SMAD4 Chromosome 18
SMAD family member 4
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What This Gene Does
This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasing blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, May 2022]
Gene Info
Gene Group
SMAD family
Locus Type
gene with protein product
Location
18q21.2
Ensembl
ENSG00000141646
Associated Conditions (34)
Juvenile polyposis syndrome
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
Hereditary cancer-predisposing syndrome
Familial thoracic aortic aneurysm and aortic dissection
Generalized juvenile polyposis/juvenile polyposis coli
Myhre syndrome
Carcinoma of pancreas
SMAD4-related disorder
Isolated thoracic aortic aneurysm
Hereditary hemorrhagic telangiectasia
Heritable Thoracic Aortic Disease
Heritable thoracic aortic disease without juvenile polyposis and hereditary hemorrhagic telangiectasia
Familial cancer of breast
Pulmonary hypertension
primary
1
Pulmonary arterial hypertension
Familial pancreatic carcinoma
Moyamoya angiopathy
Intellectual disability
+14 more conditions
Key Variants
RS1052676207
Conflicting classifications of pathogenicity
Juvenile polyposis syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Hereditary cancer-predisposing syndrome
Health Risk
RS1057520412
Conflicting classifications of pathogenicity
Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
Health Risk
RS1057520520
Conflicting classifications of pathogenicity
Hereditary cancer-predisposing syndrome, Generalized juvenile polyposis/juvenile polyposis coli, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
Health Risk
RS1057521660
Conflicting classifications of pathogenicity
Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection
Health Risk
RS1057524809
Conflicting classifications of pathogenicity
Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection
Health Risk
RS1060500731
Conflicting classifications of pathogenicity
Juvenile polyposis syndrome, Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome
Health Risk
RS1060500745
Conflicting classifications of pathogenicity
Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
Health Risk
RS1060504025
Conflicting classifications of pathogenicity
Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection
Health Risk
RS1060504026
Conflicting classifications of pathogenicity
Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection
Health Risk
RS1060504028
Conflicting classifications of pathogenicity
Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
Health Risk
RS1060504029
Conflicting classifications of pathogenicity
Hereditary cancer-predisposing syndrome, Juvenile polyposis syndrome, Familial thoracic aortic aneurysm and aortic dissection
Health Risk
RS1064794204
Conflicting classifications of pathogenicity
Hereditary cancer-predisposing syndrome, Juvenile polyposis syndrome, Myhre syndrome
Health Risk
All Variants (390)
| RSID | Category | Clinical Significance | Conditions |
|---|---|---|---|
| RS946539148 | Health Risk | Conflicting classifications of pathogenicity | Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection |
| RS956212866 | Health Risk | Conflicting classifications of pathogenicity | Hereditary cancer-predisposing syndrome, Juvenile polyposis syndrome, Familial thoracic aortic aneurysm and aortic dissection |
| RS965942065 | Health Risk | Conflicting classifications of pathogenicity | Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection |
| RS1057519739 | Health Risk | Likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection |
| RS1060500744 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS1316902116 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome |
| RS1555685142 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Juvenile polyposis syndrome |
| RS1555685149 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection |
| RS1555685248 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS1555685622 | Health Risk | Likely pathogenic | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome |
| RS1555686086 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS1555686624 | Health Risk | Likely pathogenic | Myhre syndrome, Generalized juvenile polyposis/juvenile polyposis coli, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome |
| RS1555687572 | Health Risk | Likely pathogenic | Generalized juvenile polyposis/juvenile polyposis coli, Generalized juvenile polyposis/juvenile polyposis coli |
| RS1568208715 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS1568211588 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome, Neoplasm |
| RS1568211615 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS1909795990 | Health Risk | Likely pathogenic | Generalized juvenile polyposis/juvenile polyposis coli, Generalized juvenile polyposis/juvenile polyposis coli |
| RS1909895611 | Health Risk | Likely pathogenic | Generalized juvenile polyposis/juvenile polyposis coli, Juvenile polyposis syndrome, Hereditary cancer-predisposing syndrome |
| RS1909899495 | Health Risk | Likely pathogenic | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome |
| RS2144402036 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Juvenile polyposis syndrome |
| RS2144428309 | Health Risk | Likely pathogenic | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome |
| RS2144433681 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS2144451738 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS2144473450 | Health Risk | Likely pathogenic | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome |
| RS2144479914 | Health Risk | Likely pathogenic | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome |
| RS2511367483 | Health Risk | Likely pathogenic | Myhre syndrome, Myhre syndrome |
| RS2511369609 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS281875324 | Health Risk | Likely pathogenic | Hereditary cancer-predisposing syndrome, Hereditary cancer-predisposing syndrome |
| RS377767346 | Health Risk | Likely pathogenic | Hereditary cancer-predisposing syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Juvenile polyposis syndrome |
| RS377767348 | Health Risk | Likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome, Juvenile polyposis syndrome |
| RS377767349 | Health Risk | Likely pathogenic | Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome |
| RS377767350 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS377767354 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS377767355 | Health Risk | Likely pathogenic | Hereditary cancer-predisposing syndrome, Juvenile polyposis syndrome, Generalized juvenile polyposis/juvenile polyposis coli |
| RS377767382 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS377767386 | Health Risk | Likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome, Juvenile polyposis syndrome |
| RS777803301 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS786205514 | Health Risk | Likely pathogenic | — |
| RS864622252 | Health Risk | Likely pathogenic | Generalized juvenile polyposis/juvenile polyposis coli, Juvenile polyposis syndrome, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome |
| RS876660556 | Health Risk | Likely pathogenic | Juvenile polyposis syndrome, Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome |
| RS1060500733 | Health Risk | Pathogenic | Juvenile polyposis syndrome, Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome |
| RS1060500739 | Health Risk | Pathogenic | Juvenile polyposis syndrome, Familial thoracic aortic aneurysm and aortic dissection, Hereditary cancer-predisposing syndrome |
| RS1060500740 | Health Risk | Pathogenic | Juvenile polyposis syndrome, Squamous cell lung carcinoma, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome |
| RS1060500742 | Health Risk | Pathogenic | Juvenile polyposis syndrome, Juvenile polyposis syndrome |
| RS1064793271 | Health Risk | Pathogenic | — |
| RS121912576 | Health Risk | Pathogenic | Carcinoma of pancreas, Carcinoma of pancreas |
| RS121912577 | Health Risk | Pathogenic | Carcinoma of pancreas, Carcinoma of pancreas |
| RS121912578 | Health Risk | Pathogenic | Carcinoma of pancreas, Carcinoma of pancreas |
| RS121912579 | Health Risk | Pathogenic | Carcinoma of pancreas, Carcinoma of pancreas |
| RS1555685156 | Health Risk | Pathogenic | Hereditary cancer-predisposing syndrome, Familial thoracic aortic aneurysm and aortic dissection, Juvenile polyposis syndrome |