Alt. symbols: CRP1

Approved name: CCAAT enhancer binding protein epsilon
Alt. names: CCAAT/enhancer binding protein (C/EBP), epsilon, CCAAT/enhancer binding protein epsilon

Location: 14q11.2: 23117036 - 23120256 (-)
Gene type: protein_coding, 3 transcripts.

Scores: LoFtool: 0.507000 | pLI: 0.00239238 | LOEUF: 0.995

HGNC: 1836

NCBI: 1053, RefSeq: NG_009617.1

Ensembl: ENSG00000092067.7

LRG_45 | Status: public

OMIM: 600749

Expression | ProteinAtlas

CEBPE encodes the transcriptional activator CRP1 or C/EBPe (PMID: 26019275), a member of the CCAAT/enhancer binding protein family that can recognize two different motifs: the CCAAT homology sequence common to many promoters and the enhanced core homology sequence common to many enhancers (PMID: 8661101). It is required for the promyelocyte-myelocyte transition in myeloid differentiation (PMID: 10359588).

Homozygous missense CEBPE mutations lead to C/EBPe-associated autoinflammation and immune impairment of neutrophils (CAIN) [OMIM: 245480], which is characterized by recurrent fevers (every 2-4 weeks and lasting 4-5 days), abdominal pain and oral ulcers, as well as the development of sterile abscesses of the tongue, paronychia, and hemorrhagic diatheses not related to platelet abnormalities (PMID: 31201888). Laboratory tests show elevated inflammatory markers and defective neutrophil segmentation . These mutations lead to markedly decreased C/EBPε association with transcriptional repressors and increased occupancy on chromatin, leading to over-expression of many NLRP3- related and IFN-dependent inflammatory genes in neutrophils and IL-1 and IL-18 hypersecretion via aberrant caspase-5–mediated activation of the noncanonical inflammasome pathway in patient macrophages. However, patients do not appear to suffer serious long-term complications, presenting an average life span of more than 70 years. Notably, both monoallelic and biallelic CEBPE LOF mutations have also been associated with AD and AR forms of neutrophil-specific granule deficiency (SGD), characterized by complete loss of specific neutrophilic granules, severely impaired neutrophil function and pronounced susceptibility to bacterial infections with early mortality [OMIM: 245480]. [Load More]