The protein encoded by this gene is a member of the SMAD family, which transduces signals from TGF-beta family members. The encoded protein is activated by bone morphogenetic proteins and interacts with SMAD4. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010] See more...

Aliases for SMAD9 Gene

Aliases for SMAD9 Gene

  • SMAD Family Member 9 2 3 4 5
  • SMAD8 2 3 4
  • Mothers Against Decapentaplegic Homolog 9 3 4
  • MAD Homolog 9 3 4
  • SMAD8/9 2 3
  • MADH6 3 4
  • MADH9 3 4
  • MAD, Mothers Against Decapentaplegic Homolog 9 (Drosophila) 2
  • Mothers Against Decapentaplegic, Drosophila, Homolog Of, 9 3
  • SMAD, Mothers Against DPP Homolog 9 (Drosophila) 2
  • SMAD, Mothers Against DPP Homolog 9 3
  • Mothers Against DPP Homolog 9 4
  • SMAD8A 3
  • SMAD8B 3
  • SMAD 9 4
  • SMAD9 5
  • Madh6 4
  • Smad9 4
  • PPH2 3

External Ids for SMAD9 Gene

Previous HGNC Symbols for SMAD9 Gene

  • MADH6
  • MADH9

Previous GeneCards Identifiers for SMAD9 Gene

  • GC13M035221
  • GC13M036320
  • GC13M037418
  • GC13M018230

Summaries for SMAD9 Gene

Entrez Gene Summary for SMAD9 Gene

  • The protein encoded by this gene is a member of the SMAD family, which transduces signals from TGF-beta family members. The encoded protein is activated by bone morphogenetic proteins and interacts with SMAD4. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

GeneCards Summary for SMAD9 Gene

SMAD9 (SMAD Family Member 9) is a Protein Coding gene. Diseases associated with SMAD9 include Pulmonary Hypertension, Primary, 2 and Heritable Pulmonary Arterial Hypertension. 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 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity. An important paralog of this gene is SMAD1.

UniProtKB/Swiss-Prot Summary for SMAD9 Gene

  • Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD9 is a receptor-regulated SMAD (R-SMAD).

Gene Wiki entry for SMAD9 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SMAD9 Gene

Genomics for SMAD9 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SMAD9 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH13J036918 Promoter/Enhancer 2.2 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 628.1 +1.1 1085 3.6 PRDM10 FOXA1 RBFOX2 PATZ1 ZNF501 ZNF341 ZBTB20 TAF1 SP2 FOXA2 SMAD9 lnc-SMAD9-1 SERTM1 RFXAP piR-35568-002
GH13J036997 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 9.9 -79.3 -79335 5 ZNF221 SP1 HNRNPL GATAD2A CTCF TEAD4 PRDM10 REST ZNF629 TFE3 EXOSC8 ALG5 lnc-ALG5-1 RFXAP SUPT20H SPART-AS1 SMAD9 CSNK1A1L lnc-ALG5-2
GH13J036858 Enhancer 0.8 Ensembl ENCODE 18.4 +63.0 63043 1.8 CTCF PKNOX1 RXRB REST RAD21 CEBPA SMC3 ZFHX2 ZNF654 ZNF660 SMAD9 LAMTOR3P1 RFXAP CCNA1 SERTM1 SUPT20H piR-35568-002 SMAD9-IT1
GH13J036862 Enhancer 0.7 Ensembl 15.9 +58.4 58364 1.2 TEAD4 DDX20 ZNF740 ESR1 MEF2D NR2F2 GTF2A2 TFDP1 HDAC8 STAT1 piR-35568-002 RFXAP EXOSC8 SMAD9 LAMTOR3P1 SPART-AS1 SMAD9-IT1
GH13J036865 Enhancer 0.8 Ensembl 10.5 +52.3 52264 5.8 GATAD2A RCOR2 RXRB IRF2 CEBPA SOX13 TCF7 ZNF10 CTBP1 ZKSCAN8 RFXAP EXOSC8 SMAD9 SPART-AS1 piR-35568-002 lnc-SMAD9-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SMAD9 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SMAD9

Top Transcription factor binding sites by QIAGEN in the SMAD9 gene promoter:
  • AML1a
  • FOXI1
  • FOXO1
  • FOXO1a
  • GATA-6
  • HFH-3
  • Lmo2
  • SRY
  • YY1

Genomic Locations for SMAD9 Gene

Genomic Locations for SMAD9 Gene
chr13:36,844,831-36,920,765
(GRCh38/hg38)
Size:
75,935 bases
Orientation:
Minus strand
chr13:37,418,968-37,494,902
(GRCh37/hg19)
Size:
75,935 bases
Orientation:
Minus strand

Genomic View for SMAD9 Gene

Genes around SMAD9 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMAD9 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SMAD9 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMAD9 Gene

Proteins for SMAD9 Gene

  • Protein details for SMAD9 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15198-SMAD9_HUMAN
    Recommended name:
    Mothers against decapentaplegic homolog 9
    Protein Accession:
    O15198
    Secondary Accessions:
    • A2A2Y6
    • O14989
    • Q5TBA1

    Protein attributes for SMAD9 Gene

    Size:
    467 amino acids
    Molecular mass:
    52493 Da
    Quaternary structure:
    • Interaction with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit. Interacts with RANBP3L (PubMed:25755279).

    Three dimensional structures from OCA and Proteopedia for SMAD9 Gene

    Alternative splice isoforms for SMAD9 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SMAD9 Gene

Post-translational modifications for SMAD9 Gene

  • Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.
  • Ubiquitination at Lys159
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SMAD9 Gene

Domains & Families for SMAD9 Gene

Gene Families for SMAD9 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for SMAD9 Gene

Suggested Antigen Peptide Sequences for SMAD9 Gene

GenScript: Design optimal peptide antigens:
  • SMAD family member 9 (SMAD9_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O15198

UniProtKB/Swiss-Prot:

SMAD9_HUMAN :
  • Belongs to the dwarfin/SMAD family.
Family:
  • Belongs to the dwarfin/SMAD family.
genes like me logo Genes that share domains with SMAD9: view

Function for SMAD9 Gene

Molecular function for SMAD9 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD9 is a receptor-regulated SMAD (R-SMAD).

Phenotypes From GWAS Catalog for SMAD9 Gene

Gene Ontology (GO) - Molecular Function for SMAD9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding TAS 25534700
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISM 19274049
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IEA --
GO:0005515 protein binding IPI 16189514
genes like me logo Genes that share ontologies with SMAD9: view
genes like me logo Genes that share phenotypes with SMAD9: view

Human Phenotype Ontology for SMAD9 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SMAD9 Gene

MGI Knock Outs for SMAD9:

Animal Model Products

  • Taconic Biosciences Mouse Models for SMAD9

CRISPR Products

miRNA for SMAD9 Gene

miRTarBase miRNAs that target SMAD9

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SMAD9

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SMAD9 Gene

Localization for SMAD9 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMAD9 Gene

Cytoplasm. Nucleus. Note=In the cytoplasm in the absence of ligand. Migration to the nucleus when complexed with SMAD4 (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SMAD9 gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SMAD9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005622 intracellular TAS --
GO:0005634 nucleus IEA,TAS 19018011
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IEA --
genes like me logo Genes that share ontologies with SMAD9: view

Pathways & Interactions for SMAD9 Gene

PathCards logo

SuperPathways for SMAD9 Gene

genes like me logo Genes that share pathways with SMAD9: view

Pathways by source for SMAD9 Gene

7 Qiagen pathways for SMAD9 Gene
  • BMP Pathway
  • Cardiomyocyte Differentiation through BMP Receptors
  • Factors Promoting Cardiogenesis in Vertebrates
  • JAK-STAT Pathway
  • Molecular Mechanisms of Cancer
1 Cell Signaling Technology pathway for SMAD9 Gene
1 GeneTex pathway for SMAD9 Gene

SIGNOR curated interactions for SMAD9 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for SMAD9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0007179 transforming growth factor beta receptor signaling pathway IEA --
GO:0030509 BMP signaling pathway TAS 19018011
GO:0060395 SMAD protein signal transduction NAS 14687659
GO:0071773 cellular response to BMP stimulus NAS 14687659
genes like me logo Genes that share ontologies with SMAD9: view

Drugs & Compounds for SMAD9 Gene

No Compound Related Data Available

Transcripts for SMAD9 Gene

mRNA/cDNA for SMAD9 Gene

3 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SMAD9

Alternative Splicing Database (ASD) splice patterns (SP) for SMAD9 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b
SP1: -
SP2:

Relevant External Links for SMAD9 Gene

GeneLoc Exon Structure for
SMAD9

Expression for SMAD9 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SMAD9 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SMAD9 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SMAD9

SOURCE GeneReport for Unigene cluster for SMAD9 Gene:

Hs.123119

mRNA Expression by UniProt/SwissProt for SMAD9 Gene:

O15198-SMAD9_HUMAN
Tissue specificity: Expressed in heart, brain, placenta, lung, skeletal muscle, prostate, testis, ovary and small intestine. Also expressed in fetal brain, lung and kidney.

Evidence on tissue expression from TISSUES for SMAD9 Gene

  • Nervous system(4.6)
  • Eye(4.5)
  • Kidney(2.9)
  • Muscle(2.8)
  • Heart(2.7)
  • Blood(2.7)
  • Skin(2.6)
  • Thyroid gland(2.6)
  • Intestine(2.5)
  • Liver(2.4)
  • Lung(2.3)
  • Bone marrow(2.2)
  • Bone(2.2)
  • Pancreas(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SMAD9 Gene

Germ Layers:
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • respiratory
Regions:
Head and neck:
  • ear
Thorax:
  • heart
  • lung
General:
  • blood
  • blood vessel
genes like me logo Genes that share expression patterns with SMAD9: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Protein tissue co-expression partners for SMAD9 Gene

Orthologs for SMAD9 Gene

This gene was present in the common ancestor of animals.

Orthologs for SMAD9 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SMAD9 30 31
  • 99.36 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SMAD9 31
  • 92 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SMAD9 31
  • 92 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia SMAD9 30 31
  • 91.12 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SMAD9 30 31
  • 90.51 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Smad9 30
  • 87.52 (n)
Mouse
(Mus musculus)
Mammalia Smad9 30 17 31
  • 86.98 (n)
OneToOne
Chicken
(Gallus gallus)
Aves SMAD9 30 31
  • 81.08 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SMAD9 31
  • 86 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia smad9 30
  • 77.28 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC69016 30
Zebrafish
(Danio rerio)
Actinopterygii smad9 30 31
  • 74.96 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Mad 31
  • 63 (a)
ManyToMany
Worm
(Caenorhabditis elegans)
Secernentea sma-2 30 31
  • 56.72 (n)
OneToMany
Species where no ortholog for SMAD9 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for SMAD9 Gene

ENSEMBL:
Gene Tree for SMAD9 (if available)
TreeFam:
Gene Tree for SMAD9 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SMAD9: view image

Paralogs for SMAD9 Gene

Paralogs for SMAD9 Gene

(7) SIMAP similar genes for SMAD9 Gene using alignment to 1 proteins:

  • SMAD9_HUMAN
genes like me logo Genes that share paralogs with SMAD9: view

Variants for SMAD9 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SMAD9 Gene

SNP ID Clinical significance and condition Chr 13 pos Variation AA Info Type
672486 Benign: not provided 36,865,827(-) C/A INTRON_VARIANT
675286 Benign: not provided 36,848,895(-) G/A INTRON_VARIANT
680403 Likely Benign: not provided 36,853,402(-) T/G INTRON_VARIANT
683862 Benign: not provided 36,866,009(-) T/C INTRON_VARIANT
711581 Likely Benign: not provided 36,867,369(-) G/A SYNONYMOUS_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for SMAD9 Gene

Structural Variations from Database of Genomic Variants (DGV) for SMAD9 Gene

Variant ID Type Subtype PubMed ID
esv3303892 CNV mobile element insertion 20981092
esv3443934 CNV insertion 20981092
esv3631788 CNV loss 21293372
esv3631790 CNV loss 21293372
esv3892329 CNV loss 25118596
esv3892330 CNV gain 25118596
nsv1006 CNV insertion 18451855
nsv1070584 CNV deletion 25765185
nsv1145659 CNV deletion 24896259
nsv522336 CNV gain 19592680
nsv64081 CNV deletion 16902084

Variation tolerance for SMAD9 Gene

Residual Variation Intolerance Score: 25.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.48; 28.94% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SMAD9 Gene

Human Gene Mutation Database (HGMD)
SMAD9
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SMAD9

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMAD9 Gene

Disorders for SMAD9 Gene

MalaCards: The human disease database

(35) MalaCards diseases for SMAD9 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
pulmonary hypertension, primary, 2
  • pph2
heritable pulmonary arterial hypertension
  • familial pulmonary arterial hypertension
pulmonary hypertension
  • primary pulmonary hypertension
pulmonary arterial hypertension associated with congenital heart disease
  • pah associated with congenital heart disease
juvenile polyposis syndrome
  • jps
- elite association - COSMIC cancer census association via MalaCards
Search SMAD9 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SMAD9_HUMAN
  • Pulmonary hypertension, primary, 2 (PPH2) [MIM:615342]: A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs. {ECO:0000269 PubMed:21898662}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Additional Disease Information for SMAD9

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with SMAD9: view

No data available for Genatlas for SMAD9 Gene

Publications for SMAD9 Gene

  1. Cloning and characterization of a novel member of the human Mad gene family (MADH6). (PMID: 9205116) Watanabe TK … Takahashi E (Genomics 1997) 2 3 4
  2. Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation. (PMID: 25755279) Chen F … Feng XH (Molecular and cellular biology 2015) 3 4
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  5. The Smad pathway. (PMID: 10708948) Wrana JL … Attisano L (Cytokine & growth factor reviews 2000) 3 4

Products for SMAD9 Gene

  • Signalway ELISA kits for SMAD9

Sources for SMAD9 Gene