Alt. symbols: MEF | ELFR

Approved name: E74 like ETS transcription factor 4
Alt. names: E74-like factor 4 (ets domain transcription factor)

Location: Xq26.1: 130063955 - 130110716 (-)
Gene type: protein_coding, 3 transcripts.

Scores: LoFtool: 0.359000 | pLI: 0.61146408 | LOEUF: 0.644

HGNC: 3319

NCBI: 2000, RefSeq: NG_016388.1

Ensembl: ENSG00000102034.18

LRG_335 | Status: public

OMIM: 300775

Expression | ProteinAtlas

ELF4 encodes a transcriptional activator that binds promoters of many hematopoietic target genes including growth factors such as CSF2, IL3, and IL8, as well as PRF1 in natural killer (NK) cells (PMID: 27932483). As such, it plays a role in the development and function of NK and NK T-cells and in innate immunity, but also controls the proliferation and homing of CD8+ T-cells via KLF4 and KLF2 (PMID: 19412182). ELF4 has also been implicated in control of cellular senescence in a p53-dependent manner and may promote transformation through inhibition of the p16 pathway (PMID: 27932483).

X-linked LOF variants in the ETS transcription factor gene ELF4 were identified in multiple unrelated male patients with early-onset fevers, mucosal autoinflammation and IBD that responded to IL-1, TNF or IL-12p40 blockade (PMID: 34326534). Two of three patients had suboptimal vaccine responses or significantly elevated serum CXCL1 levels. Labs from 1 patient showed low NK cells and low CD27+ memory B cells, increased numbers of naïve CD4+ and CD8+ T cells compared to healthy controls, and eleva ted calprotectin. Another showed lymphocytosis, thrombocytosis and elevated ESR with normal IgG and IgE, normal T cells and slightly elevated B cells. Like the mouse models, patient cells showed impaired ELF4-mediated suppression of inflammatory TH17 cell responses and increased production of pro-inflammatory cytokines such as IL-1β and IL-6, as well as intracellular IL-12p40 from patient monocytes. [Load More]