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Aliases for SMAD4 Gene

Aliases for SMAD4 Gene

  • SMAD Family Member 4 2 3 4 5
  • Deletion Target In Pancreatic Carcinoma 4 3 4
  • MAD Homolog 4 3 4
  • MADH4 3 4
  • DPC4 3 4
  • MAD, Mothers Against Decapentaplegic Homolog 4 (Drosophila) 2
  • Mothers Against Decapentaplegic, Drosophila, Homolog Of, 4 3
  • SMAD, Mothers Against DPP Homolog 4 (Drosophila) 2
  • Mothers Against Decapentaplegic Homolog 4 3
  • Deleted In Pancreatic Carcinoma Locus 4 3
  • SMAD, Mothers Against DPP Homolog 4 3
  • Mothers Against DPP Homolog 4 4
  • SMAD 4 4
  • HSMAD4 4
  • MYHRS 3
  • Smad4 4
  • JIP 3

External Ids for SMAD4 Gene

Previous HGNC Symbols for SMAD4 Gene

  • MADH4

Previous GeneCards Identifiers for SMAD4 Gene

  • GC18P046809
  • GC18P046810
  • GC18P048556
  • GC18P045411
  • GC18P048494

Summaries for SMAD4 Gene

Entrez Gene Summary for SMAD4 Gene

  • This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to TGF-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Oct 2009]

GeneCards Summary for SMAD4 Gene

SMAD4 (SMAD Family Member 4) is a Protein Coding gene. Diseases associated with SMAD4 include Polyposis, Juvenile Intestinal and Juvenile Polyposis/Hereditary Hemorrhagic Telangiectasia Syndrome. Among its related pathways are Regulation of nuclear SMAD2/3 signaling and DREAM Repression and Dynorphin Expression. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and sequence-specific DNA binding. An important paralog of this gene is SMAD2.

UniProtKB/Swiss-Prot for SMAD4 Gene

  • In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5-GTCT/AGAC-3) within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.

Gene Wiki entry for SMAD4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SMAD4 Gene

Genomics for SMAD4 Gene

Regulatory Elements for SMAD4 Gene

Enhancers for SMAD4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH18F051189 1.8 FANTOM5 Ensembl ENCODE 86.4 +166.2 166167 9.4 HDGF PKNOX1 CREB3L1 WRNIP1 ZFP64 ARID4B SIN3A FEZF1 DMAP1 ZNF2 SMAD4 MEX3C ELAC1 LOC105372118 PIR40243
GH18F050277 0.2 ENCODE 47.1 -748.5 -748526 5.4 HDGF PKNOX1 ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 ZNF302 SMAD4 RPL17 CXXC1 CFAP53 MBD1
GH18F050283 0.4 ENCODE 43.1 -742.2 -742239 5.0 HDGF PKNOX1 CREB3L1 ZFP64 ARID4B SIN3A DMAP1 YY1 ZNF143 ZNF207 RPL17 SMAD4 ELAC1 CXXC1 CFAP53 MBD1
GH18F050239 0.2 ENCODE 42.4 -788.0 -787969 1.8 ZSCAN5A KLF1 JUN ZNF223 INSM2 KLF17 HIC1 ZNF791 ZNF366 RBAK SMAD4 RPL17 CFAP53 MEX3C DYM SKA1 CXXC1 ENSG00000277310 RN7SL310P
GH18F051034 1.1 Ensembl ENCODE 18.1 +10.5 10507 9.0 ATF1 PKNOX1 MLX ZFP64 ARID4B ZNF48 YY1 ZNF766 GLIS2 ZNF548 ME2 SMAD4 RPL17P46 MRO LOC105372117 GC18M051107
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around SMAD4 on UCSC Golden Path with GeneCards custom track

Genomic Location for SMAD4 Gene

Chromosome:
18
Start:
51,028,394 bp from pter
End:
51,085,045 bp from pter
Size:
56,652 bases
Orientation:
Plus strand

Genomic View for SMAD4 Gene

Genes around SMAD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMAD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SMAD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMAD4 Gene

Proteins for SMAD4 Gene

  • Protein details for SMAD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13485-SMAD4_HUMAN
    Recommended name:
    Mothers against decapentaplegic homolog 4
    Protein Accession:
    Q13485
    Secondary Accessions:
    • A8K405

    Protein attributes for SMAD4 Gene

    Size:
    552 amino acids
    Molecular mass:
    60439 Da
    Quaternary structure:
    • Found in a complex with SMAD1 and YY1 (By similarity). Interacts with CITED2 (By similarity). Monomer; in the absence of TGF-beta activation. Heterodimer; on TGF-beta activation. Composed of two molecules of a C-terminally phosphorylated R-SMAD molecule, SMAD2 or SMAD3, and one molecule of SMAD4 to form the transcriptional active SMAD2/SMAD3-SMAD4 complex. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11/LKB1, STK11IP and TRIM33. Interacts with ZNF423; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with ZNF521; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with USP9X. Interacts (via the MH1 and MH2 domains) with RBPMS. Interacts with WWTR1 (via coiled-coil domain). Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. Interacts with CITED1. Interacts with PDPK1 (via PH domain) (By similarity). Interacts with VPS39; this interaction affects heterodimer formation with SMAD3, but not with SMAD2, and leads to inhibition of SMAD3-dependent transcription activation. Interactions with VPS39 and SMAD2 may be mutually exclusive. Interacts with ZC3H3 (By similarity). Interacts (via MH2 domain) with ZNF451 (via N-terminal zinc-finger domains) (PubMed:24324267). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts weakly with ZNF8 (PubMed:12370310). Interacts with NUP93 and IPO7; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling (PubMed:26878725). Interacts with CREB3L1, the interaction takes place upon TGFB1 induction and SMAD4 acts as CREB3L1 coactivator to induce the expression of genes involved in the assembly of collagen extracellular matrix (PubMed:25310401).

    Three dimensional structures from OCA and Proteopedia for SMAD4 Gene

neXtProt entry for SMAD4 Gene

Post-translational modifications for SMAD4 Gene

  • Monoubiquitinated on Lys-519 by E3 ubiquitin-protein ligase TRIM33. Monoubiquitination hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiqitination by USP9X restores its competence to mediate TGF-beta signaling.
  • Phosphorylated by PDPK1.
  • Ubiquitination at Lys 113 and Lys 519
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for SMAD4 (SMAD4)
  • Cloud-Clone Corp. Antibodies for SMAD4

No data available for DME Specific Peptides for SMAD4 Gene

Domains & Families for SMAD4 Gene

Gene Families for SMAD4 Gene

Suggested Antigen Peptide Sequences for SMAD4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q13485

UniProtKB/Swiss-Prot:

SMAD4_HUMAN :
  • The MH1 domain is required for DNA binding.
  • Belongs to the dwarfin/SMAD family.
Domain:
  • The MH1 domain is required for DNA binding.
  • The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import.
  • Contains 1 MH1 (MAD homology 1) domain.
  • Contains 1 MH2 (MAD homology 2) domain.
Family:
  • Belongs to the dwarfin/SMAD family.
genes like me logo Genes that share domains with SMAD4: view

Function for SMAD4 Gene

Molecular function for SMAD4 Gene

UniProtKB/Swiss-Prot Function:
In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5-GTCT/AGAC-3) within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.

Gene Ontology (GO) - Molecular Function for SMAD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IEA --
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IDA 9389648
GO:0000987 core promoter proximal region sequence-specific DNA binding IDA 18832382
GO:0000988 contributes_to transcription factor activity, protein binding IDA 18832382
GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding IEA --
genes like me logo Genes that share ontologies with SMAD4: view
genes like me logo Genes that share phenotypes with SMAD4: view

Human Phenotype Ontology for SMAD4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SMAD4 Gene

MGI Knock Outs for SMAD4:

Animal Model Products

miRNA for SMAD4 Gene

miRTarBase miRNAs that target SMAD4
Targeted motifs for SMAD4 Gene
HOMER Transcription Factor Regulatory Elements motif SMAD4
  • Consensus sequence: VBSYGTCTGG Submotif: canonical Cell Type: ESC GEO ID: GSE29422

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for SMAD4

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targets for SMAD4 Gene

Localization for SMAD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMAD4 Gene

Cytoplasm. Nucleus. Note=Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD (PubMed:15799969). PDPK1 prevents its nuclear translocation in response to TGF-beta (PubMed:17327236). {ECO:0000269 PubMed:15799969, ECO:0000269 PubMed:17327236}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SMAD4 Gene COMPARTMENTS Subcellular localization image for SMAD4 gene
Compartment Confidence
cytosol 5
nucleus 5
cytoskeleton 4
extracellular 2
plasma membrane 2

Gene Ontology (GO) - Cellular Components for SMAD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA 21828274
GO:0005622 intracellular IEA --
GO:0005634 nucleus IDA 9311995
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IDA,IPI 12374795
genes like me logo Genes that share ontologies with SMAD4: view

Pathways & Interactions for SMAD4 Gene

genes like me logo Genes that share pathways with SMAD4: view

SIGNOR curated interactions for SMAD4 Gene

Gene Ontology (GO) - Biological Process for SMAD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter TAS --
GO:0001541 ovarian follicle development IEA --
GO:0001658 branching involved in ureteric bud morphogenesis IEA --
GO:0001666 response to hypoxia IMP 12411310
GO:0001701 in utero embryonic development IEA --
genes like me logo Genes that share ontologies with SMAD4: view

Drugs & Compounds for SMAD4 Gene

(31) Drugs for SMAD4 Gene - From: ClinicalTrials, ApexBio, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Capecitabine Approved, Investigational Pharma RNA processing inhibitor and thymidylate synthase inhibitor, F-pyrimidines 1296
Gemcitabine Approved Pharma Ribonucleotide reductase and DNA synthesis inhibitor, Nucleoside Analogs 1974
Paclitaxel Approved, Vet_approved Pharma Tubulin and Bcl2 inhibitor, Taxanes 2758
Pirfenidone Investigational Pharma TGF-β production inhibitor, Antifibrotic agent; regulates cytokine levels in vivo 49
Albumin-Bound Paclitaxel Pharma 2757

(14) Additional Compounds for SMAD4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(4) ApexBio Compounds for SMAD4 Gene

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
genes like me logo Genes that share compounds with SMAD4: view

Transcripts for SMAD4 Gene

Unigene Clusters for SMAD4 Gene

SMAD family member 4:
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for SMAD4

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SMAD4 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b · 7c ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17
SP1: - - - -
SP2: - -
SP3: - - - - -
SP4:
SP5:
SP6: - - - -
SP7: - - -
SP8: -
SP9:
SP10: - -

Relevant External Links for SMAD4 Gene

GeneLoc Exon Structure for
SMAD4
ECgene alternative splicing isoforms for
SMAD4

Expression for SMAD4 Gene

mRNA expression in normal human tissues for SMAD4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SMAD4 Gene

This gene is overexpressed in Ovary (12.2), Liver (7.3), and Peripheral blood mononuclear cells (6.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SMAD4 Gene



Protein tissue co-expression partners for SMAD4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of SMAD4 Gene:

SMAD4

SOURCE GeneReport for Unigene cluster for SMAD4 Gene:

Hs.75862
genes like me logo Genes that share expression patterns with SMAD4: view

Primer Products

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for SMAD4 Gene

Orthologs for SMAD4 Gene

This gene was present in the common ancestor of animals.

Orthologs for SMAD4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SMAD4 34 35
  • 99.76 (n)
dog
(Canis familiaris)
Mammalia MADH4 35
  • 99 (a)
OneToOne
SMAD4 34
  • 95.65 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 97 (a)
OneToMany
-- 35
  • 95 (a)
OneToMany
cow
(Bos Taurus)
Mammalia SMAD4 34 35
  • 95.05 (n)
oppossum
(Monodelphis domestica)
Mammalia -- 35
  • 93 (a)
OneToMany
-- 35
  • 65 (a)
OneToMany
mouse
(Mus musculus)
Mammalia Smad4 34 16 35
  • 91.53 (n)
rat
(Rattus norvegicus)
Mammalia Smad4 34
  • 91.06 (n)
chicken
(Gallus gallus)
Aves SMAD7A 35
  • 26 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia SMAD4 35
  • 96 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia smad4.1 34
  • 77.21 (n)
Str.8149 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.885 34
zebrafish
(Danio rerio)
Actinopterygii smad4 35
  • 99 (a)
OneToMany
SMAD4 (6 of 6) 35
  • 97 (a)
OneToMany
SMAD4 (5 of 6) 35
  • 79 (a)
OneToMany
zmp:0000000768 34
  • 73.66 (n)
CT955987.1 35
  • 72 (a)
OneToMany
SMAD4 (3 of 6) 35
  • 71 (a)
OneToMany
SMAD4 (4 of 6) 35
  • 69 (a)
OneToMany
madh4 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2009 34
fruit fly
(Drosophila melanogaster)
Insecta Med 34 35
  • 60.45 (n)
worm
(Caenorhabditis elegans)
Secernentea sma-4 35
  • 36 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8788 35
  • 55 (a)
OneToOne
Species where no ortholog for SMAD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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 SMAD4 Gene

ENSEMBL:
Gene Tree for SMAD4 (if available)
TreeFam:
Gene Tree for SMAD4 (if available)

Paralogs for SMAD4 Gene

Paralogs for SMAD4 Gene

genes like me logo Genes that share paralogs with SMAD4: view

Variants for SMAD4 Gene

Sequence variations from dbSNP and Humsavar for SMAD4 Gene

SNP ID Clin Chr 18 pos Sequence Context AA Info Type
rs121912581 Juvenile polyposis syndrome (JPS) [MIM:174900], Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT) [MIM:175050], Pathogenic 51,065,521(+) TTGAT(A/G)GATAC reference, missense
rs281875320 Myhre syndrome (MYHRS) [MIM:139210], Pathogenic 51,078,308(+) TGCAT(A/G)CTCAG reference, missense
rs281875321 Myhre syndrome (MYHRS) [MIM:139210], Pathogenic 51,078,307(+) ATGCA(C/T)ACTCA reference, missense
rs281875322 Myhre syndrome (MYHRS) [MIM:139210], Pathogenic 51,078,306(+) TATGC(A/G)TACTC reference, missense
rs281875324 Juvenile polyposis syndrome (JPS) [MIM:174900], Pathogenic 51,065,456(+) CTTTG(A/G)AATGG reference, missense

Structural Variations from Database of Genomic Variants (DGV) for SMAD4 Gene

Variant ID Type Subtype PubMed ID
esv3342561 CNV insertion 20981092
esv3583062 CNV loss 25503493

Variation tolerance for SMAD4 Gene

Residual Variation Intolerance Score: 23.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.54; 11.75% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SMAD4 Gene

Human Gene Mutation Database (HGMD)
SMAD4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SMAD4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMAD4 Gene

Disorders for SMAD4 Gene

MalaCards: The human disease database

(48) MalaCards diseases for SMAD4 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
polyposis, juvenile intestinal
  • juvenile polyposis syndrome, infantile form
juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
  • jp/hht syndrome
myhre syndrome
  • facial dysmorphism - intellectual deficit - short stature - hearing loss
pancreatic cancer
  • pancreatic carcinoma, somatic
hereditary hemorrhagic telangiectasia
  • osler hemorrhagic telangiectasia syndrome
- elite association - COSMIC cancer census association via MalaCards
Search SMAD4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SMAD4_HUMAN
  • Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269 PubMed:16959974}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
  • Juvenile polyposis syndrome (JPS) [MIM:174900]: Autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers. {ECO:0000269 PubMed:12417513, ECO:0000269 PubMed:9811934}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT) [MIM:175050]: JP/HHT syndrome phenotype consists of the coexistence of juvenile polyposis (JIP) and hereditary hemorrhagic telangiectasia (HHT) [MIM:187300] in a single individual. JIP and HHT are autosomal dominant disorders with distinct and non-overlapping clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in SMAD4 or BMPR1A, and the latter is a vascular malformation disorder caused by mutations in ENG or ACVRL1. All four genes encode proteins involved in the transforming-growth-factor-signaling pathway. Although there are reports of patients and families with phenotypes of both disorders combined, the genetic etiology of this association is unknown. {ECO:0000269 PubMed:15031030}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Myhre syndrome (MYHRS) [MIM:139210]: A syndrome characterized by pre- and postnatal growth deficiency, mental retardation, generalized muscle hypertrophy and striking muscular build, decreased joint mobility, cryptorchidism, and unusual facies. Dysmorphic facial features include microcephaly, midface hypoplasia, prognathism, and blepharophimosis. Typical skeletal anomalies are short stature, square body shape, broad ribs, iliac hypoplasia, brachydactyly, flattened vertebrae, and thickened calvaria. Other features, such as congenital heart disease, may also occur. {ECO:0000269 PubMed:22158539, ECO:0000269 PubMed:22243968}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Note=SMAD4 variants may be associated with susceptibility to pulmonary hypertension, a 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}.
  • Pancreatic cancer (PNCA) [MIM:260350]: A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue. {ECO:0000269 PubMed:8553070}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Relevant External Links for SMAD4

Genetic Association Database (GAD)
SMAD4
Human Genome Epidemiology (HuGE) Navigator
SMAD4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SMAD4
genes like me logo Genes that share disorders with SMAD4: view

No data available for Genatlas for SMAD4 Gene

Publications for SMAD4 Gene

  1. The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis. (PMID: 18823382) Calva-Cerqueira D. … Howe J.R. (Clin. Genet. 2009) 3 22 46 64
  2. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). (PMID: 15031030) Gallione C.J. … Marchuk D.A. (Lancet 2004) 3 4 22 64
  3. Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation. (PMID: 11818334) Wan M. … Cao X. (EMBO Rep. 2002) 3 4 22 64
  4. Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. (PMID: 12417513) Sayed M.G. … Howe J.R. (Ann. Surg. Oncol. 2002) 3 4 46 64
  5. Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. (PMID: 9811934) Houlston R. … Tomlinson I. (Hum. Mol. Genet. 1998) 3 4 22 64

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