SMAD7 Gene

HGNC Family	SMAD family (SMAD)
Name	SMAD family member 7
Description	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. [provided by RefSeq, Jun 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSMAD7 is a critical intracellular inhibitor of transforming growth factor‐beta (TGF‑β) and bone morphogenetic protein (BMP) signaling that functions through multiple mechanisms. It binds directly to activated type I receptors to prevent the phosphorylation of receptor‐regulated Smads and, in addition, forms complexes with adaptor proteins (e.g., GADD34–PP1) to promote receptor dephosphorylation. SMAD7 also translocates to the nucleus where it interferes with the assembly of functional Smad–DNA complexes, thereby attenuating transcriptional responses. Through these events, SMAD7 establishes a negative feedback loop that modulates TGF‑β/BMP signal intensity and duration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe stability and activity of SMAD7 are further refined by a network of post‐translational modifications and protein–protein interactions. Acetylation, mediated by the acetyltransferase p300, protects SMAD7 from degradation, whereas histone deacetylases (HDACs) remove these modifications, thereby enhancing its ubiquitination. Several E3 ubiquitin ligases—such as WWP1 and the versatile WWP2 isoforms, as well as Jab1/CSN5 and Arkadia—interact with SMAD7 to promote its nuclear export or proteasomal degradation. Such regulatory events ensure that SMAD7 levels remain tuned in response to extracellular cues, ultimately influencing receptor turnover and the magnitude of TGF‑β/BMP signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe modulation of SMAD7 expression and function has profound implications in diverse disease contexts. Genetic variants in SMAD7 are associated with an altered risk for colorectal cancer, and oncogenic signaling (for example, via HER2/Neu–ER81 pathways) has been shown to upregulate SMAD7 transcription in several cancers. Conversely, microRNAs—including miR‑106b–25, miR‑25, miR‑181a, and miR‑182—target SMAD7, thereby relieving its inhibitory effects and unleashing TGF‑β–induced epithelial-to-mesenchymal transition (EMT), increased invasion, and metastatic spread. In fibrotic disorders such as scleroderma and hypertrophic scarring, as well as in conditions like fibrodysplasia ossificans progressiva (FOP), altered SMAD7 activity contributes to dysregulated extracellular matrix production and abnormal differentiation. Moreover, pathogen-induced modulation of SMAD7 (for example, during MERS‑CoV infection) further underscores its role in controlling cell survival and apoptosis. Collectively, these studies reveal that balanced SMAD7 expression is pivotal not only for maintaining normal TGF‑β signaling but also for preventing disease progression in cancer, fibrotic disorders, and beyond."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chie Suzuki, Gyo Murakami, Minoru Fukuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Smurf1 regulates the inhibitory activity of Smad7 by targeting Smad7 to the plasma membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M201901200"}], "href": "https://doi.org/10.1074/jbc.M201901200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12151385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12151385"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sofia Edlund, Shizhong Bu, Norbert Schuster, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200307151"}], "href": "https://doi.org/10.1083/jcb.200307151"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14718519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14718519"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Suping Zhang, Teng Fei, Lixia Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01636-06"}], "href": "https://doi.org/10.1128/MCB.01636-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17438144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17438144"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Peter Broderick, Luis Carvajal-Carmona, Alan M Pittman, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Abrogation of transforming growth factor-beta signaling by SMAD7 inhibits collagen gel contraction of human dermal fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M502071200"}], "href": "https://doi.org/10.1074/jbc.M502071200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15788410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15788410"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "A L Smith, R Iwanaga, D J Drasin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The miR-106b-25 cluster targets Smad7, activates TGF-β signaling, and induces EMT and tumor initiating cell characteristics downstream of Six1 in human breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2012.11"}], "href": "https://doi.org/10.1038/onc.2012.11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22286770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22286770"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Tushar D Bhagat, Li Zhou, Lubomir Sokol, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Environmental sensing by mature B cells is controlled by the transcription factors PU.1 and SpiB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-01605-1"}], "href": "https://doi.org/10.1038/s41467-017-01605-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29127283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29127283"}]}]}]}
Synonyms	MADH8, CRCS3
Proteins	SMAD7_HUMAN
NCBI Gene ID	4092
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SMAD7 has 13,167 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 132 datasets.

Click the + buttons to view associations for SMAD7 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SMAD7 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SMAD7 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SMAD7 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SMAD7 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SMAD7 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SMAD7 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SMAD7 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving SMAD7 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SMAD7 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SMAD7 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SMAD7 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SMAD7 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SMAD7 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with SMAD7 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SMAD7 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SMAD7 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SMAD7 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SMAD7 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SMAD7 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SMAD7 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SMAD7 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SMAD7 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SMAD7 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SMAD7 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SMAD7 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SMAD7 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing SMAD7 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SMAD7 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SMAD7 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SMAD7 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SMAD7 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SMAD7 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SMAD7 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SMAD7 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SMAD7 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SMAD7 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SMAD7 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SMAD7 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SMAD7 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SMAD7 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SMAD7 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.