SAR1B

Chr 5AR

secretion associated Ras related GTPase 1B

Also known as: ANDD, CMRD, GTBPB, SARA2

NCBI Gene: 51128ENSG00000152700UniProt: Q9Y6B6

The protein encoded by this gene is a small GTPase that acts as a homodimer. The encoded protein is activated by the guanine nucleotide exchange factor PREB and is involved in protein transport from the endoplasmic reticulum to the Golgi. This protein is part of the COPII coat complex. Defects in this gene are a cause of chylomicron retention disease (CMRD), also known as Anderson disease (ANDD). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

Chylomicron retention diseaseMIM #246700
AR
210
ClinVar variants
46
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SAR1B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 60 VUS of 210 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.99LOEUF
pLI 0.002
Z-score 1.60
OE 0.50 (0.27–0.99)
Tolerant

Typical tolerance to LoF variation

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.
0.81Z-score
OE missense 0.78 (0.65–0.93)
83 obs / 106.7 exp
Tolerant

Mild missense constraint

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.0.50 (0.27–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.65–0.93)
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.0.93
0≤1.21.6
LoF obs/exp: 6 / 12.0Missense obs/exp: 83 / 106.7Syn Z: 0.32

ClinVar Variant Classifications

210 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic10
VUS60
Likely Benign92
Benign9
Conflicting3
36
Pathogenic
10
Likely Pathogenic
60
VUS
92
Likely Benign
9
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
2
24
0
36
Likely Pathogenic
3
2
5
0
10
VUS
0
50
10
0
60
Likely Benign
0
0
53
39
92
Benign
0
0
8
1
9
Conflicting
—3
Total135410040210

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

View in ClinVar →

Protein Context — Lollipop Plot

SAR1B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Chylomicron retention disease

MIM #246700

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SAR1B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism.
Auclair N et al.·J Lipid Res
2023
Chylomicron retention disease: genetics, biochemistry, and clinical spectrum.
Levy E et al.·Curr Opin Lipidol
2019Review
Update on the molecular biology of dyslipidemias.
Ramasamy I·Clin Chim Acta
2016Review
[Chylomicron retention disease caused by SAR1B gene variations in 2 cases and literatures review].
Zhang YQ et al.·Zhonghua Er Ke Za Zhi
2024Review
Anderson or chylomicron retention disease: molecular impact of five mutations in the SAR1B gene on the structure and the functionality of Sar1b protein.
Charcosset M et al.·Mol Genet Metab
2008Functional
Chylomicron retention disease caused by a new pathogenic variant in sar1b protein: a rare case report from Syria.
Doya LJ et al.·BMC Pediatr
2021Case report
Insights from human congenital disorders of intestinal lipid metabolism.
Levy E·J Lipid Res
2015Review
Molecular analysis of APOB, SAR1B, ANGPTL3, and MTTP in patients with primary hypocholesterolemia in a clinical laboratory setting: Evidence supporting polygenicity in mutation-negative patients.
Blanco-Vaca F et al.·Atherosclerosis
2019Cohort
Animal model of Sar1b deficiency presents lipid absorption deficits similar to Anderson disease.
Levic DS et al.·J Mol Med (Berl)
2015Functional
Novel mutations of SAR1B gene in four children with chylomicron retention disease.
Simone ML et al.·J Clin Lipidol
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Case Report: Neonatal-onset chylomicron retention disease presenting as isolated failure to thrive with compound heterozygous SAR1B variants: the value of early genetic testing and challenges of long-term management.
Liu B et al.·Front Pediatr
2026🔓 Open AccessCase report
Dietary phospholipids alleviate high fat diet-induced intestinal lipid deposition through ATF4-PPARα-MTTP/SAR1B pathway in yellow catfish.
Zheng H et al.·J Nutr Biochem
2026
Leucine Alleviates Endoplasmic Reticulum-Stress Mediated Lipotoxic Injury Induced by High-Fat Diet Via Sar1b/Sestrin2/Ampkα1 Pathways in Acanthopagrus Schlegelii.
Zhao W et al.·J Nutr
2026
Advances in the basic function of the small GTPase SAR1B and its regulatory role in the biological behavior of tumor cells (Review).
Yang Q et al.·Mol Clin Oncol
2026🔓 Open AccessReview
Fenofibrate Treatment Inhibits Very-Low-Density Lipoprotein Transport Vesicle Formation by Reducing Sar1b Protein Expression.
Winterfeldt K et al.·Int J Mol Sci
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools