NODAL
nodal growth differentiation factor, the group of Transforming growth factor beta superfamily
Basic information
Region (hg38): 10:70431936-70447951
Links
Phenotypes
GenCC
Source:
- situs inversus (Disputed Evidence), mode of inheritance: AD
- heterotaxy, visceral, 5, autosomal (Definitive), mode of inheritance: AD
- situs inversus (Supportive), mode of inheritance: AD
- heterotaxy, visceral, 5, autosomal (Strong), mode of inheritance: AD
- heterotaxy, visceral, 5, autosomal (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Heterotaxy, visceral, 5, autosomal | AD | Cardiovascular | The condition can involve congenital cardiac anomalies, and awareness may allow early management; Cardiac transplantation has been described | Cardiovascular; Gastrointestinal; Pulmonary; Renal | 19064609 |
| The condition can involve multiple congenital anomalies; Cardiac transplantation has been described |
ClinVar
This is a list of variants' phenotypes submitted to
- Heterotaxy,_visceral,_5,_autosomal (92 variants)
- not_provided (36 variants)
- Inborn_genetic_diseases (28 variants)
- Holoprosencephaly_sequence (23 variants)
- NODAL-related_disorder (13 variants)
- not_specified (6 variants)
- Heart,_malformation_of (3 variants)
- Visceral_heterotaxy (2 variants)
- Wolff-Parkinson-White_pattern (1 variants)
- Situs_inversus (1 variants)
- Basal_cell_carcinoma,_susceptibility_to,_4 (1 variants)
- Congenitally_corrected_transposition_of_the_great_arteries (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NODAL gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018055.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 25 | 34 | ||||
| missense | 67 | 11 | 83 | |||
| nonsense | 4 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 9 | |||||
| splice donor/acceptor (+/-2bp) | 4 | |||||
| Total | 7 | 12 | 74 | 36 | 6 |
Highest pathogenic variant AF is 0.0000129972
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NODAL | protein_coding | protein_coding | ENST00000287139 | 3 | 15637 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.970 | 0.0297 | 125742 | 0 | 6 | 125748 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.971 | 156 | 194 | 0.804 | 0.0000114 | 2239 |
| Missense in Polyphen | 57 | 78.963 | 0.72186 | 958 | ||
| Synonymous | 1.31 | 68 | 83.2 | 0.817 | 0.00000474 | 707 |
| Loss of Function | 3.39 | 1 | 15.3 | 0.0654 | 8.26e-7 | 146 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000578 | 0.0000578 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000264 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Essential for mesoderm formation and axial patterning during embryonic development. {ECO:0000250}.;
- Disease
- DISEASE: 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.;
- Pathway
- TGF-beta signaling pathway - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);TGF-Core;Cardiac Progenitor Differentiation;Differentiation Pathway;Endoderm Differentiation;Mesodermal Commitment Pathway;Tgif disruption of Shh signaling;Developmental Biology;Regulation of signaling by NODAL;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;TGF-beta super family signaling pathway canonical;GPCR signaling-G alpha s Epac and ERK;Signaling by NODAL;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;BMP2 signaling TGF-beta MV
(Consensus)
Recessive Scores
- pRec
- 0.426
Intolerance Scores
- loftool
- 0.272
- rvis_EVS
- -0.29
- rvis_percentile_EVS
- 32.94
Haploinsufficiency Scores
- pHI
- 0.657
- hipred
- Y
- hipred_score
- 0.593
- ghis
- 0.514
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.834
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nodal
- Phenotype
- hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); taste/olfaction phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype;
Zebrafish Information Network
- Gene name
- ndr1
- Affected structure
- hatching gland cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;trophectodermal cellular morphogenesis;neural fold formation;liver development;placenta development;embryonic placenta development;maternal placenta development;vasculature development;heart looping;inhibition of neuroepithelial cell differentiation;brain development;embryonic pattern specification;polarity specification of proximal/distal axis;regulation of signaling receptor activity;regulation of gastrulation;positive regulation of vascular endothelial growth factor production;negative regulation of cell development;positive regulation of pathway-restricted SMAD protein phosphorylation;stem cell population maintenance;positive regulation of cell-cell adhesion;BMP signaling pathway;positive regulation of activin receptor signaling pathway;floor plate morphogenesis;endodermal cell differentiation;cell migration involved in gastrulation;regulation of apoptotic process;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;regulation of MAPK cascade;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;axial mesodermal cell fate specification;mesendoderm development;cell development;digestive tract morphogenesis;embryonic cranial skeleton morphogenesis;formation of anatomical boundary;positive regulation of epithelial cell proliferation;positive regulation of DNA-binding transcription factor activity;embryonic process involved in female pregnancy;maternal process involved in parturition;positive regulation of SMAD protein signal transduction;SMAD protein signal transduction;left lung morphogenesis;negative regulation of androgen receptor signaling pathway;epiblast cell-extraembryonic ectoderm cell signaling involved in anterior/posterior axis specification;positive regulation of ERK1 and ERK2 cascade;transforming growth factor beta receptor signaling pathway involved in primitive streak formation;nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry;positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry;negative regulation of trophoblast cell migration;negative regulation of chorionic trophoblast cell proliferation;regulation of stem cell population maintenance
- Cellular component
- extracellular space
- Molecular function
- cytokine activity;transforming growth factor beta receptor binding;growth factor activity;morphogen activity;type I activin receptor binding