Combined Immunodeficiency

Gene: RAG1

Green List (high evidence)

RAG1 (recombination activating 1)
EnsemblGeneIds (GRCh38): ENSG00000166349
EnsemblGeneIds (GRCh37): ENSG00000166349
OMIM: 179615, Gene2Phenotype
RAG1 is in 9 panels

1 review

Danielle Ariti (University of Melbourne)

Green List (high evidence)

Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity
4 unrelated individuals; one mouse model
All 4 patients reported with alpha/beta T-cell lymphopaenia with gamma/delta T-cell expansion, severe CMV infection, and autoimmunity (anaemia in 3 patients and neutropaenia in 1).
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Combined cellular and humoral immune defects with granulomas
4 individuals from 3 unrelated families
Individuals presented with immunodeficiency disease with extensive granulomatous disease involving the skin, mucous membranes, and internal organs, hypogammaglobulinaemia and decreased numbers of T and B cells.
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Omenn syndrome
14 unrelated individuals; Two mouse models
Individuals typically presented with severe combined immunodeficiency associated with erythrodermia, eosinophilia, hepatosplenomegaly, lymphadenopathy, and elevated serum IgE levels.
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Severe combined immunodeficiency, B cell-negative
8 unrelated individuals; two mouse models
Individuals typically presented with failure to thrive, recurrent infections, diarrhoea and severe T cell and B cell immunodeficiency.
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Homozygous and compound heterozygous (missense, nonsense and del) variants were reported in all disease phenotypes resulting in loss of function for all disease phenotypes.
*multiple of the same variants were reported across disease phenotypes as well.

(Green for all disease phenotypes)
Created: 24 Aug 2021, 1:31 a.m. | Last Modified: 24 Aug 2021, 1:31 a.m.
Panel Version: 0.365

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Melbourne Genomics Health Alliance Immunology Flagship
  • Victorian Clinical Genetics Services
Phenotypes
  • Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889
  • Combined cellular and humoral immune defects with granulomas MIM# 233650
  • Omenn syndrome MIM# 603554
  • Severe combined immunodeficiency, B cell-negative MIM# 601457
OMIM
179615
Clinvar variants
Variants in RAG1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

24 Aug 2021, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: rag1 has been classified as Green List (High Evidence).

24 Aug 2021, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: RAG1 were changed from to Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457

24 Aug 2021, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: RAG1 were set to

24 Aug 2021, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: RAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: RAG1 was added gene: RAG1 was added to Combined immunodeficiency_MelbourneGenomics_AustralianGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Immunology Flagship Mode of inheritance for gene: RAG1 was set to Unknown