FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: amyotrophic lateral sclerosis 16 (postulated)
Open Close
General Information
Name
amyotrophic lateral sclerosis 16 (postulated)
FlyBase ID
FBhh0001222
Disease Ontology Term
Parent Disease
OMIM
AMYOTROPHIC LATERAL SCLEROSIS 16, JUVENILE; ALS16
Overview

This report describes amyotrophic lateral sclerosis 16 (postulated), which is a subtype of amyotrophic lateral sclerosis; ALS16 exhibits autosomal recessive inheritance. The gene implicated in this disease is SIGMAR1, which encodes a sigma-1 receptor that is highly expressed in the central nervous system. Sigma-1 receptors are found in the ER and plasma membranes; dynamic changes in localization of these receptors may contribute to their regulatory functions. There is no gene with significant homology to SIGMAR1 in Drosophila.

UAS constructs of the human Hsap\SIGMAR1 gene have been introduced into flies, including wild-type and a variant implicated in ALS16. Variant(s) implicated in human disease tested (as transgenic human gene, SIGMAR1): the E102Q variant form of the human gene has been introduced into flies. Pan-neuronal expression of the E102Q variant induces abnormal eye morphology and locomotor defects in a dose-dependent manner. Pan-neuronal expression of wild-type Hsap\SIGMAR1 rescues locomotor phenotypes exhibited by a Drosophila model of ALS10.

[updated Jul. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: amyotrophic lateral sclerosis
Symptoms and phenotype

Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. ALS usually begins with asymmetric involvement of the muscles in middle adult life. Approximately 10% of ALS cases are familial (Siddique and Deng, 1996, pubmed:8875253). ALS is sometimes referred to as 'Lou Gehrig disease' after the famous American baseball player who was diagnosed with the disorder. [from MIM:105400, 2015.02.11]

(OMIM, 2013-)
Specific Disease Summary: amyotrophic lateral sclerosis 16 (postulated)
OMIM report

[AMYOTROPHIC LATERAL SCLEROSIS 16, JUVENILE; ALS16](https://omim.org/entry/614373)

Human gene(s) implicated

[SIGMA NONOPIOID INTRACELLULAR RECEPTOR 1; SIGMAR1](https://omim.org/entry/601978)

Symptoms and phenotype

Based on study of one family, ALS16 exhibits early childhood onset of neurological symptoms. [from MIM:614373; 2020.07.18]

(OMIM, 2013-)
Genetics

Juvenile amyotrophic lateral sclerosis-16 (ALS16) appears to b caused by homozygous mutation in the SIGMAR1 gene; one family has been reported. [from MIM:614373; 2020.07.18]

(OMIM, 2013-)
Cellular phenotype and pathology
Molecular information

SIGMAR1 encodes a non-opioid receptor protein that interacts with a variety of psychotomimetic drugs, including cocaine and amphetamines; a member of the sigma 1 receptor family. This receptor is believed to play an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems. It functions in lipid transport from the endoplasmic reticulum and may act through regulation of the biogenesis of lipid microdomains at the plasma membrane. It is necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria. [from Gene Cards, SIGMAR1; 2020.07.18]

(FlyBase Curators, 2013-)

Sigma-1 receptors are predominantly localized at the endoplasmic reticulum of both neurons and oligodendrocytes. From behavioral studies, sigma-1 receptors have been shown to be involved in higher-ordered brain functions including memory and drug dependence (Hayashi and Su, 2005; pubmed:18369400).

(FlyBase Curators, 2013-)

Sigma-1 receptors localize mainly at the mitochondria-associated endoplasmic reticulum membrane (MAM). Upon stimulation, they translocate from MAM to plasma membrane (PM) and nucleus, where they interact with many proteins and ion channels (Yang et al. 2019; pubmed:31178723.)

(FlyBase Curators, 2013-)
External links
Disease synonyms
ALS16
amyotrophic lateral sclerosis 16, juvenile
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
SIGMAR1; sigma non-opioid intracellular receptor 1
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

There is no gene with significant homology to SIGMAR1 in Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (0)
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (0 groups)
      Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
      Hsap\SIGMAR1
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Hsap\SIGMAR1E102Q.UAS
      model of  amyotrophic lateral sclerosis type 16
      CEA
      (Couly et al., 2020)
      Modifiers Based on Experimental Evidence ( 2 )
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Related mammalian, viral, bacterial, or synthetic transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Hsap\SIGMAR1UAS.cCa
      P{UAS-hSIGMAR1.C}
      Hsap\SIGMAR1E102Q.UAS
      P{UAS-hSIGMAR1.E102Q}
      Hsap\SIGMAR1UAS.Tag:HA
      PBac{UAS-hSIGMAR1.HA}
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      References (5)