ASXL1是抑癌基因，编码一种多梳家族蛋白，是参与转录调节的染色质结合剂，可以重塑染色质，使基因发生表观遗传沉默。ASXL1是ASXL基因家族成员之一，家族成员还包括ASXL2和ASXL3，这些蛋白都具有C末端植物同源结构域（PHD结构域），预测通过甲基化赖氨酸来识别组蛋白H3尾部。ASXL1直接与多梳抑制复合物2(PRC2)相互作用，并且在招募PRC2到染色质以及随后的H3K27me3组蛋白修饰中起重要作用。ASXL1还独立地与染色质蛋白BAP1相互作用，BAP1-ASXL1复合物可以调节多梳抑制复合物1（PRC1）所放置的H2AK119泛素标记。ASXL1发生突变会导致Polycomb靶基因不能被有效抑制，进而导致基因表达失调。Bohring-Opitz综合征的患者中发现ASXL1的胚系杂合突变，Bohring-Opitz综合征是导致独特的颅面畸形的发育障碍。ASXL1功能丧失的体细胞突变在造血系统恶性肿瘤中非常常见，包括骨髓增生异常综合征（MDS），慢性粒单核细胞白血病（CMML），骨髓纤维化（MF）和急性髓性白血病（AML）。此外，ASXL1突变经常与CMML中的N/K-Ras突变共同发生，从而进一步促进白血病发生。

ASXL1 is a member of the Polycomb group of proteins, and is a chromatin binder that is involved in transcription regulation. ASXL1 is a member of the ASXL gene family that includes ASXL1, ASXL2 and ASXL3, which all have a C-terminal plant homology domain (PHD domain) that is predicted to recognize histone H3 tails via methylated lysines. ASXL1 interacts directly with the Polycomb Repressive Complex 2 (PRC2) and has a role in the recruitment of PRC2 to chromatin and subsequent H3K27me3 histone modifications. Mutations in ASXL1 result in the inability of Polycomb target genes to be effectively repressed leading to dysregulated gene expression, such as at the HOXA gene cluster. ASXL1 also independently interacts with the chromatin protein BAP1. The BAP1-ASXL1 complex can regulate the H2AK119 ubiquitin mark placed by the Polycomb Repressive Complex 1 (PRC1). Germline heterozygous mutations in ASXL1 have been found in patients with Bohring-Opitz syndrome, a developmental disorder that results in distinctive craniofacial abnormalities. Recurrent somatic ASXL1 loss-of-function mutations are very common in hematopoietic malignancies including myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML). Furthermore, ASXL1 mutations frequently co-occur with N/K-Ras mutations in CMML to promote leukemogenesis.

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