SREBF2

Summary

SREBF2 (sterol regulatory element binding transcription factor 2, HGNC:11290) is a protein-coding gene on chromosome 22q13.2, encoding Sterol regulatory element-binding protein 2 (Q12772). Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane.

This gene encodes a member of the a ubiquitously expressed transcription factor that controls cholesterol homeostasis by regulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix-leucine zipper (bHLH-Zip) domain and binds the sterol regulatory element 1 motif. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 6721 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurocutaneous syndrome (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 256 total
• Druggable target: yes
• Transcription factor: yes — 73 downstream targets (CollecTRI)
• MANE Select transcript: NM_004599

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11290
Approved symbol	SREBF2
Name	sterol regulatory element binding transcription factor 2
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	SREBP2, bHLHd2
Ensembl gene	ENSG00000198911
Ensembl biotype	protein_coding
OMIM	600481
Entrez	6721

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 19 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000361204, ENST00000424354, ENST00000435061, ENST00000462539, ENST00000463741, ENST00000464119, ENST00000490262, ENST00000491541, ENST00000710853, ENST00000873311, ENST00000873312, ENST00000873313, ENST00000873314, ENST00000873315, ENST00000873316, ENST00000873317, ENST00000873318, ENST00000925848, ENST00000925849, ENST00000925850, ENST00000925851, ENST00000925852, ENST00000925853, ENST00000925854, ENST00000925855

RefSeq mRNA: 1 — MANE Select: NM_004599 NM_004599

CCDS: CCDS14023

Canonical transcript exons

ENST00000361204 — 19 exons

Exon	Start	End
ENSE00001626473	41870889	41871035
ENSE00001629818	41877229	41877421
ENSE00001688241	41877942	41878123
ENSE00001726292	41868611	41868792
ENSE00001729040	41873798	41874019
ENSE00001733202	41866831	41867280
ENSE00001863297	41905440	41907305
ENSE00001912807	41833105	41833358
ENSE00003498877	41897052	41897161
ENSE00003512900	41880716	41880992
ENSE00003523938	41893117	41893285
ENSE00003532095	41875543	41875724
ENSE00003561680	41884842	41885011
ENSE00003566189	41894820	41894937
ENSE00003581626	41875337	41875451
ENSE00003625682	41904863	41904974
ENSE00003661789	41902970	41903155
ENSE00003687492	41898649	41898781
ENSE00003692206	41900330	41900498

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 115.4918 / max 489.0557, expressed in 1829 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192508	96.6100	1829
192510	14.4355	1776
192509	1.9577	1057
192518	0.9411	616
192512	0.9162	483
192511	0.4385	219
192519	0.1502	58
192517	0.0425	25

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.54	gold quality
cortical plate	UBERON:0005343	98.52	gold quality
ventricular zone	UBERON:0003053	98.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.39	gold quality
cerebellar hemisphere	UBERON:0002245	98.25	gold quality
cerebellar cortex	UBERON:0002129	98.16	gold quality
right adrenal gland cortex	UBERON:0035827	97.79	gold quality
right adrenal gland	UBERON:0001233	97.68	gold quality
left adrenal gland cortex	UBERON:0035825	97.33	gold quality
left adrenal gland	UBERON:0001234	97.31	gold quality
right frontal lobe	UBERON:0002810	97.30	gold quality
cerebellum	UBERON:0002037	97.03	gold quality
tibial nerve	UBERON:0001323	97.02	gold quality
adrenal gland	UBERON:0002369	96.92	gold quality
adrenal cortex	UBERON:0001235	96.89	gold quality
adrenal tissue	UBERON:0018303	96.88	gold quality
prefrontal cortex	UBERON:0000451	96.79	gold quality
cingulate cortex	UBERON:0003027	96.48	gold quality
mucosa of transverse colon	UBERON:0004991	96.48	gold quality
anterior cingulate cortex	UBERON:0009835	96.44	gold quality
skin of leg	UBERON:0001511	96.42	gold quality
esophagus mucosa	UBERON:0002469	96.39	gold quality
sural nerve	UBERON:0015488	96.39	gold quality
lower esophagus mucosa	UBERON:0035834	96.38	gold quality
skin of abdomen	UBERON:0001416	96.33	gold quality
rectum	UBERON:0001052	96.19	gold quality
body of stomach	UBERON:0001161	96.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.90	gold quality
amygdala	UBERON:0001876	95.85	gold quality
paraflocculus	UBERON:0005351	95.81	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.07

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

73 targets.

Target	Regulation
AACS	Repression
ABCA1	Repression
ABCA3	Repression
ABCA7	Activation
ABCG5	Repression
ABCG8	Repression
ACLY	Activation
ACOT7	Activation
ACR	Activation
ACSL1	Activation
ACSS2	Activation
APOA2	Unknown
CASP2
CASP7
CETP	Activation
CYP4F2	Activation
CYP51A1	Unknown
CYP8B1	Repression
DDAH1	Unknown
DHCR24	Repression
EBP	Activation
FABP6	Unknown
FAS	Unknown
FASN	Activation
FDFT1	Unknown
FDPS	Unknown
FGF19	Unknown
G6PD	Activation
GNAS
HMGCR	Activation

JASPAR motifs

Motif	Name	Family
MA0596.1	SREBF2	bHLH-ZIP
MA0828.1	SREBF2	bHLH-ZIP
MA0828.2	SREBF2	bHLH-ZIP
MA0828.3	SREBF2	bHLH-ZIP
MA1933.1	ELK1::SREBF2	Ets-related::bHLH-ZIP
MA1933.2	ELK1::SREBF2	Ets-related::bHLH-ZIP
MA1939.1	ERF::SREBF2	Ets-related::bHLH-ZIP
MA1939.2	ERF::SREBF2	Ets-related::bHLH-ZIP

JASPAR matrix evidence (PMIDs): PMID:8156598, PMID:11591434, PMID:23050235

Upstream regulators (CollecTRI, top): AR, CEBPA, FBXW7, NFYA, NR1H3, PPARA, PPARG, SP1, SREBF1, SREBF2, TTF1

miRNA regulators (miRDB)

100 targeting SREBF2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-124-3P	99.89	73.74	3043

Literature-anchored findings (GeneRIF, showing 40)

• a common variation in the SREBP-2 gene is related with early-stage carotid atherosclerosis in subjects with a risk of cardiovascular events without detectable change in plasma lipid levels (PMID:12801623)
• Transport from endoplasmic reticulum to Golgi apparatus is sterol regulated and requires co-expression of SCAP and Insigs. (PMID:12842885)
• Sterol regulatory element-binding protein-2 interacts with hepatocyte nuclear factor-4 to enhance sterol isomerase gene expression in hepatocytes (PMID:12855700)
• Simvastatin increased nuclear factors, notably sterol regulatory element-binding protein-2, capable of binding to the paraoxonase promoter. (PMID:14500290)
• results show the crystal structure of importin-beta complexed with the active form of SREBP-2 (PMID:14645851)
• The lipogenic effect of SREBP2(N) in liver cells was suppressed by ATF6(N). (PMID:14765107)
• activation of Erk-MAPK pathways by hormones such as insulin might be related to a novel regulatory principle of SREBP-2 (PMID:14988395)
• High levels of SREBP-2 protein is associted with during prostate cancer progression to androgen independence (PMID:15026365)
• nSREBPs are essential for high levels of lipid synthesis in the liver and indicate that Insig’s modulate nSREBP levels by binding and retaining SCAP in the ER. (PMID:15085196)
• SREBP2 down-regulates ATP-binding cassette transporter A1 in vascular endothelial cells (PMID:15358760)
• EC nuclei showed strong SREBP staining in human atherosclerotic lesions, suggesting a role for SREBP. Endothelial cholesterol depletion & SREBP activation play a role in inflammatory processes in which phospholipid oxidation products accumulate. (PMID:15388640)
• the SREBP-2 polymorphism is related to elevated concentrations of serum TC and LDL-C in hypercholesterolemic subjects (PMID:15547298)
• the opposite regulation of hepatic lipase expression by fatty acids and statins is mediated via SREBP, possibly through interaction with upstream stimulatory factors (PMID:15721010)
• SREBP-2 homodimers and heterodimers localize in the nucleus and activate transcription. (PMID:15798184)
• Variants of SREBF2 might be genetic factors involved in the pathogenesis of vascular dementia. (PMID:16082694)
• Phagocytosis triggered the proteolytic activation of SREBP-1a and SREBP-2; upon overexpression of these proteins, phagocytosis-induced transcription and lipid synthesis were blocked; SREBPs are essential regulators of membrane biogenesis (PMID:16141315)
• Active SREBP-2 also induced expression of the CASP-2 gene and the caspase-2 protein and increased the cholesterol and triacylglycerol cellular content. (PMID:16227610)
• SREBP2 modulates brain palmitoyl-coa hydrolase gene transcription. (PMID:16335799)
• A possible gene-gene interaction between the genes encoding SREBP-2 and SCAP that modulate plasma lipids in a strictly gender-specific fashion. (PMID:16466730)
• Low density lipoproteins stimulate LRP1 transcription and decrease SREBP-2 active form which negatively regulates LRP1 transcription (PMID:16697011)
• The role of SREBP-2 in the regulation of ABCA1 transcription via generation of oxysterol ligands for liver X receptor is reported. (PMID:16901265)
• Modulation of human Niemann-Pick disease, type C1 protein expression and promoter activity by cholesterol in a =sterol regulatory element binding protein-2 dependent mechanism. (PMID:17008555)
• CYP4F2 transcription and that CYP4F2 induction by statins is mediated by SREBP-2. (PMID:17142457)
• SREBP transcription factors play an important role in disturbed lipid metabolism in renal failure. (PMID:17198935)
• The SREBP-2-595A isoform was associated with an increased risk of early-onset myocardial infarction in U.S. men. (PMID:17383658)
• Endoplasmic reticulum stress causes the activation of sterol regulatory element binding protein-2. (PMID:17604677)
• SREBP-2 can transcriptionally activate proprotein convertase subtilisin/kexin type 9 (PCSK9) via the sterol-regulatory element (SRE) in its proximal promoter region in HepG2 cells. (PMID:17921436)
• novel mechanism for flavonoid-induced cytoprotection in SH-SY5Y cells involving SREBP-2-mediated sterol synthesis that decreases lipid peroxidation by maintaining membrane integrity in the presence of oxidative stress. (PMID:18032389)
• Transport of LDL-derived cholesterol from late endosomes/lysosomes to the sterol-regulatory pool is regulated by the NPC1 protein and promotes feedback inhibition of the SREBP pathway. (PMID:18272927)
• Real-time RT-PCR analyses confirmed that exercise-induced muscle damage led to a rapid (3 h) increase in sterol response element binding protein 2 (SREBP-2). (PMID:18321953)
• growth factors inhibit sumoylation of SREBPs through their phosphorylation, thus avoiding the recruitment of an HDAC3 corepressor complex and stimulating the lipid uptake and synthesis required for cell growth. (PMID:18403372)
• Results suggest that AKAP12A may activate SREBP-2 by increasing cholesterol efflux, and is a novel regulator of cellular cholesterol metabolism. (PMID:18579430)
• SREBF2 is a novel loci for schizophrenia susceptibility and controlled cholesterol biosynthesis. (PMID:18936756)
• This study is the first report to evaluate the association between SREBP-2 gene polymorphisms and the susceptibility of avascular necrosis in the Korean population. (PMID:18954446)
• that down regulation of Srebf2 may be the triggering factor for down regulation of the cholesterol biosynthesis pathway (PMID:18959802)
• The cholesterol contant of endoplasmic reticulum exceeds 5% of total endoplasmic reticulum lipids (molar basis), sterol regulatory element binding transcription factor 2 transport is abruptly blocked. (PMID:19041766)
• SREBP@ mRNa leves are 7- and 3-fold higher in non-alcohol fatty liver disease patients compared with controls. (PMID:19231010)
• The individuals carrying the G allele of SREBP-2 have more favorable lipid profiles than those carrying the C allele in Han but not in Hei Yi Zhuang. (PMID:19263511)
• Results show that caspase 7, as an SREBP-1/2 target, can be induced under mevalonate-restricting conditions, which might help overcome its shortage. (PMID:19323650)
• ox-LDL can dose-dependently enhance the expressions of SREBP-2 and HMGCR mRNA in macrophages from patients with acute coronary syndrome. (PMID:19460711)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	srebf2	ENSDARG00000063438
mus_musculus	Srebf2	ENSMUSG00000022463
rattus_norvegicus	Srebf2	ENSRNOG00000007400

Paralogs (3): SREBF1 (ENSG00000072310), USF2 (ENSG00000105698), USF1 (ENSG00000158773)

Protein

Protein identifiers

Sterol regulatory element-binding protein 2 — Q12772 (reviewed: Q12772)

Alternative names: Class D basic helix-loop-helix protein 2, Sterol regulatory element-binding transcription factor 2

All UniProt accessions (4): Q12772, A0AA34QVX2, G3V0I8, H0Y7E5

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane. Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis. Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis. Binds to the sterol regulatory element 1 (SRE-1) (5’-ATCACCCCAC-3’). Has dual sequence specificity binding to both an E-box motif (5’-ATCACGTGA-3’) and to SRE-1 (5’-ATCACCCCAC-3’). Regulates transcription of genes related to cholesterol synthesis pathway.

Subunit / interactions. Forms a tight complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum membrane and the Golgi apparatus. Interacts with PAQR3; the interaction anchors the SCAP-SREBP complex to the Golgi apparatus in low cholesterol conditions. Interacts (via C-terminal domain) with RNF139. Homodimer; efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein. Interacts with LMNA.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cytoplasmic vesicle. COPII-coated vesicle membrane Nucleus.

Tissue specificity. Ubiquitously expressed in adult and fetal tissues.

Post-translational modifications. Processed in the Golgi apparatus, releasing the protein from the membrane. At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum. In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) protease. The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain, releasing the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7. Cleavage and activation is induced by mediated cholesterol efflux. Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression. SCAP-free SREBF2 is ubiquitinated by the BCR(ARMC5) complex, leading to its degradation. Ubiquitinated; the nuclear form has a rapid turnover and is rapidly ubiquitinated and degraded by the proteasome in the nucleus.

Activity regulation. Activation by cleavage is down-regulated upon activation of SIRT3-dependent PRKAA1/AMPK-alpha signaling cascade which leads to inhibition of ATP-consuming lipogenesis to restore cellular energy balance.

Similarity. Belongs to the SREBP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12772-1	1	yes
Q12772-2	2

RefSeq proteins (1): NP_004590* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00010

UniProt features (52 total): mutagenesis site 16, sequence variant 6, region of interest 4, compositionally biased region 4, site 3, topological domain 3, splice variant 3, chain 2, modified residue 2, transmembrane region 2, sequence conflict 2, helix 2, cross-link 1, turn 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1UKL	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12772-F1	62.76	0.09

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 468–469 (cleavage; by caspase-3 and caspase-7); 484–485 (cleavage; by mbtps2); 522–523 (cleavage; by mbtps1)

Post-translational modifications (3): 855, 1098, 464

Mutagenesis-validated functional residues (16):

Position	Phenotype
342	abolished transactivation activity.
478–481	loss of cleavage by s2p.
478	no effect on proteolytic processing in response to low sterol.
479–481	loss of cleavage by s2p.
479	no effect on cleavage by s2p.
481	no effect on cleavage by s2p.
484–485	no effect on cleavage by s2p.
484	no effect on cleavage by s2p.
485	no effect on cleavage by s2p.
490–491	restores cleavage by s2p; when associated with f-495 and l-496. no effect on site of cleavage by s2p.
495–496	loss of cleavage by s2p.
495	reduced cleavage by s2p.
496	reduced cleavage by s2p.
519	loss of proteolytic processing in response to low sterol.
519	no effect on proteolytic processing in response to low sterol.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-1989781	PPARA activates gene expression
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-6807062	Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-191273	Cholesterol biosynthesis
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids
R-HSA-9675108	Nervous system development
R-HSA-9843745	Adipogenesis

MSigDB gene sets: 376 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, MORF_DNMT1, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_REGULATION_OF_AUTOPHAGY, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, GOBP_STEROL_HOMEOSTASIS, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, GCANCTGNY_MYOD_Q6, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_HDAC1, GOBP_PROTEIN_TARGETING

GO Biological Process (19): negative regulation of transcription by RNA polymerase II (GO:0000122), lipid metabolic process (GO:0006629), cholesterol metabolic process (GO:0008203), regulation of Notch signaling pathway (GO:0008593), cellular response to starvation (GO:0009267), positive regulation of cholesterol storage (GO:0010886), SREBP signaling pathway (GO:0032933), cholesterol homeostasis (GO:0042632), positive regulation of cholesterol biosynthetic process (GO:0045542), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to low-density lipoprotein particle stimulus (GO:0071404), cellular response to laminar fluid shear stress (GO:0071499), negative regulation of cholesterol efflux (GO:0090370), negative regulation of amyloid-beta clearance (GO:1900222), regulation of mitophagy (GO:1901524), positive regulation of miRNA transcription (GO:1902895), obsolete positive regulation of protein targeting to mitochondrion (GO:1903955), regulation of DNA-templated transcription (GO:0006355), steroid metabolic process (GO:0008202)

GO Molecular Function (10): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), protein dimerization activity (GO:0046983), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (13): Golgi membrane (GO:0000139), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), ER to Golgi transport vesicle membrane (GO:0012507), SREBP-SCAP-Insig complex (GO:0032937), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Metabolism of steroids	2
Metabolism of lipids	2
Developmental Biology	2
Regulation of lipid metabolism by PPARalpha	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Adipogenesis	1
Cholesterol biosynthesis	1
Nervous system development	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
regulation of transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
intracellular membrane-bounded organelle	3
transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
endomembrane system	2
negative regulation of DNA-templated transcription	1
primary metabolic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
Notch signaling pathway	1
regulation of signal transduction	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
cholesterol storage	1
positive regulation of lipid storage	1
regulation of cholesterol storage	1
ER-nucleus signaling pathway	1
cellular response to sterol depletion	1
sterol homeostasis	1
cholesterol biosynthetic process	1
regulation of cholesterol biosynthetic process	1
positive regulation of cholesterol metabolic process	1
positive regulation of sterol biosynthetic process	1
positive regulation of alcohol biosynthetic process	1
response to lipoprotein particle	1
cellular response to lipoprotein particle stimulus	1
response to laminar fluid shear stress	1
cellular response to fluid shear stress	1
regulation of cholesterol efflux	1
negative regulation of cholesterol transport	1
cholesterol efflux	1
negative regulation of multicellular organismal process	1
amyloid-beta clearance	1
regulation of amyloid-beta clearance	1
mitophagy	1
regulation of macroautophagy	1

Protein interactions and networks

STRING

2540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SREBF2	SCAP	Q12770	996
SREBF2	TP53	P04637	965
SREBF2	INSIG1	O15503	952
SREBF2	HMGCR	P04035	942
SREBF2	ABCA1	O95477	939
SREBF2	ABCG5	Q9H222	920
SREBF2	XPR1	Q9UBH6	914
SREBF2	ABCG8	Q9H221	913
SREBF2	HMGCS1	Q01581	904
SREBF2	NR1H3	Q13133	888
SREBF2	NPC1	O15118	878
SREBF2	ATF6	P18850	878
SREBF2	ABCG1	P45844	875
SREBF2	INSIG2	Q9Y5U4	865
SREBF2	MBTPS1	Q14703	838

IntAct

155 interactions, top by confidence:

A	B	Type	Score
SREBF2	FHL2	psi-mi:“MI:0915”(physical association)	0.670
HLA-DPA1	SREBF2	psi-mi:“MI:0915”(physical association)	0.670
SREBF2	SP1	psi-mi:“MI:0915”(physical association)	0.630
SP1	SREBF2	psi-mi:“MI:0915”(physical association)	0.630
SREBF2	NFYC	psi-mi:“MI:0915”(physical association)	0.560
HNF4A	SREBF2	psi-mi:“MI:0407”(direct interaction)	0.540
SREBF2	HNF4A	psi-mi:“MI:0915”(physical association)	0.540
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
DKK3	NME4	psi-mi:“MI:0914”(association)	0.530
CGRRF1	B4GALT3	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
CHRND	TPST2	psi-mi:“MI:0914”(association)	0.530
RNF170	ERLIN1	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
TP53	SREBF2	psi-mi:“MI:0915”(physical association)	0.520
SREBF2	TP53	psi-mi:“MI:0915”(physical association)	0.520
MED15	SREBF2	psi-mi:“MI:0915”(physical association)	0.500
CREBBP	SREBF2	psi-mi:“MI:0915”(physical association)	0.500
SREBF2	Kpnb1	psi-mi:“MI:0407”(direct interaction)	0.440
	SREBF2	psi-mi:“MI:0407”(direct interaction)	0.440
SREBF2		psi-mi:“MI:0407”(direct interaction)	0.440
	RXRA	psi-mi:“MI:0915”(physical association)	0.400
SREBF2	NR1H4	psi-mi:“MI:0915”(physical association)	0.400
SMAD3	SREBF2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (378): SREBF2 (Affinity Capture-Western), HDAC3 (Affinity Capture-Western), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SREBF2 (Reconstituted Complex), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS)

ESM2 similar proteins: A0A571BF63, A0A8M9QN10, A2ARM1, A2CI97, A3KNA7, A4D1P6, A9C3W3, B2RYI0, E9Q7E2, F1QNV4, O95475, P49848, P56524, P70302, P83093, P84903, Q0VDN7, Q12769, Q12772, Q13586, Q2HJE1, Q32N92, Q3T1I5, Q3U1N2, Q3UGY8, Q58CP9, Q58HI1, Q5E9R0, Q5R902, Q5ZLL7, Q60429, Q62311, Q63801, Q6GQ26, Q6NZM9, Q6P4L9, Q6P4R8, Q6PIJ4, Q6ZPR5, Q7TMQ7

Diamond homologs: A2T713, A2T7L8, A3KNA7, A4IFU7, O02818, O14948, O43019, O75030, O88368, O97676, P19484, P22415, P36956, P56720, Q08874, Q12772, Q3T1I5, Q3U1N2, Q4WIN1, Q59RL7, Q5XFQ6, Q60416, Q60429, Q61069, Q63302, Q64092, Q6GQ26, Q6XBT4, Q9R210, Q9UUD1, Q9WTN3, Q9WTW4, P33122, Q12398, Q4W9W8, Q5AL36, H2KZZ2, A0A286LEZ9, G5EEH5, P0DPB0

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
MAPK1	up-regulates	SREBF2	phosphorylation
MAPK3	up-regulates	SREBF2	phosphorylation
SREBF2	“up-regulates quantity by expression”	IDH1	“transcriptional regulation”
SREBF2	“up-regulates quantity by expression”	NPC1L1	“transcriptional regulation”
SREBF2	“up-regulates quantity by expression”	LDLR	“transcriptional regulation”
SREBF2	“down-regulates quantity by repression”	ABCG5	“transcriptional regulation”
SREBF2	“down-regulates quantity by repression”	ABCG8	“transcriptional regulation”
SREBF2	“up-regulates quantity by expression”	PCSK9	“transcriptional regulation”
SREBF2	“down-regulates quantity by repression”	LRP1	“transcriptional regulation”
SREBF2	“up-regulates quantity by expression”	PON1	“transcriptional regulation”
SREBF2	“up-regulates quantity by expression”	PON2	“transcriptional regulation”
SREBF2	“up-regulates quantity by expression”	SND1	“transcriptional regulation”
SREBF2	“up-regulates quantity by expression”	HMGCR	“transcriptional regulation”
SREBF2	“up-regulates quantity by expression”	SQLE	“transcriptional regulation”
Gbeta	up-regulates	SREBF2	phosphorylation
ERK1/2	up-regulates	SREBF2	phosphorylation
RNF139	“down-regulates quantity”	SREBF2	ubiquitination
MBTPS1	“up-regulates activity”	SREBF2	cleavage
MBTPS2	“up-regulates activity”	SREBF2	cleavage
SCAP	“up-regulates activity”	SREBF2	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SUMOylation of transcription factors	5	28.0×	2e-04
SUMOylation of intracellular receptors	6	19.8×	2e-04
Activation of gene expression by SREBF (SREBP)	5	12.7×	5e-03
SUMOylation of transcription cofactors	5	11.9×	5e-03
PPARA activates gene expression	9	8.3×	3e-04
SLC-mediated transmembrane transport	9	5.2×	5e-03
Transport of small molecules	14	3.5×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of intracellular pH	7	31.9×	2e-06
zinc ion transmembrane transport	5	26.6×	5e-04
sodium ion import across plasma membrane	5	23.6×	7e-04
intracellular zinc ion homeostasis	5	18.2×	2e-03
potassium ion transmembrane transport	8	8.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

256 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	174
Likely benign	18
Benign	36

Top pathogenic / likely-pathogenic (0)

SpliceAI

3369 predictions. Top by Δscore:

Variant	Effect	Δscore
22:41833356:ACGG:A	donor_loss	1.0000
22:41833358:GGT:G	donor_loss	1.0000
22:41833359:G:GC	donor_loss	1.0000
22:41833360:T:G	donor_loss	1.0000
22:41868608:A:AG	acceptor_gain	1.0000
22:41868609:A:G	acceptor_gain	1.0000
22:41868610:G:GT	acceptor_gain	1.0000
22:41868610:GTC:G	acceptor_gain	1.0000
22:41868790:CCGGT:C	donor_loss	1.0000
22:41868791:CGGTA:C	donor_loss	1.0000
22:41868792:GGT:G	donor_loss	1.0000
22:41868793:G:C	donor_loss	1.0000
22:41868793:G:GG	donor_gain	1.0000
22:41870883:A:AG	acceptor_gain	1.0000
22:41870884:T:G	acceptor_gain	1.0000
22:41870884:TCCA:T	acceptor_loss	1.0000
22:41870885:CCA:C	acceptor_loss	1.0000
22:41870886:CA:C	acceptor_loss	1.0000
22:41870887:A:AG	acceptor_gain	1.0000
22:41870887:AG:A	acceptor_gain	1.0000
22:41870888:G:GG	acceptor_gain	1.0000
22:41870888:G:GT	acceptor_loss	1.0000
22:41870888:GG:G	acceptor_gain	1.0000
22:41870888:GGTC:G	acceptor_gain	1.0000
22:41870888:GGTCC:G	acceptor_gain	1.0000
22:41871030:G:GG	donor_gain	1.0000
22:41871031:TACCA:T	donor_gain	1.0000
22:41871032:ACCA:A	donor_gain	1.0000
22:41871034:CA:C	donor_gain	1.0000
22:41871034:CAGTA:C	donor_loss	1.0000

AlphaMissense

7396 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:41866837:T:C	L32P	1.000
22:41873933:C:A	H335N	1.000
22:41873933:C:G	H335D	1.000
22:41873935:T:A	H335Q	1.000
22:41873935:T:G	H335Q	1.000
22:41873938:T:A	N336K	1.000
22:41873938:T:G	N336K	1.000
22:41873943:T:A	I338N	1.000
22:41873943:T:G	I338S	1.000
22:41873945:G:A	E339K	1.000
22:41873946:A:T	E339V	1.000
22:41873947:G:C	E339D	1.000
22:41873947:G:T	E339D	1.000
22:41873954:T:C	Y342H	1.000
22:41873954:T:G	Y342D	1.000
22:41873955:A:G	Y342C	1.000
22:41873957:C:A	R343S	1.000
22:41873957:C:G	R343G	1.000
22:41873958:G:C	R343P	1.000
22:41873967:T:A	I346N	1.000
22:41873967:T:C	I346T	1.000
22:41873967:T:G	I346S	1.000
22:41873971:T:A	N347K	1.000
22:41873971:T:G	N347K	1.000
22:41873979:T:C	I350T	1.000
22:41873979:T:G	I350S	1.000
22:41873988:T:C	L353S	1.000
22:41875343:A:C	K366Q	1.000
22:41875343:A:G	K366E	1.000
22:41875344:A:C	K366T	1.000

dbSNP variants (sampled 300 via entrez): RS1000007978 (22:41852202 G>C), RS1000012020 (22:41892620 C>T), RS1000063826 (22:41853641 C>A), RS1000117583 (22:41865299 T>G), RS1000126741 (22:41831969 C>T), RS1000170850 (22:41849029 T>C), RS1000265510 (22:41848755 G>A), RS1000304057 (22:41903793 C>A,T), RS1000417632 (22:41882168 A>T), RS1000435082 (22:41832264 G>A,C), RS1000469874 (22:41881779 A>G), RS1000499079 (22:41831719 C>A,T), RS1000527282 (22:41836372 A>C,G), RS1000594518 (22:41884904 G>T), RS1000649573 (22:41878358 G>C)

Disease associations

OMIM: gene MIM:600481 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurocutaneous syndrome	Moderate	Autosomal dominant
multiple congenital anomalies/dysmorphic syndrome	Limited	Autosomal dominant
hereditary spastic paraplegia	Limited	Autosomal recessive

Mondo (3): multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042), hereditary spastic paraplegia (MONDO:0019064), neurocutaneous syndrome (MONDO:0042983)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002337_172	Amyotrophic lateral sclerosis (sporadic)	1.000000e-06
GCST002539_95	Schizophrenia	2.000000e-09
GCST005146_54	Birth weight	4.000000e-12
GCST006269_1122	General cognitive ability	6.000000e-10
GCST006269_1179	General cognitive ability	3.000000e-08
GCST006803_13	Schizophrenia	2.000000e-14
GCST008362_131	Birth weight	3.000000e-13
GCST010002_83	Refractive error	2.000000e-27
GCST010132_1	Processed meat consumption	1.000000e-08
GCST011124_12	Caffeine consumption from tea	2.000000e-10
GCST90011898_171	Alanine aminotransferase levels	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0004337	intelligence
EFO:0008111	diet measurement
EFO:0010091	tea consumption measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020752	Neurocutaneous Syndromes	C10.562; C16.131.077.350.712; C16.131.831.350.712; C16.320.850.250.712; C17.800.804.350.712; C17.800.827.250.712
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795166 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2228314	SREBF2		0.00	0
rs133290	SREBF2		0.00	0
rs2267439	SREBF2		0.00	0
rs9607850	SREBF2		0.00	0

ChEMBL bioactivities

19 potent at pChembl≥5 of 28 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	IC50	300	nM	CHEMBL169046
6.16	IC50	700	nM	CHEMBL1824673
6.05	IC50	900	nM	CHEMBL1824674
6.00	IC50	1000	nM	CHEMBL1824673
5.72	IC50	1900	nM	CHEMBL1824676
5.64	IC50	2300	nM	CHEMBL1824675
5.55	IC50	2800	nM	CHEMBL1824669
5.52	IC50	3000	nM	CHEMBL1824670
5.50	IC50	3200	nM	CHEMBL1824664
5.31	IC50	4900	nM	CHEMBL1824671
5.25	IC50	5600	nM	FATOSTATIN
5.17	IC50	6800	nM	CHEMBL1824658
5.15	IC50	7100	nM	CHEMBL1824672
5.11	IC50	7700	nM	CHEMBL1824661
5.07	IC50	8600	nM	CHEMBL1824668
5.02	IC50	9600	nM	CHEMBL1824665
5.02	IC50	9500	nM	CHEMBL1824666
5.01	IC50	9800	nM	CHEMBL1616869
5.00	IC50	1e+04	nM	FATOSTATIN

PubChem BioAssay actives

19 with measured affinity, of 50 total; 17 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S,8S,9S,10R,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	0.3000	uM
N-[4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]phenyl]methanesulfonamide	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	0.7000	uM
N-[4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]phenyl]thiophene-2-sulfonamide	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	0.9000	uM
tert-butyl N-[4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]phenyl]carbamate	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	1.9000	uM
4-methyl-N-[4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	2.3000	uM
N-propan-2-yl-4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]aniline	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	2.8000	uM
N-benzyl-4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]aniline	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	3.0000	uM
4-(2-methoxyphenyl)-2-(2-propyl-4-pyridinyl)-1,3-thiazole	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	3.2000	uM
N-(cyclopropylmethyl)-4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]aniline	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	4.9000	uM
4-(4-methylphenyl)-2-(2-propyl-4-pyridinyl)-1,3-thiazole	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	5.6000	uM
2-(2-ethyl-4-pyridinyl)-4-(4-methylphenyl)-1,3-thiazole	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	6.8000	uM
N-[4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]phenyl]acetamide	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	7.1000	uM
[4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]phenyl] benzoate	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	7.7000	uM
4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]aniline	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	8.6000	uM
3-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]phenol	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	9.5000	uM
4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]phenol	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	9.6000	uM
4-(4-bromophenyl)-2-(2-propyl-4-pyridinyl)-1,3-thiazole	615677: Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	ic50	9.8000	uM

CTD chemical–gene interactions

121 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
fatostatin	increases reaction, increases response to substance, affects localization, decreases reaction, increases cleavage (+2 more)	7
Cholesterol	affects cotreatment, increases abundance, increases reaction, affects reaction, affects binding (+6 more)	4
bisphenol A	increases expression, increases reaction, increases import, affects reaction, increases activity	3
25-hydroxycholesterol	increases expression, decreases activity, affects cotreatment, decreases cleavage, decreases reaction (+2 more)	3
Quercetin	affects localization, decreases reaction, increases metabolic processing, increases expression, affects binding (+1 more)	3
Valproic Acid	increases methylation, decreases expression	3
triphenyl phosphate	affects expression, increases expression	2
tris(1,3-dichloro-2-propyl)phosphate	increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
pyrazolanthrone	decreases reaction, increases expression, affects localization, increases metabolic processing	2
dorsomorphin	increases cleavage, increases reaction, affects cotreatment, decreases expression	2
Resveratrol	decreases reaction, increases activity, increases cleavage, increases expression, affects cotreatment	2
Caffeine	decreases reaction, increases expression, increases phosphorylation	2
Tretinoin	decreases expression, increases expression	2
Simvastatin	increases expression, affects binding, decreases reaction, increases reaction	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
alliin	decreases reaction, increases expression	1
geraniol	increases expression	1
lead acetate	increases expression, decreases reaction	1
tributyl phosphate	increases expression	1
isoquercitrin	increases cleavage, increases expression, affects response to substance, affects cotreatment, increases activity	1
mono-(2-ethylhexyl)phthalate	increases expression	1
fisetin	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
linalool	affects binding, decreases reaction, decreases expression	1

ChEMBL screening assays

22 unique, capped per target: 22 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1827133	Binding	Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay	Synthesis and evaluation of diarylthiazole derivatives that inhibit activation of sterol regulatory element-binding proteins. — J Med Chem

Cellosaurus cell lines

11 cell lines: 7 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A6S1	SEES3-1V human SREBF2, clone1	Embryonic stem cell	Male
CVCL_A6S2	SEES3-1V human SREBF2, clone2	Embryonic stem cell	Male
CVCL_A6S3	SEES3-1V human SREBF2, clone3	Embryonic stem cell	Male
CVCL_B8Q7	Abcam HCT 116 SREBF2 KO	Cancer cell line	Male
CVCL_B9SN	Abcam A-549 SREBF2 KO	Cancer cell line	Male
CVCL_D9T1	Ubigene HEK293 SREBF2 KO	Transformed cell line	Female
CVCL_LB32	PathHunter U2OS SREBP2 Nuclear Translocation	Cancer cell line	Female
CVCL_TQ42	HAP1 SREBF2 (-) 1	Cancer cell line	Male
CVCL_TQ43	HAP1 SREBF2 (-) 2	Cancer cell line	Male
CVCL_TQ44	HAP1 SREBF2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

55 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia
NCT05767268	Not specified	COMPLETED	Assessment of the Psychophysical State During Rehabilitation Treatment With Lokomat
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06156813	Not specified	RECRUITING	Turkish Lower-Extremity Motor Activity Log (LE-MAL)
NCT06229626	Not specified	RECRUITING	Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
NCT06260982	Not specified	UNKNOWN	Cognitive Disorders in Hereditary Spastic Paraplegia Type 4
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network
NCT06572046	Not specified	RECRUITING	STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies
NCT06573866	Not specified	RECRUITING	Enhancement of Quality of Work And Life
NCT06680063	Not specified	COMPLETED	Correlation Between Clinical Assessment and Neurophysiological Assessment in Spinal Cord Injury