NODAL nodal growth differentiation factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: NODALprovided by HGNC
Official Full Name: nodal growth differentiation factorprovided by HGNC
Primary source: HGNC:HGNC:7865
See related: Ensembl:ENSG00000156574 MIM:601265; AllianceGenome:HGNC:7865
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: HTX5
Summary: 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]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 10q22.1

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (70431936..70447951, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (71301367..71317383, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (72191692..72207707, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NODAL variants are associated with a continuum of laterality defects from simple D-transposition of the great arteries to heterotaxy.
Title: NODAL variants are associated with a continuum of laterality defects from simple D-transposition of the great arteries to heterotaxy.
A network of transcription factors governs the dynamics of NODAL/Activin transcriptional responses.
Title: A network of transcription factors governs the dynamics of NODAL/Activin transcriptional responses.
A case for revisiting Nodal signaling in human pluripotent stem cells.
Title: A case for revisiting Nodal signaling in human pluripotent stem cells.
PCSK9 regulates the NODAL signaling pathway and cellular proliferation in hiPSCs.
Title: PCSK9 regulates the NODAL signaling pathway and cellular proliferation in hiPSCs.
Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids.
Title: Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids.
Tril dampens Nodal signaling through Pellino2- and Traf6-mediated activation of Nedd4l.
Title: Tril dampens Nodal signaling through Pellino2- and Traf6-mediated activation of Nedd4l.
Normal Skin Cells Increase Aggressiveness of Cutaneous Melanoma by Promoting Epithelial-to-Mesenchymal Transition via Nodal and Wnt Activity.
Title: Normal Skin Cells Increase Aggressiveness of Cutaneous Melanoma by Promoting Epithelial-to-Mesenchymal Transition via Nodal and Wnt Activity.
Implication of rare genetic variants of NODAL and ACVR1B in congenital heart disease patients from Indian population.
Title: Implication of rare genetic variants of NODAL and ACVR1B in congenital heart disease patients from Indian population.
Embryonic protein NODAL regulates the breast tumor microenvironment by reprogramming cancer-derived secretomes.
Title: Embryonic protein NODAL regulates the breast tumor microenvironment by reprogramming cancer-derived secretomes.
Nodal-induced L1CAM/CXCR4 subpopulation sustains tumor growth and metastasis in colorectal cancer derived organoids.
Title: Nodal-induced L1CAM/CXCR4 subpopulation sustains tumor growth and metastasis in colorectal cancer derived organoids.

Submit: New GeneRIF Correction See all GeneRIFs (116)

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

Associated conditions

Description	Tests
Heterotaxy, visceral, 5, autosomal MedGen: C3495537 OMIM: 270100 GeneReviews: Not available	Compare labs
Holoprosencephaly sequence MedGen: C0079541 GeneReviews: Holoprosencephaly Overview	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2013-08-08) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2013-08-08) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC171388P1 (e-PCR)
- UniSTS:271632

A008L32 (e-PCR)
- UniSTS:70554

NoName (e-PCR)
- UniSTS:488116

RH44263 (e-PCR)
- UniSTS:27086

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables growth factor activity	IEA Inferred from Electronic Annotation more info
enables morphogen activity	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables type I activin receptor binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in axial mesodermal cell fate specification	IEA Inferred from Electronic Annotation more info
involved_in brain development	IEA Inferred from Electronic Annotation more info
involved_in cell migration involved in gastrulation	IEA Inferred from Electronic Annotation more info
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in determination of left/right asymmetry in lateral mesoderm	ISS Inferred from Sequence or Structural Similarity more info
involved_in digestive tract morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic cranial skeleton morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic pattern specification	IEA Inferred from Electronic Annotation more info
involved_in embryonic placenta development	IEA Inferred from Electronic Annotation more info
involved_in embryonic process involved in female pregnancy	IEA Inferred from Electronic Annotation more info
involved_in endodermal cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in epiblast cell-extraembryonic ectoderm cell signaling involved in anterior/posterior axis specification	IEA Inferred from Electronic Annotation more info
involved_in floor plate morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in formation of anatomical boundary	IEA Inferred from Electronic Annotation more info
involved_in germ cell development	IEA Inferred from Electronic Annotation more info
involved_in heart looping	IEA Inferred from Electronic Annotation more info
involved_in inhibition of neuroepithelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in left lung morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in liver development	IEA Inferred from Electronic Annotation more info
involved_in maternal placenta development	IEA Inferred from Electronic Annotation more info
involved_in maternal process involved in parturition	IEA Inferred from Electronic Annotation more info
involved_in mesendoderm development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of androgen receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of chorionic trophoblast cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of trophoblast cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in neural fold formation	IEA Inferred from Electronic Annotation more info
involved_in nodal signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in placenta development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in polarity specification of proximal/distal axis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of SMAD protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of activin receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell-cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of epithelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vascular endothelial growth factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in primitive streak formation	IEA Inferred from Electronic Annotation more info
involved_in regulation of gastrulation	IEA Inferred from Electronic Annotation more info
involved_in regulation of stem cell population maintenance	TAS Traceable Author Statement more info	PubMed
involved_in somatic stem cell population maintenance	IEA Inferred from Electronic Annotation more info
involved_in transforming growth factor beta receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in trophectodermal cellular morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in vasculature development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: nodal homolog

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

NG_012448.2 RefSeqGene

Range

11268..21013

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001329906.2 → NP_001316835.1 nodal homolog isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream translation start site compared to variant 1. The encoded isoform (2) has a shorter N-terminus, and lacks the signal peptide and a portion of the propeptide compared to isoform 1.

Source sequence(s)

AC022532, AI670948, BC039861

Conserved Domains (1) summary

smart00204
Location:114 → 213

TGFB; Transforming growth factor-beta (TGF-beta) family
NM_018055.5 → NP_060525.3 nodal homolog isoform 1 preproprotein

See identical proteins and their annotated locations for NP_060525.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC022532, BC033585, BC104976

Consensus CDS

CCDS7304.1

UniProtKB/Swiss-Prot

Q2M3A5, Q8N4V3, Q96S42

UniProtKB/TrEMBL

H7C0E4

Related

ENSP00000287139.3, ENST00000287139.8

Conserved Domains (2) summary

smart00204
Location:247 → 346

TGFB; Transforming growth factor-beta (TGF-beta) family

pfam00688
Location:29 → 166

TGFb_propeptide; TGF-beta propeptide

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

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

70431936..70447951 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024448028.2 → XP_024303796.1 nodal homolog isoform X1

Conserved Domains (1) summary

smart00204
Location:114 → 213

TGFB; Transforming growth factor-beta (TGF-beta) family