SIGMAR1 Gene
Sigma Non-Opioid Intracellular Receptor 1
Gene Information Card
| Symbol | SIGMAR1 |
|---|---|
| Full Name | Sigma Non-Opioid Intracellular Receptor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9p13.3 |
| NCBI Gene ID | 10280 ncbi.nlm.nih.gov/gene/10280 |
| Ensembl ID | ENSG00000147955 |
| UniProt ID | Q99720 |
| OMIM ID | 601978 |
| HGNC ID | 10857 |
| Aliases | SR-BP, SRBP, SIGMAR, OPRS1, ALS16, FTDALS2 |
Description
SIGMAR1 encodes the sigma-1 receptor, a transmembrane chaperone protein primarily localized at the endoplasmic reticulum (ER)-mitochondria interface (MAM). It modulates calcium signaling, ER stress response, lipid transport, and ion channel activity. Mutations in SIGMAR1 are associated with juvenile amyotrophic lateral sclerosis (ALS16) and frontotemporal dementia (FTDALS2).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis 16 (ALS16) | Loss-of-function mutations impair ER-mitochondria calcium homeostasis and increase ER stress, leading to motor neuron degeneration. | OMIM #614373; ClinVar |
| Frontotemporal Dementia and/or ALS 2 (FTDALS2) | Dominant-negative or loss-of-function mutations disrupt sigma-1 receptor chaperone activity, contributing to TDP-43 pathology. | OMIM #619155; ClinVar |
| Distal Hereditary Motor Neuropathy (dHMN) | Missense mutations (e.g., p.Glu138Gln) cause axonal degeneration via impaired ER stress response. | PubMed; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal Cord | 10.2 | Medium |
| Liver | 8.1 | Low |
| Heart | 6.3 | Low |
| Skeletal Muscle | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used in neurodegeneration studies |
| HEK293 (embryonic kidney) | 9.8 | Moderate; common for recombinant expression |
| U-87 MG (glioblastoma) | 11.2 | High; relevant for CNS cancer models |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.304G>C (p.Glu102Gln) | Missense | Rare | Loss of function; associated with ALS16 |
| c.412G>A (p.Glu138Lys) | Missense | Rare | Dominant-negative; linked to FTDALS2 |
| c.151+1G>T | Splice site | Rare | Loss of function; causes exon skipping in ALS |
Mutation functional classification
Loss of Function (LOF)
p.Glu102Gln and splice-site mutations reduce sigma-1 receptor chaperone activity, impairing ER-mitochondria calcium transfer and increasing ER stress.
Gain of Function (GOF)
Not reported for SIGMAR1.
Dominant Negative (DN)
p.Glu138Lys disrupts receptor oligomerization and function, leading to TDP-43 aggregation.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 – protein binding | • GO:0005783 – endoplasmic reticulum |
| • GO:0005789 – endoplasmic reticulum membrane | • GO:0031966 – mitochondrial membrane |
| • GO:0032869 – cellular response to calcium ion | • GO:0034976 – response to endoplasmic reticulum stress |
| • GO:0042802 – identical protein binding | • GO:0051209 – release of sequestered calcium ion into cytosol |
Pathways
• Unfolded Protein Response (UPR) – Sigma-1 receptor modulates IRE1 and PERK signaling.
• Calcium Signaling – Regulates IP3 receptor activity at MAM.
• Neurotrophin Signaling – Interacts with TrkB and BDNF pathways.
Protein Summary
The sigma-1 receptor (UniProt Q99720) is a 223-amino-acid transmembrane chaperone protein predominantly located at the mitochondria-associated ER membrane (MAM). It contains a single transmembrane domain and a C-terminal ligand-binding domain. The protein forms oligomers and interacts with IP3 receptors, BiP, and other chaperones to regulate calcium flux, lipid metabolism, and ER stress. Mutations cause motor neuron diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIGMAR1 Knockout HEK293 Cell Line | EDJ-KQ15261 | Human | 10280 | Details Get a Quote |
| SIGMAR1 Knockout A-549 Cell Line | EDJ-KQ18095 | Human | 10280 | Details Get a Quote |
| SIGMAR1 Knockout HCT 116 Cell Line | EDJ-KQ45945 | Human | 10280 | Details Get a Quote |
| SIGMAR1 Knockout HeLa Cell Line | EDJ-KQ45946 | Human | 10280 | Details Get a Quote |
| Sigmar1 Knockout NSC-34 Cell Line | EDJ-KZ46 | Mouse | 10280 | Details Get a Quote |
| SIGMAR1 Knockout Hep-G2 Cell Line | EDC09854 | Human | 10280 | Details Get a Quote |
Displaying Records 1 To 6 Of 6 Records
