CAD

Chr 2AR

carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase

Nuclease that induces DNA fragmentation and chromatin condensation during apoptosis. Degrades naked DNA and induces apoptotic morphology

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 50MIM #616457
AR
583
ClinVar variants
36
Pathogenic / LP
1.00
pLI score· haploinsufficient
12
Active trials
Clinical SummaryCAD
🧬
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.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 167 VUS of 583 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (2)

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

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.120.25)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.630.71)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
01.21.6
LoF obs/exp: 19 / 110.9Missense obs/exp: 913 / 1363.6Syn Z: -0.93

ClinVar Variant Classifications

583 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic13
VUS167
Likely Benign378
Benign1
Conflicting1
23
Pathogenic
13
Likely Pathogenic
167
VUS
378
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
13
0
23
Likely Pathogenic
11
1
1
0
13
VUS
1
147
13
6
167
Likely Benign
0
0
153
225
378
Benign
0
0
1
0
1
Conflicting
1
Total22148181231583

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

CAD-related uridine-responsive epileptic encephalopathy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

Developmental and epileptic encephalopathy 50

MIM #616457

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CAD
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Acute Myeloid Leukemia

Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)

RECRUITING
NCT05554393Phase PHASE2National Cancer Institute (NCI)Started 2024-09-13
AzacitidineBiospecimen CollectionBone Marrow Aspiration
CardiomyopathyIschemic Heart DiseaseCardiac Amyloidosis

A Study Of Deep Learning For Echo Analysis, Tracking, And Evaluation

NOT YET RECRUITING
NCT07308704Mayo ClinicStarted 2026-02
Transthoracic Echocardiography (TTE)
Pre-diabetes

High Protein Diet on Transcriptomic, Metabolomics, Hepatic and Pancreatic Fat Anatomy and Physiology in Asian Indians With Pre-diabetes

NOT YET RECRUITING
NCT05925933Phase NADiabetes Foundation, IndiaStarted 2023-10-01
Intervention
Episodic MigraineChronic Migraine

CGRP Inhibition, Autonomic Function, and Migraine

RECRUITING
NCT04628429Medical University of ViennaStarted 2020-10-01
ErenumabGalcanezumabFremanezumab
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
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
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®)
Healthy VolunteersAtherosclerotic Heart Disease

ClinSeq: A Large-Scale Medical Sequencing Clinical Research Pilot Study

ACTIVE NOT RECRUITING
NCT00410241National Human Genome Research Institute (NHGRI)Started 2007-01-05
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
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
Clonal Hematopoiesis

Donor CHIP and Allogeneic HSCT Outcome

RECRUITING
NCT04689750The University of Hong KongStarted 2021-01-01
Next generation sequencing
Coronary Heart Disease

Adipose Tissue and Inflammation in Coronary Heart Disease

ACTIVE NOT RECRUITING
NCT02760914Oslo University HospitalStarted 2016-06