SIGMAR1

Chr 9AR

sigma non-opioid intracellular receptor 1

Also known as: ALS16, DSMA2, HMNR2, OPRS1, SIG-1R, SR-BP, SR-BP1, SRBP

NCBI Gene: 10280ENSG00000147955UniProt: Q99720OMIM: 601978

The sigma-1 receptor functions in lipid transport from the endoplasmic reticulum, regulates various receptors and ion channels, and is necessary for proper mitochondrial axonal transport in motor neurons. Mutations cause juvenile amyotrophic lateral sclerosis and distal hereditary motor neuronopathy with autosomal recessive inheritance. These conditions primarily affect the motor neuron system, with juvenile onset distinguishing them from typical adult-onset ALS.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.742 OMIM phenotypes
Clinical Summary— SIGMAR1
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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.168
Z-score 2.15
OE 0.28 (0.13–0.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.46Z-score
OE missense 0.64 (0.54–0.77)
85 obs / 132.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.13–0.74)
0≤0.351.4
Missense OE0.64 (0.54–0.77)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 3 / 10.5Missense obs/exp: 85 / 132.3Syn Z: 0.66

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SIGMAR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SIRT3-mediated mitophagy by deacetylating ATP5F1A involved in the protective effects of SIGMAR1/Sigma-1 receptor against ferroptosis and microvascular hyperpermeability in lipopolysaccharide-induced acute lung injury.
Gao F et al.·Autophagy
2026
A Novel YTHDF2/SIGMAR1 Axis in Astrocytes Regulates Neuroinflammation and Cognitive Impairment in Diabetic Encephalopathy.
Xu F et al.·Inflammation
2026Open Access
SigmaR1 is an auxiliary translocon factor with lipid-binding activity that regulates protein and lipid droplet homeostasis.
Hu X et al.·Nat Commun
2025Open Access
SIGMAR1 Drives the Development of Neuropathic Pain by Promoting AMPA Receptor Membrane Trafficking Through Interacting with NPTX1 in Male Mice.
Ren J et al.·Neurosci Bull
2025
SIGMAR1 gene-related neuromuscular disorders - what do we know?
Kalita M et al.·Neurol Neurochir Pol
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients