SAMD12 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of SAMD12, a gene associated with benign adult familial myoclonic epilepsy and potential tumor suppression.
Gene Information Card
| Symbol | SAMD12 |
|---|---|
| Full Name | sterile alpha motif domain containing 12 |
| Gene Type | protein coding |
| Chromosomal Location | 8q24.12 |
| NCBI Gene ID | 401474 ncbi.nlm.nih.gov/gene/401474 |
| Ensembl ID | ENSG00000177570 |
| UniProt ID | Q5VUJ5 |
| OMIM ID | 618073 |
| HGNC ID | 26523 |
| Aliases | LOC401474 |
Description
SAMD12 encodes a protein containing a sterile alpha motif (SAM) domain, which is often involved in protein-protein interactions and may play a role in signal transduction or transcriptional regulation. The gene is located on chromosome 8q24.12. Mutations in SAMD12, specifically expansions of a pentanucleotide repeat (TTTCA and TTTTA) in intron 4, are a known cause of benign adult familial myoclonic epilepsy (BAFME), also known as familial cortical myoclonic tremor with epilepsy. The repeat expansion leads to abnormal RNA accumulation and potential gain-of-function toxicity. SAMD12 has also been implicated in various cancers, though its precise role remains under investigation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Benign Adult Familial Myoclonic Epilepsy (BAFME) | Intronic pentanucleotide repeat expansion (TTTCA/TTTTA) in SAMD12 leads to RNA toxicity and dysregulation of neuronal function. | Multiple studies, including large family cohorts, have identified the repeat expansion as a causative mutation for BAFME (e.g., Ishiura et al., 2018; Cen et al., 2018). |
| Hepatocellular Carcinoma (HCC) | Downregulation of SAMD12 expression is observed in HCC tissues; may act as a tumor suppressor by inhibiting cell proliferation and migration. | Expression and functional studies in HCC cell lines and clinical samples (e.g., Zhang et al., 2021). |
| Colorectal Cancer | SAMD12 expression is reduced in colorectal cancer tissues; low expression correlates with poor prognosis, suggesting a tumor-suppressive role. | Clinical and in vitro studies (e.g., Wang et al., 2020). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Liver | 3.1 | Low |
| Colon | 2.8 | Low |
| Kidney | 2.5 | Low |
| Lung | 1.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 2.0 | Low expression |
| A549 (lung cancer) | 1.5 | Very low |
| MCF7 (breast cancer) | 1.2 | Very low |
| K562 (leukemia) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| TTTCA/TTTTA repeat expansion in intron 4 | Repeat expansion | Pathogenic in BAFME; frequency varies by population (e.g., ~1 in 10,000 in some Asian populations) | Gain-of-function RNA toxicity; leads to abnormal RNA foci and neuronal dysfunction. |
| Missense variants (e.g., p.Arg123His) | Missense | Rare; not clearly pathogenic | Unknown; may affect protein stability or interaction. |
| Copy number loss | Deletion | Rare in cancer | Loss of function; may contribute to tumor suppression loss. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., deletions or downregulation) are observed in cancers, suggesting a tumor-suppressive role. Reduced SAMD12 expression may lead to increased cell proliferation and migration.
Gain of Function (GOF)
The repeat expansion in BAFME is considered a gain-of-function mutation, as it produces toxic RNA that sequesters RNA-binding proteins, leading to neuronal dysfunction.
Dominant Negative (DN)
No evidence for dominant-negative effects of SAMD12 mutations.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • RNA binding |
| • nucleus | • cytoplasm |
| • regulation of transcription | • DNA-templated |
Pathways
• Not well characterized; may be involved in RNA metabolism and gene regulation.
Protein Summary
The SAMD12 protein contains a sterile alpha motif (SAM) domain, which is a conserved protein module involved in protein-protein interactions and often found in signaling or scaffolding proteins. The exact function of SAMD12 is not fully understood, but it is localized to the nucleus and cytoplasm. It may play a role in transcriptional regulation or RNA processing. In BAFME, the repeat expansion in the intron leads to the production of a toxic RNA that accumulates in nuclear foci, disrupting RNA-binding proteins and causing neuronal hyperexcitability. In cancer, SAMD12 appears to act as a tumor suppressor, with reduced expression correlating with poor prognosis in liver and colorectal cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SAMD12 Knockout HEK293 Cell Line | EDJ-KQ11638 | Human | 401474 | Details Get a Quote |
| SAMD12 Knockout HCT 116 Cell Line | EDJ-KQ39994 | Human | 401474 | Details Get a Quote |
| SAMD12 Knockout HeLa Cell Line | EDJ-KQ39995 | Human | 401474 | Details Get a Quote |
| SAMD12 Knockout A-549 Cell Line | EDJ-KQ68768 | Human | 401474 | Details Get a Quote |
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