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Likely inborn error of metabolism

Gene: ISCU

Green List (high evidence)
ISCU (iron-sulfur cluster assembly enzyme)
EnsemblGeneIds (GRCh38): ENSG00000136003
EnsemblGeneIds (GRCh37): ENSG00000136003
OMIM: 611911, Gene2Phenotype
ISCU is in 9 panels

4 reviews

Sarah Leigh (Genomics England Curator)

This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Created: 15 Aug 2019, 12:15 p.m. | Last Modified: 23 Jun 2020, 2:13 p.m.
Panel Version: 2.12
Comment on mode of inheritance: Comment on mode of inheritance: PMID 29079705 reports a novel de novo dominant variant missense p.G97V variant has been reported and therefore this may represent a specific mechanism of action. Further evidence is needed to determine which (if any) other monoallelic variants will cause disease beyond mitochondrial myopathy, which justifies the mode of inheritance recorded.
Created: 12 Aug 2019, 11:17 a.m. | Last Modified: 23 Jun 2020, 2:13 p.m.
Panel Version: 2.12
Comment on list classification: Sufficient published reported biallelic cases, with supportive functional studies. The most frequent reported variant c.343+382G>C g.108567650G>C is deep in intron five of the gene and strengthens a weak splicing acceptor site, with consequent retention of a 100-bp intronic sequence upstream of the known terminal exon, introduction of a stop codon and decreased levels of ISCU mRNA and protein (PMID 18304497). This may be missed by standard sequencing.
Created: 16 Apr 2019, 2:32 p.m. | Last Modified: 6 Aug 2019, 10:57 a.m.
Panel Version: 1.469

Publications

Created: 16 Apr 2019, 2:32 p.m.
Last Modified: 23 Jun 2020, 2:13 p.m.
Panel version: 1.156

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Multiple individuals mostly from Swedish ancestry reported in the literature; there is a common founder variant, which has been observed in combination with a number of other variants. Please also note report of a patient with a de novo single variant in this gene, and disease, backed up with functional data.
Created: 30 Aug 2018, 5:52 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Myopathy with lactic acidosis, hereditary, MIM#255125

Publications

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

Created: 30 Aug 2018, 5:52 a.m.

Panel version: Imported from Mitochondrial disorders panel version 1.67

Arianna Tucci (Genomics England Curator)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rhabdomyolysis and metabolic muscle disorders

Publications

Created: 13 Jan 2017, 4:13 p.m.

Panel version: Imported from Undiagnosed metabolic disorders panel version 0.76

Shamima Rahman (UCL Institute of Child Health)

Green List (high evidence)

Created: 8 Feb 2016, 10:31 a.m.

Panel version: Imported from Mitochondrial disorders panel version 0.37

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review Green
  • London North GLH
  • NHS GMS
  • Victorian Clinical Genetics Services
Phenotypes
  • Myopathy with lactic acidosis, hereditary, 255125
  • Disorders of iron homeostasis
  • Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
  • Rhabdomyolysis and metabolic muscle disorders
Tags
non-coding-known-pathogenic
OMIM
611911
Clinvar variants
Variants in ISCU
Penetrance
None
Publications
Panels with this gene

History Filter Activity

15 Aug 2019, Gel status: 3

Added Tag

Sarah Leigh (Genomics England Curator)

Tag non-coding-known-pathogenic tag was added to gene: ISCU.

15 Aug 2019, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: ISCU were set to 18304497; 29079705; 18296749; 19567699; 20206689

12 Aug 2019, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: ISCU was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

6 Aug 2019, Gel status: 3

Added New Source, Set mode of inheritance, Set Phenotypes, Set publications, Status Update

Sarah Leigh (Genomics England Curator)

Source Expert Review Green was added to ISCU. Mode of inheritance for gene ISCU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes Myopathy with lactic acidosis, hereditary, 255125; Disorders of iron homeostasis for gene: ISCU Publications for gene ISCU were changed from 27604308 to 18304497; 29079705; 18296749; 19567699; 20206689 Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

13 Feb 2019, Gel status: 2

Added New Source, Added New Source

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to ISCU. Source London North GLH was added to ISCU.

8 Jan 2019, Gel status: 2

Panel promoted to version 1.0

Ellen McDonagh (Genomics England Curator)

Sarah Leigh: Associated with relevant pheno

16 Dec 2018, Gel status: 2

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Added phenotypes Myopathy with lactic acidosis, hereditary, 255125; Disorders of iron homeostasis for gene: ISCU

16 Dec 2018, Gel status: 2

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

Ellen McDonagh (Genomics England Curator)

gene: ISCU was added gene: ISCU was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: ISCU was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ISCU were set to 27604308 Phenotypes for gene: ISCU were set to Rhabdomyolysis and metabolic muscle disorders; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only))