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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SREBF2
sterol regulatory element binding transcription factor 2
Chromosome 22 · 22q13.2
NCBI Gene: 6721Ensembl: ENSG00000198911.14HGNC: HGNC:11290UniProt: Q12772
262PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription Factor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
C-8 sterol isomerase activitypositive regulation of cholesterol storagenegative regulation of cholesterol effluxpositive regulation of transcription by RNA polymerase IIneurodegenerative diseaseHypercholesterolemiahepatocellular carcinomainfectious disease
✦AI Summary

SREBF2 encodes a master transcription factor that regulates cholesterol biosynthesis and cellular lipid homeostasis. The protein binds to sterol regulatory elements (SRE-1) and E-box motifs to activate transcription of cholesterol synthesis genes 1. Beyond its canonical role in cholesterol metabolism, SREBF2 integrates multiple cellular processes including inflammation, where the SCAP-SREBP2 complex translocates from endoplasmic reticulum to Golgi to facilitate NLRP3 inflammasome activation in macrophages 1. In cancer, SREBF2 upregulation promotes aggressive serrated tumorigenesis through enhanced cholesterol biosynthesis 2, while in pancreatic cancer, SREBF2-driven CYP51A1 expression confers resistance to pH-dependent cell death 3. SREBF2 also maintains intestinal stem cell function through cholesterol-mediated stemness restoration 4 and controls regulatory T cell homeostasis in adipose tissue, with disruption leading to metabolic dysfunction in obesity 5. Additionally, SREBF2 regulates astrocyte lipid metabolism and ApoE secretion in neuroinflammatory conditions 6. Disease associations include migraine susceptibility 7 and polycystic ovary syndrome, where SREBF2 suppression promotes ferroptosis 8. These findings establish SREBF2 as a central metabolic regulator with broad therapeutic implications.

Sources cited
1
SREBF2 binds to sterol regulatory elements and integrates cholesterol metabolism with NLRP3 inflammasome activation
PMID: 30366764
2
SREBF2 upregulation through PKCλ/ι deficiency promotes aggressive serrated colorectal tumorigenesis
PMID: 38092754
3
SREBF2-driven CYP51A1 expression confers resistance to pH-dependent cell death in pancreatic cancer
PMID: 40055353
4
SREBF2 activation enhances cholesterol biosynthesis and maintains intestinal stem cell stemness
PMID: 37647408
5
SREBF2-mediated cholesterol homeostasis controls regulatory T cell function in visceral adipose tissue
PMID: 39792637
6
SREBF2 regulates astrocyte cholesterol synthesis and ApoE secretion in response to microglial oxysterols
PMID: 36849076
7
SREBF2 is identified as a novel migraine susceptibility gene through transcriptome-wide association studies
PMID: 38840241
8
SREBF2 suppression by PER1 promotes ferroptosis and lipid metabolism dysfunction in PCOS
PMID: 38653359
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.46Moderate
HypercholesterolemiaOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.11Weak
infectious diseaseOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.10Weak
neoplasmOpen Targets
0.10Suggestive
esophageal squamous cell carcinomaOpen Targets
0.09Suggestive
posterior cortical atrophyOpen Targets
0.09Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
COVID-19Open Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
diffuse large B-cell lymphomaOpen Targets
0.08Suggestive
rectum cancerOpen Targets
0.07Suggestive
cancerOpen Targets
0.07Suggestive
ulnar-mammary syndromeOpen Targets
0.07Suggestive
early-onset non-syndromic cataractOpen Targets
0.07Suggestive
leukemiaOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TP53Protein interaction100%ABCG5Protein interaction100%SP1Protein interaction99%KPNB1Protein interaction96%MBTPS1Protein interaction95%PPARGC1BProtein interaction92%
Tissue Expression6 tissues
Heart
100%
Brain
81%
Lung
67%
Liver
64%
Bone Marrow
58%
Ovary
50%
Gene Interaction Network
Click a node to explore
SREBF2TP53ABCG5SP1KPNB1MBTPS1PPARGC1B
PROTEIN STRUCTURE
Preparing viewer…
PDB1UKL · 3.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.47 [0.37–0.59]
RankingsWhere SREBF2 stands among ~20K protein-coding genes
  • #1,445of 20,598
    Most Researched262 · top 10%
  • #4,028of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedSREBF2
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Cholesterol Homeostatic Regulator SCAP-SREBP2 Integrates NLRP3 Inflammasome Activation and Cholesterol Biosynthetic Signaling in Macrophages.
PMID: 30366764
Immunity · 2018
1.00
2
Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis.
PMID: 38092754
Nat Commun · 2023
0.90
3
A cross-tissue transcriptome-wide association study reveals novel susceptibility genes for migraine.
PMID: 38840241
J Headache Pain · 2024
0.80
4
Regulation of astrocyte lipid metabolism and ApoE secretionby the microglial oxysterol, 25-hydroxycholesterol.
PMID: 36849076
J Lipid Res · 2023
0.70
5
SREBF1c and SREBF2 gene polymorphisms are associated with acute coronary syndrome and blood lipid levels in Mexican population.
PMID: 31490983
PLoS One · 2019
0.68