SMAD7
SMAD family member 7, the group of SMAD family
Basic information
Region (hg38): 18:48919853-48950965
Previous symbols: [ "MADH8", "MADH7" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
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 | 8 | |||||
| missense | 27 | 32 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 2 | |||||
| Total | 0 | 0 | 27 | 9 | 6 |
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) | ||
| 18-48921744-C-T | SMAD7-related disorder | Likely benign (Jun 20, 2019) | ||
| 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) | ||
| 18-48948445-T-G | SMAD7-related disorder | Likely benign (Jul 10, 2024) | ||
| 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) |
GnomAD
Source:
| 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:
- 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