CREB5

Chr 7

cAMP responsive element binding protein 5

Also known as: CRE-BPA, CREB-5, CREBPA

NCBI Gene: 9586ENSG00000146592UniProt: Q02930

The product of this gene belongs to the CRE (cAMP response element)-binding protein family. Members of this family contain zinc-finger and bZIP DNA-binding domains. The encoded protein specifically binds to CRE as a homodimer or a heterodimer with c-Jun or CRE-BP1, and functions as a CRE-dependent trans-activator. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

87
ClinVar variants
24
Pathogenic / LP
0.22
pLI score
0
Active trials
Clinical Summary— CREB5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 63 VUS of 87 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.48LOEUF
pLI 0.223
Z-score 3.48
OE 0.24 (0.13–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.61Z-score
OE missense 0.74 (0.67–0.83)
230 obs / 309.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.24 (0.13–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.67–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 6 / 24.7Missense obs/exp: 230 / 309.9Syn Z: 0.18

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic3
VUS63
21
Pathogenic
3
Likely Pathogenic
63
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
3
0
3
VUS
0
59
4
0
63
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total05928087

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CREB5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Anchored multiplex PCR for targeted next-generation sequencing.
Zheng Z et al.·Nat Med
2014
An oncohistone-driven H3.3K27M/CREB5/ID1 axis maintains the stemness and malignancy of diffuse intrinsic pontine glioma.
Zhou W et al.·Nat Commun
2025
Endoplasmic reticulum stress-related super enhancer promotes epithelial-mesenchymal transformation in hepatocellular carcinoma through CREB5 mediated activation of TNC.
Wang A et al.·Cell Death Dis
2025
Strategies for arterial graft optimization at the single-cell level.
Hu Z et al.·Nat Cardiovasc Res
2024
MicroRNA-204/CREB5 axis regulates vasculogenic mimicry in breast cancer cells.
Contreras-Sanzón E et al.·Cancer Biomark
2022
RGS1 and CREB5 are direct and common transcriptional targets of ZNF384-fusion proteins.
Yamada C et al.·Cancer Med
2024
Plasma microRNA-320c as a Potential Biomarker for the Severity of Knee Osteoarthritis and Regulates cAMP Responsive Element Binding Protein 5 (CREB5) in Chondrocytes.
Zhou R et al.·Dis Markers
2024
The DNAm levels of CREB5 (cg11301281) were associated with clopidogrel resistance.
Li J et al.·J Clin Lab Anal
2022
Long noncoding RNA SNHG4 promotes the malignant progression of hepatocellular carcinoma through the miR-211-5p/CREB5 axis.
Qiu J et al.·Cancer Med
2023
Circular RNA Hsa_circ_0007376 Promotes Malignancy of Gastric Cancer Cells by Regulating MiR-556-5p/CREB5 Axis.
Liu C et al.·Tohoku J Exp Med
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CREB5 Inhibits Neuronal Ferroptosis via Transactivating ApoL6 to Regulate Lipid Droplet Metabolism After Spinal Cord Injury.
Xi X et al.·CNS Neurosci Ther
2026
miR-769-5p as a Novel Biomarker and Functional Mediator in Alzheimer's Disease: Targeting CREB5 to Alleviate Oxidative Injury.
Ma P et al.·APMIS
2026Functional
Kisspeptins inhibit ectopic endometrial cell invasion and angiogenesis by suppressing PI3K/AKT signaling pathway via CREB5 in endometriosis.
Kong L et al.·Int J Med Sci
2026🔓 Open Access
CREB5 promotes nodal metastasis of cervical cancer by regulation of APLN-induced lymphangiogenesis.
Xia M et al.·Cell Death Discov
2025🔓 Open Access
CREB5 Promotes the Proliferation of Neural Stem/Progenitor Cells in the Rat Subventricular Zone via the Regulation of NFIX Expression.
Yu T et al.·Cells
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools