NODAL

Chr 10AD

nodal growth differentiation factor

Also known as: HTX5

NCBI Gene: 4838ENSG00000156574UniProt: Q96S42OMIM: 601265

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]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Heterotaxy, visceral, 5, autosomalMIM #270100
AD

Clinical highlights

Gene-disease validity (ClinGen)
congenital heart disease with heterotaxy syndrome · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
6402
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.31
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — NODAL
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.31LOEUF
pLI 0.970
Z-score 3.39
OE 0.07 (0.02–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
0.97Z-score
OE missense 0.80 (0.70–0.92)
156 obs / 194.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.07 (0.02–0.31)
0≤0.351.4
Missense OE?0.80 (0.70–0.92)
0≤0.61.4
Synonymous OE?0.82
0≤1.21.6
LoF obs/exp: 1 / 15.3Missense obs/exp: 156 / 194.1Syn Z: 1.31

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NODAL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Breast Cancer - ER+, HER2-, PIK3CA Gene Mutation

PI3K Pathway Activation Markers in ER-Positive, HER2-Negative Breast Cancer: A Clinicopathologic Study

NOT YET RECRUITING
NCT07387861Assiut UniversityStarted 2026-03
Not applicable- observational study
Chronic Lymphocytic Leukemia

Lymph Node Microenvironment Modifications in Patients With CLL Treated With Venetoclax-based Regimens

NOT YET RECRUITING
NCT04790045Phase PHASE4Paolo GhiaStarted 2023-11-01
Venetoclax
Mature B-Cell NeoplasmNon Hodgkin LymphomaDLBCL

Study of SGR-1505 in Mature B-Cell Neoplasms

RECRUITING
NCT05544019Phase PHASE1Schrödinger, Inc.Started 2023-04-10
SGR-1505
Mantle Cell LymphomaFollicular LymphomaSplenic Marginal Zone Lymphoma

Study of Kappa Chimeric Antigen Receptor (CAR) T Lymphocytes Co-Expressing the Kappa and CD28 CARs for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

RECRUITING
NCT04223765Phase PHASE1UNC Lineberger Comprehensive Cancer CenterStarted 2020-11-12
CAR.k.28FludarabineCyclophosphamide
Carcinoma, Non-Small-Cell Lung

A Study of Neoadjuvant Amivantamab With Either Lazertinib or Chemotherapy in Participants With Resectable EGFR-Mutated NSCLC

RECRUITING
NCT07586202Phase PHASE2Janssen Research & Development, LLCStarted 2026-07-28
AmivantamabLazertinibCarboplatin
Endometrial CancerARID1A Gene MutationRecurrent Endometrial Carcinoma

Avelumab and M1774 in ARID1A-mutated Endometrial Cancer

RECRUITING
NCT06518564Phase PHASE2Panagiotis Konstantinopoulos, MD, PhDStarted 2024-11-14
AvelumabM1774
Bladder CancerMuscle-invasive Bladder Cancer

Multi-parametric MRI in Patients Suspected for Muscle Invasive Bladder Cancer: a New Local Staging Paradigm

RECRUITING
NCT05779631Phase NARadboud University Medical CenterStarted 2023-12-06
mpMRI plus a same-day cystoscopic bladder biopsyTURBT
Renal Cell CarcinomaMelanomaSolid Tumor

Study of ARRY-614 Plus Either Nivolumab or Nivolumab+Ipilimumab

ACTIVE NOT RECRUITING
NCT04074967Phase PHASE1, PHASE2Dan ZandbergStarted 2020-06-11
Phase Ib ARRY-614 + nivolumabPhase Ib ARRY-614 + nivolumab+ipilimumabPhase II ARRY-614 + nivolumab
LymphadenectomyEndometrial CancerGene, p53

SENTInel Node Mapping Versus Comprehensive Lymphadenectomy in p53-Mutated Endometrial Cancer: A Non-Inferiority Randomized Trial

NOT YET RECRUITING
NCT06900582Phase NAUniversity Hospital, Strasbourg, FranceStarted 2026-06
Sentinel Lymph Node MappingComprehensive pelvic and para-aortic lymphadenectomy
HPVOropharynx CancerHPV-Related Carcinoma

A Study on Using Cell-Free Tumor DNA (ctDNA) Testing to Decide When to StartRoutine Treatment in People With Human Papilloma Virus (HPV)- Associated Oropharynx Cancer (OPC)

RECRUITING
NCT05307939Phase PHASE2Memorial Sloan Kettering Cancer CenterStarted 2022-03-24
HPV ctDNA AssayMRI StudiesEORTC QLQ H&N 35 and C30
Rhythm NodalMetabolism and Nutrition DisorderMetabolism Disorder, Lipid

The Biological Rhythm of Human Metabolite

RECRUITING
NCT03669809Shandong Provincial HospitalStarted 2011-05-01
Breast Cancer

Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

ACTIVE NOT RECRUITING
NCT02955394Phase PHASE2University of Colorado, DenverStarted 2017-09-21
EnzalutamideFulvestrant

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients