SMAD7

SMAD family member 7, the group of SMAD family

Basic information

Region (hg38): 18:48919852-48950965

Previous symbols: [ "MADH8", "MADH7" ]

Links

ENSG00000101665 ∙ NCBI:4092 ∙ OMIM:602932 ∙ HGNC:6773 ∙ Uniprot:O15105 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMAD7 gene.

• Inborn genetic diseases (25 variants)
• not provided (5 variants)
• not specified (1 variants)
• Colorectal cancer, susceptibility to, 3 (1 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMAD7 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	3	4
missense			23	4	1	28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	23	5	4

Variants in SMAD7

This is a list of pathogenic ClinVar variants found in the SMAD7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-48921367-C-T		SMAD7-related disorder	Likely benign (Jan 26, 2024)
18-48921487-G-A		not specified	Uncertain significance (Mar 20, 2023)
18-48921539-C-T		not specified	Uncertain significance (May 08, 2023)
18-48921567-G-A			Benign (Apr 26, 2018)
18-48921591-C-T			Uncertain significance (-)
18-48921620-C-T		not specified	Uncertain significance (Nov 08, 2022)
18-48927093-T-T		Colorectal cancer, susceptibility to, 3	risk factor (May 01, 2008)
18-48942510-G-A		Hereditary breast ovarian cancer syndrome	Uncertain significance (Aug 01, 2020)
18-48942535-G-T		not specified	Uncertain significance (Aug 02, 2021)
18-48942576-G-A		SMAD7-related disorder	Benign (Nov 04, 2019)
18-48948376-C-T		SMAD7-related disorder	Likely benign (Jul 24, 2020)
18-48948426-G-A		not specified	Uncertain significance (Mar 14, 2023)
18-48948426-G-T		not specified	Uncertain significance (Mar 19, 2020)
18-48948427-G-A			Benign (Dec 31, 2019)
18-48948427-G-T		SMAD7-related disorder	Benign (Dec 31, 2019)
18-48949943-T-C		not specified	Uncertain significance (Oct 26, 2022)
18-48949992-G-T		not specified	Uncertain significance (Mar 13, 2023)
18-48949994-G-T		not specified	Uncertain significance (Feb 21, 2024)
18-48949995-C-A		not specified	Likely benign (Apr 07, 2023)
18-48950012-G-A		not specified	Likely benign (Apr 07, 2023)
18-48950037-C-T		not specified	Uncertain significance (Apr 07, 2022)
18-48950144-G-A		not specified	Uncertain significance (Sep 20, 2023)
18-48950163-C-T		not specified	Uncertain significance (Jul 20, 2021)
18-48950170-G-A		SMAD7-related disorder	Likely benign (Jun 10, 2019)
18-48950171-G-A		not specified	Uncertain significance (Aug 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMAD7	protein_coding	protein_coding	ENST00000262158	4	30859

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.549	0.451	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	154	224	0.689	0.0000126	2685
Missense in Polyphen		52	99.23	0.52403		1148
Synonymous	-1.97	131	105	1.24	0.00000648	901
Loss of Function	2.91	3	15.3	0.196	6.67e-7	177

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000127	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000896	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000366	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:12023024, ECO:0000269|PubMed:14718519, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:9892009}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:17934461}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: TGF-beta signaling pathway - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);TGF-Core;EGF-Ncore;Transcriptional activity of SMAD2-SMAD3-SMAD4 heterotrimer;Apoptosis-related network due to altered Notch3 in ovarian cancer;Lung fibrosis;TGF-beta Signaling Pathway;Hfe effect on hepcidin production;ESC Pluripotency Pathways;Protein alkylation leading to liver fibrosis;TGF-beta Receptor Signaling;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription;TGF-beta super family signaling pathway canonical;UCH proteinases;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;BMP receptor signaling;tgf beta signaling pathway;BMP Signalling Pathway;Ub-specific processing proteases;Deubiquitination;IFN-gamma pathway;Signaling by TGF-beta Receptor Complex;BMP2 signaling TGF-beta MV;Signaling by BMP;Signaling by TGF-beta family members;Downregulation of TGF-beta receptor signaling;TGF-beta receptor signaling activates SMADs;ALK1 signaling events;Signaling events mediated by HDAC Class I;Regulation of nuclear SMAD2/3 signaling;TGF-beta receptor signaling (Consensus)

Recessive Scores

• pRec: 0.363

Haploinsufficiency Scores

• pHI: 0.647
• hipred: Y
• hipred_score: 0.771
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Smad7
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: smad7
• Affected structure: muscle
• Phenotype tag: abnormal
• Phenotype quality: hypoplastic

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;ureteric bud development;negative regulation of T cell cytokine production;transforming growth factor beta receptor signaling pathway;regulation of epithelial to mesenchymal transition;negative regulation of epithelial to mesenchymal transition;negative regulation of peptidyl-threonine phosphorylation;negative regulation of transcription by competitive promoter binding;protein deubiquitination;regulation of transforming growth factor beta receptor signaling pathway;positive regulation of cell-cell adhesion;negative regulation of cell migration;BMP signaling pathway;negative regulation of transforming growth factor beta receptor signaling pathway;negative regulation of BMP signaling pathway;negative regulation of protein ubiquitination;positive regulation of protein ubiquitination;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;regulation of activin receptor signaling pathway;negative regulation of peptidyl-serine phosphorylation;adherens junction assembly;response to laminar fluid shear stress;cellular protein-containing complex localization;negative regulation of DNA-binding transcription factor activity;positive regulation of transcription by RNA polymerase II;artery morphogenesis;protein stabilization;negative regulation of ubiquitin-protein transferase activity;ventricular cardiac muscle tissue morphogenesis;regulation of cardiac muscle contraction;regulation of ventricular cardiac muscle cell membrane depolarization;pathway-restricted SMAD protein phosphorylation;negative regulation of pathway-restricted SMAD protein phosphorylation;ventricular septum morphogenesis;cellular response to transforming growth factor beta stimulus;cellular response to leukemia inhibitory factor;negative regulation of T-helper 17 type immune response;negative regulation of T-helper 17 cell differentiation
• Cellular component: fibrillar center;nucleus;nucleoplasm;transcription factor complex;cytoplasm;centrosome;cytosol;plasma membrane;cell-cell adherens junction;catenin complex;protein-containing complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;protein binding;collagen binding;beta-catenin binding;transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity;ubiquitin protein ligase binding;type I transforming growth factor beta receptor binding;transcription regulatory region DNA binding;metal ion binding;activin binding;I-SMAD binding