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Symbol NODAL contributors: mct - updated : 22-11-2016
HGNC name nodal homolog (mouse)
HGNC id 7865
interspecies homolog to murine Nodal
  • TGF-beta superfamily
  • CATEGORY regulatory , signaling growth factor
    basic FUNCTION
  • embryonic regulator involved in the control of the TGFD beta signaling pathway during developement,
  • involved in the direction of cardiac looping
  • having a key role in melanoma cell plasticity and tumorigenicity, thereby providing a molecular target for regulating tumor progression
  • play a key role in specification and patterning of vertebrate embryos
  • implicated in the establishment of the Antero–Posterior axis and generation of mesoderm and definitive endoderm
  • not only crucial in cell invasion, but also mediates multi-potent, plastic phenotypes and other stem cell-like properties in human melanoma
  • suppress cell proliferation and to stimulate the expression of cyclin G2 (CCNG2) in epithelial ovarian cancer cells
  • NODAL signaling promotes CCNG2 transcription by upregulating FOXO3 expression, inhibiting FOXO3 phosphorylation and enhancing its synergistic interaction with Smads
  • NBL1 might act synergistically with NODAL
  • NODAL signaling provides a molecular control mechanism that regulates male germ cell potency in normal development and testicular cancer
  • endogenous NODAL signaling regulates germ cell potency during mammalian testis development
  • during development, NODAL depends on growth and differentiation factor GDF1 and on the shared co-receptor CFC1 to specify visceral left-right axis asymmetry
  • is an essential embryonic morphogen that is associated with progression of breast and other cancers
  • plays likely a regulatory role in Sertoli cells and germ cells via a paracrine and autocrine pathway, respectively
  • NODAL produced by human male germ cells regulates proliferation and numerous gene expression of Sertoli cells
  • CELLULAR PROCESS cell organization/biogenesis
    signaling signal transduction
  • activin/nodal signaling pathway (inhibition of activin/nodal signaling results in the loss of hESC (embryonic stem cells) pluripotency and trophoblast differentiation, similar to BMP4-induced trophoblast differentiation from hESCs)
  • CITED2 plays a role in left–right patterning through the NODAL-PITX2C pathway
  • signaling by the TGFB1 morphogen NODAL and its co-receptor TDGF1 is active during a crucial window of male germ cell development
  • NODAL signaling promotes male germ cell fate and suppresses female programming in somatic cells
  • a component
  • central component with EBAF, LEFTYB, PITX2 of the left-right asymetry determination (L/R) complex
    small molecule
  • inducing LEFTYB
  • signaling via MADH2 through binding with activin receptor ACVR1C
  • interacting with Cripto (TDGF1)
  • interacting with GDF1 (regulates the activity and signaling range of NODAL through direct interaction)
  • TGIF1, TGIF2 function is required for gastrulation, and provide the first clear evidence that Tgifs limit the transcriptional response to NODAL signaling during early embryogenesis
  • CITED2 may interact with both NODAL and BMP signalling in establishing laterality
  • NODAL signaling regulates endodermal cell motility and actin dynamics via RAC1 and PREX1
  • transient inhibition of NODAL by CER1 induces Brahma-associated factor 60c (SMARCD3)
  • NANOG promotes liver cancer cell invasion by inducing epithelial-mesenchymal transition through NODAL/SMAD3 signaling pathway
  • NODAL·GDF1 heterodimers with bound prodomains enable serum-independent nodal signaling and endoderm differentiation
  • secreted antagonists, such as CER1, tightly regulate NODAL signaling during embryonic development
  • FOXA2 can be a regulator of NODAL expression
  • MSX2 controls mesendoderm lineage commitment by simultaneous suppression of SOX2 and induction of NODAL expression through direct binding and activation of the NODAL promoter
  • TGIF1 and TGIF2 regulate the TGFB1/NODAL signaling pathway and sonic hedgehog (SHH) signaling independently
  • cell & other
    Other antagonized by EBAF, LEFTYB
    NODAL signaling pathway is activated in both male germ cells and somatic cells
    corresponding disease(s) HTX5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in metastatic melanomas
    constitutional germinal mutation      
    cause sporadic left–right (LR) patterning defects
    constitutional       loss of function
    reductions in the biological activity of NODAL alleles in congenital heart defects
    tumoral     --over  
    expression levels are significantly higher in astrocytomas, glioblastomas, oligodendrogliomas, and in malignant glioma cells compared with non-tumor tissues
    tumoral     --over  
    correlated with reduced patient survival in pancreatic cancer
    constitutional     --low  
    decreased expression of NODAL combined with haploinsufficiency for FOXA2 is the likely cause for heterotaxy, panhypopituitarism, and biliary atresia in a family (pMID: 25765999)
    Susceptibility to congenital heart disease (CHD)
    Variant & Polymorphism other
  • contribution to CHD of copy number changes in NODAL
  • Candidate gene
    Therapy target inhibition of Nodal signaling may be considered as a novel therapeutic strategy in glioma treatment