APOB

Chr 2ADAR

apolipoprotein B

This gene encodes apolipoprotein B, the main protein component of chylomicrons and low-density lipoproteins that serves as the ligand for LDL receptor-mediated uptake of cholesterol-containing particles. Mutations cause familial hypercholesterolemia type 2 and hypobetalipoproteinemia with both autosomal dominant and autosomal recessive inheritance patterns. The gene is highly intolerant to loss-of-function variants, reflecting its essential role in lipid metabolism.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAD/ARLOEUF 0.462 OMIM phenotypes
Clinical SummaryAPOB
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Gene-Disease Validity (ClinGen)
familial hypobetalipoproteinemia 1 · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.000
Z-score 7.20
OE 0.37 (0.300.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-1.70Z-score
OE missense 1.10 (1.061.14)
2482 obs / 2254.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.37 (0.300.46)
00.351.4
Missense OE1.10 (1.061.14)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 56 / 151.7Missense obs/exp: 2482 / 2254.4Syn Z: -1.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveAPOB-related hypercholesterolaemiaDNAD
DN
0.74top 25%
GOF
0.3094th %ile
LOF
0.3358th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
LOF1 literature citation · LOEUF 0.46

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

LOFIdentification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemiaPMID:27179706

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

APOB · 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

Obesity (Disorder)Bariatric Surgery

Impact of a Pro-diversity Gut Microbiota Diet After a Bariatric Surgery on Gut Microbiota, Eating Behaviour and Sensory Function

RECRUITING
NCT07268508Phase NAHospices Civils de LyonStarted 2025-11-05
Nutritional counseling
Familial Hypercholesterolemia

EPIRUS FH Reverse Cascade Screening

NOT YET RECRUITING
NCT05825612Hellenic Atherosclerosis SocietyStarted 2023-05
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.
NASHHCCGenetic Predisposition

Evaluation of Risk of hEpatocellular Carcinoma

RECRUITING
NCT06523179Phase NAFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoStarted 2018-01-01
quantify the impact of genetic risk factors
Fasting

Fasting Effects on Metabolism and Immunity Study in Human

RECRUITING
NCT06779201Phase NAXuanwu Hospital, BeijingStarted 2024-09-01
Fasting
Healthy Population

Italian Digital Primary Cardiovascular Prevention Study

ACTIVE NOT RECRUITING
NCT05339841Phase NACentro Cardiologico MonzinoStarted 2022-06-10
Mobile health application
Celiac Disease

Efficacy of Cholesterol-lowering L. Plantarum on Cardiometabolic Health Biomarkers in Coeliac Disease Patients

ACTIVE NOT RECRUITING
NCT06178107Phase NAUniversity of RoehamptonStarted 2022-04-12
LP-LDL ProbioticPlacebo Comparator
Refractory HypercholesterolemiaFamilial Hypercholesterolemia

Safety and Efficacy Study of NGGT006 in Refractory Hypercholesterolemia Patients

NOT YET RECRUITING
NCT06293729Phase EARLY_PHASE1Suzhou Municipal HospitalStarted 2024-06-01
NGGT006
Type 2 DiabetesPrediabetes (Insulin Resistance, Impaired Glucose Tolerance)Prediabetes / Type 2 Diabetes

Effects of Different Fish Oil Types on Type 2 Diabetes Risk Factors in High-Risk Adults

NOT YET RECRUITING
NCT07575438Phase PHASE2May Faraj, PDt, PhDStarted 2026-07
Fish Oil
Type 2 DiabetesInflammationInsulin Sensitivity/Resistance

Targeting Risk Factors for Diabetes in Subjects With Normal Blood Cholesterol Using Omega-3 Fatty Acids

RECRUITING
NCT04485871Phase NAInstitut de Recherches Cliniques de MontrealStarted 2019-12-19
Omega-3 fatty acids
Polycystic Ovary SyndromeHypothalamic Amenorrhea

Body Fat as Determinant of Female Gonadal Dysfunction

RECRUITING
NCT03841981Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalStarted 2020-01-31
Anthropometric and physical examinationIndirect calorimetry, accelerometer and seven-day dietary recallBiochemical, hormonal and metabolic phenotyping
Morbid Obesity

Dairy Lipids and Cardiometabolic Risk

RECRUITING
NCT05783466Phase NAHospices Civils de LyonStarted 2023-06-28
Low-fat dairy productsWhole-fat dairy productsMilk polar lipid enriched whole-fat dairy products
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
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