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    SMAD9 SMAD family member 9 [ Homo sapiens (human) ]

    Gene ID: 4093, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SMAD9provided by HGNC
    Official Full Name
    SMAD family member 9provided by HGNC
    Primary source
    HGNC:HGNC:6774
    See related
    Ensembl:ENSG00000120693 MIM:603295; AllianceGenome:HGNC:6774
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PPH2; MADH6; MADH9; SMAD8; SMAD8A; SMAD8B; SMAD8/9
    Summary
    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]
    Expression
    Broad expression in thyroid (RPKM 18.3), prostate (RPKM 5.8) and 17 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SMAD9 in Genome Data Viewer
    Location:
    13q13.3
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (36844831..36920854, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (36064076..36139427, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (37418968..37494375, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903158 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5267 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7589 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7590 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:37396223-37396437 Neighboring gene regulatory factor X associated protein Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:37414257-37414991 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:37453240-37453740 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5268 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5269 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:37500289-37500790 Neighboring gene late endosomal/lysosomal adaptor, MAPK and MTOR activator 3 pseudogene 1 Neighboring gene ribosomal protein L29 pseudogene 28

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Cloning and characterization of a novel member of the human Mad gene family (MADH6). Watanabe TK, et al. Genomics, 1997 Jun 15. PMID 9205116
    2. Absence of SMAD9(v90m) mutation in juvenile polyposis syndrome. Graafmans LDC, et al. J Clin Pathol, 2017 Jul. PMID 28424237
    3. A Rare Mutation in SMAD9 Associated With High Bone Mass Identifies the SMAD-Dependent BMP Signaling Pathway as a Potential Anabolic Target for Osteoporosis. Gregson CL, et al. J Bone Miner Res, 2020 Jan. PMID 31525280, Free PMC Article
    4. Exome Sequencing Reveals Germline SMAD9 Mutation That Reduces Phosphatase and Tensin Homolog Expression and Is Associated With Hamartomatous Polyposis and Gastrointestinal Ganglioneuromas. Ngeow J, et al. Gastroenterology, 2015 Oct. PMID 26122142
    5. CREBZF, a novel Smad8-binding protein. Lee JH, et al. Mol Cell Biochem, 2012 Sep. PMID 22707059

    See all (74) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Long noncoding RNA BMPR1B-AS1 stability regulated by IGF2BP2 affects the decidualization in endometriosis patients through the SMAD1/5/9 pathway.
      Title: Long noncoding RNA BMPR1B-AS1 stability regulated by IGF2BP2 affects the decidualization in endometriosis patients through the SMAD1/5/9 pathway.
    2. Secreted phosphoprotein 24 kD (Spp24) inhibits the growth of human osteosarcoma through the BMP-2/Smad signaling pathway.
      Title: Secreted phosphoprotein 24 kD (Spp24) inhibits the growth of human osteosarcoma through the BMP-2/Smad signaling pathway.
    3. A Rare Mutation in SMAD9 Associated With High Bone Mass Identifies the SMAD-Dependent BMP Signaling Pathway as a Potential Anabolic Target for Osteoporosis.
      Title: A Rare Mutation in SMAD9 Associated With High Bone Mass Identifies the SMAD-Dependent BMP Signaling Pathway as a Potential Anabolic Target for Osteoporosis.
    4. Cyclic AMP appears to promote SMAD1/5/8 pathway activity intracellularly and has the ability to activate canonical SMAD1/5/8 downstream targets.
      Title: Non-canonical cyclic AMP SMAD1/5/8 signalling in human granulosa cells.
    5. The SNPs of the rs6435156 and rs1048829 locus in the BMPR2 gene, the rs121909287 loci in the ACVRL1 gene, and the rs397514716 locus in the SMAD9 gene were associated with a risk of essential hypertension (EH) in Han Chinese.
      Title: Association of the gene polymorphisms of BMPR2, ACVRL1, SMAD9 and their interactions with the risk of essential hypertension in the Chinese Han population.
    6. Our results exclude a significant role for the SMAD9v90m mutation in juvenile polyposis syndrome
      Title: Absence of SMAD9(v90m) mutation in juvenile polyposis syndrome.
    7. Differential expression of TGF-beta superfamily members and role of Smad1/5/9-signalling in chondral versus endochondral chondrocyte differentiation.
      Title: Differential expression of TGF-β superfamily members and role of Smad1/5/9-signalling in chondral versus endochondral chondrocyte differentiation.
    8. Mutations in SMAD9 gene encoding for transforming growth factor (TGF)-[beta] superfamily have been identified in Pulmonary Arterial Hypertension.
      Title: New targets for pulmonary arterial hypertension: going beyond the currently targeted three pathways.
    9. Phosphorylated Smad1/5/8/9 specifically bound to the BREs of Smad8/9 gene. The present study reveals that Smad8/9 is a unique R-Smad regulated through the BMP pathway at the mRNA level.
      Title: Smad8/9 Is Regulated Through the BMP Pathway.
    10. Case Report: hamartomatous olyposis and gastrointestinal ganglioneuromas with SMAD9 germline mutation that reduces PTEN expression.
      Title: Exome Sequencing Reveals Germline SMAD9 Mutation That Reduces Phosphatase and Tensin Homolog Expression and Is Associated With Hamartomatous Polyposis and Gastrointestinal Ganglioneuromas.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat-treated pulmonary arterial smooth muscle cells modulate levels of phosphorylated SMAD1/5/8 proteins and SMAD1/5/8-SMAD4 protein complex, which are repressed by cocaine exposure PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables I-SMAD binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in BMP signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in BMP signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in BMP signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in SMAD protein signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in SMAD protein signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in SMAD protein signal transduction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in anatomical structure morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to BMP stimulus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in osteoblast differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in stem cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in transforming growth factor beta receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    part_of SMAD protein complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    part_of heteromeric SMAD protein complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    mothers against decapentaplegic homolog 9
    Names
    MAD homolog 9
    Mothers against decapentaplegic, drosophila, homolog of, 9
    SMAD, mothers against DPP homolog 9
    NP_001120689.1
    NP_001365550.1
    NP_005896.1
    XP_005266460.1
    XP_005266461.1
    XP_006719890.1
    XP_047286310.1
    XP_047286311.1
    XP_047286312.1
    XP_047286313.1
    XP_047286314.1
    XP_047286315.1
    XP_047286316.1
    XP_047286317.1
    XP_047286318.1
    XP_047286319.1
    XP_047286320.1
    XP_047286321.1
    XP_047286322.1
    XP_047286323.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016963.1 RefSeqGene

      Range
      5001..80442
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_703

    mRNA and Protein(s)

    1. NM_001127217.3 → NP_001120689.1  mothers against decapentaplegic homolog 9 isoform a

      See identical proteins and their annotated locations for NP_001120689.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a) represents the longer transcript and encodes the longer isoform (a).
      Source sequence(s)
      AL138706, BC011559, CN291481, D83760
      Consensus CDS
      CCDS45032.1
      UniProtKB/Swiss-Prot
      A2A2Y6, O14989, O15198, Q5TBA1
      Related
      ENSP00000369154.4, ENST00000379826.5
      Conserved Domains (2) summary
      cd10490
      Location:13 → 136
      MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
      cl00056
      Location:267 → 467
      MH2; C-terminal Mad Homology 2 (MH2) domain

    2. NM_001378621.1 → NP_001365550.1  mothers against decapentaplegic homolog 9 isoform b

      Status: REVIEWED

      Source sequence(s)
      AL138706
      Consensus CDS
      CCDS9360.1
      Conserved Domains (2) summary
      cd10490
      Location:13 → 136
      MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
      cl00056
      Location:230 → 430
      MH2; C-terminal Mad Homology 2 (MH2) domain

    3. NM_005905.6 → NP_005896.1  mothers against decapentaplegic homolog 9 isoform b

      See identical proteins and their annotated locations for NP_005896.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (b) lacks an alternate in-frame exon, compared to variant a, resulting in a shorter protein (isoform b), compared to isoform a.
      Source sequence(s)
      AL138706, BC011559, CN291481
      Consensus CDS
      CCDS9360.1
      Related
      ENSP00000239885.6, ENST00000350148.10
      Conserved Domains (2) summary
      cd10490
      Location:13 → 136
      MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
      cl00056
      Location:230 → 430
      MH2; C-terminal Mad Homology 2 (MH2) domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      36844831..36920854 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006719827.4 → XP_006719890.1  mothers against decapentaplegic homolog 9 isoform X1

      Conserved Domains (2) summary
      cd10490
      Location:13 → 136
      MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
      cl00056
      Location:267 → 420
      MH2; C-terminal Mad Homology 2 (MH2) domain

    2. XM_047430366.1 → XP_047286322.1  mothers against decapentaplegic homolog 9 isoform X8

    3. XM_005266404.4 → XP_005266461.1  mothers against decapentaplegic homolog 9 isoform X7

      Conserved Domains (2) summary
      cd10490
      Location:13 → 136
      MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
      cl00056
      Location:144 → 297
      MH2; C-terminal Mad Homology 2 (MH2) domain

    4. XM_047430365.1 → XP_047286321.1  mothers against decapentaplegic homolog 9 isoform X6

    5. XM_005266403.4 → XP_005266460.1  mothers against decapentaplegic homolog 9 isoform X5

      Conserved Domains (2) summary
      cd10490
      Location:13 → 136
      MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
      cl00056
      Location:181 → 334
      MH2; C-terminal Mad Homology 2 (MH2) domain

    6. XM_047430361.1 → XP_047286317.1  mothers against decapentaplegic homolog 9 isoform X3

    7. XM_047430354.1 → XP_047286310.1  mothers against decapentaplegic homolog 9 isoform X1

    8. XM_047430367.1 → XP_047286323.1  mothers against decapentaplegic homolog 9 isoform X8

    9. XM_047430362.1 → XP_047286318.1  mothers against decapentaplegic homolog 9 isoform X3

    10. XM_047430357.1 → XP_047286313.1  mothers against decapentaplegic homolog 9 isoform X2

      UniProtKB/Swiss-Prot
      A2A2Y6, O14989, O15198, Q5TBA1

    11. XM_047430356.1 → XP_047286312.1  mothers against decapentaplegic homolog 9 isoform X1

    12. XM_047430358.1 → XP_047286314.1  mothers against decapentaplegic homolog 9 isoform X2

      UniProtKB/Swiss-Prot
      A2A2Y6, O14989, O15198, Q5TBA1

    13. XM_047430363.1 → XP_047286319.1  mothers against decapentaplegic homolog 9 isoform X4

    14. XM_047430355.1 → XP_047286311.1  mothers against decapentaplegic homolog 9 isoform X1

    15. XM_047430364.1 → XP_047286320.1  mothers against decapentaplegic homolog 9 isoform X4

    16. XM_047430359.1 → XP_047286315.1  mothers against decapentaplegic homolog 9 isoform X2

      UniProtKB/Swiss-Prot
      A2A2Y6, O14989, O15198, Q5TBA1

    17. XM_047430360.1 → XP_047286316.1  mothers against decapentaplegic homolog 9 isoform X2

      UniProtKB/Swiss-Prot
      A2A2Y6, O14989, O15198, Q5TBA1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      36064076..36139427 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O15198.1 GenPept UniProtKB/Swiss-Prot:O15198

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