CREB1

Chr 2

cAMP responsive element binding protein 1

CREB1 encodes a phosphorylation-dependent transcription factor that binds to cAMP response elements to regulate gene expression in response to hormonal stimulation and is involved in circadian rhythms and cellular differentiation. Mutations cause autosomal dominant developmental delay, intellectual disability, and seizures, often with additional features including autism spectrum disorder and behavioral abnormalities. This gene is highly constrained against loss-of-function variants (pLI 0.997), indicating that heterozygous mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
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
Some data sources returned errors (1)

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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 OE0.05 (0.020.22)
00.351.4
Missense OE0.40 (0.330.48)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 1 / 21.3Missense obs/exp: 73 / 183.9Syn Z: 0.90
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.

3D Protein StructureAlphaFold
Clinical Literature
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