HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
STARD4
StAR related lipid transfer domain containing 4
Chromosome 5 · 5q22.1
NCBI Gene: 134429Ensembl: ENSG00000164211.14HGNC: HGNC:18058UniProt: B0AZS2
29PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpositive regulation of bile acid biosynthetic processpositive regulation of cholesterol metabolic processcytoplasmatrial fibrillationbenign prostatic hyperplasiaoral mucosa leukoplakialower urinary tract symptom
✦AI Summary

STARD4 is a cytosolic sterol transfer protein that plays a critical role in intracellular cholesterol transport and homeostasis 1. The protein consists almost entirely of a START domain and belongs to a subfamily with STARD5 and STARD6, sharing approximately 30% amino acid identity with these homologues 2. STARD4 functions as a non-vesicular cholesterol transporter, rapidly equilibrating sterol between membranes, particularly those with anionic lipid headgroups 3. The protein localizes to the cytoplasm and endoplasmic reticulum (ER), where it co-localizes with ACAT-1 and increases ACAT activity 2-fold by delivering cholesterol for esterification 4. STARD4 expression is negatively regulated by cholesterol via SREBP-2 through a functional sterol regulatory element in its promoter 5 and is induced during early ER stress through ATF6 and an ERSE-like element 6. Stable reduction of STARD4 results in increased total cholesterol, slower cholesterol trafficking, altered membrane fluidity, and compensatory changes in lipid homeostasis 1. In disease contexts, STARD4 acts as a tumor suppressor in prostate cancer by regulating cholesterol metabolism and AR signaling, with reduced expression correlating with adverse prognosis 7.

Sources cited
1
STARD4 is a sterol transport protein involved in cholesterol homeostasis and its reduction affects cholesterol regulation
PMID: 31917335
2
STARD4 belongs to a START protein subfamily with STARD5 and STARD6, sharing 30% amino acid identity
PMID: 12011452
3
STARD4 rapidly equilibrates sterol between membranes, especially those with anionic lipid headgroups
PMID: 27421092
4
STARD4 localizes to cytoplasm and ER, co-localizes with ACAT-1, and increases ACAT activity 2-fold
PMID: 21767660
5
STARD4 expression is negatively regulated by cholesterol via SREBP-2 through a sterol regulatory element
PMID: 15760897
6
STARD4 is induced during early ER stress through ATF6 and an ERSE-like element
PMID: 16579971
7
STARD4 acts as tumor suppressor in prostate cancer through cholesterol metabolism regulation and AR signaling
PMID: 41331871
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.43Moderate
benign prostatic hyperplasiaOpen Targets
0.34Weak
oral mucosa leukoplakiaOpen Targets
0.30Weak
lower urinary tract symptomOpen Targets
0.28Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.27Weak
cardiac transplantOpen Targets
0.24Weak
eye injuryOpen Targets
0.23Weak
response to stimulusOpen Targets
0.23Weak
metabolic diseaseOpen Targets
0.22Weak
Brugada syndromeOpen Targets
0.19Weak
chronic rhinosinusitis without nasal polypsOpen Targets
0.14Weak
neoplasmOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
ankyloglossiaOpen Targets
0.09Suggestive
posterior cortical atrophyOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.07Suggestive
oral squamous cell carcinomaOpen Targets
0.05Suggestive
ulcerative colitisOpen Targets
0.05Suggestive
urinary tract obstructionOpen Targets
0.05Suggestive
gallbladder disease 1Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PCTPProtein interaction94%STARD3Protein interaction72%RELCHShared pathway33%STARD6Co-mentioned in literature30%TSPO2Shared pathway25%SERAC1Shared pathway25%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
49%
Heart
47%
Lung
40%
Brain
23%
Ovary
13%
Gene Interaction Network
Click a node to explore
STARD4PCTPSTARD3RELCHSTARD6TSPO2SERAC1
PROTEIN STRUCTURE
Preparing viewer…
PDB6L1M · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.65LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.20 [0.88–1.65]
RankingsWhere STARD4 stands among ~20K protein-coding genes
  • #12,245of 20,598
    Most Researched29
  • #15,894of 17,882
    Most Constrained (LOEUF)1.65
Genes detectedSTARD4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Differential regulation of STARD1, STARD4 and STARD6 in the human ovary.
PMID: 38829257
J Endocrinol · 2024
1.00
2
STARD4 suppresses tumorigenesis and attenuates enzalutamide resistance via lipid metabolic reprogramming and AR stabilization in prostate cancer.
PMID: 41331871
J Exp Clin Cancer Res · 2025
0.90
3
Regulation of human STARD4 gene expression under endoplasmic reticulum stress.
PMID: 16579971
Biochem Biophys Res Commun · 2006
0.80
4
Role of STARD4 and NPC1 in intracellular sterol transport.
PMID: 27421092
Biochem Cell Biol · 2016
0.70
5
Stable reduction of STARD4 alters cholesterol regulation and lipid homeostasis.
PMID: 31917335
Biochim Biophys Acta Mol Cell Biol Lipids · 2020
0.60