Genes in panel

Neurodegenerative disorders - adult onset

Gene: FIG4

Green List (high evidence)

FIG4 (FIG4 phosphoinositide 5-phosphatase)
EnsemblGeneIds (GRCh38): ENSG00000112367
EnsemblGeneIds (GRCh37): ENSG00000112367
OMIM: 609390, Gene2Phenotype
FIG4 is in 14 panels

5 reviews

Ian Berry (Leeds Genetics Laboratory)

Red List (low evidence)

Association of FIG4 with ALS remains in question. Main evidence is from Chow 2009 paper PMID: 19118816 where 5 proven deleterious variants were identified in a 473 patient cohort. There are 666 rare (<5 instances) protein altering & splice donor/acceptor variants in gnomAD v.2.1 https://gnomad.broadinstitute.org/gene/ENSG00000112367?dataset=gnomad_r2_1, with a denominator of ~125,000 patients. Other studies of FIG4 in ALS cohorts are under-powered to show a clear enrichment of proven deleterious alleles.

Using Pearson's Chi-squared test these two cohorts do not have a significant difference in rare/deleterious variant rate at p.<0.05.

I haven't seen any convincing segregation evidence for a FIG4 variant in a large ALS family, and am unaware of any functional studies or animal models showing a convincing genotype-phenotype association. I do not think this gene (yet) clearly satisfies the threshold of probability for a dominant cause of ALS.
Created: 14 May 2021, 10:19 a.m. | Last Modified: 14 May 2021, 10:19 a.m.
Panel Version: 2.174

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Chow et al. (2009) reported 5 unrelated patients diagnosed with probable or definite ALS. Two had a family history of the disorder. All had adult onset and showed prominent corticospinal tract findings. Nerve conduction velocity studies were normal, but EMG studies showed some denervation. Autosomal recessive Charcot-Marie Tooth disease type 4J (CMT4J; 611228) is an allelic disorder with a much more severe phenotype.Green
Created: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.
Panel Version: 1.99

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Charcot-Marie-Tooth disease, type 4J, 611228; Amyotrophic Lateral Sclerosis, Dominant

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

Green List (high evidence)

Late onset reported.
Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.
Panel Version: 1.72

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Charcot-Marie-Tooth disease, type 4J, 611228; Amyotrophic Lateral Sclerosis, Dominant

Publications

Variants in this GENE are reported as part of current diagnostic practice

Louise Daugherty (Genomics England Curator)

I don't know

Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed.
Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.
Panel Version: 1.101
Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.
Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.
Panel Version: 1.74
Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.
Created: 23 Apr 2019, 5:35 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Wessex and West Midlands GLH
  • Yorkshire and North East GLH
  • NHS GMS
  • London North GLH
  • Expert Review Green
Phenotypes
  • Charcot-Marie-Tooth disease, type 4J, OMIM:611228
  • Amyotrophic lateral sclerosis 11, OMIM:612577
OMIM
609390
Clinvar variants
Variants in FIG4
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: FIG4 were changed from Charcot-Marie-Tooth disease, type 4J, 611228; Amyotrophic Lateral Sclerosis, Dominant to Charcot-Marie-Tooth disease, type 4J, OMIM:611228; Amyotrophic lateral sclerosis 11, OMIM:612577

2 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to FIG4.

23 Jul 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene FIG4 were changed from PMID: 19118816 to 19118816; 23888880

23 Jul 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to FIG4.

23 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to FIG4.

23 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to FIG4.

25 Jan 2019, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Louise Daugherty: Comment on phenotypes: amended

18 Dec 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: FIG4 was added gene: FIG4 was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green Mode of inheritance for gene: FIG4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FIG4 were set to PMID: 19118816 Phenotypes for gene: FIG4 were set to Charcot-Marie-Tooth disease, type 4J, 611228; Amyotrophic Lateral Sclerosis, Dominant