Amyotrophic lateral sclerosis/motor neuron disease

Gene: OPTN

Green List (high evidence)

OPTN (optineurin)
EnsemblGeneIds (GRCh38): ENSG00000123240
EnsemblGeneIds (GRCh37): ENSG00000123240
OMIM: 602432, Gene2Phenotype
OPTN is in 4 panels

1 review

Ellen McDonagh (Genomics England Curator)

This gene is on the ALS/MND NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual: "OPTN mutations which maybe recessive in inheritance or dominant with reduced penetrance". Multiple cases and variants reported in OMIM and within literature search, with functional evidenc studies also supporting a role of the variants in the disease.
Created: 15 Jun 2016, 1:23 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
familial amyotrophic lateral sclerosis (ALS12)

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Amyotrophic Lateral Sclerosis, Recessive
  • Glaucoma 1, open angle, E, 137760
OMIM
602432
Clinvar variants
Variants in OPTN
Penetrance
Complete
Publications
  • PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."
  • PMID: 26503823
  • PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS
  • (ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS
  • (iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient
  • and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."
  • PMID: 26203661
  • PMID: 25943890
  • PMID: 25859013 - functional evidence
  • PMID: 25681989
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

15 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

15 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

15 Jun 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823; PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS; (ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS; (iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient; and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."; PMID: 26203661; PMID: 25943890; PMID: 25859013 - functional evidence; PMID: 25681989

15 Jun 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823; PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS; (ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS; (iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient; and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."; PMID: 26203661; PMID: 25943890

15 Jun 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823; PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS; (ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS; (iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient; and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."; PMID: 26203661

15 Jun 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823

15 Jun 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."

13 Jun 2016, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for OPTN was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene OPTN was set to BIALLELIC, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

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

18 Aug 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene OPTN was set to BIALLELIC, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

OPTN 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 OPTN was set to BIALLELIC, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

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

18 Aug 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene OPTN was set to BIALLELIC, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

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

18 Aug 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene OPTN was set to BIALLELIC, autosomal or pseudoautosomal

18 Aug 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

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

18 Aug 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

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