Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: REXO2EnsemblGeneIds (GRCh38): ENSG00000076043
EnsemblGeneIds (GRCh37): ENSG00000076043
OMIM: 607149, Gene2Phenotype
REXO2 is in 1 panel
2 reviews
Achchuthan Shanmugasundram (Genomics England Curator)
Comment on list classification: There is one patient reported with monoallelic variant in REXO2, and functional evidence is available in support of the association. Hence, this gene should be rated amber with the current evidence.Created: 15 Aug 2025, 6:43 p.m. | Last Modified: 15 Aug 2025, 6:43 p.m.
Panel Version: 8.40
PMID:39107301 (2024) reported a female infant of Chinese descent, born to healthy non-consanguineous parents, presented at 2 years of age with whole-body rash with histological features of hyperkeratosis, parakeratosis and acanthosis, with infiltration of lymphocytes and eosinophils around small blood vessels. She has recurrent infections (frequent and severe pneumonia). The patient was identified with a heterozygous de novo variant (p.Thr132Ala) inn REXO2 gene.
There is extensive functional data available for p.Thr132Ala variant, which demonstrated that this de novo variant acts in a dominant negative way to prevent REXO2 cleavage of RNA, which instead accumulates in the cytosol to trigger MDA5.
This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype. It is rated amber in PanelApp Australia.Created: 15 Aug 2025, 6:40 p.m. | Last Modified: 15 Aug 2025, 6:40 p.m.
Panel Version: 8.37
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
type 1 interferonopathy, MONDO:0700264
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Dmitrijs Rots (Children's Clinical University Hospital)
PMID: 39107301 described a de novo variant in a single case with IEI with extensive functional evidence
Sources: LiteratureCreated: 17 Oct 2024, 4:32 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
- PMID: 39107301
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Amber
- Phenotypes
-
- type 1 interferonopathy, MONDO:0700264
- OMIM
- 607149
- Clinvar variants
- Variants in REXO2
- Penetrance
- unknown
- Publications
- Mode of Pathogenicity
- Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
- Panels with this gene
History Filter Activity
Entity classified by Genomics England curator
Achchuthan Shanmugasundram (Genomics England Curator)Gene: rexo2 has been classified as Amber List (Moderate Evidence).
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: REXO2 were changed from to type 1 interferonopathy, MONDO:0700264
Set publications
Achchuthan Shanmugasundram (Genomics England Curator)Publications for gene: REXO2 were set to PMID: 39107301
Created, Added New Source, Set mode of inheritance, Set publications, Set penetrance, Set mode of pathogenicity
Dmitrijs Rots (Children's Clinical University Hospital)gene: REXO2 was added gene: REXO2 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: REXO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: REXO2 were set to PMID: 39107301 Penetrance for gene: REXO2 were set to unknown Mode of pathogenicity for gene: REXO2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: REXO2 was set to AMBER