SIL1 Nucleotide Exchange Factor
Key regulator of endoplasmic reticulum protein folding and quality control
Gene Information Card
| Symbol | SIL1 |
|---|---|
| Full Name | SIL1 nucleotide exchange factor |
| Gene Type | protein-coding |
| Chromosomal Location | 5q31.2 |
| NCBI Gene ID | 64374 ncbi.nlm.nih.gov/gene/64374 |
| Ensembl ID | ENSG00000120725 |
| UniProt ID | Q9H173 |
| OMIM ID | 608005 |
| HGNC ID | 24624 |
| Aliases | BAP, MSS, ULG5 |
Description
The SIL1 gene encodes a nucleotide exchange factor for the endoplasmic reticulum (ER) chaperone BiP (HSPA5). SIL1 facilitates the release of ADP from BiP, enabling ATP binding and recycling of the chaperone, which is critical for proper protein folding and quality control in the ER. Mutations in SIL1 cause Marinesco-Sjögren syndrome, a multisystem disorder characterized by cerebellar ataxia, cataracts, and myopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Marinesco-Sjögren syndrome | Loss-of-function mutations in SIL1 impair BiP nucleotide exchange, leading to ER stress and defective protein folding in neurons and muscle cells. | OMIM #248800; multiple case reports and functional studies |
| Cataract | ER stress and protein aggregation in lens epithelial cells due to SIL1 deficiency. | OMIM #248800; clinical observations |
| Myopathy | Accumulation of misfolded proteins in skeletal muscle, causing progressive weakness. | OMIM #248800; muscle biopsy studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Skeletal muscle | 10.8 | Medium |
| Heart | 9.2 | Medium |
| Liver | 7.1 | Low |
| Kidney | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical adenocarcinoma |
| HEK 293 | 14.1 | Embryonic kidney |
| SH-SY5Y | 12.7 | Neuroblastoma |
| HepG2 | 8.9 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.936_937delCT | Frameshift | Rare | Loss of function; truncation of protein |
| c.1130G>A | Missense | Rare | p.Arg377His; disrupts BiP binding |
| c.1286T>C | Missense | Rare | p.Leu429Pro; impairs nucleotide exchange activity |
Mutation functional classification
Loss of Function (LOF)
Most SIL1 mutations are loss-of-function, leading to reduced or absent protein activity, ER stress, and cell death.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding (GO:0005524) | • endoplasmic reticulum (GO:0005783) |
| • ubiquitin protein ligase binding (GO:0031625) | • unfolded protein binding (GO:0051082) |
| • chaperone binding (GO:0051087) |
Pathways
• Unfolded Protein Response (UPR)
• ER-associated degradation (ERAD)
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
Protein Summary
SIL1 is a 461-amino acid protein localized to the endoplasmic reticulum lumen. It acts as a nucleotide exchange factor for BiP, promoting ATP/ADP exchange essential for BiP's chaperone cycle. The protein contains a conserved SIL1 domain and interacts with BiP via its C-terminal region. Deficiency leads to ER stress and activation of the unfolded protein response.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIL1 Knockout HeLa Cell Line | EDC90107 | Human | 64374 | Details Get a Quote |
| SIL1 Knockout HEK293 Cell Line | EDJ-KQ11338 | Human | 64374 | Details Get a Quote |
| SIL1 Knockout A-549 Cell Line | EDJ-KQ40756 | Human | 64374 | Details Get a Quote |
| SIL1 Knockout HCT 116 Cell Line | EDJ-KQ40758 | Human | 64374 | Details Get a Quote |
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