SIGMAR1

Chr 9

sigma non-opioid intracellular receptor 1

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

NCBI Gene: 10280 ENSG00000147955 UniProt: Q99720

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a receptor protein that interacts with a variety of psychotomimetic drugs, including cocaine and amphetamines. The receptor is believed to play an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems. As indicated by its previous name, opioid receptor sigma 1 (OPRS1), the product of this gene was erroneously thought to function as an opioid receptor; it is now thought to be a non-opioid receptor. Mutations in this gene has been associated with juvenile amyotrophic lateral sclerosis 16. Alternative splicing of this gene results in transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2013]

ResearchGenerating clinical summary…

LOEUF 0.74

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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ClinVar Variants

27 unique Pathogenic / Likely Pathogenic· 94 VUS of 229 total submissions

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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 →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.28 (0.13–0.74)

0≤0.351.4

Missense OE?0.64 (0.54–0.77)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 3 / 10.5Missense obs/exp: 85 / 132.3Syn Z: 0.66

ClinVar Variant Classifications

229 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic13

VUS94

Likely Benign84

Benign13

Conflicting3

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	13	1	0	0	14
Likely Pathogenic	9	4	0	0	13
VUS	3	88	2	1	94
Likely Benign	1	16	25	42	84
Benign	0	1	9	3	13
Conflicting	—				3
Total	26	110	36	46	221

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

71 pathogenic / likely-pathogenic (of 81) ClinVar copy-number / structural variants overlap SIGMAR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →