Amelogenesis imperfecta

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 7 panels

2 reviews

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P. At least 4 variants reported in three cases, together with supporting evidence.
4 Jan 2018, 2:54 p.m.
Comment on phenotypes: Hypocalcified amelogenesis imperfecta; and dysplastic dental enamel. Monoalleic gain of function variants associated with Myopathy, tubular aggregate, 2 615883
4 Jan 2018, 2:52 p.m.

Claire Smith (University of Leeds)

Green List (high evidence)

Mutations in STIM1 and ORAI1 have been identified in patients with a variety of phenotypes including immunodeficiency, autoimmune disease, myopathy, anhydrosis / hypohydrosis and syndromic enamel defects (Feske et al. 2006, McCarl et al. 2009, Picard et al. 2009, Byun et al. 2010, Fuchs et al. 2012, Bohm et al. 2013, Hedberg et al. 2014, Nesin et al. 2014, Wang et al. 2014). Both dominant and recessive mutations in STIM1 and ORAI1 have been noted to cause pathology, however it is unclear whether the presence of enamel defects is always assessed or recorded since some patients die within the first year of life (McCarl et al. 2009). It is thought that dominant disease is a result of constitutive activation of STIM1 and ORAI1 leading to elevated intracellular calcium that does not appear to affect enamel maturation, but causes muscle and immunological phenotypes in isolation (Bohm et al. 2013, Nesin et al. 2014). In contrast, recessive disease appears to be the result of loss of function of STIM1 and ORAI1 that leads to depleted intracellular calcium and an enamel phenotype in addition to other pathology (Feske 2010, Wang et al. 2014).

Enamel defects have been reported for 2 families with ORAI1 mutations (Feske et al. 2006, McCarl et al. 2009). The ORAI1 mutations identified so far in syndromic AI patients include an homozygous missense mutation within the first transmembrane domain, this led to loss of CRAC channel function and therefore also of SOCE (Feske et al. 2006, Feske 2010). A second patient was found to carry a compound heterozygous combination of 2 missense mutations, in the first and third transmembrane domain respectively, resulting in an absence of ORAI1 protein (McCarl et al. 2009, Feske 2010).

ORAI1 has been found to be expressed in ameloblasts and has been linked to ameloblast modulation during maturation.
16 Nov 2017, 3:54 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency 9, 612782; Amelogenesis imperfecta

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
Phenotypes
  • Immunodeficiency 9, 612782
OMIM
610277
Clinvar variants
Variants in ORAI1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Feb 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith

4 Jan 2018, Gel status: 3

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

4 Jan 2018, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for ORAI1 were set to Immunodeficiency 9, 612782

4 Jan 2018, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for ORAI1 were set to 20004786; 26469693; 16582901

4 Jan 2018, Gel status: 3

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

4 Jan 2018, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for ORAI1 were set to 20004786; 26469693

5 Dec 2017, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for ORAI1 were set to PMID: 20004786; 26469693

8 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for ORAI1 were set to Immunodeficiency 9, 612782; Hypocalcified amelogenesis imperfecta; Dysplastic dental enamel.

8 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for ORAI1 were set to Immunodeficiency 9, 612782; Hypocalcified amelogenesis imperfecta; Dysplastic dental enamel).

8 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for ORAI1 were set to Immunodeficiency 9, 612782 (includes Hypocalcified amelogenesis imperfecta and Dysplastic dental enamel).

8 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

ORAI1 was created by rfoulger

8 Jun 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

ORAI1 was added to Amelogenesis Imperfectapanel. Sources: UKGTN