SIDT2: SID1 Transmembrane Family Member 2 – A Key Regulator of Lipid Metabolism and Autophagy
Explore the genomic architecture, expression patterns, disease associations, and functional significance of SIDT2, a lysosomal RNA and lipid transporter implicated in metabolic and neurological disorders.
Gene Information Card
| Symbol | SIDT2 |
|---|---|
| Full Name | SID1 transmembrane family member 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 51092 ncbi.nlm.nih.gov/gene/51092 |
| Ensembl ID | ENSG00000149527 |
| UniProt ID | Q8NBJ9 |
| OMIM ID | 617551 |
| HGNC ID | 25934 |
| Aliases | C11orf9, CGI-43, FLJ22318, MGC133079 |
Description
SIDT2 encodes a multi-pass transmembrane protein belonging to the SID1 family, which is characterized by its role in double-stranded RNA uptake. SIDT2 is predominantly localized to lysosomal membranes and is involved in the transport of RNA and lipids across membranes. It plays a critical role in autophagy, lipid metabolism, and innate immune responses. Mutations in SIDT2 have been linked to a rare autosomal recessive lysosomal storage disorder presenting with hepatomegaly, hypoglycemia, and neurological features. The gene is widely expressed, with highest levels in the liver, kidney, and brain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive spinocerebellar ataxia with epilepsy (SCAR23) | Loss-of-function mutations impair lysosomal RNA and lipid transport, leading to accumulation of undegraded substrates and neuronal dysfunction. | ClinVar and OMIM report pathogenic variants in SIDT2 associated with this condition. |
| Hepatic steatosis and metabolic syndrome | SIDT2 deficiency disrupts lipid droplet homeostasis and autophagy, promoting fat accumulation in hepatocytes. | Mouse models and in vitro studies demonstrate altered lipid metabolism upon SIDT2 knockdown. |
| Type 2 diabetes (potential) | SIDT2 influences insulin secretion and beta-cell function via regulation of autophagy and lipid metabolism. | GWAS and functional studies suggest a role in glucose homeostasis. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 42.3 | High |
| Kidney | 35.1 | High |
| Brain | 28.7 | Medium |
| Heart | 22.4 | Medium |
| Skeletal Muscle | 18.9 | Medium |
| Lung | 12.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 55.2 | High expression; used in lipid metabolism studies |
| HEK293 (embryonic kidney) | 30.4 | Moderate expression; common for overexpression assays |
| SH-SY5Y (neuroblastoma) | 25.8 | Moderate; relevant for neurological studies |
| A549 (lung carcinoma) | 15.3 | Low; less studied |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1292G>A (p.Arg431Gln) | Missense | Rare (MAF <0.01) | Loss of function; impairs RNA transport and lysosomal function |
| c.1756C>T (p.Arg586Ter) | Nonsense | Rare | Premature truncation; complete loss of protein function |
| c.234delA (p.Gly79AlafsTer12) | Frameshift | Rare | Loss of function; associated with SCAR23 |
| c.1015A>G (p.Thr339Ala) | Missense | Low frequency | Potential hypomorphic allele; reduced stability |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic SIDT2 mutations are loss-of-function, leading to impaired lysosomal RNA and lipid transport, disrupted autophagy, and accumulation of substrates. This underlies the clinical phenotype of SCAR23 and metabolic abnormalities.
Gain of Function (GOF)
No evidence for gain-of-function mutations in SIDT2; all reported pathogenic variants are loss-of-function.
Dominant Negative (DN)
No dominant-negative effects have been described; SIDT2 mutations are inherited in an autosomal recessive pattern.
View complete mutation data：
Gene Ontology (GO)
| • RNA transmembrane transporter activity | • lipid binding |
| • lysosomal membrane | • integral component of membrane |
| • autophagy | • lipid metabolic process |
| • response to virus | • double-stranded RNA binding |
Pathways
• Lysosomal degradation and autophagy
• Lipid metabolism and storage
• Innate immune response to viral RNA
Protein Summary
SIDT2 is a 9-pass transmembrane protein of ~90 kDa, primarily localized to lysosomal membranes. It contains a conserved SID1 domain responsible for RNA binding and transport. The protein is essential for the translocation of double-stranded RNA from the lysosomal lumen into the cytoplasm, thereby facilitating RNA degradation and immune sensing. Additionally, SIDT2 interacts with lipid droplets and regulates lipophagy, a selective autophagic pathway for lipid breakdown. Its deficiency leads to lysosomal dysfunction, lipid accumulation, and neurodegeneration. Structural studies suggest that SIDT2 forms oligomers and may function as a channel or transporter.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIDT2 Knockout HEK293 Cell Line | EDJ-KQ10912 | Human | 51092 | Details Get a Quote |
| SIDT2 Knockout HeLa Cell Line | EDJ-KQ18214 | Human | 51092 | Details Get a Quote |
| SIDT2 Knockout A-549 Cell Line | EDJ-KQ38652 | Human | 51092 | Details Get a Quote |
| SIDT2 Knockout HCT 116 Cell Line | EDJ-KQ38653 | Human | 51092 | Details Get a Quote |
