SAMD9L Gene (Sterile Alpha Motif Domain Containing 9 Like)
Key regulator of cell proliferation, innate immunity, and interferon signaling; mutations linked to ataxia-pancytopenia syndrome and myeloid malignancies.
Gene Information Card
| Symbol | SAMD9L |
|---|---|
| Full Name | Sterile Alpha Motif Domain Containing 9 Like |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.2 |
| NCBI Gene ID | 219285 ncbi.nlm.nih.gov/gene/219285 |
| Ensembl ID | ENSG00000177409 |
| UniProt ID | Q8IVG9 |
| OMIM ID | 611170 |
| HGNC ID | 1349 |
| Aliases | DRIF2, FLJ39873, MGC138290 |
Description
SAMD9L encodes a protein containing a sterile alpha motif (SAM) domain and is involved in cell proliferation, endosome fusion, and innate immune responses. It acts as a negative regulator of cell growth and is induced by type I interferons. Germline gain-of-function mutations cause ataxia-pancytopenia syndrome (ATXPC) and predispose to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Somatic loss-of-function mutations or deletions are frequently observed in myeloid malignancies, suggesting a tumor suppressor role.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ataxia-pancytopenia syndrome (ATXPC) | Germline gain-of-function mutations lead to increased growth suppression and bone marrow failure. | OMIM #159550; ClinVar |
| Myelodysplastic syndrome (MDS) | Somatic loss-of-function mutations or 7q21 deletions remove growth suppression, promoting clonal expansion. | COSMIC; ClinVar |
| Acute myeloid leukemia (AML) | Recurrent somatic deletions/mutations of SAMD9L on 7q21 contribute to leukemogenesis. | COSMIC; NCBI Gene |
| Monosomy 7 / del(7q) MDS/AML | Loss of SAMD9L (and other genes) on chromosome 7q is a common event in therapy-related MDS/AML. | ClinVar; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Lung | 8.9 | Low |
| Liver | 6.3 | Low |
| Whole blood | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.3 | High expression |
| HL-60 (promyelocytic) | 11.8 | Medium expression |
| HEK293 (embryonic kidney) | 7.2 | Low expression |
| HeLa (cervical) | 5.6 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2956C>T (p.Arg986Trp) | Missense | Germline; rare | Gain-of-function; associated with ATXPC |
| c.2672T>C (p.Leu891Pro) | Missense | Germline; rare | Gain-of-function; associated with ATXPC |
| c.1234del (p.Glu412Argfs*2) | Frameshift deletion | Somatic; ~2% in MDS | Loss-of-function; tumor suppressor inactivation |
| Whole gene deletion (7q21.2) | Copy number loss | Somatic; ~5% in MDS/AML | Loss-of-function; haploinsufficiency |
Mutation functional classification
Loss of Function (LOF)
Somatic deletions or truncating mutations that remove the SAM domain or disrupt protein stability, leading to loss of growth suppression and increased proliferation in myeloid cells.
Gain of Function (GOF)
Germline missense mutations (e.g., p.Arg986Trp, p.Leu891Pro) that enhance the growth-suppressive activity of SAMD9L, causing bone marrow failure and ataxia.
Dominant Negative (DN)
Not well documented; some missense variants may interfere with wild-type protein function, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Interferon signaling (Reactome R-HSA-913531)
• Endosomal sorting (GO:0016197)
Protein Summary
The SAMD9L protein (UniProt Q8IVG9) is a 1,589-amino-acid cytoplasmic protein with an N-terminal sterile alpha motif (SAM) domain and a C-terminal region involved in endosome localization. It is induced by type I interferons and negatively regulates cell proliferation. The SAM domain mediates protein-protein interactions and is critical for its growth-suppressive function. Mutations that alter SAM domain integrity or protein levels are linked to hematopoietic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SAMD9L Knockout HEK293 Cell Line | EDJ-KQ15162 | Human | 219285 | Details Get a Quote |
| SAMD9L Knockout A-549 Cell Line | EDJ-KQ47936 | Human | 219285 | Details Get a Quote |
| SAMD9L Knockout U-87MG ATCC Cell Line | EDJ-KZ442 | Human | 219285 | Details Get a Quote |
| SAMD9L Knockout HeLa Cell Line | EDJ-KQ59061 | Human | 219285 | Details Get a Quote |
| SAMD9L Knockout HCT 116 Cell Line | EDJ-KQ75931 | Human | 219285 | Details Get a Quote |
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