CAD

Chr 2AR

carbamoyl-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]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 50MIM #616457
AR

Clinical highlights

Gene-disease validity (ClinGen)
developmental and epileptic encephalopathy, 50 · ARDefinitivesufficient 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
7784
Pubs (1 yr)
P/LP submissions
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — CAD
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.25LOEUF
pLI 1.000
Z-score 8.09
OE 0.17 (0.120.25)
Highly constrained

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

Missense Constraint?
4.34Z-score
OE missense 0.67 (0.630.71)
913 obs / 1363.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.17 (0.120.25)
00.351.4
Missense OE?0.67 (0.630.71)
00.61.4
Synonymous OE?1.05
01.21.6
LoF obs/exp: 19 / 110.9Missense obs/exp: 913 / 1363.6Syn Z: -0.93

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Ischemic Heart DiseaseChronic Coronary SyndromeOptical Coherence Tomography (OCT)

Evaluating the Role of IGF-1 and S-Klotho In Plaque Phenotype and Vulnerability: the VISION Study.

ACTIVE NOT RECRUITING
NCT06522074Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2024-10-15
Coronary angiography with OCT
Coronary Artery DiseaseArterial Stiffness, Blood PressureAORTIC VALVE DISEASES

Expanded Studies on the SCAPIS Stockholm Reexamination Cohort

RECRUITING
NCT07476703Danderyd HospitalStarted 2024-04-08
Coronary computer tomography (CCTA)Echocardiograhy and aortic ultrasoundLiver elastography
Sickle Cell Disease

Blood Collection for Research Related to Certain Diseases Involving Blood Vessels

ENROLLING BY INVITATION
NCT00047996National Heart, Lung, and Blood Institute (NHLBI)Started 2002-11-04
Coronary Arterial Disease (CAD)

Health Improvements by Understanding the Determinants of Residual Risk in Coronary Artery Disease and New Targets for Prevention and Treatment

RECRUITING
NCT06601153Fondazione Toscana Gabriele MonasterioStarted 2023-07-07
Cardiac CT
Coronary Artery Disease (CAD) (E.G., Angina, Myocardial Infarction, and Atherosclerotic Heart Disease (ASHD))Peripheral Artery Disease

REGistry of Long-term AnTithrombotic TherApy-1

RECRUITING
NCT04347200National Medical Research Center for Cardiology, Ministry of Health of Russian FederationStarted 2015-01-15
Antiplatelet Drug
Hereditary Hemorrhagic Telangiectasia

Cardiac Evaluation in Hereditary Hemorrhagic Telangiectasia

NOT YET RECRUITING
NCT07101575Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-08-05
Transthoracic echocardiography
PRS-based Primary Prevention of CVD

Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention

ACTIVE NOT RECRUITING
NCT06820086Phase PHASE4Mikk JÜRISSONStarted 2025-03-26
Rosuvastatin 20mg
Gene PolymorphismASCVD

NPC1L1 Gene Polymorphism and the Efficacy and Safety of Hybutimibe

NOT YET RECRUITING
NCT06641661Qianfoshan HospitalStarted 2024-11-01
Hybutimibe 10mg QD
Coronary Artery DiseaseAtherosclerosis, Coronary

Latvian Early Atherosclerosis Registry

RECRUITING
NCT06393894Pauls Stradins Clinical University HospitalStarted 2019-04-01
Near infrared spectroscopyGenetic testing for LDLR, APOB, PCSK9 and LDLRAP1 mutations and niR-126, -145 and -155 expression.
Acute Myeloid Leukemia

A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations

RECRUITING
NCT04293562Phase PHASE3Children's Oncology GroupStarted 2020-07-21
Allogeneic Hematopoietic Stem Cell TransplantationAsparaginase Erwinia chrysanthemiBiospecimen Collection
Familial Hypercholesterolemia

Child-Parent Familial Hypercholesterolemia Screening

RECRUITING
NCT04529967Children's Hospital of Fudan UniversityStarted 2025-04-01
no interventions
Coronary Artery Disease (CAD)

Epicardial Delivery of XC001 Gene Therapy to Promote Angiogenesis in CAD Patients Undergoing Treatment With CABG

NOT YET RECRUITING
NCT07118449Phase PHASE2XyloCor Therapeutics, Inc.Started 2025-08-27
XC001A195/placebo