STARD3

Chr 17

StAR related lipid transfer domain containing 3

Also known as: CAB1, MLN64, es64

NCBI Gene: 10948ENSG00000131748UniProt: Q14849

This gene encodes a member of a subfamily of lipid trafficking proteins that are characterized by a C-terminal steroidogenic acute regulatory domain and an N-terminal metastatic lymph node 64 domain. The encoded protein localizes to the membranes of late endosomes and may be involved in exporting cholesterol. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

1
Active trials
8
Pathogenic / LP
78
ClinVar variants
4
Pubs (1 yr)
0.9
Missense Z
0.67
LOEUF
Clinical Summary— STARD3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 61 VUS of 78 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.67LOEUF
pLI 0.000
Z-score 2.95
OE 0.41 (0.26–0.67)
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.
0.91Z-score
OE missense 0.85 (0.76–0.94)
241 obs / 284.0 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.0.41 (0.26–0.67)
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 (0.76–0.94)
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.1.09
0≤1.21.6
LoF obs/exp: 12 / 29.2Missense obs/exp: 241 / 284.0Syn Z: -0.77

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS61
Likely Benign8
Benign1
8
Pathogenic
61
VUS
8
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
58
3
0
61
Likely Benign
0
6
1
1
8
Benign
0
0
0
1
1
Total06412278

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

View in ClinVar →

Protein Context — Lollipop Plot

STARD3 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Overexpression of STARD3 attenuates oxidized LDL-induced oxidative stress and inflammation in retinal pigment epithelial cells.
Almarhoun M et al.·Biochim Biophys Acta Mol Cell Biol Lipids
2021
Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells.
Meneses-Salas E et al.·Cell Mol Life Sci
2020
Overexpression of STARD3 in human monocyte/macrophages induces an anti-atherogenic lipid phenotype.
Borthwick F et al.·Clin Sci (Lond)
2010
Clinical Relevance of Gastroesophageal Cancer Associated SNPs for Oncologic Outcome After Curative Surgery.
Jung JO et al.·Ann Surg Oncol
2022
The HER2 amplicon in breast cancer: Topoisomerase IIA and beyond.
Jacot W et al.·Biochim Biophys Acta
2013Review
17q12-21 - the pursuit of targeted therapy in breast cancer.
Glynn RW et al.·Cancer Treat Rev
2010Review
Detection of novel PPP1R1B::STARD3 fusion transcript in acute myeloid leukemia: a case report.
Firouzabadi ED et al.·J Med Case Rep
2024Case report
Asthma susceptibility variants are more strongly associated with clinically similar subgroups.
Lavoie-Charland E et al.·J Asthma
2016
ANGPTL3 serum concentration and rare genetic variants in Finnish population.
Tikka A et al.·Scand J Clin Lab Invest
2017
Identification of the copy number variant biomarkers for breast cancer subtypes.
Pan X et al.·Mol Genet Genomics
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
STARD3: A Prospective Target for Cancer Therapy
Asif K et al.·Cancers (Basel)
2021
STARD3: A New Biomarker in HER2-Positive Breast Cancer
Lodi M et al.·Cancers (Basel)
2023
Is STARD3 A New Biomarker for Breast Cancer?
Korucu AN et al.·Eur J Breast Health
2024
Using of transporter proteins to improve the uptake efficiency of hydrophobic compounds by Escherichia coli: a coordinated synthesis of START protein and P450scc system proteins to enhance cholesterol biotransformation
Zamalutdinova SV et al.·Bioresour Bioprocess
2025
Exploring the lutein therapeutic potential in steatotic liver disease: mechanistic insights and future directions
Balboa E et al.·Front Pharmacol
2024
Differential Expression and Prognostic Significance of STARD3 Gene in Breast Carcinoma
Fararjeh AFS et al.·Int J Mol Cell Med
2021
Linking Late Endosomal Cholesterol with Cancer Progression and Anticancer Drug Resistance
Nguyen MKL et al.·Int J Mol Sci
2022
The sterol transporter STARD3 transports sphingosine at ER-lysosome contact sites
Hempelmann P et al.·bioRxiv
2023
Top 8 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients