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25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SREBF1
sterol regulatory element binding transcription factor 1
Chromosome 17 Β· 17p11.2
NCBI Gene: 6720Ensembl: ENSG00000072310.19HGNC: HGNC:11289UniProt: B3KR77
471PubMed Papers
22Diseases
0Drugs
6Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
SREBP signaling pathwaysequence-specific double-stranded DNA bindingregulation of transcription by RNA polymerase IInegative regulation of triglyceride metabolic processhereditary mucoepithelial dysplasiaIFAP syndrome 2neurodegenerative diseaseIFAP syndrome 1, with or without BRESHECK syndrome
✦AI Summary

SREBF1 (sterol regulatory element binding transcription factor 1) is a master transcriptional regulator of lipogenic gene expression that controls de novo lipid synthesis and cholesterol homeostasis. As a key lipogenic transcription factor, SREBF1 activates genes encoding enzymes involved in fatty acid and cholesterol biosynthesis 1. The protein functions through a regulated activation mechanism: in response to sterol depletion, SREBF1 is cleaved and translocates from the endoplasmic reticulum to the Golgi apparatus, enabling nuclear accumulation and transcriptional activity 2. SREBF1 plays critical roles in both normal metabolism and disease. In hepatocytes, SREBF1 expression is suppressed by AMPK activation, a key mechanism underlying the glucose-lowering and lipid-improving effects of metformin in type 2 diabetes 3. In cancer cells, SREBF1 concurrently regulates lipid synthesis and lipophagy to maintain cholesterol homeostasis and support rapid tumor growth 4. SREBF1 is also implicated in nonalcoholic fatty liver disease (NAFLD), where its activation promotes hepatic steatosis through upregulation of lipogenic enzymes like SCD1 1. Recent evidence identifies SREBF1 as a disease-relevant transcription factor in Alzheimer's disease pathogenesis 5. Therapeutic targeting of SREBF1 through protein degradation or translocation inhibition shows promise for treating metabolic diseases and cancers characterized by dysregulated lipid metabolism 26.

Sources cited
1
SREBF1 identified as a disease-relevant transcription factor in Alzheimer's disease through trajectory analysis of glial populations
PMID: 34239132
2
SREBF1 concurrently regulates lipid synthesis and lipophagy to maintain cholesterol homeostasis and promote tumor growth
PMID: 37927089
3
SREBP-1c is a key lipogenic transcription factor that regulates SCD1 expression and hepatic triglyceride synthesis in NAFLD
PMID: 31226399
4
Metformin activates AMPK to suppress SREBP-1 expression, reducing hepatic lipogenic enzyme expression and improving lipid metabolism
PMID: 11602624
5
SREBP1 translocates from the ER to Golgi apparatus for activation; this translocation can be inhibited by FMO2 binding, suppressing de novo lipogenesis
PMID: 37874228
6
SREBF1 protein stability can be regulated through ubiquitination-mediated degradation, controlling lipid metabolism in renal cell carcinoma
PMID: 36694250
Disease Associationsβ“˜22
hereditary mucoepithelial dysplasiaOpen Targets
0.71Strong
IFAP syndrome 2Open Targets
0.71Strong
neurodegenerative diseaseOpen Targets
0.48Moderate
IFAP syndrome 1, with or without BRESHECK syndromeOpen Targets
0.45Moderate
type 2 diabetes mellitusOpen Targets
0.40Weak
Alzheimer diseaseOpen Targets
0.38Weak
Parkinson diseaseOpen Targets
0.38Weak
multiple sclerosisOpen Targets
0.37Weak
Hirschsprung diseaseOpen Targets
0.37Weak
lysosomal storage diseaseOpen Targets
0.37Weak
coronary artery diseaseOpen Targets
0.36Weak
prostate carcinomaOpen Targets
0.28Weak
intelligenceOpen Targets
0.24Weak
smoking initiationOpen Targets
0.23Weak
obesityOpen Targets
0.22Weak
diabetes mellitusOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
attention deficit hyperactivity disorderOpen Targets
0.19Weak
IGA glomerulonephritisOpen Targets
0.18Weak
breast cancerOpen Targets
0.15Weak
IFAP syndrome 2UniProt
Mucoepithelial dysplasia, hereditaryUniProt
Pathogenic Variants6
NM_004176.5(SREBF1):c.1579C>T (p.Arg527Cys)Pathogenic
IFAP syndrome 1, with or without BRESHECK syndrome|IFAP syndrome 2|Hereditary mucoepithelial dysplasia|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 527
NM_004176.5(SREBF1):c.406_418del (p.Thr136fs)Likely pathogenic
Hereditary mucoepithelial dysplasia
β˜…β˜†β˜†β˜†2025β†’ Residue 136
NM_004176.5(SREBF1):c.91+1G>CLikely pathogenic
Hereditary mucoepithelial dysplasia
β˜…β˜†β˜†β˜†2024
NM_004176.5(SREBF1):c.1580G>A (p.Arg527His)Likely pathogenic
Hereditary mucoepithelial dysplasia|not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 527
NM_004176.5(SREBF1):c.1582_1584del (p.Asn528del)Pathogenic
IFAP syndrome 2|IFAP syndrome 1, with or without BRESHECK syndrome
β˜†β˜†β˜†β˜†2020β†’ Residue 528
NM_004176.5(SREBF1):c.1589T>C (p.Leu530Pro)Pathogenic
IFAP syndrome 1, with or without BRESHECK syndrome|IFAP syndrome 2
β˜†β˜†β˜†β˜†2020β†’ Residue 530
View on ClinVar β†—
Related Genes
PPARGC1AProtein interaction100%FOXO1Protein interaction100%NR1H4Protein interaction98%RXRBProtein interaction98%EP300Protein interaction97%MED15Protein interaction96%
Tissue Expression6 tissues
Liver
100%
Ovary
27%
Bone Marrow
22%
Lung
19%
Brain
10%
Heart
8%
Gene Interaction Network
Click a node to explore
SREBF1PPARGC1AFOXO1NR1H4RXRBEP300MED15
PROTEIN STRUCTURE
Preparing viewer…
PDB1AM9 Β· 2.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.66LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.52 [0.41–0.66]
RankingsWhere SREBF1 stands among ~20K protein-coding genes
  • #570of 20,598
    Most Researched471 Β· top 5%
  • #3,290of 5,498
    Most Pathogenic Variants6
  • #4,847of 17,882
    Most Constrained (LOEUF)0.66
Genes detectedSREBF1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer's disease.
PMID: 34239132
Nat Genet Β· 2021
1.00
2
SREBF1/SREBP-1 concurrently regulates lipid synthesis and lipophagy to maintain lipid homeostasis and tumor growth.
PMID: 37927089
Autophagy Β· 2024
0.90
3
Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway.
PMID: 31226399
Free Radic Biol Med Β· 2019
0.80
4
Role of AMP-activated protein kinase in mechanism of metformin action.
PMID: 11602624
J Clin Invest Β· 2001
0.70
5
FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1.
PMID: 37874228
Hepatology Β· 2025
0.60