The ASXL1 gene spans around 80 kb of genomic DNA and is composed of 12 exons.

Alternative splicing results in multiple transcript variants.

The longer ASXL1 transcript encodes a 1541 amino acid (170 kDa) protein. Mammalian ASXL proteins are characterized by an amino-terminal ASX homology (ASXH) region containing 2 putative nuclear receptor coregulator binding motifs (NR box), 3 other NR box motifs and a C-terminal plant homeodomain protein-protein interaction domain. Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which may be required for an association with nuclear receptors.

ASXL1 is expressed all hematopoietic cell fractions in mice. Asxl1 knockout mice exhibit mild defects in differentiation of lymphoid and myeloid progenitors, but not in multipotent progenitors and do not develop MDS or other hematological malignancy.
ASXL1 is widely expressed at low level in heart, brain, skeletal muscle, placenta, pancreas, spleen, prostate, small intestine, colon, peripheral blood, leukocytes, bone marrow and fetal liver. Highly expressed in testes.

Nucleus (probable).

- ASXL1 acts as a co-regulator of retinoic acid (RA) receptor in RA sensitive cell lines, and as a co-repressor of RA receptor in RA resistant cell lines. Either a coactivator or corepressor for the retinoid receptors retinoic acid receptor and retinoid X receptor in a cell type-specific manner.
- ASXL1 cooperates with HP1 (heterochromatin protein 1) to modulate histone H3 demethylase LSD1 activity, leading to a change in histone H3 methylation and RAR repression.
- ASXL1 belongs to the Enhancer of Trithorax and Polycomb (ETP) group in drosophila.
- ASXL1 is required for maintenance of both activation and silencing of Hox genes in mice and drosophila in a context-dependent manner.
- ASXL1 is one of the fusion protein partners of PAX5 in B-cell precursor acute lymphoblastic leukemias.
- ASXL1 may function as a tumor suppressor in myeloid malignancies by affecting stem or progenitor cell self renewal or differentiation.

There are 3 mammalian homologs of the Additional sex combs (Asx) gene of Drosophila: ASXL1, 2 (chromosome 2p24 in humans) and 3 (chromosome 18q11 in humans).

Acquired ASXL1 mutations are frequently frameshift and nonsense. All mutations are in exon 12, mostly around the Gly-rich domain (amino acids 642-685). The most common somatic mutation is p.Gly646Trpfsx12.
These mutations cause truncation of the ASXL1 protein downstream of the ASXH domain leading to the loss of the C-terminal PHD domain.
Some possible single nucleotide polymorphisms have been described: p.Arg1224Thr, p.Thr769Ala, p.Gly1007Arg, p.Thr688Met, p.Gln1074Leu, p.Arg693Gly, p.T1139K, p.Gly652Ser, p.Val1072Asp...

All mutations have been found in myeloid diseases so far. A fusion has been found in B-cell leukemia.