence:

A	B	Type	Score
SMURF2	SMAD7	psi-mi:“MI:0407”(direct interaction)	0.800
SMAD7	SMURF2	psi-mi:“MI:0407”(direct interaction)	0.800
SMAD7	SMURF2	psi-mi:“MI:0915”(physical association)	0.800
SMAD7	SMURF1	psi-mi:“MI:0407”(direct interaction)	0.720
SMAD7	YAP1	psi-mi:“MI:0407”(direct interaction)	0.720
SMAD7	YAP1	psi-mi:“MI:0915”(physical association)	0.720
YAP1	SMAD7	psi-mi:“MI:0407”(direct interaction)	0.720
COPS5	SMAD7	psi-mi:“MI:0915”(physical association)	0.640
SMAD7	COPS5	psi-mi:“MI:0915”(physical association)	0.640
COPS5	SMAD7	psi-mi:“MI:0403”(colocalization)	0.640
NEDD4L	SMAD7	psi-mi:“MI:0407”(direct interaction)	0.610

BioGRID (285): COPS5 (Affinity Capture-Western), LEF1 (Affinity Capture-Western), SMAD7 (Affinity Capture-Western), Wwp2 (Affinity Capture-Luminescence), CBL (Affinity Capture-Western), SMAD7 (Affinity Capture-Western), CBL (Reconstituted Complex), SMAD7 (Reconstituted Complex), TCF7L2 (Affinity Capture-Western), PARD3 (Reconstituted Complex), TGFBR1 (Affinity Capture-Western), NR4A1 (Affinity Capture-Western), SMAD7 (Affinity Capture-Western), SMAD7 (Affinity Capture-Western), SMURF2 (Affinity Capture-Western)

ESM2 similar proteins: A0A5F9C6I2, A2BDA5, A4IG66, A4IIM9, A9ZLX4, D3ZXK7, O00750, O14525, O15105, O15169, O15259, O15360, O35253, O54828, O70240, O88406, O88566, P49805, Q1JPG0, Q3B7M3, Q3SZD5, Q5JV73, Q5T011, Q5XJS0, Q5XPI3, Q61137, Q62925, Q66K64, Q6AYG1, Q6P1H6, Q6P2E9, Q6PFH3, Q7L4E1, Q7TP65, Q86UW9, Q86XL3, Q8BK03, Q8CDG3, Q8CF97, Q8N9B5

Diamond homologs: O15105, O35182, O35253, O43541, O88406, Q9W734, O15198, O54835, O70436, O70437, P84022, P84023, P84024, P84025, P97471, Q13485, Q15796, Q1HE26, Q1W668, Q21733, Q5R7C0, Q62432, Q8BUN5, Q9GKQ9, Q9I9P9, Q9JIW5, P42003

SIGNOR signaling

48 interactions.

A	Effect	B	Mechanism
SMAD7	“up-regulates activity”	SMURF2	relocalization
SMAD7	down-regulates	TAB1	binding
RNF111	down-regulates	SMAD7	binding
RNF111	down-regulates	SMAD7	ubiquitination
SMAD7	up-regulates	PPP1R15A	binding
WWP1	up-regulates	SMAD7	binding
WWP1	“up-regulates activity”	SMAD7	relocalization
SMAD7	up-regulates	CTNNB1
EP300	up-regulates	SMAD7	acetylation
ITCH	down-regulates	SMAD7	ubiquitination
UCHL5	up-regulates	SMAD7	binding
SMAD7	up-regulates	PPP1CA	binding
AXIN1	down-regulates	SMAD7	binding
SIRT1	down-regulates	SMAD7	deacetylation
SMAD7	up-regulates	TAB2	binding
SMAD7	up-regulates	TAB3	binding
SMAD7	down-regulates	SMAD1
SMAD7	“down-regulates activity”	TGFBR1	binding
SMAD7	“up-regulates activity”	SMURF1	relocalization
SMURF2	“down-regulates activity”	SMAD7	ubiquitination
HDAC3	up-regulates	SMAD7	binding
SMAD7	“form complex”	SMAD7/HDAC1/E2F-1	binding
WWP1	“up-regulates activity”	SMAD7	ubiquitination
SMAD7	“up-regulates activity”	SMURF	relocalization
SMURF	“down-regulates activity”	SMAD7	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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
Signaling by TGFB family members	5	21.4×	2e-04
Signaling by WNT	5	20.7×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of transforming growth factor beta receptor signaling pathway	5	25.6×	2e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	7	10.7×	3e-04
negative regulation of gene expression	5	10.2×	5e-03
DNA damage response	5	7.9×	9e-03
protein ubiquitination	6	7.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

886 predictions. Top by Δscore:

Variant	Effect	Δscore
18:48921907:GAAT:G	acceptor_gain	1.0000
18:48921909:AT:A	acceptor_gain	1.0000
18:48921909:ATCTA:A	acceptor_loss	1.0000
18:48921910:TC:T	acceptor_loss	1.0000
18:48921911:C:CC	acceptor_gain	1.0000
18:48921911:C:CG	acceptor_loss	1.0000
18:48921912:T:G	acceptor_loss	1.0000
18:48942551:GTCTG:G	acceptor_gain	1.0000
18:48942553:CTG:C	acceptor_gain	1.0000
18:48942554:TG:T	acceptor_gain	1.0000
18:48942563:T:TC	acceptor_gain	1.0000
18:48942564:T:C	acceptor_gain	1.0000
18:48942564:T:TC	acceptor_gain	1.0000
18:48921906:GGAAT:G	acceptor_gain	0.9900
18:48921908:AAT:A	acceptor_gain	0.9900
18:48942475:TCTTA:T	donor_loss	0.9900
18:48942476:CTTAC:C	donor_loss	0.9900
18:48942477:TTAC:T	donor_loss	0.9900
18:48942478:TAC:T	donor_loss	0.9900
18:48942554:TGCTG:T	acceptor_loss	0.9900
18:48942555:GCT:G	acceptor_loss	0.9900
18:48942556:C:CC	acceptor_gain	0.9900
18:48942557:T:C	acceptor_loss	0.9900
18:48942558:G:C	acceptor_gain	0.9900
18:48942558:G:GC	acceptor_gain	0.9900
18:48942562:A:AC	acceptor_gain	0.9900
18:48942562:A:C	acceptor_gain	0.9900
18:48942563:T:C	acceptor_gain	0.9900
18:48948539:G:C	donor_gain	0.9800
18:48949806:TCTCA:T	donor_loss	0.9800

AlphaMissense

2736 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:48921397:A:G	L419P	1.000
18:48921401:A:G	W418R	1.000
18:48921401:A:T	W418R	1.000
18:48921402:G:C	C417W	1.000
18:48921403:C:T	C417Y	1.000
18:48921406:G:T	P416Q	1.000
18:48921408:G:C	C415W	1.000
18:48921409:C:T	C415Y	1.000
18:48921410:A:G	C415R	1.000
18:48921418:A:T	I412N	1.000
18:48921428:G:C	R409G	1.000
18:48921428:G:T	R409S	1.000
18:48921433:T:C	Y407C	1.000
18:48921434:A:G	Y407H	1.000
18:48921442:C:A	G404V	1.000
18:48921442:C:T	G404D	1.000
18:48921443:C:A	G404C	1.000
18:48921443:C:G	G404R	1.000
18:48921444:C:A	W403C	1.000
18:48921444:C:G	W403C	1.000
18:48921445:C:A	W403L	1.000
18:48921445:C:G	W403S	1.000
18:48921446:A:G	W403R	1.000
18:48921446:A:T	W403R	1.000
18:48921448:C:A	G402V	1.000
18:48921448:C:T	G402D	1.000
18:48921449:C:A	G402C	1.000
18:48921449:C:G	G402R	1.000
18:48921449:C:T	G402S	1.000
18:48921450:C:A	K401N	1.000

dbSNP variants (sampled 300 via entrez): RS1000004220 (18:48932006 C>G,T), RS1000058116 (18:48931846 T>C), RS1000116989 (18:48937150 G>A), RS1000137110 (18:48933711 G>A), RS1000147643 (18:48946662 C>T), RS1000153829 (18:48936023 C>T), RS1000180196 (18:48950789 A>G), RS1000184701 (18:48936030 A>C), RS1000200416 (18:48941499 G>A), RS1000241760 (18:48952679 T>A,C), RS1000366757 (18:48922116 C>T), RS1000373092 (18:48936262 T>C), RS1000476662 (18:48939383 A>C), RS1000517533 (18:48951873 G>A), RS1000651118 (18:48942632 A>G)

Disease associations

OMIM: gene MIM:602932 | disease phenotypes: MIM:612229

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Limited	Autosomal dominant
colorectal cancer, susceptibility to, 3	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (2): colorectal cancer, susceptibility to, 3 (MONDO:0012820), congenital heart disease (MONDO:0005453)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0003003	Colon cancer

GWAS associations

50 associations (top):

Study	Trait	p-value
GCST000113_1	Colorectal cancer	1.000000e-12
GCST000168_3	Colorectal cancer	8.000000e-28
GCST000169_3	Colorectal cancer	2.000000e-06
GCST001161_2	Colorectal cancer	1.000000e-07
GCST001713_21	Dental caries	4.000000e-06
GCST001725_58	Inflammatory bowel disease	1.000000e-09
GCST001787_4	Colorectal cancer	2.000000e-10
GCST002340_1	Colorectal cancer	3.000000e-11
GCST002454_19	Colorectal cancer	2.000000e-08
GCST002919_16	Colorectal cancer	4.000000e-23
GCST003017_21	Colorectal cancer	2.000000e-15
GCST003882_1	Parental longevity (at least one long-lived parent)	2.000000e-07
GCST004601_181	Red blood cell count	4.000000e-09
GCST004604_36	Hematocrit	2.000000e-10
GCST004615_117	Hemoglobin concentration	9.000000e-10
GCST005149_13	Colorectal cancer	9.000000e-07
GCST005150_34	Colorectal cancer	3.000000e-07
GCST005591_9	Colorectal cancer	3.000000e-12
GCST005984_67	Glomerular filtration rate	1.000000e-08
GCST005985_18	Creatinine levels	5.000000e-09
GCST006061_102	Atrial fibrillation	9.000000e-11
GCST006061_103	Atrial fibrillation	2.000000e-10
GCST006414_38	Atrial fibrillation	2.000000e-11
GCST006979_274	Heel bone mineral density	3.000000e-26
GCST006979_275	Heel bone mineral density	3.000000e-12
GCST007344_42	Estimated glomerular filtration rate	6.000000e-09
GCST007552_20	Colorectal cancer	5.000000e-15
GCST007552_5	Colorectal cancer	2.000000e-27
GCST007856_41	Colorectal cancer or advanced adenoma	4.000000e-74
GCST007876_70	Estimated glomerular filtration rate	5.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007796	parental longevity
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0009270	heel bone mineral density
EFO:0004327	electrocardiography
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4939827	SMAD7		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	5
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
Resveratrol	increases expression	3
Tretinoin	increases expression	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
manganese chloride	increases methylation, affects cotreatment, decreases expression, increases abundance	2
entinostat	increases expression, affects cotreatment	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, affects methylation	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Calcitriol	increases expression, decreases expression, decreases reaction	2
Cisplatin	increases expression, affects cotreatment, decreases expression	2
Endosulfan	decreases expression, decreases reaction	2
Formaldehyde	decreases expression, increases expression	2
Silver	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	decreases expression, decreases reaction	2
Aflatoxin B1	increases methylation	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
GSK-J4	increases expression	1
vericiguat	decreases expression, decreases reaction	1
triphenyl phosphate	affects expression	1
geraniol	increases expression	1
methylselenic acid	increases expression	1
beta-lapachone	decreases expression, increases expression	1
tanshinone	decreases expression, decreases reaction, increases reaction	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
tobacco tar	decreases expression	1
benzo(e)pyrene	increases methylation	1

Cellosaurus cell lines

12 cell lines: 6 cancer cell line, 5 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6H5	SEES3-1V human SMAD7, clone1	Embryonic stem cell	Male
CVCL_A6H6	SEES3-1V human SMAD7, clone2	Embryonic stem cell	Male
CVCL_A6H7	SEES3-1V human SMAD7, clone3	Embryonic stem cell	Male
CVCL_B2GK	Abcam HeLa SMAD7 KO	Cancer cell line	Female
CVCL_B8PM	Abcam HCT 116 SMAD7 KO	Cancer cell line	Male
CVCL_B9S2	Abcam A-549 SMAD7 KO	Cancer cell line	Male
CVCL_D8AU	Ubigene A-549 SMAD7 KO	Cancer cell line	Male
CVCL_D8VL	Ubigene HCT 116 SMAD7 KO	Cancer cell line	Male
CVCL_D9SB	Ubigene HEK293 SMAD7 KO	Transformed cell line	Female
CVCL_E0PD	Ubigene HeLa SMAD7 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE