Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: ORAI1

Green List (high evidence)

ORAI1 (ORAI calcium release-activated calcium modulator 1)
EnsemblGeneIds (GRCh38): ENSG00000276045
EnsemblGeneIds (GRCh37): ENSG00000182500
OMIM: 610277, Gene2Phenotype
ORAI1 is in 10 panels

3 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

Variable age of onset and presentation but adult onset, proximal weakness and increased CK all reported, agree sufficient phenotypic overlap.
Created: 1 Jul 2020, 7:30 a.m. | Last Modified: 1 Jul 2020, 7:30 a.m.
Panel Version: 0.35

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy, tubular aggregate, 2 (MIM#615883)

Crystle Lee (Victorian Clinical Genetics Services)

I don't know

OMIM notes both proximal and diffuse muscle weakness. There is some phenotypic overlap.

PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
Sources: Expert Review
Created: 30 Jun 2020, 10:59 p.m.

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

Phenotypes
Myopathy, tubular aggregate, 2 (MIM#615883)

Publications

Natalie Tan (Victorian Clinical Genetics Services)

Green List (high evidence)

PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)
Created: 20 Apr 2020, 5:58 a.m. | Last Modified: 20 Apr 2020, 6:03 a.m.
Panel Version: 0.2440

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Progressive myopathy; contractures

Publications

Mode of pathogenicity
Other

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • Myopathy, tubular aggregate, 2 (MIM#615883)
OMIM
610277
Clinvar variants
Variants in ORAI1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Apr 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: orai1 has been classified as Green List (High Evidence).

1 Jul 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: orai1 has been classified as Amber List (Moderate Evidence).

1 Jul 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: orai1 has been classified as Amber List (Moderate Evidence).

30 Jun 2020, Gel status: 0

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

Crystle Lee (Victorian Clinical Genetics Services)

gene: ORAI1 was added gene: ORAI1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review Mode of inheritance for gene: ORAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ORAI1 were set to 31448844 Phenotypes for gene: ORAI1 were set to Myopathy, tubular aggregate, 2 (MIM#615883) Review for gene: ORAI1 was set to AMBER