SREBF1

Chr 17AD

sterol regulatory element binding transcription factor 1

Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). 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 (By similarity)

OMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.452 OMIM phenotypes
Clinical SummarySREBF1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.45LOEUF
pLI 0.015
Z-score 4.40
OE 0.28 (0.180.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.98Z-score
OE missense 0.79 (0.730.85)
548 obs / 694.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.28 (0.180.45)
00.351.4
Missense OE?0.79 (0.730.85)
00.61.4
Synonymous OE?0.88
01.21.6
LoF obs/exp: 12 / 43.2Missense obs/exp: 548 / 694.5Syn Z: 1.70
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateSREBF1-related ichthyosis, follicular, with atrichia and photophobia syndromeOTHERAD
moderateSREBF1-related mucoepithelial dysplasia, hereditaryOTHERAD

This gene — mechanism propensity

DN
0.6064th %ile
GOF
0.3986th %ile
LOF
0.48top 25%

The Badonyi & Marsh model scores dominant-negative highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation · LOEUF 0.45

Literature Evidence

LOFHypercholesterolemia in children with Smith-Magenis syndrome: del (17) (p11.2p11.2)1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 12180145

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SREBF1 · protein map & ClinVar variants

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