Amyotrophic lateral sclerosis/motor neuron disease
Gene: SIGMAR1

SIGMAR1 (sigma non-opioid intracellular receptor 1)
EnsemblGeneIds (GRCh38): ENSG00000147955
EnsemblGeneIds (GRCh37): ENSG00000147955
OMIM: 601978, Gene2Phenotype
SIGMAR1 is in 6 panels

2 reviews

Alice Gardham (Genomics England)

Comment when marking as ready: Reported in one family with juvenile ALS and two families with ALS +/- fronto temporal dementia
Created: 19 Dec 2016, 3:34 p.m.

Comment on publications: 27821430
Created: 19 Dec 2016, 3:31 p.m.

Created: 19 Dec 2016, 3:31 p.m.

Panel version: 0.147

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Is green on the Charcot-Marie Tooth disease version 1.1 panel.
Created: 3 Nov 2016, 7:04 p.m.

Created: 3 Nov 2016, 7:04 p.m.

Panel version: 0.129

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Radboud University Medical Center, Nijmegen

Phenotypes

Amyotrophic lateral sclerosis 16, juvenile, 614373

OMIM

601978

Clinvar variants

Variants in SIGMAR1

Penetrance

Complete

Publications

PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis and c.672*31A>G (rs4879809) - the C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls
PubMed: 21842496 - E102Q variant identified in a Saudi Arabian family to be associated with amyotrophic lateral sclerosis 16, juvenile
PMID: 26088964 is a commentary on PMID: 25678561 raising a lack of evidence for SIGMARI to be pathogenic, and that previous reports of patients with SIGMARI variants were also shown to harbour C9orf72 expansions
PMID: 26088963 - in reply, authors state that there is in vitro and in vivo evidence, and expression evidence, and that a case reported did not have the C9orf72 expansion
PMID: 26078401 - c.151+1G>T variant in SIGMARI resulted in a 60 bp deletion in the transcript, and segrated with the distal hereditary motor neuropathy in a Chinese family.

Panels with this gene

History Filter Activity

19 Dec 2016, Gel status: 4

panel promoted to version 1

Alice Gardham (Genomics England)

Promoted to version 1 on 19th December 2016 following external review and internal curation

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

19 Dec 2016, Gel status: 4

Set publications

Alice Gardham (Genomics England)

Publications for SIGMAR1 were set to PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis and c.672*31A>G (rs4879809) - the C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls; PubMed: 21842496 - E102Q variant identified in a Saudi Arabian family to be associated with amyotrophic lateral sclerosis 16, juvenile; PMID: 26088964 is a commentary on PMID: 25678561 raising a lack of evidence for SIGMARI to be pathogenic, and that previous reports of patients with SIGMARI variants were also shown to harbour C9orf72 expansions; PMID: 26088963 - in reply, authors state that there is in vitro and in vivo evidence, and expression evidence, and that a case reported did not have the C9orf72 expansion; PMID: 26078401 - c.151+1G>T variant in SIGMARI resulted in a 60 bp deletion in the transcript, and segrated with the distal hereditary motor neuropathy in a Chinese family.

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

3 Nov 2016, Gel status: 2