Chromosome 21 open reading frame 58 (C21orf58)

Chromosome 21 open reading frame 58 (C21orf58) encodes a protein mainly localized in the nucleus and cytoplasm, characterized by conserved domains mediating protein-protein interactions[1]. C21orf58 acts as an oncogenic adaptor, facilitating the formation of a ternary complex with JAK2 and STAT3, leading to abnormal STAT3 activation, which promotes cell growth, tumorigenesis, and resistance to therapies such as sorafenib in hepatocellular carcinoma[2][3]. Its expression is low and constitutive across tissues, but can be aberrantly elevated in certain cancers and disease states[1][2][4][5]. Recent studies identify C21orf58 as a promising therapeutic target in HCC, with alminoprofen shown to inhibit its function and suppress malignancy. However, the endogenous physiological functions outside cancer contexts remain largely uncharacterized, and no paralogs have been identified in humans[1].

Other names

C21orf58Uncharacterized protein C21orf58Chromosome 21 open reading frame 58hypothetical protein LOC54058

Inhibition of JAK2/STAT3 pathway via blockade of adaptor ternary complex formation