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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

SMAD6 Gene

protein-coding GIFtS: 61
GCID: GC15P066994

SMAD family member 6

(Previous names: MAD, mothers against decapentaplegic homolog 6 (Drosophila),...)
(Previous symbols: MADH7, MADH6)

Explore 30 diseases affiliated with
SMAD6 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

This gene clusters with an RNA gene
Subcategory (RNA class): lncRNA

Quality score for the ORGUL clustered with this gene is 3

Aliases
SMAD Family Member 6¹ ² ³		MAD, Mothers Against Decapentaplegic Homolog 6 (Drosophila)¹
MADH6¹ ² ³ ⁵		SMAD, Mothers Against DPP Homolog 6 (Drosophila)¹
HsT17432¹ ²		AOVD2²
MADH7¹ ²		Mothers Against Decapentaplegic Homolog 6²
Mothers Against DPP Homolog 6² ³		Mothers Against Decapentaplegic, Drosophila, Homolog Of, 6²
HSMAD6¹		SMAD, Mothers Against DPP Homolog 6²
MAD Homolog 6² ³		Smad6³
SMAD 6² ³

External Ids:	HGNC: 6772¹	Entrez Gene: 4091²	Ensembl: ENSG00000137834⁷	OMIM: 602931⁵	UniProtKB: O43541³

ORGUL members:
	NONCODE:n407949

Export aliases for SMAD6 gene to outside databases

Previous GC identifers: GC15P064681 GC15P064781 GC15P043830

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for SMAD6:

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 encoding different isoforms have been found for this

gene.(provided by RefSeq, May 2009)

UniProtKB/Swiss-Prot: SMAD6_HUMAN, O43541

Function: Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its

direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression

of proinflammatory genes. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated

SMAD1-binding. Binds to regulatory elements in target promoter regions

Gene Wiki entry for SMAD6 (Mothers against decapentaplegic homolog 6)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000015.9 NC_018926.1 NT_010194.17

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the SMAD6 gene promoter:
AML1a
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: SMAD6 promoter sequence

Search SABiosciences Chromatin IP Primers for SMAD6

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat SMAD6

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 15q21-q22 Ensembl cytogenetic band: 15q22.31 HGNC cytogenetic band: 15q21-q22

SMAD6 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SMAD6 gene location

GeneLoc information about chromosome 15 GeneLoc Exon Structure

GeneLoc location for GC15P066994: view genomic region (about GC identifiers)

Start:	66,994,566 bp from pter	End:	67,074,338 bp from pter
Size:	79,773 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: SMAD6_HUMAN, O43541 (See protein sequence)

Recommended Name: Mothers against decapentaplegic homolog 6

Size: 496 amino acids; 53497 Da

Subunit: Interacts with NEDD4L (By similarity). Interacts with WWP1 (By similarity). Interacts with STAMBP and PRKX.

Interacts with RNF111 and AXIN1. Interacts with TGF-beta type I receptor superfamily members, including ACVR1B, BMPR1B

and TGFBR1. In response to BMP2, but not to TGFB treatment, interacts with SMAD1, but not with SMAD2, nor with SMAD4;

this interaction may inhibit SMAD1 binding to SMAD4. Interacts with HOXC8 and HOXC9. Interacts with PELI1; this

interaction interferes with PELI1 complex formation with TRAF6, IRAK1, IRAK4 and MYD88 in response to IL1B and hence

negatively regulates IL1R-TLR signaling

Subcellular location: Nucleus

Secondary accessions: A9J6M5 O43654 Q15799 Q7Z7L4 Q96E31 Q9UKZ3

Alternative splicing: 3 isoforms: O43541-1 O43541-2 O43541-4

Explore the universe of human proteins at neXtProt for SMAD6: NX_O43541

Post-translational modifications:

Phosphorylated by BMP type 1 receptor kinase and by PRKX¹

Ubiquitinated by WWP1 (By similarity)¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_O43541

SMAD6 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001136333.1 NP_005576.3

ENSEMBL proteins:

ENSP00000288840 ENSP00000452955 ENSP00000453446 ENSP00000452694 ENSP00000396961

ENSP00000345054

Reactome Protein details: O43541
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	Uscn Proteins for SMAD6

Gene Ontology (GO): 4 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	16491121
GO:0005667	transcription factor complex	IEA	--
GO:0005737	cytoplasm	TAS	19018011
GO:0005829	cytosol	TAS	--

SMAD6 for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for SMAD6

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

SMAD6 for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR013019 MAD_homology_MH1

IPR008984 SMAD_FHA_domain

IPR001132 SMAD_dom_Dwarfin-type

IPR017855 SMAD_dom-like

IPR013790 Dwarfin

Graphical View of Domain Structure for InterPro Entry O43541

ProtoNet protein and cluster: O43541

1 Blocks protein family: IPB001132 Dwarfin protein

UniProtKB/Swiss-Prot: SMAD6_HUMAN, O43541

Similarity: Belongs to the dwarfin/SMAD family

Similarity: Contains 1 MH1 (MAD homology 1) domain

Similarity: Contains 1 MH2 (MAD homology 2) domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: SMAD6_HUMAN, O43541

Function: Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its

direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression

of proinflammatory genes. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated

SMAD1-binding. Binds to regulatory elements in target promoter regions

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		hsa-miR-106a hsa-miR-134 hsa-miR-25 hsa-miR-767-5p hsa-miR-374a hsa-miR-410 hsa-miR-93 hsa-miR-3118

		SwitchGear 3'UTR luciferase reporter plasmid: SMAD6 3' UTR sequence

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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SMAD6

Gene Ontology (GO): 5/12 molecular function terms (GO ID links to tree view) (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003682	chromatin binding	IDA	16491121
GO:0003700	sequence-specific DNA binding transcription factor activity	IEA	--
GO:0005515	protein binding	IPI	11483516
GO:0030617	transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity	IMP	19047146
GO:0031625	ubiquitin protein ligase binding	IPI	11278251

SMAD6 for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for SMAD6:

Decreased G3BP1 protein expres

Animal Models:
4 MGI mutant phenotypes (inferred from 1 allele) (MGI details for Smad6):

cardiovascular system

homeostasis/metabolism

mortality/aging

muscle

SMAD6 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/9 super-pathways (see all 9) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Signaling by BMP

	Signaling by BMP	1.00			BMP receptor signaling	0.31
	BMP signalling and regulation	0.35

Integrated Pancreatic Cancer Pathway

Integrated Pancreatic Cancer Pathway

1.00

Integrated Pancreatic Cancer Pathway

0.99

TGF-beta/Smad Signaling

TGF-beta/Smad Signaling

1.00

Integrated Breast Cancer Pathway

Integrated Breast Cancer Pathway

1.00

TGF Beta Signaling Pathway

TGF Beta Signaling Pathway

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

1 Cell Signaling Technology (CST) Pathway for SMAD6

TGF-beta/Smad Signaling

5/7 BioSystems Pathways for SMAD6 (see all 7)

	Integrated Breast Cancer Pathway
	BMP signalling and regulation
	TGF Beta Signaling Pathway
	Integrated Pancreatic Cancer Pathway
	Integrated Pancreatic Cancer Pathway

2 Reactome Pathways for SMAD6

	Signal Transduction
	Signaling by BMP

2 Kegg Pathways (Kegg details for SMAD6):

	Endocytosis
	TGF-beta signaling pathway

SMAD6 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for SMAD6

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/45 Interacting proteins for SMAD6 (O43541^{1, 2, 3} ENSP00000288840⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 45)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
MAPK6	Q16659²^,³	MINT-8261978 I2D: score=2
SMURF2	Q9HAU4²^,³, ENSP00000262435⁴	MINT-61796 I2D: score=5 STRING: ENSP00000262435
RUNX2	Q13950¹^,³, ENSP00000352514⁴	EBI-976374,EBI-976402 I2D: score=2 STRING: ENSP00000352514
STAMBP	O95630¹^,³, ENSP00000344742⁴	EBI-4324970,EBI-396676 I2D: score=2 STRING: ENSP00000344742
RPS6KA5	O75582²^,³, ENSP00000261991⁴	MINT-8269692 I2D: score=2 STRING: ENSP00000261991

About this table

Gene Ontology (GO): 5/16 biological process terms (GO ID links to tree view) (see all 16): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001657	ureteric bud development	IEA	--
GO:0006351	transcription, DNA-dependent	IEA	--
GO:0006955	immune response	IMP	16886151
GO:0007179	transforming growth factor beta receptor signaling pathway	IEA	--
GO:0007352	zygotic specification of dorsal/ventral axis	IMP	9436979

SMAD6 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

SMAD6 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for SMAD6
2 Novoseek chemical compound relationships for SMAD6 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
tgf beta1	45.8	1	20196115 (1)
tyrosine	0	1	12397035 (1)

Search CenterWatch for drugs/clinical trials and news about SMAD6

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for SMAD6 gene (2 alternative transcripts):

NM_001142861.2 NM_005585.4

Unigene Cluster for SMAD6:

SMAD family member 6

Hs.153863 [show with all ESTs]

Unigene Representative Sequence: NR_027654

6 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000288840(uc010bhx.3 uc002aqf.3) ENST00000557916 ENST00000559931

ENST00000558937 ENST00000457357 ENST00000338426(uc002aqg.3)

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		hsa-miR-106a hsa-miR-134 hsa-miR-25 hsa-miR-767-5p hsa-miR-374a hsa-miR-410 hsa-miR-93 hsa-miR-3118

		SwitchGear 3'UTR luciferase reporter plasmid: SMAD6 3' UTR sequence

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Additional cDNA sequence:

AF035528.1 AF037469.1 AF043640.1 AM909653.1 BC012986.2 BC029288.1 NR_027654.1 U59914.1

4 DOTS entries:

DT.448546 DT.40197628 DT.101958886 DT.92016400

24/221 AceView cDNA sequences (see all 221):

BM704524 AI453564 AI199866 AI275043 AI769301 BQ631353 AI436355 BE467124

AW182279 AI024992 BQ012484 BF594048 BU727453 BF057532 BG055424 BQ776596

CB055216 AA007517 AA136175 BU734250 AF037469 BI789075 AW572964 BG055459

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

SMAD6 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: AAAGAAGAAG

About this image

SMAD6 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

7 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Extraembryonic Mesoderm

Extraembryonic Mural Cells

Extraembryonic Tissues

Lateral Plate Mesoderm

Splanchnic Mesoderm

Mural Cells

Pericytes, Smooth Muscle

Lung

Lung Bud

Lung Bud Progenitor Cells

Lung

Heart

Atrioventricular Canal

Atrioventricular Canal Cells

Myocardium

Heart

Endocardium

Cushion Mesenchymal Cells

Endocardium

Heart

Endocardium

Endocardial Tube Cells

Endocardium

Heart

Outflow Tract

Heart

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 2 LifeMap Cells

Name

Category

HyStem+BMP4-induced SM30 cells (HyStem+BMP4 inductio...)

Adipose, Bone, Cartilage

HyStem+BMP4-induced 7SMOO32 cells (HyStem+BMP4 inductio...)

Adipose

See SMAD6 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for SMAD6

SOURCE GeneReport for Unigene cluster: Hs.153863

UniProtKB/Swiss-Prot: SMAD6_HUMAN, O43541

Tissue specificity: Ubiquitous in various organs, with higher levels in lung. Isoform B is up-regulated in diseased

heart tissue

SABiosciences Expression via Pathway-Focused PCR Arrays including SMAD6:

Fibrosis in human mouse rat

TGFB/BMP Signaling Pathway in human mouse rat

TGFB Signaling Targets in human mouse rat

Stem Cell Signaling in human mouse rat

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SMAD6

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for SMAD6 gene from 5/18 species (see all 18) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	SMAD6¹	SMAD family member 6	74.75(n) 77.16(a)		374096 NM_204248.1 NP_989579.1
lizard (Anolis carolinensis)	Reptilia	SMAD6⁶	--	67(a)	1 ↔ 1	GL343467.1(205561-240842)
African clawed frog (Xenopus laevis)	Amphibia	Xl.2593²	Xenopus laevis Smad6 mRNA, partial cds	80.04(n)		AF041839.1
zebrafish (Danio rerio)	Actinopterygii	wufk08g05²	Transcribed sequence with moderate similarity to protein more	83.03(n)		57081833
fruit fly (Drosophila melanogaster)	Insecta	Dad⁶	Daughters against dpp	20(a)	1 → many	3R(12879729-12896135)

ENSEMBL Gene Tree for SMAD6 (if available)
TreeFam Gene Tree for SMAD6 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for SMAD6 gene

SMAD2² SMAD3² SMAD1² SMAD5² SMAD9² SMAD4² SMAD7²

1 SIMAP similar gene for SMAD6 using alignment to 4 protein entries: SMAD6_HUMAN (see all proteins):

SMAD7

SMAD6 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 15 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs187537276^1,2		--	66992688(+)	`ACTCAA/GTACGC`	2	--	us2k¹		0	--	--	--	--
rs146717700^1,2		--	66992691(+)	`CAATAC/TGCACG`	2	--	us2k¹		0	--	--	--	--
rs74623641^1,2	F,	--	66992692(+)	`AATACG/ACACGA`	2	--	us2k¹		1		WA	118
rs8041981^1,2	C,F,A,	--	66992715(+)	`GTAATA/CCACAG`	2	--	us2k¹		8		NA CSA WA EA	368
rs140409374^1,2		--	66992731(+)	`GATAAA/TCCACA`	2	--	us2k¹		0	--	--	--	--
rs193301969^1,2		--	66992748(+)	`ATACAC/TGGGGA`	2	--	us2k¹		0	--	--	--	--
rs142652225^1,2		--	66992750(+)	`ACACGC/GGGATA`	2	--	us2k¹		0	--	--	--	--
rs151008339^1,2		--	66992794(+)	`AAGATA/GTATTA`	2	--	us2k¹		0	--	--	--	--
rs79112691^1,2		--	66992820(+)	`AAAAGA/TGACTG`	2	--	us2k¹		0	--	--	--	--
rs8042545^1,2	C,F,	--	66992821(+)	`AAAGTG/AACTGA`	2	--	us2k¹ tfbs³		6		NA WA EA	364

HapMap Linkage Disequilibrium report for SMAD6 (66994566 - 67074338 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for SMAD6: --
Human Gene Mutation Database (HGMD): SMAD6

Locus Specific Mutation Databases (LSDB): SMAD6

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

SMAD6 for disorders About GeneDecksing

OMIM gene information: 602931 OMIM disorders: --

UniProtKB/Swiss-Prot: SMAD6_HUMAN, O43541

Defects in SMAD6 are the cause of aortic valve disease 2 (AOVD2) [MIM:614823]. A common defect in the aortic

valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification and

insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting

in hypoplastic left heart syndrome. Note=SMAD6 variants may contribute to increased risk of congenital cardiovascular

malformations (CVM). CVM is a major cause of mortality and morbidity in childhood. In most sporadic cases that cannot

be attributed to particular malformation syndromes or teratogenic exposures, there remains a substantial excess

familial risk, indicating a significant genetic contribution to disease susceptibility (PubMed:22275001)

20/30 diseases for SMAD6 (see all 30): About MalaCards

squamous cell carcinoma sickle cell anemia oral squamous cell carcinoma esophageal squamous cell carcinoma

adult t-cell leukemia leukemia/lymphoma lupus erythematosus hepatocellular carcinoma

hemochromatosis t-cell leukemia keloids pancreatic cancer

gastric adenocarcinoma carcinoma anemia hematopoiesis

thyroid carcinoma leukemia esophagitis pancreatitis

5 Novoseek disease relationships for SMAD6 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
pancreatic cancer	14.8	1	11135319 (1)
carcinoma squamous cell	0	2	15736400 (1), 14633701 (1)
renal disease	0	1	12397035 (1)
hepatocellular carcinoma	0	1	11408948 (1)
tumors	0	2	10942134 (1), 14633701 (1)

Human Genome Epidemiology (HuGE) Navigator: SMAD6 (9 documents)

Export disorders for SMAD6 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for SMAD6 gene, integrated from 9 sources (see all 162):
(articles sorted by number of sources associating them with SMAD6)

Utopia: connect your pdf to the dynamic
world of online information

Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. (PubMed id 9256479)^{1, 3, 9} Topper J.N.... Falb D. (1997)
Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads. (PubMed id 11483516)^{1, 2, 9} Itoh F.... Itoh S. (2001)
Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members. (PubMed id 9712726)^{1, 2, 9} Afrakhte M.... ten Dijke P. (1998)
Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1. (PubMed id 16951688)^{1, 2, 9} Choi K.C....Park S.H. (2006)
Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation. (PubMed id 22275001)^{1, 2} Tan H.L.... Keavney B.D. (2012)
Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation. (PubMed id 16491121)^{1, 2} Glesne D. and Huberman E. (2006)
Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. (PubMed id 16601693)^{1, 2} Liu W.... Lin S.-C. (2006)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Arkadia amplifies TGF-beta superfamily signaling through degradation of Smad7. (PubMed id 14657019)^{1, 2} Koinuma D.... Miyazono K. (2003)
TGF-beta signaling by Smad proteins. (PubMed id 10708949)^{1, 2} Miyazono K. (2000)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 4091	HGNC: 6772	AceView: SMAD6	Ensembl:ENSG00000137834	euGenes: HUgn4091
ECgene: SMAD6	Kegg: 4091	H-InvDB: SMAD6

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for SMAD6	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for SMAD6	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for SMAD6 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for SMAD6 gene:
Search GeneIP for patents involving SMAD6

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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