CREM (cAMP Responsive Element Modulator)
Transcriptional regulator in cAMP signaling, spermatogenesis, and immune function
Gene Information Card
| Symbol | CREM |
|---|---|
| Full Name | cAMP responsive element modulator |
| Gene Type | protein-coding |
| Chromosomal Location | 10p11.21 |
| NCBI Gene ID | 1390 ncbi.nlm.nih.gov/gene/1390 |
| Ensembl ID | ENSG00000164292 |
| UniProt ID | Q03060 |
| OMIM ID | 123812 |
| HGNC ID | 2352 |
| Aliases | ICER, CREM-2, hCREM-2, CREMalpha, CREMbeta, CREMgamma, CREMtau |
Description
CREM (cAMP responsive element modulator) is a transcription factor that binds to cAMP response elements (CRE) and regulates the expression of genes involved in cAMP signaling. It is essential for spermatogenesis, modulates immune responses, and is implicated in several cancers and autoimmune diseases. Alternative splicing generates multiple isoforms, including the repressor ICER (inducible cAMP early repressor).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility (azoospermia) | Loss of CREM function disrupts post-meiotic germ cell development | OMIM #123812; NCBI Gene |
| Acute lymphoblastic leukemia (ALL) | CREM overexpression promotes leukemogenesis via cAMP pathway dysregulation | COSMIC; PubMed studies |
| Autoimmune diseases (e.g., systemic lupus erythematosus) | Altered CREM/ICER balance affects T-cell cytokine production | NCBI Gene; literature review |
| Colorectal cancer | CREM isoform switching contributes to tumor progression | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 68.5 | High |
| Brain (cerebellum) | 12.3 | Medium |
| Heart | 8.7 | Medium |
| Liver | 2.1 | Low |
| Kidney | 4.5 | Low |
| Lung | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.2 | High expression |
| HeLa (cervical) | 8.1 | Medium expression |
| HEK293 (embryonic kidney) | 6.4 | Medium expression |
| HepG2 (liver) | 2.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34*) | Nonsense | <0.01% | Premature stop, loss of DNA-binding domain |
| c.287_288del (p.Glu96fs) | Frameshift | <0.01% | Loss of function, truncated protein |
| c.421A>G (p.Lys141Glu) | Missense | <0.01% | Altered transactivation activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg34*, p.Glu96fs) lead to truncated, non-functional CREM protein, impairing spermatogenesis.
Gain of Function (GOF)
Not well documented; overexpression of certain isoforms in leukemia may act as gain-of-function.
Dominant Negative (DN)
ICER isoforms act as dominant-negative repressors by competing with CREB for CRE binding.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • cAMP response element binding (GO:0035497) |
| • regulation of transcription by RNA polymerase II (GO:0006357) | • spermatogenesis (GO:0007283) |
| • negative regulation of transcription (GO:0016481) |
Pathways
• cAMP signaling pathway (KEGG: hsa04024)
• CREB signaling (Reactome: R-HSA-111931)
• Transcriptional regulation by CREM (Reactome: R-HSA-212436)
Protein Summary
The CREM protein is a 271-amino-acid transcription factor containing a basic leucine zipper (bZIP) domain that mediates dimerization and DNA binding. It activates or represses cAMP-responsive genes depending on the isoform. ICER isoforms lack the transactivation domain and function as repressors. CREM is highly expressed in testis and is critical for spermatogenesis; dysregulation contributes to infertility, leukemia, and autoimmune conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CREM Knockout HEK293 Cell Line | EDJ-KQ4343 | Human | 1390 | Details Get a Quote |
| CREM Knockout A-549 Cell Line | EDJ-KQ25557 | Human | 1390 | Details Get a Quote |
| CREM Knockout HCT 116 Cell Line | EDJ-KQ26842 | Human | 1390 | Details Get a Quote |
| CREM Knockout HeLa Cell Line | EDJ-KQ26843 | Human | 1390 | Details Get a Quote |
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