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

Gene ID: 4093, updated on 5-Mar-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
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Genomic context

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Location:
13q13.3
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (36844831..36920854, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (36064076..36139427, complement)
105.20220307 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. 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
  2. Absence of SMAD9(v90m) mutation in juvenile polyposis syndrome. Graafmans LDC, et al. J Clin Pathol, 2017 Jul. PMID 28424237
  3. Cloning and characterization of a novel member of the human Mad gene family (MADH6). Watanabe TK, et al. Genomics, 1997 Jun 15. PMID 9205116
  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. Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling. Tsukamoto S, et al. Sci Rep, 2014 Dec 23. PMID 25534700, Free PMC Article

See all (66) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Our results exclude a significant role for the SMAD9v90m mutation in juvenile polyposis syndrome
    Title: Absence of SMAD9(v90m) mutation in juvenile polyposis syndrome.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. a detailed computational model for TGF-beta signalling that incorporates elements of previous models together with crosstalking between Smad1/5/8 and Smad2/3 channels through a negative feedback loop dependent on Smad7.
    Title: Computational modelling of Smad-mediated negative feedback and crosstalk in the TGF-β superfamily network.
Submit: New GeneRIF Correction See all GeneRIFs (19)

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)

Genotypes

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 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 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 
part_of 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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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_2023_10

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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