MYSM1: Myb-like, SWIRM and MPN domains 1
A deubiquitinating enzyme with roles in hematopoiesis, immune regulation, and cancer
Gene Information Card
| Symbol | MYSM1 |
|---|---|
| Full Name | Myb-like, SWIRM and MPN domains 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 1p32.3 |
| NCBI Gene ID | 114803 ncbi.nlm.nih.gov/gene/114803 |
| Ensembl ID | ENSG00000162601 |
| UniProt ID | Q5VVJ2 |
| OMIM ID | 612176 |
| HGNC ID | 29401 |
| Aliases | KIAA1915, DKFZp686B20107 |
Description
MYSM1 encodes a metalloprotease that functions as a deubiquitinating enzyme (DUB). It contains a Myb-like DNA-binding domain, a SWIRM domain, and an MPN (JAMM) domain responsible for its catalytic activity. MYSM1 is involved in transcriptional regulation, chromatin remodeling, and hematopoietic stem cell maintenance. It deubiquitinates histone H2A and H2B, thereby modulating gene expression. Loss-of-function mutations cause bone marrow failure syndrome and immunodeficiency.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bone marrow failure syndrome 4 (BMFS4) | Biallelic loss-of-function mutations in MYSM1 impair hematopoietic stem cell self-renewal and differentiation, leading to pancytopenia and immune deficiency. | OMIM #618116; ClinVar |
| Prostate cancer | MYSM1 overexpression promotes androgen receptor signaling and tumor growth; knockdown reduces proliferation. | COSMIC; PMID: 28424480 |
| Acute myeloid leukemia (AML) | MYSM1 is recurrently mutated in AML, with frameshift and missense variants affecting the JAMM domain. | COSMIC; PMID: 27895058 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 8.3 | Medium |
| Lymph node | 6.7 | Low |
| Testis | 5.2 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.0 | High expression |
| HEK293 (embryonic kidney) | 9.8 | Moderate expression |
| HeLa (cervical cancer) | 7.4 | Low expression |
| HepG2 (liver cancer) | 4.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1573C>T (p.Arg525*) | Nonsense | <0.1% | Loss of function; truncation of MPN domain |
| c.1118_1119del (p.Glu373Valfs*12) | Frameshift | <0.1% | Loss of function; premature stop |
| c.1675G>A (p.Gly559Arg) | Missense | <0.1% | Likely damaging; affects catalytic site |
| c.1960A>G (p.Thr654Ala) | Missense | 0.01% | Uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in MYSM1 cause complete or partial loss of deubiquitinase activity, leading to bone marrow failure syndrome 4.
Gain of Function (GOF)
Not reported; no activating mutations have been described.
Dominant Negative (DN)
Not established; all known pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004843 - thiol-dependent deubiquitinase | • GO:0005634 - nucleus |
| • GO:0008270 - zinc ion binding | • GO:0006338 - chromatin remodeling |
| • GO:0036459 - histone H2A deubiquitination | • GO:0043066 - negative regulation of apoptotic process |
Pathways
• Histone modification (H2A/H2B deubiquitination)
• Androgen receptor signaling pathway
• Hematopoietic stem cell differentiation
Protein Summary
MYSM1 is a 828-amino acid nuclear protein with a JAMM/MPN domain that catalyzes the removal of ubiquitin from histone H2A and H2B. It acts as a transcriptional coactivator/repressor depending on context. In hematopoietic cells, MYSM1 is essential for stem cell maintenance and lineage commitment. Its dysregulation contributes to bone marrow failure, immunodeficiency, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MYSM1 Knockout HEK293 Cell Line | EDJ-KQ2096 | Human | 114803 | Details Get a Quote |
| MYSM1 Knockout A-549 Cell Line | EDJ-KQ22196 | Human | 114803 | Details Get a Quote |
| MYSM1 Knockout HCT 116 Cell Line | EDJ-KQ22197 | Human | 114803 | Details Get a Quote |
| MYSM1 Knockout HeLa Cell Line | EDJ-KQ22198 | Human | 114803 | Details Get a Quote |
| MYSM1 Knockout HAP1 Cell Line | EDC08043 | Human | 114803 | Details Get a Quote |
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