CAD
Chr 2ARcarbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
Also known as: CDG1Z, DEE50, EIEE50, GATD4
The de novo synthesis of pyrimidine nucleotides is required for mammalian cells to proliferate. This gene encodes a trifunctional protein which is associated with the enzymatic activities of the first 3 enzymes in the 6-step pathway of pyrimidine biosynthesis: carbamoylphosphate synthetase (CPS II), aspartate transcarbamoylase, and dihydroorotase. This protein is regulated by the mitogen-activated protein kinase (MAPK) cascade, which indicates a direct link between activation of the MAPK cascade and de novo biosynthesis of pyrimidine nucleotides. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene — mechanism propensity
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CAD · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Safety and Efficacy of Meplazumab in Patients With Coronary Artery Disease
RECRUITINGEAS Familial Hypercholesterolaemia Studies Collaboration
RECRUITINGCombination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
RECRUITINGPolygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention
ACTIVE NOT RECRUITINGHealth Improvements by Understanding the Determinants of Residual Risk in Coronary Artery Disease and New Targets for Prevention and Treatment
RECRUITINGExpanded Studies on the SCAPIS Stockholm Reexamination Cohort
RECRUITINGEvaluating the Role of IGF-1 and S-Klotho In Plaque Phenotype and Vulnerability: the VISION Study.
ACTIVE NOT RECRUITINGA Precision Medicine Approach to Identify Patients Undergoing Elective PCI at Risk of Peri-PCI Myocardial Infarction
RECRUITINGDual Antiplatelet Therapy Escalation From Standard-dose Clopidogrel to Low-Dose Prasugrel in Patients With High Bleeding and Ischemic Risk Undergoing PCI: A Prospective, Randomized Pharmacodynamic Study (TAILOR-BLEED-2)
RECRUITINGSingapOre Lung Cancer Screening Through Integrating CT With Other biomarkErs (SOLSTICE)
RECRUITINGThe Healthy Elderly Longevity Cohort
RECRUITINGKlotho Gene, Red Complex Bacteria and Periodontal Viruses in Patients With and Without Periodontitis and Acute Coronary Syndrome
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools