USF1
protein-codingupstream transcription factor 1, the group of Basic helix-loop-helix proteins
Gene summary
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. [provided by RefSeq, Feb 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0011237
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to USF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007122.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 25 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 27 | 0 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009053.1 | 10 | MANE Select | |
| Ensembl | ENSP00000357000.3 | 10 | MANE Select | |
| RefSeq | NP_001263302.1 | 10 | Standard | |
| RefSeq | NP_996888.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Signaling by Nuclear Receptors
- Estrogen-dependent gene expression
- ESR-mediated signaling
- Signaling mediated by p38-alpha and p38-beta
Biological Process
- regulation of transcription from RNA polymerase II promoter by glucose
- positive regulation of transcription from RNA polymerase II promoter by glucose
- response to hypoxia
- glucose metabolic process
- regulation of transcription by RNA polymerase II
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- double-stranded DNA binding
- protein binding
- enzyme binding
- protein kinase binding
Cellular Component
- nuclear chromatin
- nucleus
- nucleoplasm
- transcription factor complex
- NURF complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368021
- Coding exons
- 10
- Length
- 6727
- Individuals with no LoFs
- 125325
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 423
- Defined
- 125748
- p
- 0.00168
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.14 | 107 | 190 | 0.563 | 0.0000113 | 2006 |
| Missense (PolyPhen) | 27 | 63.998 | 0.42189 | 692 | ||
| Synonymous | 0.107 | 70 | 71.2 | 0.984 | 0.00000411 | 620 |
| Loss of Function | 3.02 | 7 | 22.5 | 0.312 | 0.00000136 | 208 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0071 | 0.0067 | notable |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00070 | 0.00069 | rare |
| East Asian | 0.00077 | 0.00076 | rare |
| Finnish | 0.0029 | 0.0029 | notable |
| European (Non-Finnish) | 0.0018 | 0.0018 | notable |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0.0028 | 0.0028 | notable |
dbNSFP Gene Annotations
Source:
- Function
- 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.;
- Disease
- DISEASE: Hyperlipidemia combined 1 (HYPLIP1) [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. {ECO:0000269|PubMed:14991056}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.637
Intolerance Scores
- LoFtool
- 0.273
- RVIS EVS
- -0.41
- RVIS percentile EVS
- 26.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |