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... See more...

Aliases for NODAL Gene

Aliases for NODAL Gene

  • Nodal Growth Differentiation Factor 2 3 5
  • Nodal Homolog 3 4
  • Nodal, Mouse, Homolog 2
  • Nodal Homolog (Mouse) 2
  • NODAL 5
  • HTX5 3

External Ids for NODAL Gene

Previous GeneCards Identifiers for NODAL Gene

  • GC10U990041
  • GC10P072086
  • GC10M071536
  • GC10M071862
  • GC10M072191
  • GC10M066185

Summaries for NODAL Gene

Entrez Gene Summary for NODAL Gene

  • 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]

GeneCards Summary for NODAL Gene

NODAL (Nodal Growth Differentiation Factor) is a Protein Coding gene. Diseases associated with NODAL include Heterotaxy, Visceral, 5, Autosomal and Dextrocardia With Situs Inversus. Among its related pathways are Signaling by NODAL and PEDF Induced Signaling. Gene Ontology (GO) annotations related to this gene include cytokine activity and transforming growth factor beta receptor binding. An important paralog of this gene is BMP8A.

UniProtKB/Swiss-Prot Summary for NODAL Gene

  • Essential for mesoderm formation and axial patterning during embryonic development.

Gene Wiki entry for NODAL Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NODAL Gene

Genomics for NODAL Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NODAL Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J070441 Promoter/Enhancer 1.6 EPDnew FANTOM5 Ensembl ENCODE 642.3 +5.7 5680 2.3 GATAD2A NFKBIZ KDM1A RXRB EZH2 CEBPA NRF1 SOX13 TCF7 FOXA2 NODAL EIF4EBP2 ENSG00000280401 piR-48964
GH10J070447 Enhancer 0.3 Ensembl 609 -0.1 -50 1.2 TEAD3 NODAL EIF4EBP2 NPFFR1 LRRC20 PALD1
GH10J070477 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 10.9 -31.3 -31277 3.4 CTCF ZBTB33 PRDM10 ZNF629 LEF1 ZNF692 BACH1 JUND LARP7 PRDM1 PALD1 NODAL PCBD1 lnc-NODAL-1 PRF1
GH10J070403 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 10.5 +42.8 42772 3.6 CEBPG SP1 CREB1 GATAD2A HNRNPL TEAD4 PRDM10 REST ZNF629 TFE3 EIF4EBP2 piR-34414 lnc-LRRC20-2 piR-56759-054 LRRC20 PALD1 NODAL ENSG00000280401
GH10J070322 Enhancer 1.7 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 9.8 +123.6 123603 4.9 HNRNPL GATAD2A CTCF ZBTB33 RCOR2 JUND ZIC2 ZSCAN4 RBFOX2 RXRB PPA1 NPFFR1 NODAL LRRC20 HE856082 RF00017-687
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NODAL on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NODAL

Top Transcription factor binding sites by QIAGEN in the NODAL gene promoter:
  • AP-4
  • c-Ets-1
  • c-Myc
  • COMP1
  • CP2
  • LCR-F1
  • Max
  • NF-kappaB
  • NF-kappaB1
  • RelA

Genomic Locations for NODAL Gene

Genomic Locations for NODAL Gene
chr10:70,431,936-70,447,951
(GRCh38/hg38)
Size:
16,016 bases
Orientation:
Minus strand
chr10:72,191,692-72,207,707
(GRCh37/hg19)
Size:
16,016 bases
Orientation:
Minus strand

Genomic View for NODAL Gene

Genes around NODAL on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for NODAL Gene

Proteins for NODAL Gene

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

    Protein Symbol:
    Q96S42-NODAL_HUMAN
    Recommended name:
    Nodal homolog
    Protein Accession:
    Q96S42
    Secondary Accessions:
    • Q2M3A5
    • Q8N4V3

    Protein attributes for NODAL Gene

    Size:
    347 amino acids
    Molecular mass:
    39561 Da
    Quaternary structure:
    • Homodimer; disulfide-linked.

    Three dimensional structures from OCA and Proteopedia for NODAL Gene

neXtProt entry for NODAL Gene

Post-translational modifications for NODAL Gene

  • Glycosylation at Asn72 and Asn199

Other Protein References for NODAL Gene

No data available for DME Specific Peptides for NODAL Gene

Domains & Families for NODAL Gene

Gene Families for NODAL Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for NODAL Gene

InterPro:
Blocks:
  • Transforming growth factor beta (TGFb)
  • Growth factor cystine knot superfamily signature
ProtoNet:

Suggested Antigen Peptide Sequences for NODAL Gene

GenScript: Design optimal peptide antigens:
  • Nodal homolog (NODAL_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96S42

UniProtKB/Swiss-Prot:

NODAL_HUMAN :
  • Belongs to the TGF-beta family.
Family:
  • Belongs to the TGF-beta family.
genes like me logo Genes that share domains with NODAL: view

Function for NODAL Gene

Molecular function for NODAL Gene

UniProtKB/Swiss-Prot Function:
Essential for mesoderm formation and axial patterning during embryonic development.
GENATLAS Biochemistry:
NODAL,homolog of the mouse nodal,TGFB family member,involved in the control of the direction of cardiac looping and the development of left-right asymetry

Phenotypes From GWAS Catalog for NODAL Gene

Gene Ontology (GO) - Molecular Function for NODAL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IBA 21873635
GO:0008083 growth factor activity IEA --
GO:0016015 morphogen activity NAS 21159651
GO:0048018 receptor ligand activity IEA --
GO:0070698 type I activin receptor binding IBA,IMP 21356369
genes like me logo Genes that share ontologies with NODAL: view
genes like me logo Genes that share phenotypes with NODAL: view

Human Phenotype Ontology for NODAL Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NODAL Gene

MGI Knock Outs for NODAL:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NODAL

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for NODAL Gene

Localization for NODAL Gene

Subcellular locations from UniProtKB/Swiss-Prot for NODAL Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NODAL gene
Compartment Confidence
extracellular 5
cytoskeleton 2
nucleus 2
plasma membrane 1
mitochondrion 1
endoplasmic reticulum 1
cytosol 1
peroxisome 0
lysosome 0
golgi apparatus 0

Gene Ontology (GO) - Cellular Components for NODAL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IBA,IDA 21656830
genes like me logo Genes that share ontologies with NODAL: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for NODAL Gene

Pathways & Interactions for NODAL Gene

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

Pathways by source for NODAL Gene

1 GeneGo (Thomson Reuters) pathway for NODAL Gene
  • Development Role of Activin A in cell differentiation and proliferation
1 GeneTex pathway for NODAL Gene

SIGNOR curated interactions for NODAL Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for NODAL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0001701 in utero embryonic development IEA --
GO:0001702 gastrulation with mouth forming second IEA --
GO:0001707 mesoderm formation IEA --
GO:0001829 trophectodermal cell differentiation IEA --
genes like me logo Genes that share ontologies with NODAL: view

Drugs & Compounds for NODAL Gene

(1) Drugs for NODAL Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with NODAL: view

Transcripts for NODAL Gene

mRNA/cDNA for NODAL Gene

2 REFSEQ mRNAs :
5 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NODAL

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

No ASD Table

Relevant External Links for NODAL Gene

GeneLoc Exon Structure for
NODAL

Expression for NODAL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NODAL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NODAL Gene

This gene is overexpressed in Muscle - Skeletal (x6.5).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NODAL

SOURCE GeneReport for Unigene cluster for NODAL Gene:

Hs.370414

Evidence on tissue expression from TISSUES for NODAL Gene

  • Nervous system(4.4)
  • Skin(2.5)
  • Heart(2.2)
  • Muscle(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NODAL Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • respiratory
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • face
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • nose
  • pharynx
  • pituitary gland
  • skull
  • tooth
Thorax:
  • heart
  • heart valve
  • lung
Abdomen:
  • intestine
  • kidney
  • large intestine
  • liver
  • pancreas
  • small intestine
  • spleen
  • stomach
Pelvis:
  • uterus
General:
  • blood
  • blood vessel
  • skin
genes like me logo Genes that share expression patterns with NODAL: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for NODAL Gene

Orthologs for NODAL Gene

This gene was present in the common ancestor of animals.

Orthologs for NODAL Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NODAL 30 31
  • 98.46 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NODAL 30 31
  • 85.69 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NODAL 30 31
  • 84.73 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Nodal 30 17 31
  • 81.94 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nodal 30
  • 81.17 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia NODAL 31
  • 70 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NODAL 31
  • 61 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NODAL 30 31
  • 52.47 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NODAL 31
  • 32 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100497218 30
  • 49.83 (n)
Zebrafish
(Danio rerio)
Actinopterygii ndr2 30 31
  • 26 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta scw 31
  • 17 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea tig-2 31
  • 15 (a)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 23 (a)
OneToOne
Species where no ortholog for NODAL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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 NODAL Gene

ENSEMBL:
Gene Tree for NODAL (if available)
TreeFam:
Gene Tree for NODAL (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NODAL: view image

Paralogs for NODAL Gene

(8) SIMAP similar genes for NODAL Gene using alignment to 2 proteins:

  • NODAL_HUMAN
  • H7C0E4_HUMAN
genes like me logo Genes that share paralogs with NODAL: view

Variants for NODAL Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NODAL Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
660583 Uncertain Significance: Visceral heterotaxy 5, autosomal 70,435,498(-) G/C MISSENSE_VARIANT
663619 Pathogenic: Visceral heterotaxy 5, autosomal 70,435,730(-) GC/G FRAMESHIFT_VARIANT
690399 Uncertain Significance: Congenitally corrected transposition of the great arteries 70,435,621(-) T/TG FRAMESHIFT_VARIANT
697001 Likely Benign: Visceral heterotaxy 5, autosomal 70,433,064(-) G/A MISSENSE_VARIANT
697197 Likely Benign: Visceral heterotaxy 5, autosomal 70,433,056(-) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for NODAL Gene

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

Variant ID Type Subtype PubMed ID
esv32737 CNV gain+loss 17666407
esv3623765 CNV loss 21293372
nsv1043245 CNV loss 25217958

Variation tolerance for NODAL Gene

Residual Variation Intolerance Score: 92.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.05; 21.49% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NODAL Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for NODAL Gene

MalaCards: The human disease database

(31) MalaCards diseases for NODAL Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search NODAL in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NODAL_HUMAN
  • Heterotaxy, visceral, 5, autosomal (HTX5) [MIM:270100]: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can been associated with variety of congenital defects including cardiac malformations. HTX5 clinical features include situs inversus viscerum or situs ambiguus, congenital heart defect, transposition of the great vessels ventricular septal defect, atrial septal defect, truncus communis, and dextrocardia. {ECO:0000269 PubMed:19064609, ECO:0000269 PubMed:9354794}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for NODAL

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

No data available for Genatlas for NODAL Gene

Publications for NODAL Gene

  1. Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations. (PMID: 19064609) Mohapatra B … Ware SM (Human molecular genetics 2009) 3 4 41
  2. X-linked situs abnormalities result from mutations in ZIC3. (PMID: 9354794) Gebbia M … Casey B (Nature genetics 1997) 2 3 4
  3. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  4. A large-scale candidate gene association study of age at menarche and age at natural menopause. (PMID: 20734064) He C … Hunter DJ (Human genetics 2010) 3 41
  5. MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer. (PMID: 20819778) Zhang X … Wu X (Carcinogenesis 2010) 3 41

Products for NODAL Gene

  • Signalway ELISA kits for NODAL
  • Signalway Proteins for NODAL

Sources for NODAL Gene