SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9): A Multifunctional Tumor Suppressor and Immune Regulator
Explore the genomic architecture, clinical significance, and functional roles of SAMD9, a gene implicated in inflammatory diseases, hematologic disorders, and cancer.
Gene Information Card
| Symbol | SAMD9 |
|---|---|
| Full Name | Sterile alpha motif domain-containing protein 9 |
| Gene Type | Protein-coding |
| Chromosomal Location | 7q21.2 |
| NCBI Gene ID | 54809 ncbi.nlm.nih.gov/gene/54809 |
| Ensembl ID | ENSG00000100243 |
| UniProt ID | Q5K651 |
| OMIM ID | 610456 |
| HGNC ID | 1348 |
| Aliases | C7orf5, DRIF1, OEF1, SAMD9 |
Description
SAMD9 encodes a protein containing a sterile alpha motif (SAM) domain, which is involved in protein-protein interactions and may play a role in signal transduction. The protein is implicated in cell proliferation, apoptosis, and immune regulation. Mutations in SAMD9 are associated with a spectrum of conditions, including MIRAGE syndrome (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy), ataxia-pancytopenia syndrome, and various cancers. SAMD9 functions as a tumor suppressor in certain contexts, and its dysregulation contributes to hematologic malignancies and inflammatory disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| MIRAGE syndrome | Gain-of-function mutations lead to increased growth restriction and apoptosis, causing multisystem developmental abnormalities. | OMIM 610456; ClinVar |
| Ataxia-pancytopenia syndrome (ATXPC) | Heterozygous missense mutations cause haploinsufficiency or dominant-negative effects, leading to cerebellar ataxia and bone marrow failure. | OMIM 610456; ClinVar |
| Myelodysplastic syndrome (MDS) | Somatic mutations, including loss-of-function and copy-neutral loss of heterozygosity, contribute to clonal hematopoiesis and disease progression. | COSMIC; ClinVar |
| Acute myeloid leukemia (AML) | SAMD9 mutations, particularly in the SAM domain, are recurrent in AML and may promote leukemogenesis via dysregulated growth signaling. | COSMIC; ClinVar |
| Inflammatory bowel disease (IBD) | Rare germline variants may predispose to intestinal inflammation through altered immune responses. | ClinVar; literature |
| Solid tumors (e.g., pancreatic, lung) | Reduced expression or loss-of-function mutations may contribute to tumor progression via loss of growth suppression. | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Lymph Node | 10.2 | Medium |
| Spleen | 9.8 | Medium |
| Lung | 8.1 | Low |
| Kidney | 7.3 | Low |
| Liver | 5.6 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression; relevant to hematologic malignancies |
| HeLa (cervical cancer) | 8.7 | Moderate expression |
| A549 (lung carcinoma) | 6.2 | Low expression |
| MCF7 (breast cancer) | 4.5 | Low expression |
| HepG2 (liver cancer) | 3.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2950C>T (p.Arg984Cys) | Missense | Rare (germline) | Gain-of-function; associated with MIRAGE syndrome |
| c.2672T>C (p.Leu891Pro) | Missense | Rare (germline) | Gain-of-function; associated with ataxia-pancytopenia syndrome |
| c.1837C>T (p.Arg613Ter) | Nonsense | Somatic (sporadic) | Loss-of-function; tumor suppressor inactivation in MDS/AML |
| c.2200_2201del (p.Val734fs) | Frameshift | Somatic | Loss-of-function; associated with myeloid malignancies |
| c.2773A>G (p.Thr925Ala) | Missense | Somatic (recurrent) | Gain-of-function; may promote clonal expansion in MDS |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) reduce SAMD9 protein levels or activity, impairing its tumor suppressor function. This can lead to uncontrolled cell proliferation and is observed in myelodysplastic syndrome and acute myeloid leukemia.
Gain of Function (GOF)
Gain-of-function mutations (e.g., missense in the SAM domain) enhance SAMD9's growth-restrictive and pro-apoptotic activities, leading to developmental disorders like MIRAGE syndrome and ataxia-pancytopenia syndrome.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type SAMD9 function, contributing to haploinsufficiency phenotypes such as bone marrow failure and neurological deficits.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • signal transduction |
| • cell proliferation | • apoptotic process |
| • negative regulation of cell growth | • immune response |
| • inflammatory response | • sterile alpha motif domain binding |
Pathways
• p53 signaling pathway
• TNF signaling pathway
• Cytokine-cytokine receptor interaction
• Apoptosis
• Hematopoietic cell lineage
Protein Summary
The SAMD9 protein is a 1,589-amino-acid protein with a sterile alpha motif (SAM) domain at the N-terminus, which mediates protein-protein interactions. It localizes to the cytoplasm and is involved in regulating cell growth and apoptosis. SAMD9 acts as a tumor suppressor by inhibiting cell proliferation and promoting apoptosis in response to stress signals. It also plays a role in innate immune responses and inflammation. The protein is widely expressed in hematopoietic tissues, with lower levels in other organs. Mutations affecting SAMD9 function are linked to several genetic syndromes and cancers, highlighting its critical role in cellular homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SAMD9 Knockout HEK293 Cell Line | EDJ-KQ2552 | Human | 54809 | Details Get a Quote |
| SAMD9L Knockout HEK293 Cell Line | EDJ-KQ15162 | Human | 219285 | Details Get a Quote |
| SAMD9 Knockout A-549 Cell Line | EDJ-KQ23199 | Human | 54809 | Details Get a Quote |
| SAMD9 Knockout HCT 116 Cell Line | EDJ-KQ23200 | Human | 54809 | Details Get a Quote |
| SAMD9 Knockout HeLa Cell Line | EDJ-KQ23201 | Human | 54809 | 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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