USF1

Summary

USF1 (upstream transcription factor 1, HGNC:12593) is a protein-coding gene on chromosome 1q23.3, encoding Upstream stimulatory factor 1 (P22415). Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5’-CACGTG-3’) that is found in a variety of viral and cellular promoters.

This gene encodes a member of the basic helix-loop-helix leucine zipper family, and can function as a cellular transcription factor. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs. This gene has been linked to familial combined hyperlipidemia (FCHL). Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been defined on chromosome 21.

Source: NCBI Gene 7391 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperlipidemia, combined, 1 (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 36 total
• Transcription factor: yes — 243 downstream targets (CollecTRI)
• MANE Select transcript: NM_007122

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12593
Approved symbol	USF1
Name	upstream transcription factor 1
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	UEF, MLTFI, bHLHb11
Ensembl gene	ENSG00000158773
Ensembl biotype	protein_coding
OMIM	191523
Entrez	7391

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000368019, ENST00000368020, ENST00000368021, ENST00000472217, ENST00000473969, ENST00000491629, ENST00000496363, ENST00000528768, ENST00000529476, ENST00000531842, ENST00000534633, ENST00000935833, ENST00000961612, ENST00000961613

RefSeq mRNA: 3 — MANE Select: NM_007122 NM_001276373, NM_007122, NM_207005

CCDS: CCDS1214

Canonical transcript exons

ENST00000368021 — 11 exons

Exon	Start	End
ENSE00001428030	161045858	161045977
ENSE00001446148	161039251	161040009
ENSE00003495906	161043268	161043360
ENSE00003540750	161040202	161040330
ENSE00003551473	161040576	161040670
ENSE00003614683	161042555	161042670
ENSE00003618498	161041651	161041846
ENSE00003650827	161040814	161040872
ENSE00003658950	161042116	161042217
ENSE00003659861	161042833	161042882
ENSE00003685508	161041324	161041411

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6022 / max 208.2075, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15567	11.2849	1797
15568	9.8822	1786
15566	3.0777	1452
15565	0.3574	193

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.63	gold quality
monocyte	CL:0000576	97.67	gold quality
leukocyte	CL:0000738	97.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.07	gold quality
right lung	UBERON:0002167	97.03	gold quality
cortical plate	UBERON:0005343	96.73	gold quality
upper lobe of left lung	UBERON:0008952	96.56	gold quality
vermiform appendix	UBERON:0001154	96.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.36	gold quality
cerebellar hemisphere	UBERON:0002245	96.32	gold quality
spleen	UBERON:0002106	96.17	gold quality
cerebellar cortex	UBERON:0002129	96.17	gold quality
bone marrow cell	CL:0002092	95.99	gold quality
ganglionic eminence	UBERON:0004023	95.88	gold quality
mucosa of transverse colon	UBERON:0004991	95.88	gold quality
transverse colon	UBERON:0001157	95.81	gold quality
metanephros cortex	UBERON:0010533	95.80	gold quality
apex of heart	UBERON:0002098	95.72	gold quality
right lobe of liver	UBERON:0001114	95.56	gold quality
body of stomach	UBERON:0001161	95.43	gold quality
right coronary artery	UBERON:0001625	95.33	gold quality
adenohypophysis	UBERON:0002196	95.33	gold quality
right lobe of thyroid gland	UBERON:0001119	95.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.32	gold quality
left uterine tube	UBERON:0001303	95.31	gold quality
body of uterus	UBERON:0009853	95.31	gold quality
right ovary	UBERON:0002118	95.29	gold quality
tibial nerve	UBERON:0001323	95.21	gold quality
mucosa of stomach	UBERON:0001199	95.19	gold quality
rectum	UBERON:0001052	95.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

243 targets.

Target	Regulation
ABCA1	Activation
ACACA
ACACB	Activation
ADAM10	Activation
ADCYAP1
ADGRE4P
ADH1A
ADH1B
ADH1C
AGT	Repression
AGTRAP
AIRN
AKAP12	Unknown
AKR1A1
AKR1B1
ALB
ALX3	Unknown
AP1
APC	Activation
APEX1	Unknown
APLN
APOA2	Unknown
APOA5	Activation
APOC3	Unknown
APP	Unknown
ASCL2	Repression
ASPH	Unknown
ATF4
AVP	Unknown
B2M	Activation

JASPAR motifs

Motif	Name	Family
MA0093.1	USF1	bHLH-ZIP
MA0093.2	USF1	bHLH-ZIP
MA0093.3	USF1	bHLH-ZIP
MA0093.4	USF1	bHLH-ZIP

JASPAR matrix evidence (PMIDs): PMID:8052536, PMID:23332764

Upstream regulators (CollecTRI, top): AP1, ATF4, CREB1, PAX3, SREBF2, TBP, TFAP2A, USF1, USF2

miRNA regulators (miRDB)

28 targeting USF1, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-581	98.39	67.42	835
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-6772-3P	97.04	65.89	784
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-6724-5P	96.41	63.11	507
HSA-MIR-5586-5P	96.29	68.02	685

Literature-anchored findings (GeneRIF, showing 40)

• requirement of carboxy ester lipase gene E-box for activation binds upstream regulatory factor 1 and 2 (PMID:11945176)
• Cooperative E-box regulation of human GLI1 by TWIST and this protein (PMID:11948912)
• demonstrated a novel mechanism for USF activation, which contributes to differential vasopressin expression in lung cancer. (PMID:12403649)
• data indicated that upstream-stimulatory-factor (USF) might be involved in the basal transcriptional machinery of apolipoprotein E by binding to a non-canonical E-box motif within the proximal promoter (PMID:12444925)
• transfection of expression vectors containing USF-1 or USF-2 cDNAs activated CYP1A2 reporter gene activity, while a dominant-negative USF-2 expression vector blocked such activity. (PMID:12663044)
• we report the molecular cloning and functional characterization of a novel alternative splicing variant of human USF1 (hUSF1), termed USF1/BD. (PMID:12851711)
• These findings suggest that increased protein levels and DNA binding of USF1 and USF2 mediate the inhibitory effects of hypoxia and of Mash-2 on CYP19 gene expression in human placenta (PMID:12917334)
• USF1 transcription is regulated by cha, a basic helix-loop-helix transcription factor (PMID:12923186)
• USF1/2 activates the hTERT promoter exclusively in hTERT-positive cells in a manner that is enhanced by the coactivator p300 and attenuated upon inhibiting p38-MAP kinase, a known modulator of USF activity. (PMID:12970752)
• USF and Sp1 proteins interact and regulate human deoxycytidine kinase promoter activity (PMID:14514691)
• transcription factors upstream stimulatory factor (USF) and c-Myc may exert opposing effects on PIGR promoter activity (PMID:14644095)
• encodes a transcription factor known to regulate several genes of glucose and lipid metabolism (PMID:14991056)
• familial combined hyperlipidemia was linked and associated with the USF1 gene in 60 extended Finnish families (PMID:14991056)
• role in regulating transcription of many genes involved in lipid and glucose homeostasis (PMID:15054483)
• the influencing feature of both glucose and lipid homeostasis showing case-control heterogeneity (PMID:15175273)
• USF1 and 2 transactivate rat and human PF4 promoters and may play an important role in megakaryocytic gene expression (PMID:15187018)
• results demonstrate for the first time that USF proteins bind to the human HO-1 promoter in vivo and are required for high-level expression of HO-1 by haem and cadmium in human renal epithelial cells (PMID:15242350)
• UV-induced expression of POMC and MC1R is dependent on the p-38-activated upstream stimulating factor-1 (PMID:15358786)
• These results demonstrate that USF1/USF2 and TFII-I interact cooperatively at the upstream RBEIII element and are necessary for the induction of latent HIV-1 in response to T-cell activation signals. (PMID:15767439)
• USF1 and USF2 mRNA levels were reduced in non-small cell lung carcinomas; AP2-alpha levels were elevated; regression analysis demonstrated that reduced USF2 mRNA & increased AP2-alpha mRNA levels were predictive of downregulated PIGR mRNA expression (PMID:15864740)
• We replicated the association between USF1 and traits related to familial combined hyperlipidemia. (PMID:15959806)
• role of USF1 in familial combined hyperlipidemia in an outbred population links the 16q24.1 region to an FCHL-component trait in Mexicans (PMID:15976322)
• Polymorphism in the usf1 gene is associated with increased lipolytic effect of catecholamines in fat cells, which is localized at the postadrenoceptor level, possibly, at least, involving protein kinase A. (PMID:15985485)
• Upstream transcription factor 1 (USF1), is the first gene associated with familial combined hyperlipidemia. (PMID:16076849)
• unable to find any evidence to support the hypothesis that genetic variation in the Upstream transcription factor 1 (USF1) gene makes a significant contribution to type 2 diabetes susceptibility in the French Caucasian population (PMID:16186412)
• early in gestation when the placenta is relatively hypoxic, increased USF1/2 may block trophoblast differentiation and CYP19 gene expression (PMID:16199862)
• USF1 increased endogenous hRFC-A1/A2 transcripts. (PMID:16225938)
• Using the chromatin immunoprecipitation assay (ChIP), we show that USF is bound in vivo to the E-box regulatory element(s). Depletion of the endogenous USF pool evokes a severe inhibition of S100A6 gene promoter activity. (PMID:16288473)
• USF transcription factors have thus been involved as key regulators of a wide number of gene regulation network including stress and immune response, cell cycle and proliferation. (review) (PMID:16386222)
• upstream transcription factor 1 has a part in the etiology of familial combined hyperlipidemia and its component traits, although the mechanism of causality still remains largely unknown. (PMID:16531745)
• USF1 may have a role in cardiovascular disease in women (PMID:16699592)
• These data exclude USF1 as a major contributor to type 2 diabetes susceptibility and the basis for the chromosome 1q linkage. They reveal only limited evidence for replication of USF1 effects on continuous metabolic traits. (PMID:16936202)
• The data suggest that TFII-I and USF regulate chromatin structure accessibility and recruitment of transcription complexes in the beta-globin gene locus. (PMID:16943425)
• Upstream transcription factor 1 gene polymorphisms are associated with high antilipolytic insulin sensitivity and show gene-gene interactions (PMID:17016691)
• Previously identified risk haplotype of USF1 showed a suggestive association with famiilial combined hyperlipidemia and contributed to the related lipid traits in Dutch families. (PMID:17065663)
• significant associations between relatively common USF1 genetic variants and Cardiovascular risk factors were observed in French Canadians (PMID:17309647)
• Overexpression of USF-1 and USF-2 significantly suppressed TSH-stimulated thymidine uptake while maintaining TSH-stimulated cAMP production in FRTL-5 cells. Significantly suppressed BrdU uptake in carcinoma cells. (PMID:17379962)
• L-PGDS gene expression in TE671 cells was activated by USF1 through the aE-box within intron 4 and cooperatively by AP-2beta in the promoter in a cell-type-specific manner. (PMID:17574780)
• USF1 influences cardiovascular risk factors in a sex-dependent manner in familial combined hyperlipidemia/coronary atherosclerosis. A significant interaction between sex and genotype was shown to affect triglycerides and BMI. (PMID:17673701)
• Results demonstrated that the E-box at -566 bp to -561 bp is the negative regulatory element, and the specific and constitutive binding of the upstream stimulating factor-1 to this E-box is the key mechanism of the negative regulation of PAI-1 expression. (PMID:17765897)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	usf1l	ENSDARG00000014463
danio_rerio	usf1	ENSDARG00000041689
mus_musculus	Usf1	ENSMUSG00000026641
rattus_norvegicus	Tstd1	ENSRNOG00000004255

Paralogs (3): SREBF1 (ENSG00000072310), USF2 (ENSG00000105698), SREBF2 (ENSG00000198911)

Protein

Protein identifiers

Upstream stimulatory factor 1 — P22415 (reviewed: P22415)

Alternative names: Class B basic helix-loop-helix protein 11, Major late transcription factor 1

All UniProt accessions (7): A0A0S2Z4U5, B1AQP1, E9PJ52, E9PME6, E9PQA2, P22415, H0YD59

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5’-CACGTG-3’) that is found in a variety of viral and cellular promoters.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a homodimer or a heterodimer (USF1/USF2). Interacts with varicella-zoster virus IE62 protein.

Subcellular location. Nucleus.

Disease relevance. Hyperlipidemia, familial combined, 1 (FCHL1) [MIM:602491] A disorder characterized by a variable pattern of elevated levels of serum total cholesterol, triglycerides or both. It is observed in a percentage of individuals with premature coronary heart disease. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
P22415-1	1	yes
P22415-2	2, usf1-bd

RefSeq proteins (3): NP_001263302, NP_009053, NP_996888 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR051732	USF	Family

Pfam: PF00010

UniProt features (14 total): region of interest 3, turn 2, helix 2, compositionally biased region 2, chain 1, domain 1, strand 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1AN4	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22415-F1	62.89	0.31

Functional residue map

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

Post-translational modifications (1): 306

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation

MSigDB gene sets: 0 (showing top):

GO Biological Process (17): positive regulation of transcription from RNA polymerase II promoter by glucose (GO:0000432), response to hypoxia (GO:0001666), glucose metabolic process (GO:0006006), regulation of transcription by RNA polymerase II (GO:0006357), response to UV (GO:0009411), glucose mediated signaling pathway (GO:0010255), late viral transcription (GO:0019086), cellular response to insulin stimulus (GO:0032869), glucose homeostasis (GO:0042593), positive regulation of transcription by RNA polymerase II (GO:0045944), carbon catabolite regulation of transcription (GO:0045990), negative regulation of fibrinolysis (GO:0051918), lipid homeostasis (GO:0055088), cellular response to glucose stimulus (GO:0071333), regulation of transcription from RNA polymerase II promoter by glucose (GO:0000430), regulation of DNA-templated transcription (GO:0006355), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (19): 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 activator activity, RNA polymerase II-specific (GO:0001228), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), bHLH transcription factor binding (GO:0043425), sequence-specific DNA binding (GO:0043565), protein-containing complex binding (GO:0044877), protein heterodimerization activity (GO:0046982), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ESR-mediated signaling	1
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
protein binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
DNA-templated transcription	2
protein dimerization activity	2
DNA binding	2
binding	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
regulation of transcription from RNA polymerase II promoter by glucose	1
carbon catabolite activation of transcription from RNA polymerase II promoter	1
positive regulation of transcription by glucose	1
response to stress	1
response to decreased oxygen levels	1
hexose metabolic process	1
response to light stimulus	1
hexose mediated signaling	1
cellular response to glucose stimulus	1
viral transcription	1
response to insulin	1
cellular response to peptide hormone stimulus	1
carbohydrate homeostasis	1
positive regulation of DNA-templated transcription	1
cellular response to nutrient	1
positive regulation of blood coagulation	1
positive regulation of response to external stimulus	1
fibrinolysis	1
negative regulation of biological process	1
regulation of fibrinolysis	1
chemical homeostasis	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
carbon catabolite regulation of transcription from RNA polymerase II promoter	1
regulation of transcription by glucose	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1

Protein interactions and networks

STRING

1782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USF1	USF2	Q15853	982
USF1	GTF2I	P78347	849
USF1	SMARCD3	Q6STE5	813
USF1	RFX5	P48382	753
USF1	TAF7	Q15545	737
USF1	CTNNB1	P35222	736
USF1	IRF1	P10914	732
USF1	YY1	P25490	712
USF1	CREB1	P16220	704
USF1	APOB	P04114	698
USF1	TBP	P20226	697
USF1	CEBPB	P17676	686
USF1	ATF3	P18847	668
USF1	FASN	P49327	660
USF1	CTCF	P49711	645

IntAct

83 interactions, top by confidence:

A	B	Type	Score
PRKDC	XRCC6	psi-mi:“MI:0217”(phosphorylation reaction)	0.900
FOSL1	USF1	psi-mi:“MI:0915”(physical association)	0.780
USF1	USF1	psi-mi:“MI:0915”(physical association)	0.670
USF1	KAT2B	psi-mi:“MI:0192”(acetylation reaction)	0.620
TRAF2	USF1	psi-mi:“MI:0915”(physical association)	0.560
USF1	FOS	psi-mi:“MI:0915”(physical association)	0.560
USF1	PARP1	psi-mi:“MI:0914”(association)	0.560
USF1	PARP1	psi-mi:“MI:0915”(physical association)	0.560
	USF1	psi-mi:“MI:0915”(physical association)	0.560
USF1	SNW1	psi-mi:“MI:0915”(physical association)	0.560
USF1	MAP3K7CL	psi-mi:“MI:0915”(physical association)	0.560
USF1	LAP3	psi-mi:“MI:0915”(physical association)	0.560
USF1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
USF1	HRAS	psi-mi:“MI:0915”(physical association)	0.560
USF1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (138): USF1 (Two-hybrid), USF1 (Two-hybrid), USF1 (Two-hybrid), FOSL1 (Two-hybrid), USF1 (Affinity Capture-MS), USF1 (Affinity Capture-MS), USF1 (Reconstituted Complex), USF1 (Proximity Label-MS), PLEKHF2 (Two-hybrid), ASS1 (Affinity Capture-MS), STT3A (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), USF2 (Affinity Capture-MS), RCL1 (Affinity Capture-MS), ATP5H (Affinity Capture-MS)

ESM2 similar proteins: A0JMF8, B1WAV2, F2Z3T4, O02818, O77627, O88873, O93602, P05411, P05412, P05627, P12981, P15336, P16951, P17325, P18870, P22415, P31367, P48381, P54864, P56432, P58929, P79703, Q00969, Q04073, Q07956, Q07957, Q0V989, Q0V9K5, Q16656, Q24312, Q2HJ87, Q2TAL8, Q32NR3, Q4R3I8, Q4V872, Q502P7, Q58A65, Q5EAP5, Q5FWL0, Q61069

Diamond homologs: A0A286LEZ9, A2T713, A2T7L8, A4IFU7, O02818, O14948, O75030, O88368, P0DPB0, P17106, P19484, P19532, P22415, P49379, Q05B92, Q07957, Q08874, Q10186, Q5A1E3, Q5XFQ6, Q61069, Q63302, Q64092, Q6XBT4, Q9R210, Q9WTW4, A3KNA7, O43019, O97676, P36956, P56720, Q12772, Q3T1I5, Q3U1N2, Q4WIN1, Q59RL7, Q60416, Q60429, Q6GQ26, Q9UUD1

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
PRKDC	up-regulates	USF1	phosphorylation
MAPK14	“up-regulates activity”	USF1	phosphorylation
USF1	“up-regulates quantity by expression”	POMC	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	MYH9	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	B2M	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	CBS	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	FMR1	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	CTSD	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	GATA5	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	GCK	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	S100A6	“transcriptional regulation”
CEBPA	“up-regulates activity”	USF1	binding
USF1	“up-regulates quantity by expression”	CEBPA	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	ADAM10	“transcriptional regulation”
USF1	“up-regulates activity”	JMJD1C	binding
USF1	“up-regulates quantity by expression”	Hexokinase	“transcriptional regulation”
GTF2I	“up-regulates activity”	USF1	binding
GSK3B	“up-regulates activity”	USF1	phosphorylation
USF1	“down-regulates activity”	FOSL1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1290 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161040327:TACT:T	acceptor_gain	1.0000
1:161040329:CT:C	acceptor_gain	1.0000
1:161040331:C:CC	acceptor_gain	1.0000
1:161040331:CT:C	acceptor_loss	1.0000
1:161040332:T:C	acceptor_loss	1.0000
1:161040546:T:TA	donor_gain	1.0000
1:161040568:T:TA	donor_gain	1.0000
1:161040595:T:A	donor_gain	1.0000
1:161040617:T:C	donor_gain	1.0000
1:161040666:CTCCA:C	acceptor_gain	1.0000
1:161040667:TCCA:T	acceptor_gain	1.0000
1:161040668:CCA:C	acceptor_gain	1.0000
1:161040668:CCAC:C	acceptor_gain	1.0000
1:161040669:CA:C	acceptor_gain	1.0000
1:161040669:CAC:C	acceptor_gain	1.0000
1:161040670:AC:A	acceptor_loss	1.0000
1:161040671:C:A	acceptor_loss	1.0000
1:161040671:C:CC	acceptor_gain	1.0000
1:161040672:T:A	acceptor_loss	1.0000
1:161040679:CAAAG:C	acceptor_gain	1.0000
1:161040680:A:T	acceptor_gain	1.0000
1:161040683:G:C	acceptor_gain	1.0000
1:161040683:G:GC	acceptor_gain	1.0000
1:161040887:C:T	acceptor_gain	1.0000
1:161040887:CAGGG:C	acceptor_gain	1.0000
1:161040891:G:GC	acceptor_gain	1.0000
1:161040896:C:T	acceptor_gain	1.0000
1:161040896:CAGAG:C	acceptor_gain	1.0000
1:161040897:A:T	acceptor_gain	1.0000
1:161040900:G:C	acceptor_gain	1.0000

AlphaMissense

2013 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161039999:A:G	L285P	1.000
1:161040212:A:G	L278P	1.000
1:161040281:C:G	R255P	1.000
1:161040284:A:G	L254P	1.000
1:161040293:A:T	I251N	1.000
1:161040305:G:T	A247D	1.000
1:161040306:C:G	A247P	1.000
1:161040307:T:A	K246N	1.000
1:161040307:T:G	K246N	1.000
1:161040309:T:C	K246E	1.000
1:161040312:A:G	S245P	1.000
1:161040314:A:C	L244R	1.000
1:161040314:A:G	L244P	1.000
1:161040314:A:T	L244Q	1.000
1:161040317:A:C	I243S	1.000
1:161040317:A:T	I243N	1.000
1:161040320:C:T	G242E	1.000
1:161040323:C:A	G241V	1.000
1:161040323:C:T	G241D	1.000
1:161040324:C:A	G241C	1.000
1:161040324:C:G	G241R	1.000
1:161040325:T:A	K240N	1.000
1:161040325:T:G	K240N	1.000
1:161040326:T:A	K240I	1.000
1:161040326:T:G	K240T	1.000
1:161040327:T:C	K240E	1.000
1:161040327:T:G	K240Q	1.000
1:161040328:A:C	S239R	1.000
1:161040328:A:T	S239R	1.000
1:161040329:C:A	S239I	1.000

dbSNP variants (sampled 300 via entrez): RS1000010156 (1:161040145 A>G), RS1000105620 (1:161045569 G>A,T), RS1000550967 (1:161040479 A>G), RS1000566529 (1:161043849 C>T), RS1001775964 (1:161044251 A>T), RS1002239127 (1:161042415 C>T), RS1002733596 (1:161046939 C>A,T), RS1003007934 (1:161047233 G>T), RS1003045712 (1:161044894 C>T), RS1004023281 (1:161046505 G>GGT), RS1004127617 (1:161039537 G>A), RS1004178674 (1:161039196 A>G), RS1004285247 (1:161045876 C>A,G), RS1004455226 (1:161046151 C>A), RS1004759652 (1:161044348 C>T)

Disease associations

OMIM: gene MIM:191523 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperlipidemia, combined, 1	Limited	Autosomal dominant

Mondo (1): hyperlipidemia, combined, 1 (MONDO:0011237)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001725_36	Inflammatory bowel disease	7.000000e-09
GCST003542_114	Night sleep phenotypes	7.000000e-06
GCST003542_135	Night sleep phenotypes	4.000000e-06
GCST004608_40	Granulocyte percentage of myeloid white cells	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566535	Hyperlipidemia, Combined, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
CGP 12177	increases metabolic processing, increases reaction, affects reaction	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases methylation	1
Amiodarone	increases expression	1
Atrazine	decreases expression	1
Dobutamine	increases metabolic processing, increases reaction, affects reaction	1
Doxorubicin	decreases expression	1
Colforsin	increases metabolic processing, increases reaction, affects reaction	1
Lipids	increases metabolic processing, increases reaction, affects reaction	1
Norepinephrine	affects reaction, increases metabolic processing, increases reaction	1
Plant Extracts	affects cotreatment, increases expression	1
Terbutaline	increases metabolic processing, increases reaction, affects reaction	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Vanadium	increases activity	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Coal Ash	increases activity	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7S4	SEES3-1V human USF1, clone1	Embryonic stem cell	Male
CVCL_A7S5	SEES3-1V human USF1, clone2	Embryonic stem cell	Male
CVCL_A7S6	SEES3-1V human USF1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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