CAD

Chr 2AR

carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase

The CAD protein functions as a trifunctional enzyme catalyzing the first three steps of pyrimidine nucleotide biosynthesis (carbamoylphosphate synthetase II, aspartate transcarbamoylase, and dihydroorotase activities). Mutations cause developmental and epileptic encephalopathy 50 with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, indicating its critical importance for normal cellular function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.251 OMIM phenotype
Clinical SummaryCAD
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Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy, 50 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — CAD
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

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 OE0.17 (0.120.25)
00.351.4
Missense OE0.67 (0.630.71)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 19 / 110.9Missense obs/exp: 913 / 1363.6Syn Z: -0.93
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCAD-related uridine-responsive epileptic encephalopathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4289th %ile
GOF
0.3986th %ile
LOF
0.64top 25%

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Episodic MigraineChronic Migraine

CGRP Inhibition, Autonomic Function, and Migraine

RECRUITING
NCT04628429Medical University of ViennaStarted 2020-10-01
ErenumabGalcanezumabFremanezumab
Coronary Artery Disease

Prediction of Atherosclerotic Plaque Progression

ACTIVE NOT RECRUITING
NCT05424705Na Homolce HospitalStarted 2015-01-15
OCT, NIRS
Diabetes MellitusType 2 DiabetesType 1 Diabetes

The Hong Kong Diabetes Biobank

ACTIVE NOT RECRUITING
NCT05282680Chinese University of Hong KongStarted 2014-02-01
prospective observational study
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 Myocardial Infarction With ST Elevation

Effect of Glp-1 and Antidiabetic sgLT2 Agents for myoCardial infarcTion and Ultrasensitive Inflammatory Surveillance (GALACTUS Trial)

RECRUITING
NCT07295223Phase PHASE3Instituto Mexicano del Seguro SocialStarted 2025-12-30
Dapagliflozin 10 MG Oral TabletSemaglutide (Rybelsus®)
Kawasaki DiseaseCoronary Artery Aneurysm

Rivaroxaban for Children Aged Over 2 Years With Giant Coronary Artery Aneurysms After Kawasaki Disease

RECRUITING
NCT05643651Phase PHASE4Children's Hospital of Fudan UniversityStarted 2025-06-01
Rivaroxaban Oral Tablet [Xarelto]Aspirin or ClopidogrelWarfarin
Coronary Heart Disease

Adipose Tissue and Inflammation in Coronary Heart Disease

ACTIVE NOT RECRUITING
NCT02760914Oslo University HospitalStarted 2016-06
ThrombosisBleedingCoronary Artery Disease (CAD)

Multi-Omics-Based Novel Thrombosis and Bleeding Markers and Risk Model for CHD

RECRUITING
NCT07523880Xueyan ZhaoStarted 2025-08-01
Hypertrophic Obstructive Cardiomyopathy \(HOCM\)Left Ventricular Outflow Tract ObstructionMyocardial Ischaemia

Positron Emission Tomography to Assess the Effect of Camzyos on Ischaemia in HOCM: PEACH Trial

NOT YET RECRUITING
NCT07120776Phase NAUniversity of ManchesterStarted 2025-09
Camzyos (Mavacamten)
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
InsomniaInsomnia ChronicInsomnia, Primary

SHADES Mechanistic Trial

ENROLLING BY INVITATION
NCT06041581Phase NAIndiana UniversityStarted 2024-04-25
Sleep Healthy Using The Internet (SHUTi)Telephonic CBT-IFace-to-Face CBT-I
Acute Myeloid LeukemiaAcute Myeloid Leukemia Arising From Previous Myelodysplastic SyndromeAcute Myeloid Leukemia Arising From Previous Myeloproliferative Neoplasm

Testing the Use of Combination Therapy in Patients With Persistent Low Level Acute Myeloid Leukemia Following Initial Treatment, The ERASE Study (A MyeloMATCH Treatment Trial)

NOT YET RECRUITING
NCT05554419Phase PHASE2National Cancer Institute (NCI)Started 2026-07-01
AzacitidineBone Marrow Aspiration and BiopsyCytarabine
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Precision physiology in CAD.
Di Carli MF·J Nucl Cardiol
2026
What if a patient has CAD? Go to CMR!
Garot J et al.·Arch Cardiovasc Dis
2021
The Development of B-Splines for CAD.
Riesenfeld RF et al.·IEEE Comput Graph Appl
2022
Application of CAD-CAM in Dentistry.
Maiti N et al.·Bioinformation
2024
Top 5 full-text resultsSearch PubTator3 ↗