OMIA group 2763
Severe combined immunodeficiency disease, IL2RG and RAG1-related
The chain reaches the human disease severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive, which Mondo defines as: “A rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia.” It reaches 2 more human diseases, listed below.
The chain
From the animal disease to the drugs. The page shows what each step found and where the chain stopped. It does not say whether the animal is a model of a human disease.
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Animal disease
Reached
OMIA records it in 1 species entry marked as a defect.
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Human disease
Reached
3 Mondo diseases.
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Human gene
Reached
1 human gene.
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Target evidence
Reached
3 Open Targets associations, with a best score of 0.85.
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Drugs
Reached
8 ChEMBL drugs, 5 approved. None has been tested for this disease.
Natural-model score
How complete and how well supported the chain to each human disease is, out of 100, by stated rules. It does not say that the animal is a validated model of the human disease. How the score works.
| Part | Computed from | Points |
|---|---|---|
| Target evidence | Open Targets score of 0.85 | 29.7 of 35 |
| Drugs | A drug has reached phase 1/2 for this disease | 12.5 of 25 |
| Ortholog | No gene of a naturally occurring entry reaches a human gene | 0.0 of 20 |
| Both routes | One route found this disease | 5.0 of 10 |
| Species | 0 naturally occurring species entries marked as a defect. 1 genetically engineered entry is not counted | 0.0 of 10 |
43.4 out of 100
| Part | Computed from | Points |
|---|---|---|
| Target evidence | Open Targets score of 0.74 | 25.9 of 35 |
| Drugs | A drug has reached phase 1/2 for this disease | 12.5 of 25 |
| Ortholog | No gene of a naturally occurring entry reaches a human gene | 0.0 of 20 |
| Both routes | One route found this disease | 5.0 of 10 |
| Species | 0 naturally occurring species entries marked as a defect. 1 genetically engineered entry is not counted | 0.0 of 10 |
9.1 out of 100
| Part | Computed from | Points |
|---|---|---|
| Target evidence | Open Targets score of 0.05 | 1.6 of 35 |
| Drugs | Drugs act on its genes, but no drug has been tested for this disease | 2.5 of 25 |
| Ortholog | No gene of a naturally occurring entry reaches a human gene | 0.0 of 20 |
| Both routes | One route found this disease | 5.0 of 10 |
| Species | 0 naturally occurring species entries marked as a defect. 1 genetically engineered entry is not counted | 0.0 of 10 |
Species
The chain follows only the species entries that OMIA marks as a defect.
| Species | Scientific name | OMIA entry | A defect |
|---|---|---|---|
| crab-eating macaque Genetically engineered, not naturally occurring. Not counted in the score. | Macaca fascicularis | OMIA:002763-9541 | Yes |
Genes
Each gene OMIA records for a species entry, and the human gene it reaches through Ensembl's orthologs.
| Species | Animal gene | Human gene | Ortholog |
|---|---|---|---|
| crab-eating macaque | IL2RG interleukin 2 receptor subunit gamma NCBI Gene 102144912 | IL2RG Ensembl | one to one |
| crab-eating macaque | RAG1 recombination activating gene 1 NCBI Gene 102127914 | Ensembl does not know this NCBI Gene identifier. | |
Human diseases
Two routes lead from an OMIA group to a Mondo human disease: OMIA's own Mondo link, and the group's OMIM numbers through Mondo's cross-references.
- OMIA's own Mondo link: OMIA links the group to no Mondo disease.
- OMIA's OMIM numbers: found a disease.
| Mondo disease | Name | Found by |
|---|---|---|
| MONDO:0010730 | combined immunodeficiency, X-linked | OMIA's OMIM numbers |
| MONDO:0011086 | severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive A rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia. | OMIA's OMIM numbers |
| MONDO:0010315 | T-B+ severe combined immunodeficiency due to gamma chain deficiency Severe combined immunodeficiency (SCID) due to gamma chain deficiency, also called SCID-X1, is a form of SCID characterized by severe and recurrent infections, associated with diarrhea and failure to thrive. | OMIA's OMIM numbers |
Target evidence
Each Open Targets association between one of the group's human genes and one of its human diseases, with its overall score and the score for each kind of evidence.
| Human gene | Human disease | Score | Evidence | Kinds of evidence |
|---|---|---|---|---|
| IL2RG | T-B+ severe combined immunodeficiency due to gamma chain deficiency | 0.85 | 628 | Genetic association 0.94 Genetic literature 0.84 Animal model 0.62 Literature 0.33 |
| IL2RG | combined immunodeficiency, X-linked | 0.74 | 31 | Genetic association 0.87 Genetic literature 0.73 Animal model 0.53 Literature 0.01 |
| IL2RG | severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive | 0.05 | 1 | Animal model 0.38 |
Drugs
Drugs act on IL2RG, but none has been tested for this disease.
| Drug | Acts on | How | Latest stage | Tested for this disease |
|---|---|---|---|---|
| Aldesleukin | IL2RG | agonist | Approved | No |
| Basiliximab | IL2RG | inhibitor | Approved | No |
| Daclizumab | IL2RG | inhibitor | Approved | No |
| Denileukin Diftitox | IL2RG | binding agent | Approved | No |
| Nogapendekin Alfa Inbakicept | IL2RG | agonist | Approved | No |
| Simlukafusp Alfa | IL2RG | binding agent | Phase 3 | No |
| Pegenzileukin | IL2RG | agonist | Phase 2 | No |
| Recombinant Human Interleukin-15 | IL2RG | agonist | Phase 2 | No |
The drug data is ChEMBL's, under CC BY-SA 3.0, and came through Open Targets release 26.09.