SREBF1

Summary

SREBF1 (sterol regulatory element binding transcription factor 1, HGNC:11289) is a protein-coding gene on chromosome 17p11.2, encoding Sterol regulatory element-binding protein 1 (P36956). Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane. It is a selective cancer dependency (DepMap: 25.0% of cell lines).

This gene encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a motif that is found in the promoter of the low density lipoprotein receptor gene and other genes involved in sterol biosynthesis. The encoded protein is synthesized as a precursor that is initially attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription. This cleaveage is inhibited by sterols. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative promoter usage and splicing result in multiple transcript variants, including SREBP-1a and SREBP-1c, which correspond to RefSeq transcript variants 2 and 3, respectively.

Source: NCBI Gene 6720 — RefSeq curated summary.

At a glance

• Gene–disease (curated): IFAP syndrome 2 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 15
• Clinical variants (ClinVar): 233 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 59
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 25.0% of screened cell lines
• Transcription factor: yes — 136 downstream targets (CollecTRI)
• MANE Select transcript: NM_004176

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11289
Approved symbol	SREBF1
Name	sterol regulatory element binding transcription factor 1
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	SREBP1, bHLHd1, SREBP-1c, SREBP1a
Ensembl gene	ENSG00000072310
Ensembl biotype	protein_coding
OMIM	184756
Entrez	6720

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 15 protein_coding, 13 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000261646, ENST00000355815, ENST00000395751, ENST00000395756, ENST00000395757, ENST00000423161, ENST00000447641, ENST00000469356, ENST00000470247, ENST00000471445, ENST00000476994, ENST00000478616, ENST00000485080, ENST00000486311, ENST00000487401, ENST00000490796, ENST00000577897, ENST00000578469, ENST00000580540, ENST00000581707, ENST00000583080, ENST00000583732, ENST00000584760, ENST00000662439, ENST00000892469, ENST00000892472, ENST00000892473, ENST00000892475, ENST00000892477, ENST00000892480, ENST00000918821, ENST00000918822, ENST00000918823

RefSeq mRNA: 13 — MANE Select: NM_004176 NM_001005291, NM_001321096, NM_001388385, NM_001388386, NM_001388387, NM_001388388, NM_001388389, NM_001388390, NM_001388391, NM_001388392, NM_001388393, NM_001388394, NM_004176

CCDS: CCDS11189, CCDS32583

Canonical transcript exons

ENST00000261646 — 19 exons

Exon	Start	End
ENSE00001596459	17820090	17820521
ENSE00001654308	17818260	17818374
ENSE00001776681	17819538	17819725
ENSE00003469453	17817696	17817916
ENSE00003472211	17816958	17817136
ENSE00003483174	17814245	17814410
ENSE00003486770	17814835	17814944
ENSE00003509513	17815860	17816028
ENSE00003525936	17813569	17813769
ENSE00003558337	17813368	17813479
ENSE00003564740	17815221	17815329
ENSE00003566080	17816207	17816373
ENSE00003585843	17819013	17819234
ENSE00003645408	17819320	17819454
ENSE00003658802	17816457	17816718
ENSE00003667398	17814615	17814747
ENSE00003694519	17817256	17817457
ENSE00003873048	17836727	17836986
ENSE00003883277	17811334	17812851

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 99.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.5814 / max 506.5482, expressed in 1815 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164805	27.6165	1806
164804	13.1611	1297
164806	5.5285	1713
164799	1.7022	858
164801	0.9253	520
164803	0.5693	280
164800	0.4497	206
164798	0.2412	53
164807	0.2186	80
164802	0.1690	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland	UBERON:0001234	99.38	gold quality
right adrenal gland	UBERON:0001233	99.37	gold quality
left adrenal gland cortex	UBERON:0035825	99.36	gold quality
right adrenal gland cortex	UBERON:0035827	99.27	gold quality
right lobe of liver	UBERON:0001114	98.69	gold quality
left uterine tube	UBERON:0001303	97.89	gold quality
minor salivary gland	UBERON:0001830	97.79	gold quality
lower esophagus mucosa	UBERON:0035834	97.79	gold quality
adrenal gland	UBERON:0002369	97.64	gold quality
nerve	UBERON:0001021	97.38	gold quality
tibial nerve	UBERON:0001323	97.38	gold quality
adenohypophysis	UBERON:0002196	97.12	gold quality
right ovary	UBERON:0002118	97.02	gold quality
adrenal cortex	UBERON:0001235	96.98	gold quality
ectocervix	UBERON:0012249	96.88	gold quality
gall bladder	UBERON:0002110	96.70	gold quality
mucosa of transverse colon	UBERON:0004991	96.66	gold quality
transverse colon	UBERON:0001157	96.60	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.55	gold quality
skin of abdomen	UBERON:0001416	96.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.22	gold quality
skin of leg	UBERON:0001511	96.20	gold quality
right testis	UBERON:0004534	96.20	gold quality
left testis	UBERON:0004533	96.15	gold quality
left ovary	UBERON:0002119	96.13	gold quality
esophagus mucosa	UBERON:0002469	95.95	gold quality
endocervix	UBERON:0000458	95.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.92	gold quality
right uterine tube	UBERON:0001302	95.90	gold quality
sural nerve	UBERON:0015488	95.90	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	1665.45
E-ANND-3	yes	16.43

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

136 targets.

Target	Regulation
ABCA3	Activation
ABCD2	Activation
ACACA	Activation
ACACB	Unknown
ACAT2	Activation
ACLY	Activation
ACSL1	Activation
ACSL5	Unknown
ACSS2	Activation
ADH1C	Activation
ADIPOQ	Unknown
APOA2	Unknown
APOA5	Repression
AR	Unknown
BCL2L1	Repression
BGLAP	Unknown
CASP7
CAV1	Repression
CD36	Activation
CD5L
CDKN1A	Activation
CEBPB	Activation
CETP	Unknown
CIC	Unknown
CIDEA	Activation
COL6A1	Activation
CPE	Activation
CYP17A1	Activation
CYP4F2	Activation
CYP51A1	Unknown

JASPAR motifs

Motif	Name	Family
MA0595.1	SREBF1	bHLH-ZIP
MA0829.2	SREBF1	bHLH-ZIP
MA0829.3	SREBF1	bHLH-ZIP

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

Upstream regulators (CollecTRI, top): AR, BHLHE40, BHLHE41, CCDC3, CEBPA, CEBPB, CEBPG, CREBZF, EGR1, ESR1, FBXW7, FOXC1, FOXO1, HNF4A, NCOR1, NFIL3, NFYA, NR1D2, NR1H2, NR1H3, NR1H4, NR4A1, NR5A1, PARP1, PDX1, PPARA, PPARD, PPARG, RORA, RXRA, SIRT1, SP1, SP3, SREBF1, SREBF2, STAT3, THRB, TP53, ZBTB7A

miRNA regulators (miRDB)

37 targeting SREBF1, 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-5692A	100.00	74.40	6850
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548AW	99.99	72.57	3559
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-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-6885-5P	98.71	64.33	902

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• expression altered in obesity and niddm (PMID:11916923)
• SREBP-1a and the CRE-bound proteins are essential for the SREBP-dependent response (PMID:12145339)
• transcriptional activities to different target promoters of lipogenic and cholesterogenic genes (PMID:12177166)
• expression of SREBP-1 is affected by polyunsaturated fatty acids in human cells (PMID:12213084)
• a strong graded interaction between SREBF-1a -36del/G genotypes and response of plasma apoA-I to treatment with fluvastatin. (PMID:12436350)
• Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. (PMID:12531699)
• Sphinglipids in endocytic compartments serve as a “molecular trap” for cholesterol, leading to a reduction in cholesterol at the endoplasmic reticulum, induction of sterol regulatory element-binding protein-1 cleavage, and up-regulation of LDL receptors. (PMID:12657626)
• may play discrete role in the regulation of the resistin gene expression (PMID:12730330)
• SREBP1a and APOB have roles in total and low-density lipoprotein cholesterol levels in patients with coronary artery disease (PMID:12752570)
• SREBP-1 not necessary for hepatic Akt-mediated hypoglycemic effect. Myr-Akt-induced hypertriglyceridemia and hepatic triglyceride accumulation mediated by Akt-induced SREBP-1 expression and mechanism involving fatty acid synthesis independent of SREBP-1. (PMID:14633850)
• SREBP-1 has a novel role as negative regulator of gluconeogenic genes through a cross-talk with HNF-4alpha interference with PGC-1 recruitment (PMID:14722127)
• results provide evidence that insulin action on sterol regulatory element binding protein (SREBP)-1c is dysregulated in adipose tissue from type 2 diabetic subjects (PMID:14742839)
• SREBP-1c and Sp1 interact to regulate transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in the liver (PMID:14744869)
• SREBP-1c is involved in the effect of insulin on HKII gene transcription. (PMID:14747281)
• molecular cloning of promoter; studies suggest that PDX-1 and HNF-4 both stimulate SREBP-1c gene expression (PMID:14748724)
• SREBP-1c gene is a candidate for human insulin resistance and a variant might influence diabetes risk. (PMID:14988272)
• High levels of SREBP-1 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)
• This review shows how SREBP-1 might play a role in the development of cellular features belonging to lipotoxicity and, possibly, syndrome X. (PMID:15102555)
• SREBP-1 has a role in the species differential regulation of cholesterol and bile acid homeostasis via a novel mechanism of up-regulation of the hSHP gene expression (PMID:15123650)
• Role of the SREBF-1 gene in genetic predisposition of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. (PMID:15277400)
• APOA5 gene expression is regulated by the LXR ligand T0901317 in a negative manner through SREBP-1c. (PMID:15317819)
• While the SREBP-1a and -1c isoforms differentially activate transcription, the molecular basis of this difference is unknown. Here we define the differences between these proteins that confer the enhanced activity of SREBP-1a. (PMID:15340088)
• 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)
• Tethered SREBP-1a and -2 homodimers, similar to the monomeric forms, activated target genes more robustly than tethered SREBP-1c homodimers. (PMID:15550381)
• Transfected from humans into transgenic mice, SREBP-1c and endogenous lipogenesis could be involved in beta-cell dysfunction and diabetes. (PMID:15677507)
• hCG and insulin cause a switch toward expression of the SREBP-1c isoform with consequent effects on fatty acid synthesis in culturred ganulosa cells (SRESBP-1c) (PMID:15769984)
• effect of SREBP-1a expression on lipid metabolism at the level of the cellular protein network and the protein pattern of mitochondria (PMID:15794649)
• SREBP-1 homodimers and heterodimers localize in the nucleus and activate transcription. (PMID:15798184)
• Transgenic SHR overexpressing SREBP-1a is nonobese rat model of fatty liver, disordered glucose and lipid metabolism, and hypertension. Possible model for studying pathogenesis and treatment of metabolic syndrome associated with hepatic steatosis. (PMID:15809359)
• 2 years after bilio-pancreatic diversion the degree of fat mass loss seems to interfere with regulatory binding protein 1c (SREBP-1c)gene suppression to preserve an adequate amount of fat storage (PMID:15833942)
• muscle cholesterol (p=0.045) and lathosterol (p=0.054) concentrations were elevated in the CC homozygotes supporting the view that endogenous cholesterol synthesis rate is SREBF-1 genotype-dependent. (PMID:16005884)
• activation of SREBP-1 by Akt leads to the induction of key enzymes of the cholesterol and fatty acid biosynthesis pathways, and thus membrane lipid biosynthesis (PMID:16007182)
• the SREBP-1c.BETA2.E47 complex is in a DNA looping structure which is required for efficient recruitment of CREB-binding protein/p300 (PMID:16055439)
• 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)
• SREBP-1ac mRNA was detectable in all tissues studied, although at lower levels than the major SREBP-1a & -1c isoforms. Transcription of SREBP-1ac mRNA was detectable in all tissues studied, although at lower levels than the major SREBP-1a & -1c isoforms. (PMID:16153721)
• fibroblast growth factor 7 requires both PI3K and JNK signaling pathways to induce SREBP-1 (PMID:16162944)
• SREBP-1c-mediated insulin regulation of acyl-CoA synthestase 5 expression indicate that ACS-5 is involved in the anabolic fate of fatty acids. (PMID:16198472)
• LXRalpha is a negative modulator of Abcd2, acting through a novel regulatory mechanism involving overlapping SREBP and LXRalpha binding sites (PMID:16249184)
• there is a role for sphingolipid metabolism and SREBP1 in ACTH-dependent CYP17 regulation and steroidogenesis (PMID:16306078)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	srebf1	ENSDARG00000067607
mus_musculus	Srebf1	ENSMUSG00000020538
rattus_norvegicus	Srebf1	ENSRNOG00000003463

Paralogs (3): USF2 (ENSG00000105698), USF1 (ENSG00000158773), SREBF2 (ENSG00000198911)

Protein

Protein identifiers

Sterol regulatory element-binding protein 1 — P36956 (reviewed: P36956)

Alternative names: Class D basic helix-loop-helix protein 1, Sterol regulatory element-binding transcription factor 1

All UniProt accessions (8): P36956, F6V242, J3QLB6, K7EIW8, K7EKR7, K7EMD1, K7EMT8, S4R3B4

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), 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 and lipid homeostasis. Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis. 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 the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation. Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C. Able to stimulate both lipogenic and cholesterogenic gene expression. Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver. Required for innate immune response in macrophages by regulating lipid metabolism. Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A. Primarily controls expression of lipogenic gene. Strongly activates global lipid synthesis in rapidly growing cells. The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters.

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. Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein. Interacts with CEBPA, the interaction produces a transcriptional synergy. Interacts with LMNA.

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

Tissue specificity. Expressed in a wide variety of tissues, most abundant in liver and adrenal gland. In fetal tissues lung and liver shows highest expression. Predominates in hepatoma cell lines. Also expressed in kidney, brain, white fat, and muscle. Predominantly expressed in liver and adipose tissues. Also expressed in kidney, brain, white fat, and muscle.

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. Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression. Phosphorylation at Ser-402 by SIK1 represses activity possibly by inhibiting DNA-binding. SCAP-free SREBF1 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.

Disease relevance. IFAP syndrome 2 (IFAP2) [MIM:619016] An autosomal dominant form of IFAP syndrome, a disease characterized by a peculiar triad of follicular ichthyosis, total or subtotal atrichia, and photophobia of varying degree. IFAP2 patients manifest ichthyosis follicularis or follicular hyperkeratosis, hyperkeratotic plaques, sparse to no body hair, and photophobia with punctate corneal epithelial defects, corneal pannus, and complicated cataract. Ultrastructural hair analysis shows trichorrhexis nodosa. The disease is caused by variants affecting the gene represented in this entry. Mucoepithelial dysplasia, hereditary (HMD) [MIM:158310] An autosomal dominant genodermatosis mainly characterized by chronic mucosal lesions associated with keratitis, non-scarring alopecia, keratosis pilaris and perineal intertrigo. The disease is caused by variants affecting the gene represented in this entry.

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.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Similarity. Belongs to the SREBP family.

Isoforms (6)

UniProt ID	Names	Canonical?
P36956-1	SREBP-1A	yes
P36956-2	SREBP-1B
P36956-3	SREBP-1C
P36956-4	4
P36956-5	SREBP-1aDelta
P36956-6	SREBP-1cDelta

RefSeq proteins (13): NP_001005291, NP_001308025, NP_001375314, NP_001375315, NP_001375316, NP_001375317, NP_001375318, NP_001375319, NP_001375320, NP_001375321, NP_001375322, NP_001375323, NP_004167* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00010

UniProt features (62 total): mutagenesis site 13, sequence variant 12, modified residue 8, region of interest 5, compositionally biased region 5, splice variant 5, site 3, topological domain 3, chain 2, transmembrane region 2, helix 2, short sequence motif 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1AM9	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36956-F1	64.87	0.17

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): 460–461 (cleavage; by caspase-3 and caspase-7); 490–491 (cleavage; by mbtps2); 530–531 (cleavage; by mbtps1)

Post-translational modifications (8): 98, 117, 337, 338, 396, 402, 457, 1060

Mutagenesis-validated functional residues (13):

Position	Phenotype
335	abolished transactivation activity.
455	no effect on proteolytic processing.
456	no effect on proteolytic processing.
457	no effect on proteolytic processing.
460	no effect on proteolytic processing.
466	no effect on proteolytic processing.
481	no effect on proteolytic processing.
482	no effect on proteolytic processing.
483	no effect on proteolytic processing.
484–487	strong reduction of proteolytic processing in response to low sterol.
484	loss of proteolytic processing in response to low sterol.
485	no effect on proteolytic processing.
527	loss of proteolytic processing in response to low sterol. transcriptionally inactive.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-6807062	Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-191273	Cholesterol biosynthesis
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-9029558	NR1H2 & NR1H3 regulate gene expression linked to lipogenesis
R-HSA-1368082
R-HSA-1430728	Metabolism
R-HSA-212436	Generic Transcription Pathway
R-HSA-400253
R-HSA-556833	Metabolism of lipids
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8957322	Metabolism of steroids
R-HSA-9614085	FOXO-mediated transcription

MSigDB gene sets: 528 (showing top): GOBP_CIRCADIAN_RHYTHM, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_REGULATION_OF_AUTOPHAGY, FARMER_BREAST_CANCER_CLUSTER_7, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_INSULIN_SECRETION, GOBP_PROTEIN_TARGETING, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_RESPONSE_TO_FOOD

GO Biological Process (46): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of heart rate by chemical signal (GO:0003062), regulation of transcription by RNA polymerase II (GO:0006357), lipid metabolic process (GO:0006629), cholesterol biosynthetic process (GO:0006695), response to nutrient (GO:0007584), circadian rhythm (GO:0007623), insulin receptor signaling pathway (GO:0008286), lipid biosynthetic process (GO:0008610), cellular response to starvation (GO:0009267), response to xenobiotic stimulus (GO:0009410), response to glucose (GO:0009749), response to fructose (GO:0009750), positive regulation of triglyceride biosynthetic process (GO:0010867), regulation of fatty acid metabolic process (GO:0019217), insulin secretion (GO:0030073), lung development (GO:0030324), regulation of protein stability (GO:0031647), response to food (GO:0032094), response to retinoic acid (GO:0032526), response to progesterone (GO:0032570), SREBP signaling pathway (GO:0032933), response to glucagon (GO:0033762), mRNA transcription by RNA polymerase II (GO:0042789), fat cell differentiation (GO:0045444), response to ethanol (GO:0045471), positive regulation of cholesterol biosynthetic process (GO:0045542), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of insulin secretion (GO:0046676), response to cAMP (GO:0051591), cellular response to fatty acid (GO:0071398), negative regulation of triglyceride metabolic process (GO:0090209), regulation of mitophagy (GO:1901524), positive regulation of miRNA transcription (GO:1902895), obsolete regulation of protein targeting to mitochondrion (GO:1903214), regulation of DNA-templated transcription (GO:0006355), transcription by RNA polymerase II (GO:0006366), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), intracellular receptor signaling pathway (GO:0030522)

GO Molecular Function (16): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coregulator binding (GO:0001221), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), nuclear receptor activity (GO:0004879), protein kinase binding (GO:0019901), sterol response element binding (GO:0032810), protein-containing complex binding (GO:0044877), protein dimerization activity (GO:0046983), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (15): Golgi membrane (GO:0000139), chromatin (GO:0000785), nucleus (GO:0005634), nuclear envelope (GO:0005635), 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), protein-containing complex (GO:0032991), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Metabolism of steroids	2
Cholesterol biosynthesis	1
FOXO-mediated transcription	1
Circadian clock	1
Regulation of lipid metabolism by PPARalpha	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Adipogenesis	1
NR1H2 and NR1H3-mediated signaling	1
RNA Polymerase II Transcription	1
Metabolism	1
Gene expression (Transcription)	1
Metabolism of lipids	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
response to chemical	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
binding	3
intracellular membrane-bounded organelle	3
endomembrane system	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
response to nutrient levels	2
response to hexose	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
negative regulation of DNA-templated transcription	1
regulation of heart rate	1
primary metabolic process	1
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
rhythmic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
lipid metabolic process	1
biosynthetic process	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
regulation of triglyceride biosynthetic process	1
triglyceride biosynthetic process	1
positive regulation of lipid biosynthetic process	1
positive regulation of triglyceride metabolic process	1
fatty acid metabolic process	1
regulation of ketone metabolic process	1
regulation of lipid metabolic process	1
regulation of small molecule metabolic process	1
protein secretion	1
peptide hormone secretion	1
respiratory tube development	1
animal organ development	1

Protein interactions and networks

STRING

3790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SREBF1	SCAP	Q12770	963
SREBF1	FASN	P49327	957
SREBF1	PPARG	P37231	934
SREBF1	ACACA	Q13085	928
SREBF1	HMGCR	P04035	916
SREBF1	INSIG1	O15503	912
SREBF1	NR1H3	Q13133	909
SREBF1	ABCA1	O95477	904
SREBF1	MLXIPL	Q9NP71	894
SREBF1	SCD	O00767	892
SREBF1	INS	P01308	891
SREBF1	PPARA	Q07869	885
SREBF1	INSIG2	Q9Y5U4	877
SREBF1	PPARGC1A	Q9UBK2	863
SREBF1	ACOX1	Q15067	858
SREBF1	PPARGC1B	Q86YN6	858

IntAct

33 interactions, top by confidence:

A	B	Type	Score
SREBF1	ATXN1	psi-mi:“MI:0915”(physical association)	0.670
SREBF1	HTT	psi-mi:“MI:0915”(physical association)	0.560
MEN1	SREBF1	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	SREBF1	psi-mi:“MI:0915”(physical association)	0.400
USF1	SREBF1	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
	ABCD4	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
SCAP	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
CHRNA7	UFL1	psi-mi:“MI:0914”(association)	0.350
SREBF1	PVALB	psi-mi:“MI:0914”(association)	0.350
PIGH	ILVBL	psi-mi:“MI:0914”(association)	0.350
TMEM9B	NBAS	psi-mi:“MI:0914”(association)	0.350
INSRR	SETD1A	psi-mi:“MI:0914”(association)	0.350
SCAP	SPTLC2	psi-mi:“MI:0914”(association)	0.350
TMEM268	ABCC4	psi-mi:“MI:0914”(association)	0.350
ASB14	TOMM40	psi-mi:“MI:0914”(association)	0.350
KCNG4	CA1	psi-mi:“MI:0914”(association)	0.350
SLC27A6	NBAS	psi-mi:“MI:0914”(association)	0.350
ATF3	ILVBL	psi-mi:“MI:0914”(association)	0.350
GATA2	ILVBL	psi-mi:“MI:0914”(association)	0.350
SREBF1	MTNR1B	psi-mi:“MI:0915”(physical association)	0.000
SREBF1	nrdR	psi-mi:“MI:0915”(physical association)	0.000
SREBF1	rbsC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (266): SREBF1 (Reconstituted Complex), Tcf7l1 (Reconstituted Complex), Neurod1 (Reconstituted Complex), SREBF1 (Reconstituted Complex), SREBF1 (Biochemical Activity), SREBF1 (Biochemical Activity), SREBF1 (Reconstituted Complex), SREBF1 (Affinity Capture-Western), SIRT1 (Affinity Capture-Western), SREBF1 (Affinity Capture-Western), SREBF1 (Affinity Capture-Western), ID2 (Reconstituted Complex), ID3 (Reconstituted Complex), SREBF1 (Affinity Capture-MS), SREBF1 (Affinity Capture-Western)

ESM2 similar proteins: A1A4M2, A4IFG4, A5D8P8, A6NKD9, A7E2M3, B4F7F3, E9Q6B2, F1MX48, F1SAM7, O97676, P18065, P36956, P47877, P49705, P56720, P56873, Q00709, Q00973, Q09200, Q0IHY5, Q15465, Q24JP5, Q2YD98, Q3TAS6, Q58CS8, Q5QQ49, Q5UCC4, Q60416, Q60698, Q641Q3, Q68FE7, Q6AYH6, Q6DVA0, Q6P7K5, Q6UKI2, Q6WVG3, Q80WF4, Q8IW70, Q8JGM4, Q8K064

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, A0A286LEZ9, G5EEH5, H2KZZ2, P0DPB0, P28574, P49379, P52161, P52162

SIGNOR signaling

48 interactions.

A	Effect	B	Mechanism
SREBF1	“up-regulates quantity by expression”	FASN	“transcriptional regulation”
SREBF1	“up-regulates quantity by expression”	PKM	“transcriptional regulation”
PRKACA	down-regulates	SREBF1	phosphorylation
CDK1	up-regulates	SREBF1	phosphorylation
PRKAA2	down-regulates	SREBF1	phosphorylation
PRKAA1	“down-regulates activity”	SREBF1	phosphorylation
AMPK	down-regulates	SREBF1	phosphorylation
CyclinB/CDK1	up-regulates	SREBF1	phosphorylation
GSK3B	“down-regulates quantity by destabilization”	SREBF1	phosphorylation
ERK1/2	up-regulates	SREBF1	phosphorylation
SREBF1	up-regulates	VLDL_assembly
SREBF1	“up-regulates quantity by expression”	MTTP	“transcriptional regulation”
SREBF1	“up-regulates quantity by expression”	IDH1	“transcriptional regulation”
SREBF1	“down-regulates quantity by repression”	LRP1	“transcriptional regulation”
SREBF1	“up-regulates quantity by expression”	PCSK9	“transcriptional regulation”
SREBF1	“down-regulates quantity by repression”	SND1	“transcriptional regulation”
SREBF1	“up-regulates quantity by expression”	PK	“transcriptional regulation”
SREBF1	“up-regulates quantity by expression”	ELOVL6	“transcriptional regulation”
SREBF1	“up-regulates quantity by expression”	ELOVL	“transcriptional regulation”
SREBF1	“up-regulates quantity by expression”	ACLY	“transcriptional regulation”
SREBF1	“up-regulates quantity by expression”	ACACA	“transcriptional regulation”
SIRT6	“up-regulates activity”	SREBF1	binding
Gbeta	“up-regulates activity”	SREBF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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.

GO biological processes:

GO term	Partners	Fold	FDR
response to hypoxia	5	17.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	161
Likely benign	19
Benign	11

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
932243	NM_004176.5(SREBF1):c.1579C>T (p.Arg527Cys)	Pathogenic
932244	NM_004176.5(SREBF1):c.1582_1584del (p.Asn528del)	Pathogenic
932245	NM_004176.5(SREBF1):c.1589T>C (p.Leu530Pro)	Pathogenic
3065078	NM_004176.5(SREBF1):c.91+1G>C	Likely pathogenic
4277558	NM_004176.5(SREBF1):c.406_418del (p.Thr136fs)	Likely pathogenic
981495	NM_004176.5(SREBF1):c.1580G>A (p.Arg527His)	Likely pathogenic

SpliceAI

3124 predictions. Top by Δscore:

Variant	Effect	Δscore
17:17812849:CGC:C	acceptor_gain	1.0000
17:17812850:GCCT:G	acceptor_loss	1.0000
17:17812851:CCTG:C	acceptor_loss	1.0000
17:17812852:C:CC	acceptor_gain	1.0000
17:17812852:C:CG	acceptor_loss	1.0000
17:17812853:T:A	acceptor_loss	1.0000
17:17813321:C:A	donor_gain	1.0000
17:17813362:CCTCA:C	donor_loss	1.0000
17:17813363:CTCA:C	donor_loss	1.0000
17:17813364:TCA:T	donor_loss	1.0000
17:17813365:CACC:C	donor_loss	1.0000
17:17813366:ACCT:A	donor_gain	1.0000
17:17813367:C:CT	donor_loss	1.0000
17:17813367:CCTC:C	donor_gain	1.0000
17:17813369:T:TA	donor_gain	1.0000
17:17813564:CTCA:C	donor_loss	1.0000
17:17813565:TCAC:T	donor_loss	1.0000
17:17813566:CACCC:C	donor_loss	1.0000
17:17813567:A:AC	donor_gain	1.0000
17:17813567:A:C	donor_loss	1.0000
17:17813567:AC:A	donor_gain	1.0000
17:17813567:ACCCT:A	donor_gain	1.0000
17:17813568:C:CA	donor_loss	1.0000
17:17813568:C:CC	donor_gain	1.0000
17:17813568:CC:C	donor_gain	1.0000
17:17813568:CCCT:C	donor_gain	1.0000
17:17813568:CCCTC:C	donor_gain	1.0000
17:17813766:CGGC:C	acceptor_gain	1.0000
17:17813770:C:CA	acceptor_loss	1.0000
17:17814240:CTCA:C	donor_loss	1.0000

AlphaMissense

7324 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:17818366:T:A	K359N	1.000
17:17818366:T:G	K359N	1.000
17:17818367:T:A	K359I	1.000
17:17818368:T:C	K359E	0.999
17:17818368:T:G	K359Q	0.999
17:17819044:A:G	L346P	0.999
17:17819065:A:G	I339T	0.999
17:17819065:A:T	I339N	0.999
17:17819074:C:G	R336P	0.999
17:17819075:G:T	R336S	0.999
17:17819078:A:G	Y335H	0.999
17:17819085:C:A	E332D	0.999
17:17819085:C:G	E332D	0.999
17:17819089:A:T	I331N	0.999
17:17819099:G:C	H328D	0.999
17:17818347:C:G	A366P	0.998
17:17818355:A:G	L363S	0.998
17:17819044:A:T	L346H	0.998
17:17819065:A:C	I339S	0.998
17:17819069:A:G	S338P	0.998
17:17819075:G:C	R336G	0.998
17:17819078:A:C	Y335D	0.998
17:17819086:T:A	E332V	0.998
17:17819089:A:C	I331S	0.998
17:17819097:G:C	H328Q	0.998
17:17819097:G:T	H328Q	0.998
17:17815959:A:G	W762R	0.997
17:17815959:A:T	W762R	0.997
17:17818358:A:T	V362D	0.997
17:17818367:T:G	K359T	0.997

dbSNP variants (sampled 300 via entrez): RS1000051430 (17:17816432 G>T), RS1000122792 (17:17838066 G>A), RS1000218214 (17:17837621 A>C,G), RS1000284363 (17:17822102 C>G,T), RS1000368498 (17:17828212 A>C,G,T), RS1000492432 (17:17819199 G>A,C), RS1000536737 (17:17833732 C>T), RS1000904601 (17:17819904 C>A,G,T), RS1000911973 (17:17827176 T>C,G), RS1000955288 (17:17811495 G>A), RS1000978803 (17:17814565 G>A), RS1001176817 (17:17827908 CT>C), RS1001220725 (17:17833978 A>G), RS1001303957 (17:17811678 T>G), RS1001475002 (17:17813803 G>A)

Disease associations

OMIM: gene MIM:184756 | disease phenotypes: MIM:158310, MIM:619016, MIM:308205

GenCC curated gene-disease

Disease	Classification	Inheritance
IFAP syndrome 2	Strong	Autosomal dominant
hereditary mucoepithelial dysplasia	Strong	Autosomal dominant
Hirschsprung disease	Supportive	Autosomal dominant

Mondo (6): breast ductal adenocarcinoma (MONDO:0005590), hereditary mucoepithelial dysplasia (MONDO:0008017), IFAP syndrome 2 (MONDO:0100221), obesity disorder (MONDO:0011122), IFAP syndrome 1, with or without BRESHECK syndrome (MONDO:0100213), Hirschsprung disease (MONDO:0018309)

Orphanet (5): Hereditary mucoepithelial dysplasia (Orphanet:1839), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Ichthyosis follicularis-alopecia-photophobia syndrome (Orphanet:2273), BRESEK syndrome (Orphanet:85284), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000221	Furrowed tongue
HP:0000365	Hearing impairment
HP:0000486	Strabismus
HP:0000491	Keratitis
HP:0000518	Cataract
HP:0000565	Esotropia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000790	Hematuria
HP:0001096	Keratoconjunctivitis
HP:0001097	Keratoconjunctivitis sicca
HP:0001510	Growth delay
HP:0001531	Failure to thrive in infancy
HP:0001561	Polyhydramnios
HP:0001596	Alopecia
HP:0001648	Cor pulmonale
HP:0001824	Weight loss
HP:0001880	Increased total eosinophil count
HP:0002014	Diarrhea
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002028	Chronic diarrhea
HP:0002090	Pneumonia
HP:0002164	Nail dysplasia
HP:0002208	Coarse hair
HP:0002249	Melena
HP:0002251	Aganglionic megacolon

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001126_7	Parkinson’s disease	6.000000e-08
GCST002539_86	Schizophrenia	2.000000e-08
GCST003818_19	Resting heart rate	5.000000e-08
GCST004771_10	TB-LM or TBLH-BMD (pleiotropy)	1.000000e-10
GCST004946_149	Schizophrenia	7.000000e-10
GCST006803_40	Schizophrenia	3.000000e-08
GCST008526_52	Coffee consumption	3.000000e-09
GCST011320_31	Type 2 diabetes or prostate cancer (pleiotropy)	8.000000e-10
GCST012228_521	Waist-hip index	6.000000e-09
GCST012229_192	Hip index	2.000000e-11
GCST012230_112	Waist-to-hip ratio adjusted for BMI	8.000000e-09
GCST90002381_112	Eosinophil count	7.000000e-10
GCST90002388_490	Lymphocyte count	1.000000e-22
GCST90002407_126	White blood cell count	1.000000e-20
GCST90020029_582	Waist circumference adjusted for body mass index	1.000000e-13

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004995	lean body mass
EFO:0006781	coffee consumption measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference
EFO:0004842	eosinophil count
EFO:0004587	lymphocyte count
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439
C536085	Ichthyosis follicularis atrichia photophobia syndrome (supp.)
C536476	Urban Schosser Spohn syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630818 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,496 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1040	CALCIFEDIOL ANHYDROUS	4	8,496

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11868035	Toxicity	3	HMG-CoA reductase inhibitors	Schizophrenia
rs60282872	Efficacy	3	fluvastatin

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11868035	RAI1, SREBF1	3	1.00	1	HMG-CoA reductase inhibitors
rs60282872	SREBF1	3	1.00	1	fluvastatin

ChEMBL bioactivities

25 potent at pChembl≥5 of 29 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	EC50	20	nM	T091317
6.89	EC50	130	nM	CHEMBL5597982
6.72	EC50	190	nM	CHEMBL5596248
6.72	EC50	190	nM	CHEMBL5590706
6.62	EC50	240	nM	CHEMBL5597153
6.51	EC50	310	nM	CHEMBL5596815
6.24	EC50	570	nM	CHEMBL5596386
6.16	IC50	700	nM	CHEMBL1824673
6.14	IC50	722.7	nM	CHEMBL4851466
6.11	EC50	770	nM	CHEMBL5598250
5.94	IC50	1160	nM	CHEMBL4876668
5.93	IC50	1176	nM	CALCIFEDIOL ANHYDROUS
5.89	EC50	1300	nM	CHEMBL5597394
5.89	EC50	1300	nM	CHEMBL5598331
5.82	EC50	1500	nM	CHEMBL5597291
5.80	IC50	1600	nM	CHEMBL4851396
5.75	EC50	1800	nM	CHEMBL5596939
5.55	EC50	2800	nM	CHEMBL5598279
5.54	EC50	2900	nM	CHEMBL5596811
5.52	EC50	3000	nM	CHEMBL5597319
5.52	EC50	3000	nM	CHEMBL5596248
5.37	EC50	4300	nM	CHEMBL5590383
5.30	IC50	5000	nM	CHEMBL1824658
5.16	EC50	6900	nM	CHEMBL5597943
5.07	EC50	8600	nM	CHEMBL5596907

PubChem BioAssay actives

25 with measured affinity, of 113 total; 24 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
N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	0.0200	uM
ethyl 3-[[5-chloro-3-[(4-ethoxy-3-methoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]-5-fluorobenzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	0.1300	uM
5-chloro-N-[3-chloro-5-(1,3-dioxolan-2-yl)phenyl]-3-[(4-ethoxy-3-methoxyphenyl)-methylsulfamoyl]thiophene-2-carboxamide	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	0.1900	uM
ethyl 3-chloro-5-[[5-chloro-3-[(4-ethoxy-3-methoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	0.1900	uM
2-(2-methoxyethoxy)ethyl 3-chloro-5-[[5-chloro-3-[(4-ethoxy-3-methoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	0.2400	uM
2-methoxyethyl 3-chloro-5-[[5-chloro-3-[(4-ethoxy-3-methoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	0.3100	uM
ethyl 3-chloro-5-[[5-chloro-3-[(3,4-diethoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	0.5700	uM
N-[4-[2-(2-propyl-4-pyridinyl)-1,3-thiazol-4-yl]phenyl]methanesulfonamide	1765093: Inhibition of SREBP (unknown origin) expressed in CHO-K1 cells by luciferase reporter assay	ic50	0.7000	uM
(6R)-6-[(1R,3aS,4E,7aR)-7a-methyl-4-[2-(5-phenyltetrazol-1-yl)ethylidene]-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-3,3-difluoro-2-methylheptan-2-ol	1765093: Inhibition of SREBP (unknown origin) expressed in CHO-K1 cells by luciferase reporter assay	ic50	0.7227	uM
ethyl 3-bromo-5-[[5-chloro-3-[(4-ethoxy-3-methoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	0.7700	uM
(6R)-6-[(1R,3aS,4E,7aR)-4-[2-[5-(4-fluorophenyl)tetrazol-2-yl]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-3,3-difluoro-2-methylheptan-2-ol	1765093: Inhibition of SREBP (unknown origin) expressed in CHO-K1 cells by luciferase reporter assay	ic50	1.1600	uM
calcifediol	1765093: Inhibition of SREBP (unknown origin) expressed in CHO-K1 cells by luciferase reporter assay	ic50	1.1760	uM
ethyl 3-[[5-chloro-3-[(4-ethoxy-3-methoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	1.3000	uM
methyl 3-chloro-5-[[5-chloro-3-[(4-ethoxy-3-methoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	1.3000	uM
ethyl 3-[[5-chloro-3-[(3,4-dipropoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	1.5000	uM
(6R)-6-[(1R,3aS,4E,7aR)-4-[2-[5-(4-fluorophenyl)tetrazol-1-yl]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-3,3-difluoro-2-methylheptan-2-ol	1765093: Inhibition of SREBP (unknown origin) expressed in CHO-K1 cells by luciferase reporter assay	ic50	1.6000	uM
ethyl 3-chloro-5-[[5-chloro-3-[(3,4-dimethoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	1.8000	uM
ethyl 3-[[5-chloro-3-[(4-ethoxy-2-fluorophenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	2.8000	uM
2-(2-methoxyethoxy)ethyl 3-[[5-chloro-3-[(3,4-diethoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	2.9000	uM
2-methoxyethyl 3-[[5-chloro-3-[(3,4-diethoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	3.0000	uM
ethyl 3-[[5-chloro-3-[(4-ethoxyphenyl)-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	4.3000	uM
2-(2-ethyl-4-pyridinyl)-4-(4-methylphenyl)-1,3-thiazole	1765093: Inhibition of SREBP (unknown origin) expressed in CHO-K1 cells by luciferase reporter assay	ic50	5.0000	uM
ethyl 3-[[5-chloro-3-[[4-(dimethylamino)phenyl]-methylsulfamoyl]thiophene-2-carbonyl]amino]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	6.9000	uM
ethyl 3-[5-[5-chloro-3-[(4-ethoxy-3-methoxyphenyl)-methylsulfamoyl]thiophen-2-yl]-1,3,4-oxadiazol-2-yl]benzoate	2123256: Agonist activity at SREBP1c (unknown origin) stably transfected in human HepG2 cells assessed as increase in luciferase activity by counterscreen luciferase reporter assay	ec50	8.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oleic Acid	affects cotreatment, decreases expression, decreases reaction, increases expression, increases reaction (+1 more)	15
T0901317	affects reaction, decreases expression, affects binding, decreases reaction, increases expression (+2 more)	13
fatostatin	decreases reaction, increases expression, increases cleavage, decreases expression, increases response to substance (+4 more)	12
Palmitic Acid	increases expression, increases reaction, affects reaction, affects cotreatment, decreases reaction	12
bisphenol A	decreases reaction, increases expression, affects expression, decreases methylation, affects reaction (+1 more)	11
Benzo(a)pyrene	affects methylation, affects cotreatment, decreases expression, decreases reaction, increases expression (+2 more)	10
sodium arsenite	increases abundance, increases expression, decreases methylation, decreases reaction, affects expression (+2 more)	8
dorsomorphin	decreases reaction, increases expression, decreases expression, affects cotreatment	7
Dexamethasone	increases expression, increases reaction, decreases reaction, affects expression, affects cotreatment	6
GW 3965	affects cotreatment, increases expression, decreases reaction	5
Fatty Acids, Nonesterified	affects localization, decreases reaction, increases expression, affects expression, decreases expression	5
Valproic Acid	increases reaction, affects expression, decreases expression, affects reaction, increases expression	5
Cyclosporine	decreases expression, increases expression, affects cotreatment	5
sulforaphane	increases reaction, decreases expression, decreases reaction, increases expression	4
perfluorooctanoic acid	affects cotreatment, decreases expression, increases expression	4
perfluorobutyric acid	affects cotreatment, decreases expression, increases expression	4
Resveratrol	increases activity, increases cleavage, affects cotreatment, decreases reaction, increases expression (+2 more)	4
Ethanol	increases expression, affects cotreatment, decreases expression, decreases reaction	4
Estradiol	decreases reaction, increases expression, decreases expression, affects cotreatment	4
1-Methyl-3-isobutylxanthine	decreases reaction, affects expression, affects cotreatment, increases expression, increases reaction	4
triphenyl phosphate	affects expression, increases expression	3
tributyltin	increases reaction, affects cotreatment, increases expression	3
cobaltous chloride	decreases expression, increases expression	3
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, decreases expression, increases expression, decreases reaction	3
Rosiglitazone	decreases reaction, affects cotreatment, increases expression, increases reaction	3
Arsenic Trioxide	affects cotreatment, decreases expression, decreases reaction	3
Dichlorodiphenyl Dichloroethylene	increases reaction, decreases expression, affects cotreatment, increases expression	3
Glucose	increases expression, affects cotreatment, decreases reaction	3
Lipopolysaccharides	affects response to substance, decreases reaction, increases expression, affects expression	3
Metformin	decreases expression, decreases reaction, increases expression, affects cotreatment	3

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4617297	Binding	Inhibition of SREBP (unknown origin) expressed in HEK293 cells assessed as reduction in LDLr promotor activity after 24 hrs by luciferase reporter assay	Luciferase-based HMG-CoA reductase degradation assay for activity and selectivity profiling of oxy(lano)sterols. — Bioorg Med Chem

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6R8	SEES3-1V human SREBF1, clone1	Embryonic stem cell	Male
CVCL_A6R9	SEES3-1V human SREBF1, clone2	Embryonic stem cell	Male
CVCL_A6S0	SEES3-1V human SREBF1, clone3	Embryonic stem cell	Male
CVCL_B8Q6	Abcam HCT 116 SREBF1 KO	Cancer cell line	Male
CVCL_B9SM	Abcam A-549 SREBF1 KO	Cancer cell line	Male
CVCL_E1G3	Abcam HeLa SREBF1 KO	Cancer cell line	Female
CVCL_TQ41	HAP1 SREBF1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	PHASE4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	PHASE4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	PHASE4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	PHASE4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	PHASE4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	PHASE4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	PHASE4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	PHASE4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	PHASE4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	PHASE4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	PHASE4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	PHASE4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	PHASE4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	PHASE4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	PHASE4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	PHASE4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	PHASE4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	PHASE4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	PHASE4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	PHASE4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	PHASE4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	PHASE4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	PHASE4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	PHASE4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	PHASE4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	PHASE4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)