ASXL1 Gene: Additional Sex Combs Like 1, Transcriptional Regulator
ASXL1: A key epigenetic regulator frequently mutated in myeloid malignancies and Bohring-Opitz syndrome
Gene Information Card
| Symbol | ASXL1 |
|---|---|
| Full Name | Additional Sex Combs Like 1, Transcriptional Regulator |
| Gene Type | Protein coding |
| Chromosomal Location | 20q11.21 |
| NCBI Gene ID | 171023 ncbi.nlm.nih.gov/gene/171023 |
| Ensembl ID | ENSG00000171456 |
| UniProt ID | Q8IXJ9 |
| OMIM ID | 612990 |
| HGNC ID | 18318 |
| Aliases | MDS, BOPS, KIAA0978, MGC116686 |
Description
The ASXL1 gene encodes a nuclear protein that functions as an epigenetic scaffold, interacting with the polycomb repressive complex 2 (PRC2) and other chromatin modifiers to regulate gene expression. It is involved in hematopoiesis and development. Somatic loss-of-function mutations in ASXL1 are recurrent in myeloid malignancies, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML), and are associated with poor prognosis. Germline mutations cause Bohring-Opitz syndrome (BOPS), a severe developmental disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myelodysplastic syndromes | Somatic frameshift/nonsense mutations in exon 12 lead to truncated protein, loss of PRC2 interaction, and altered H3K27me3 levels | Recurrent in ~10-20% of MDS; associated with poor prognosis (PMID: 21205863) |
| Acute myeloid leukemia | Same loss-of-function mutations as MDS; cooperates with other drivers (e.g., RUNX1, IDH2) | Present in ~5-10% of de novo AML; higher in secondary AML (PMID: 21205863) |
| Chronic myelomonocytic leukemia | Frequent truncating mutations in ASXL1 | ~40% of CMML cases (PMID: 23334667) |
| Bohring-Opitz syndrome | Germline de novo heterozygous loss-of-function mutations (typically truncating) | Rare; severe intellectual disability, distinctive facial features, feeding difficulties (OMIM #605039) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 15.2 | Medium |
| Spleen | 12.8 | Medium |
| Lymph node | 11.5 | Medium |
| Whole blood | 8.3 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 18.5 | Myelogenous leukemia line |
| HL-60 (promyeloblast) | 16.2 | Acute myeloid leukemia line |
| HEK 293 (embryonic kidney) | 12.0 | Non-hematopoietic control |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1934dupG (p.Gly646TrpfsTer12) | Frameshift | ~15% in MDS | Loss of function; truncated protein lacking C-terminal domain |
| c.1900_1922del (p.Glu635ArgfsTer15) | Frameshift | ~10% in AML | Loss of function; premature stop codon |
| c.2077C>T (p.Gln693Ter) | Nonsense | ~5% in CMML | Loss of function; nonsense-mediated decay likely |
Mutation functional classification
Loss of Function (LOF)
Majority of somatic and germline ASXL1 mutations are loss-of-function (frameshift, nonsense), leading to truncated protein that fails to recruit PRC2 and regulate H3K27me3.
Gain of Function (GOF)
Not reported; no activating mutations described.
Dominant Negative (DN)
Possible for some truncating mutants that retain partial interaction domains, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003682 - chromatin binding | • GO:0005515 - protein binding |
| • GO:0006325 - chromatin organization | • GO:0006355 - regulation of transcription |
| • DNA-templated | • GO:0005634 - nucleus |
Pathways
• Polycomb repressive complex 2 (PRC2) pathway
• Epigenetic regulation of hematopoiesis
Protein Summary
The ASXL1 protein (1534 amino acids) contains an N-terminal ASXN domain, a central ASXH domain, and a C-terminal PHD finger. It acts as a scaffold for PRC2, facilitating H3K27 trimethylation and gene silencing. Truncating mutations remove the PHD domain, disrupting PRC2 recruitment and leading to aberrant gene expression in myeloid cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ASXL1 Knockout HEK293 Cell Line | EDJ-KQ11918 | Human | 171023 | Details Get a Quote |
| ASXL1 Knockout A-549 Cell Line | EDJ-KQ40401 | Human | 171023 | Details Get a Quote |
| ASXL1 Knockout HCT 116 Cell Line | EDJ-KQ40402 | Human | 171023 | Details Get a Quote |
| ASXL1 Knockout HeLa Cell Line | EDJ-KQ40403 | Human | 171023 | Details Get a Quote |
| ASXL1 Knockout OCI-AML3 Cell Line | EDC07928 | Human | 171023 | Details Get a Quote |
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