Human Gene NODAL (ENST00000287139.8) from GENCODE V44
  Description: Homo sapiens nodal growth differentiation factor (NODAL), transcript variant 1, mRNA. (from RefSeq NM_018055)
RefSeq Summary (NM_018055): This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which regulates early embryonic development. This protein is required for maintenance of human embryonic stem cell pluripotency and may play a role in human placental development. Mutations in this gene are associated with heterotaxy, a condition characterized by random orientation of visceral organs with respect to the left-right axis. [provided by RefSeq, Aug 2016].
Gencode Transcript: ENST00000287139.8
Gencode Gene: ENSG00000156574.10
Transcript (Including UTRs)
   Position: hg38 chr10:70,431,936-70,441,681 Size: 9,746 Total Exon Count: 3 Strand: -
Coding Region
   Position: hg38 chr10:70,432,936-70,441,667 Size: 8,732 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr10:70,431,936-70,441,681)mRNA (may differ from genome)Protein (347 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGencode

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Nodal homolog; Flags: Precursor;
FUNCTION: Essential for mesoderm formation and axial patterning during embryonic development (By similarity).
SUBUNIT: Homodimer; disulfide-linked (By similarity).
SUBCELLULAR LOCATION: Secreted (By similarity).
DISEASE: Defects in NODAL are the cause of visceral heterotaxy autosomal type 5 (HTX5) [MIM:270100]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects. Clinical features of visceral heterotaxy autosomal type 5 include situs inversus viscerum or situs ambiguus, congenital heart defect, transposition of the great vessels ventricular septal defect, atrial septal defect, truncuscommunis, and dextrocardia.
SIMILARITY: Belongs to the TGF-beta family.

-  Primer design for this transcript

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-  MalaCards Disease Associations
  MalaCards Gene Search: NODAL
Diseases sorted by gene-association score: heterotaxy, visceral, 5* (1230), nodal-related visceral heterotaxy* (500), lobar holoprosencephaly* (247), dextrocardia with situs inversus* (202), alobar holoprosencephaly* (202), semilobar holoprosencephaly* (143), septopreoptic holoprosencephaly* (132), midline interhemispheric variant of holoprosencephaly* (132), microform holoprosencephaly* (124), nodal-related holoprosencephaly* (100), dextrocardia (28), visceral heterotaxy* (22), heterotaxy (20), patau syndrome (17), main bronchus cancer (16), parovarian cyst (16), duodenal obstruction (11), holoprosencephaly 7 (11), situs inversus (10), cecal benign neoplasm (10), cecal disease (10), chromosome 18p deletion syndrome (9), common bile duct disease (9), ovarian embryonal carcinoma (9), physical disorder (8), ventricular septal defect (7), cecum adenocarcinoma (7), chronic maxillary sinusitis (7), holoprosencephaly (7), agnathia-otocephaly complex (7), duodenal disease (6), discrete subaortic stenosis (6), congenital nervous system abnormality (6), appendix adenocarcinoma (6), anteroseptal myocardial infarction (5), cystic lymphangioma (5), heart septal defect (5), renal-hepatic-pancreatic dysplasia (5), gallbladder disease (5), alstrom syndrome (4), kartagener syndrome (3), heart disease (3), colorectal cancer (1), primary ciliary dyskinesia (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1.57 RPKM in Testis
Total median expression: 19.33 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -340.801000-0.341 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001839 - TGF-b_C
IPR001111 - TGF-b_N
IPR015615 - TGF-beta-rel
IPR017948 - TGFb_CS

Pfam Domains:
PF00019 - Transforming growth factor beta like domain
PF00688 - TGF-beta propeptide

ModBase Predicted Comparative 3D Structure on Q96S42
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein SequenceProtein Sequence   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005125 cytokine activity
GO:0005160 transforming growth factor beta receptor binding
GO:0008083 growth factor activity
GO:0016015 morphogen activity
GO:0048018 receptor agonist activity
GO:0070698 type I activin receptor binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001701 in utero embryonic development
GO:0001702 gastrulation with mouth forming second
GO:0001707 mesoderm formation
GO:0001829 trophectodermal cell differentiation
GO:0001831 trophectodermal cellular morphogenesis
GO:0001842 neural fold formation
GO:0001889 liver development
GO:0001890 placenta development
GO:0001892 embryonic placenta development
GO:0001893 maternal placenta development
GO:0001944 vasculature development
GO:0001947 heart looping
GO:0002085 inhibition of neuroepithelial cell differentiation
GO:0007275 multicellular organism development
GO:0007368 determination of left/right symmetry
GO:0007369 gastrulation
GO:0007399 nervous system development
GO:0007420 brain development
GO:0007492 endoderm development
GO:0007507 heart development
GO:0008284 positive regulation of cell proliferation
GO:0009880 embryonic pattern specification
GO:0009948 anterior/posterior axis specification
GO:0009952 anterior/posterior pattern specification
GO:0009966 regulation of signal transduction
GO:0010085 polarity specification of proximal/distal axis
GO:0010469 regulation of receptor activity
GO:0010470 regulation of gastrulation
GO:0010575 positive regulation of vascular endothelial growth factor production
GO:0010721 negative regulation of cell development
GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0016477 cell migration
GO:0019827 stem cell population maintenance
GO:0022409 positive regulation of cell-cell adhesion
GO:0030324 lung development
GO:0030509 BMP signaling pathway
GO:0032927 positive regulation of activin receptor signaling pathway
GO:0033505 floor plate morphogenesis
GO:0035050 embryonic heart tube development
GO:0035987 endodermal cell differentiation
GO:0038092 nodal signaling pathway
GO:0042074 cell migration involved in gastrulation
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045165 cell fate commitment
GO:0045596 negative regulation of cell differentiation
GO:0045766 positive regulation of angiogenesis
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048327 axial mesodermal cell fate specification
GO:0048382 mesendoderm development
GO:0048468 cell development
GO:0048546 digestive tract morphogenesis
GO:0048646 anatomical structure formation involved in morphogenesis
GO:0048701 embryonic cranial skeleton morphogenesis
GO:0048729 tissue morphogenesis
GO:0048859 formation of anatomical boundary
GO:0050679 positive regulation of epithelial cell proliferation
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0055123 digestive system development
GO:0060136 embryonic process involved in female pregnancy
GO:0060137 maternal process involved in parturition
GO:0060391 positive regulation of SMAD protein import into nucleus
GO:0060395 SMAD protein signal transduction
GO:0060460 left lung morphogenesis
GO:0060766 negative regulation of androgen receptor signaling pathway
GO:0060802 epiblast cell-extraembryonic ectoderm cell signaling involved in anterior/posterior axis specification
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0090009 primitive streak formation
GO:0090010 transforming growth factor beta receptor signaling pathway involved in primitive streak formation
GO:1900164 nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
GO:1900224 positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
GO:1901164 negative regulation of trophoblast cell migration
GO:1901383 negative regulation of chorionic trophoblast cell proliferation
GO:2000036 regulation of stem cell population maintenance

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space

-  Descriptions from all associated GenBank mRNAs
  BC033585 - Homo sapiens nodal homolog (mouse), mRNA (cDNA clone IMAGE:5239967), partial cds.
BC039861 - Homo sapiens nodal homolog (mouse), mRNA (cDNA clone IMAGE:5743898), partial cds.
BC104976 - Homo sapiens nodal homolog (mouse), mRNA (cDNA clone MGC:132636 IMAGE:8143979), complete cds.
BC112025 - Homo sapiens nodal homolog (mouse), mRNA (cDNA clone MGC:138230 IMAGE:8327493), complete cds.
KJ897253 - Synthetic construct Homo sapiens clone ccsbBroadEn_06647 NODAL gene, encodes complete protein.
KR712181 - Synthetic construct Homo sapiens clone CCSBHm_00036671 NODAL (NODAL) mRNA, encodes complete protein.
JD118241 - Sequence 99265 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04350 - TGF-beta signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein Q96S42 (Reactome details) participates in the following event(s):

R-HSA-1181152 Cleavage of NODAL proprotein
R-HSA-1181352 LEFTY binds NODAL
R-HSA-1181354 CERBERUS binds NODAL
R-HSA-1181155 The NODAL Receptor binds NODAL ligands
R-HSA-1181156 Type II Activin Receptor (ActRII/ACVR2) phosphorylates Type I Activin Receptor (ActRIB/ACVR1B) in response to NODAL
R-HSA-1225894 Type II Activin Receptor (ActRIIB/ACVR2B) phosphorylates Type I Activin Receptor (ActRIC/ACVR1C) in response to NODAL
R-HSA-1181355 Phosphorylation of R-SMAD2/3 by NODAL receptor
R-HSA-1181150 Signaling by NODAL
R-HSA-1433617 Regulation of signaling by NODAL
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000287139.1, ENST00000287139.2, ENST00000287139.3, ENST00000287139.4, ENST00000287139.5, ENST00000287139.6, ENST00000287139.7, NM_018055, NODAL_HUMAN, Q2M3A5, Q8N4V3, Q96S42, uc001jrc.1, uc001jrc.2, uc001jrc.3, uc001jrc.4
UCSC ID: ENST00000287139.8
RefSeq Accession: NM_018055
Protein: Q96S42 (aka NODAL_HUMAN or NODA_HUMAN)
CCDS: CCDS7304.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.