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The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]
SMAD6 (SMAD Family Member 6) is a Protein Coding gene. Diseases associated with SMAD6 include Aortic Valve Disease 2 and Craniosynostosis 7. Among its related pathways are Signaling by GPCR and Signaling by BMP. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and chromatin binding. An important paralog of this gene is SMAD7.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000976 | transcription regulatory region sequence-specific DNA binding | IDA | 16491121 |
GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding | IDA | 16491121 |
GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | ISA | -- |
GO:0003677 | DNA binding | IEA | -- |
GO:0003682 | chromatin binding | IDA | 16491121 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000790 | nuclear chromatin | ISA | -- |
GO:0005634 | nucleus | IEA,IDA | 16491121 |
GO:0005654 | nucleoplasm | IDA | -- |
GO:0005667 | transcription factor complex | IEA | -- |
GO:0005737 | cytoplasm | TAS | 19018011 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Signaling by BMP |
.33
|
|
2 | TGF-beta signaling pathway (KEGG) | ||
3 | VEGF Signaling | ||
4 | Signaling by GPCR | ||
5 | Integrated Breast Cancer Pathway |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001657 | ureteric bud development | IEA | -- |
GO:0003148 | outflow tract septum morphogenesis | ISS | -- |
GO:0003170 | heart valve development | IEA | -- |
GO:0003180 | aortic valve morphogenesis | IMP | 22275001 |
GO:0003183 | mitral valve morphogenesis | ISS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Pirfenidone | Approved, Investigational | Pharma | TGF-β production inhibitor, Antifibrotic agent; regulates cytokine levels in vivo | 86 | ||
LDN193189 Hydrochloride | Pharma | ALK inhibitor,potent and selective | 0 | |||
LY364947 | Pharma | 0 | ||||
RepSox | Pharma | ALK5 inhibitor,potent and selective, Potent and selective inhibitor of TGF-betaRI | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
Compound | Action | Cas Number |
---|---|---|
LDN193189 Hydrochloride | ALK inhibitor,potent and selective | 1062368-62-0 |
LY364947 | 396129-53-6 | |
Pirfenidone | TGF-β production inhibitor | 53179-13-8 |
RepSox | ALK5 inhibitor,potent and selective | 446859-33-2 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | SMAD6 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | SMAD6 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | SMAD6 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Smad6 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Smad6 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | SMAD6 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | SMAD6 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | SMAD6 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | SMAD6 31 |
|
OneToOne | |
African clawed frog (Xenopus laevis) |
Amphibia | Xl.2593 30 |
|
||
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | Str.2540 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | LOC564395 30 |
|
||
smad6a 31 |
|
OneToOne | |||
wufk08g05 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | Dad 31 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | daf-3 31 |
|
ManyToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.9437 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 15 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
635569 | Pathogenic: Aortic valve disease 2 | 66,781,209(+) | T/TTCGGCA | NON_CODING_TRANSCRIPT_VARIANT,INFRAME_INSERTION | |
638816 | Uncertain Significance: Radioulnar synostosis; Aortic valve disease 2 | 66,703,712(+) | CCGGCGGG/C | FRAMESHIFT_VARIANT,NON_CODING_TRANSCRIPT_VARIANT | |
640191 | Uncertain Significance: Aortic valve disease 2 | 66,781,044(+) | G/C | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT | |
641141 | Uncertain Significance: Aortic valve disease 2 | 66,703,428(+) | GC/TT | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT | |
641172 | Uncertain Significance: Aortic valve disease 2 | 66,703,941(+) | G/A | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv746e212 | CNV | loss | 25503493 |
esv3636772 | CNV | loss | 21293372 |
esv3636773 | CNV | gain | 21293372 |
nsv827370 | CNV | gain | 20364138 |
Disorder | Aliases | PubMed IDs |
---|---|---|
aortic valve disease 2 |
|
|
craniosynostosis 7 |
|
|
radioulnar synostosis, nonsyndromic |
|
|
aortic valve disease 1 |
|
|
radioulnar synostosis |
|
|