APOB

Chr 2ADAR

apolipoprotein B

NCBI Gene: 338ENSG00000084674UniProt: P04114

Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100). Apo B-100 functions as a recognition signal for the cellular binding and internalization of LDL particles by the apoB/E receptor

Primary Disease Associations & Inheritance

Hypercholesterolemia, familial, 2MIM #144010
AD
HypobetalipoproteinemiaMIM #615558
AR
5061
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical Summary— APOB
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 304 VUS of 5061 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.46LOEUF
pLI 0.000
Z-score 7.20
OE 0.37 (0.30–0.46)
Moderately constrained

More LoF-intolerant than ~75% 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.
-1.70Z-score
OE missense 1.10 (1.06–1.14)
2482 obs / 2254.4 exp
Tolerant

Tolerant to missense variation

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.0.37 (0.30–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (1.06–1.14)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 56 / 151.7Missense obs/exp: 2482 / 2254.4Syn Z: -1.40

ClinVar Variant Classifications

5061 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic9
VUS304
Likely Benign166
Benign1
Conflicting7
7
Pathogenic
9
Likely Pathogenic
304
VUS
166
Likely Benign
1
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
4
0
7
Likely Pathogenic
9
0
0
0
9
VUS
4
285
12
3
304
Likely Benign
0
46
21
99
166
Benign
0
1
0
0
1
Conflicting
—7
Total1633237102494

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

View 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.

Gene2Phenotype Curations

APOB-related hypercholesterolaemia

definitive
ADDominant NegativeAltered Gene Product Structure
Skin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
APOLIPOPROTEIN B; APOB
MIM #107730 · *

Hypercholesterolemia, familial, 2

MIM #144010

Molecular basis of disorder known

Autosomal dominant

Hypobetalipoproteinemia

MIM #615558

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Apolipoprotein B: Bridging the Gap Between Evidence and Clinical Practice.
De Oliveira-Gomes D et al.·Circulation
2024Review
Oxidized phospholipids in cardiovascular disease.
Tsimikas S et al.·Nat Rev Cardiol
2024Review
Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel.
Sturm AC et al.·J Am Coll Cardiol
2018Review
Apolipoprotein B-containing lipoproteins in atherogenesis.
Borén J et al.·Nat Rev Cardiol
2025Review
Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features.
Bertolini S et al.·Atherosclerosis
2020
Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An Expert Clinical Consensus from the National Lipid Association.
Soffer DE et al.·J Clin Lipidol
2024
Genetic spectrum of familial hypercholesterolemia and correlations with clinical expression: Implications for diagnosis improvement.
Di Taranto MD et al.·Clin Genet
2021
Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention.
Sniderman AD et al.·Eur Heart J
2024
Applying apoB to the diagnosis and therapy of the atherogenic dyslipoproteinemias: a clinical diagnostic algorithm.
Sniderman AD·Curr Opin Lipidol
2004Review
The hypobetalipoproteinemias.
Schonfeld G·Annu Rev Nutr
1995Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Familial Hypercholesterolemia

Child-Parent Familial Hypercholesterolemia Screening

RECRUITING
NCT04529967Children's Hospital of Fudan UniversityStarted 2025-04-01
no interventions
Non-alcoholic Fatty LiverAtherogenic DyslipidemiaInsulin Resistance

Genetic Pathways Leading to Fatty Liver and Atherogenic Dyslipidemia

ENROLLING BY INVITATION
NCT04209816Marja-Riitta TaskinenStarted 2019-12-01
Lipoprotein kinetics
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
Aging

Arlington Aging Study

RECRUITING
NCT06857877The University of Texas at ArlingtonStarted 2024-09-01
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
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.
Critical IllnessInflammationMalnutrition

Amino Acid Nutrition in the Critically-ill

ACTIVE NOT RECRUITING
NCT02865408Phase NAArnold KristofStarted 2017-03-01
Peptamen 1.5% via enteralProsol 20% IV to 1.75g/kg/dayProsol 20% IV to 2.5g/kg/day
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
Familial Hypercholesterolemia

EAS Familial Hypercholesterolaemia Studies Collaboration

RECRUITING
NCT04272697Imperial College LondonStarted 2015-03-22
Fasting

Fasting Effects on Metabolism and Immunity Study in Human

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

Biomarker pAtterns Reflecting habITual fOod iNtakE: the BARITONE Project

NOT YET RECRUITING
NCT07128940Phase NAGöteborg UniversityStarted 2025-09-15
Meat vs fishMeat vs VegetarianFish vs Vegetarian
Healthy VolunteersMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

RECRUITING
NCT05648214Phase PHASE1Regeneron PharmaceuticalsStarted 2022-12-27
ALN-PNPPlacebo (PB)

External Resources

Links to major genomics databases and tools