SREBF1

Chr 17AD

sterol regulatory element binding transcription factor 1

Also known as: HMD, IFAP2, SREBP1, bHLHd1

NCBI Gene: 6720ENSG00000072310UniProt: P36956OMIM: 184756

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. [provided by RefSeq, Nov 2017]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ichthyosis, follicular, with atrichia and photophobia syndrome 2MIM #619016
AD
Mucoepithelial dysplasia, hereditaryMIM #158310
AD
UniProtIFAP syndrome 2

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
235
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.45
LOEUF
LOF
Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.45LOEUF
pLI 0.015
Z-score 4.40
OE 0.28 (0.18–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.98Z-score
OE missense 0.79 (0.73–0.85)
548 obs / 694.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.28 (0.18–0.45)
0≤0.351.4
Missense OE?0.79 (0.73–0.85)
0≤0.61.4
Synonymous OE?0.88
0≤1.21.6
LoF obs/exp: 12 / 43.2Missense obs/exp: 548 / 694.5Syn Z: 1.70

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients