CREB1

Chr 2

cAMP responsive element binding protein 1

Also known as: CREB, CREB-1

This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Alternate splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

OMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.221 OMIM phenotype
Clinical SummaryCREB1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.22LOEUF
pLI 0.997
Z-score 4.07
OE 0.05 (0.020.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.91Z-score
OE missense 0.40 (0.330.48)
73 obs / 183.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.05 (0.020.22)
00.351.4
Missense OE?0.40 (0.330.48)
00.61.4
Synonymous OE?0.86
01.21.6
LoF obs/exp: 1 / 21.3Missense obs/exp: 73 / 183.9Syn Z: 0.90

This gene — mechanism propensity

DN
0.3892th %ile
GOF
0.15100th %ile
LOF
0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CREB1 · protein map & ClinVar variants

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