USF1

Chr 1

upstream transcription factor 1

Also known as: FCHL, FCHL1, HYPLIP1, MLTF, MLTFI, UEF, bHLHb11

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]

ResearchGenerating clinical summary…
DNmechanismLOEUF 0.58
Clinical SummaryUSF1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.58LOEUF
pLI 0.024
Z-score 3.02
OE 0.31 (0.180.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.14Z-score
OE missense 0.56 (0.480.66)
107 obs / 190.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.31 (0.180.58)
00.351.4
Missense OE?0.56 (0.480.66)
00.61.4
Synonymous OE?0.98
01.21.6
LoF obs/exp: 7 / 22.5Missense obs/exp: 107 / 190.2Syn Z: 0.11

This gene — mechanism propensity

DN
0.6551th %ile
GOF
0.2696th %ile
LOF
0.48top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

USF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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