Amyotrophic lateral sclerosis/motor neuron disease

Gene: SETX

Green List (high evidence)

SETX (senataxin)
EnsemblGeneIds (GRCh38): ENSG00000107290
EnsemblGeneIds (GRCh37): ENSG00000107290
OMIM: 608465, Gene2Phenotype
SETX is in 15 panels

4 reviews

Nayana Lahiri (South London GMC)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sarah Leigh (Genomics England Curator)

Comment on phenotypes: Also associated with Spinocerebellar ataxia, autosomal recessive 1 606002
Created: 12 Jan 2017, 2:55 p.m.
Comment on mode of inheritance: Biallelic for Spinocerebellar ataxia, autosomal recessive 1 606002
Created: 12 Jan 2017, 2:54 p.m.

Alice Gardham (Genomics England)

Green List (high evidence)

Comment when marking as ready: Discussed internally. Green on ataxia panel. Offered on UKGTN.
Created: 19 Dec 2016, 3:13 p.m.
Not recognised on G2P. Listed in ALS GeneReview as rare cause of motor neuropathy with pyramidal features. Offered on Sheffield ALS panel. Orphanet -testing widely available in Europe. Literature suggests that many missense variants are benign so caution with interpretation is needed. Reduced penetrance also possible as many missense variants are found in controls
Created: 24 Nov 2016, 3:08 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amyotrophic lateral sclerosis 4, juvenile 602433

Publications

Ellen McDonagh (Genomics England Curator)

Three families reported for Amyotrophic lateral sclerosis 4, juvenile with an autosomal dominant mode of inheritance in OMIM from one publication (PMID: 15106121). In silico analysis and allele frequencies raise the suggestion that variants within this gene are not pathogenic for ALS (PMID: 23129421): "epidemiologic and in silico evidence indicates that all newly identified variations and two previously published ALS4-related missense variations (C1554G and I2547T) are most likely non-pathogenic, demonstrating the problems of interpretation of SETX missense alleles in the absence of functional assays." PMID: 23881933 - several patients with SETX variants had variants in other ALS-associated genes (TARDBP, ALS2, C9orf72).
Created: 9 Sep 2016, 9:41 a.m.
Comment on list classification: Demoted from green to amber as unsure whether this gene should be included on this panel.
Created: 13 Jun 2016, 9:33 a.m.
The mode of inheritance provided in the expert list was autosomal recessive for this gene (biallelic), whereas from Illumina it was Dominant (monoallelic) for the phenotype Amyotrophic Lateral Sclerosis, Dominant. This is represented here as "BOTH monoallelic and biallelic, autosomal or pseudoautosomal".
Created: 13 Jun 2016, 9:33 a.m.
This gene is on the distal hereditary neuropathy (dHMN) NGS Panel and the autosomal recessive ataxia NGS panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual, but not included in the ALS/MND section.
Created: 13 Jun 2016, 9:32 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Amyotrophic lateral sclerosis 4, juvenile 602433
OMIM
608465
Clinvar variants
Variants in SETX
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

12 Jan 2017, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for SETX were set to Amyotrophic lateral sclerosis 4, juvenile 602433

12 Jan 2017, Gel status: 4

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for SETX was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

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

9 Sep 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for SETX were set to 22577233; 23129421; 23881933 (putative disease causing variants reported in Table 1).

9 Sep 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for SETX were set to 22577233;23129421

13 Jun 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

18 Aug 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SETX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SETX was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Expert

18 Aug 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SETX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SETX was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Radboud University Medical Center, Nijmegen

18 Aug 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SETX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SETX was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Illumina TruGenome Clinical Sequencing Services

18 Aug 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SETX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SETX was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Emory Genetics Laboratory

18 Aug 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SETX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SETX was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Expert

18 Aug 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SETX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SETX was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Radboud University Medical Center, Nijmegen

18 Aug 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SETX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

SETX was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Illumina TruGenome Clinical Sequencing Services

18 Aug 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SETX was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Sources: Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Expert