CREM
protein-codingcAMP responsive element modulator, the group of Basic leucine zipper proteins
Gene summary
This gene encodes a bZIP transcription factor that binds to the cAMP responsive element found in many viral and cellular promoters. It is an important component of cAMP-mediated signal transduction during the spermatogenetic cycle, as well as other complex processes. Alternative promoter and translation initiation site usage allows this gene to exert spatial and temporal specificity to cAMP responsiveness. Multiple alternatively spliced transcript variants encoding several different isoforms have been found for this gene, with some of them functioning as activators and some as repressors of transcription. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~86.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CREM variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_183011.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 23 | 1 | 24 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 27 | 1 | 2 | 30 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_898829.1 | 7 | MANE Select | |
| Ensembl | ENSP00000509489.1 | 7 | MANE Select | |
| RefSeq | NP_001254491.1 | 4 | Standard | |
| RefSeq | NP_001254492.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HTLV-I infection - Homo sapiens (human)
- Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
- Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
- repression of pain sensation by the transcriptional regulator dream
- regulation of spermatogenesis by crem
Biological Process
- negative regulation of transcription by RNA polymerase II
- glucose metabolic process
- regulation of transcription, DNA-templated
- fatty acid metabolic process
- glycosphingolipid metabolic process
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA binding
- protein binding
Cellular Component
- nucleus
- transcription factor complex
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000345491
- Coding exons
- 7
- Length
- 86168
- Individuals with no LoFs
- 125710
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125728
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.462 | 145 | 162 | 0.898 | 0.00000801 | 1922 |
| Missense (PolyPhen) | 41 | 58.474 | 0.70117 | 679 | ||
| Synonymous | -0.0895 | 55 | 54.2 | 1.02 | 0.00000268 | 611 |
| Loss of Function | 3.23 | 4 | 19.3 | 0.207 | 0.00000124 | 191 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000056 | 0.000053 | rare |
| South Asian | 0.00027 | 0.00026 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional regulator that binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. Isoforms are either transcriptional activators or repressors. Plays a role in spermatogenesis and is involved in spermatid maturation (PubMed:10373550). {ECO:0000269|PubMed:10373550}.;
Recessive Scores
- pRec
- 0.256
Intolerance Scores
- LoFtool
- 0.760
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 34.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |