OSBPL3

Chr 7

oxysterol binding protein like 3

Also known as: ORP-3, ORP3, OSBP3

NCBI Gene: 26031ENSG00000070882UniProt: Q9H4L5

This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. The encoded protein is involved in the regulation of cell adhesion and organization of the actin cytoskeleton. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

158
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— OSBPL3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 121 VUS of 158 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.54LOEUF
pLI 0.000
Z-score 4.29
OE 0.37 (0.26–0.54)
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.
1.18Z-score
OE missense 0.85 (0.78–0.92)
419 obs / 492.7 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.0.37 (0.26–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.78–0.92)
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.1.11
0≤1.21.6
LoF obs/exp: 20 / 54.0Missense obs/exp: 419 / 492.7Syn Z: -1.20

ClinVar Variant Classifications

158 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic3
VUS121
Likely Benign4
30
Pathogenic
3
Likely Pathogenic
121
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
3
0
3
VUS
0
115
6
0
121
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total0119390158

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

View in ClinVar →

Protein Context — Lollipop Plot

OSBPL3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by multi-omic data analysis.
Wang C et al.·BMC Gastroenterol
2023
Interferon regulatory factor 1 contributes to metabolic dysfunction associated steatotic liver disease.
Sun X et al.·Life Sci
2025
Oxysterol binding protein-like 3 (OSBPL3) is a novel driver gene that promotes tumor growth in part through R-Ras/Akt signaling in gastric cancer.
Hu Q et al.·Sci Rep
2021
Integrative analysis of an endoplasmic reticulum stress-related signature in multiple myeloma.
Wu C et al.·J Gene Med
2024
Germline and somatic genetic variability of oxysterol-related genes in breast cancer patients with early disease of the luminal subtype.
Holý P et al.·Biochimie
2022Cohort
Identification of Differentially Expressed Splice Variants by the Proteogenomic Pipeline Splicify.
Komor MA et al.·Mol Cell Proteomics
2017
Identification of hub genes in colorectal cancer based on weighted gene co-expression network analysis and clinical data from The Cancer Genome Atlas.
Zhang Y et al.·Biosci Rep
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
OSBPL3 drives colorectal cancer progression via Hippo-YAP signaling and modulates MEK inhibitor sensitivity.
Zhong Y et al.·Commun Biol
2026
OSBPL3-driven sterol metabolic reprogramming promotes oncogenic signaling and therapeutic resistance in pancreatic cancer.
Sun Q et al.·Theranostics
2026🔓 Open Access
OSBPL3 promotes LUAD metastasis and glycolysis through transcriptional upregulation of PLAU via NFE2L2.
Zhang Q et al.·Transl Oncol
2026🔓 Open Access
Exploring the potential mechanisms of OSBPL3 in metabolic dysfunction-associated steatotic liver disease by integrating bulk and single-cell RNA sequencing data.
Wang Q et al.·Medicine (Baltimore)
2025🔓 Open AccessFunctional
Hsa-miR-181a-5p Enhances the Chemosensitivity of Breast Cancer Cells to Tamoxifen by Regulation of the OSBPL3/RAS Signaling Pathway.
Lin J et al.·Cureus
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