OS
MCID: OMN001
MIFTS: 67

Omenn Syndrome (OS)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Omenn Syndrome

MalaCards integrated aliases for Omenn Syndrome:

Name: Omenn Syndrome 56 12 74 52 25 58 73 13 54 15 39 71
Histiocytic Medullary Reticulosis 25 29 6 17 71
Severe Combined Immunodeficiency with Hypereosinophilia 56 52
Combined Immunodeficiency with Hypereosinophilia 12 58
Reticuloendotheliosis, Familial, with Eosinophilia 56
Reticuloendotheliosis Familial with Eosinophilia 52
Familial Reticuloendotheliosis 25
Malignant Histiocytosis 71
Omenn's Syndrome 25
Os 73

Characteristics:

Orphanet epidemiological data:

58
omenn syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

56
Inheritance:
autosomal recessive


HPO:

31
omenn syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


Summaries for Omenn Syndrome

Genetics Home Reference : 25 Omenn syndrome is an inherited disorder of the immune system (immunodeficiency). Omenn syndrome is one of several forms of severe combined immunodeficiency (SCID), a group of disorders that cause individuals to have virtually no immune protection from bacteria, viruses, and fungi. Individuals with SCID are prone to repeated and persistent infections that can be very serious or life-threatening. Infants with Omenn syndrome typically experience pneumonia and chronic diarrhea. Often the organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people. In addition to immunodeficiency, children with Omenn syndrome develop autoimmunity, in which the immune system attacks the body's own tissues and organs. This abnormal immune reaction can cause very red skin (erythroderma), hair loss (alopecia), and an enlarged liver and spleen (hepatosplenomegaly). In addition, affected individuals have enlargement of tissues that produce infection-fighting white blood cells called lymphocytes. These include the thymus, which is a gland located behind the breastbone, and lymph nodes, which are found throughout the body. If not treated in a way that restores immune function, children with Omenn syndrome usually survive only until age 1 or 2.

MalaCards based summary : Omenn Syndrome, also known as histiocytic medullary reticulosis, is related to combined t cell and b cell immunodeficiency and hypereosinophilic syndrome, and has symptoms including diarrhea An important gene associated with Omenn Syndrome is RAG2 (Recombination Activating 2), and among its related pathways/superpathways are Innate Immune System and PEDF Induced Signaling. The drugs Fludarabine and Hydroxyurea have been mentioned in the context of this disorder. Affiliated tissues include t cells, skin and b cells, and related phenotypes are hepatomegaly and failure to thrive

Disease Ontology : 12 A severe combined immunodeficiency that has material basis in the RAG1 and RAG2 genes on chromosome 11p and the Artemis gene on chromosome 10p. It is characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly.

NIH Rare Diseases : 52 Omenn syndrome is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by erythroderma (skin redness), desquamation (peeling skin), alopecia (hair loss), chronic diarrhea, failure to thrive , lymphadenopathy (enlarged lymph nodes ), eosinophilia , hepatosplenomegaly , and elevated serum IgE levels. Patients are highly susceptible to infection and develop fungal, bacterial, and viral infections typical of SCID. In this syndrome, the SCID is associated with low IgG, IgA, and IgM and the virtual absence of B cells . There is an elevated number of T cells, but their function is impaired. Omenn syndrome has been found to be caused by mutations in the RAG1 or RAG2 genes . Additional causative genes have been identified. Early recognition of this condition is important for genetic counseling and early treatment. If left untreated, Omenn syndrome is fatal. The prognosis may be improved with early diagnosis and treatment with compatible bone marrow or cord blood stem cell transplantation.

OMIM : 56 Omenn syndrome is an autosomal recessive disorder characterized by severe combined immunodeficiency (SCID) associated with erythrodermia, hepatosplenomegaly, lymphadenopathy, and alopecia. B cells are mostly absent, T-cell counts are normal to elevated, and T cells are frequently activated and express a restricted T-cell receptor (TCR) repertoire (summary by Ege et al., 2005). (603554)

UniProtKB/Swiss-Prot : 73 Omenn syndrome: Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels.

Wikipedia : 74 Omenn syndrome is an autosomal recessive severe combined immunodeficiency. It is associated with... more...

Related Diseases for Omenn Syndrome

Diseases related to Omenn Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 754)
# Related Disease Score Top Affiliating Genes
1 combined t cell and b cell immunodeficiency 32.5 TNF RMRP RAG2 RAG1 LIG4 IL7R
2 hypereosinophilic syndrome 32.0 IL5 IL4 IL10 IGHE IFNG
3 alopecia 31.9 TNF IL4 IFNG AIRE
4 thyroiditis 31.9 TNF IL4 IL10 FOXP3
5 exanthem 31.8 TNF IL10 IFNG
6 severe combined immunodeficiency 31.7 RMRP RAG2 RAG1 LIG4 IL7R IL5
7 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 31.7 RAG1 IL10 IFNG FOXP3 AIRE
8 hashimoto thyroiditis 31.6 TNF IL5 IL4 IL10 IFNG FOXP3
9 hemolytic anemia 31.5 TNF IL4 IL10 IFNG ADA
10 graft-versus-host disease 31.4 TNF IL10 IFNG
11 adenosine deaminase deficiency 31.4 RAG2 RAG1 IL2RG ADA
12 reticular dysgenesis 31.4 RAG1 IL2RG DCLRE1C ADA
13 osteomyelitis 31.3 TNF IL4 IL10 IFNGR1 IFNG
14 lymphopenia 31.3 RAG1 IL7R IL4 IL2RG IL10 IFNG
15 acute graft versus host disease 31.2 TNF IL4 IL10 IFNG
16 polyendocrinopathy 31.2 FOXP3 AIRE
17 peritonitis 31.2 TNF IL4 IL10 IFNG ADA
18 severe combined immunodeficiency, x-linked 31.2 IL7R IL4 IL2RG ADA
19 typhoid fever 31.1 TNF IFNGR1 IFNG
20 t-b- severe combined immunodeficiency 31.1 RAG2 DCLRE1C
21 stomatitis 31.1 TNF IL4 IL10 IFNG
22 t cell deficiency 31.1 RAG1 IL7R IL2RG
23 immune deficiency disease 31.1 TNFRSF8 TNF RAG2 RAG1 LIG4 IL7R
24 autoimmune disease 31.0 TNF IL5 IL4 IL10 IFNG FOXP3
25 histiocytosis 31.0 TNFRSF8 TNF IFNG
26 myocarditis 31.0 TNF IL4 IL10 IFNG
27 bronchiolitis 31.0 TNF IL5 IL4 IL10 IFNG
28 purpura 31.0 TNF IL4 IL10 IFNG
29 candidiasis 31.0 TNF IL4 IL10 IFNG AIRE
30 ige responsiveness, atopic 31.0 IL5 IL4 IL10 IGHE IFNG
31 chronic graft versus host disease 30.9 IL10 IFNG
32 gastroenteritis 30.9 TNF IL5 IL4 IL10 IFNG
33 ileus 30.9 TNF IL10 IFNG
34 dermatitis 30.8 TNF IL5 IL4 IL10 IGHE IFNG
35 diarrhea 30.8 TNF IL5 IL10 IFNG FOXP3
36 allergic hypersensitivity disease 30.8 TNF IL5 IL4 IL10 IGHE IFNG
37 skin disease 30.8 TNFRSF8 TNF IL5 IL4 IL10 IFNG
38 neuritis 30.8 TNF IL4 IL10 IFNG
39 arthritis 30.8 TNF IL4 IL10 IFNG FOXP3
40 diphtheria 30.8 TNF IL5 IL4 IFNG
41 silicosis 30.7 TNF IL4 IL10
42 toxoplasmosis 30.7 TNF IL5 IL4 IL10 IFNGR1 IFNG
43 rhinitis 30.6 TNF IL5 IL4 IL10 IGHE IFNG
44 salmonellosis 30.6 TNF IL10 IFNGR1 IFNG
45 uveitis 30.6 TNF IL4 IL10 IFNG
46 appendicitis 30.5 TNF IL10 IFNG
47 keratopathy 30.5 TNF IL4 AIRE
48 chagas disease 30.5 TNF IL4 IL10 IFNG
49 pericarditis 30.5 TNF IFNG ADA
50 neuromyelitis optica 30.5 IL7R IL5 IL4

Graphical network of the top 20 diseases related to Omenn Syndrome:



Diseases related to Omenn Syndrome

Symptoms & Phenotypes for Omenn Syndrome

Human phenotypes related to Omenn Syndrome:

58 31 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
2 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
3 alopecia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001596
4 chronic diarrhea 58 31 hallmark (90%) Very frequent (99-80%) HP:0002028
5 lymphadenopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002716
6 erythroderma 58 31 hallmark (90%) Very frequent (99-80%) HP:0001019
7 severe combined immunodeficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0004430
8 abnormal lymphocyte morphology 31 hallmark (90%) HP:0004332
9 splenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001744
10 fever 58 31 frequent (33%) Frequent (79-30%) HP:0001945
11 dry skin 58 31 frequent (33%) Frequent (79-30%) HP:0000958
12 edema 58 31 frequent (33%) Frequent (79-30%) HP:0000969
13 pruritus 58 31 frequent (33%) Frequent (79-30%) HP:0000989
14 thickened skin 58 31 frequent (33%) Frequent (79-30%) HP:0001072
15 aplasia/hypoplasia of the eyebrow 58 31 frequent (33%) Frequent (79-30%) HP:0100840
16 eosinophilia 58 31 frequent (33%) Frequent (79-30%) HP:0001880
17 pneumonia 58 31 frequent (33%) Frequent (79-30%) HP:0002090
18 desquamation of skin soon after birth 58 31 frequent (33%) Frequent (79-30%) HP:0007549
19 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
20 anemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001903
21 abnormality of the metaphysis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000944
22 autoimmunity 58 31 occasional (7.5%) Occasional (29-5%) HP:0002960
23 short toe 58 31 occasional (7.5%) Occasional (29-5%) HP:0001831
24 thyroiditis 58 31 occasional (7.5%) Occasional (29-5%) HP:0100646
25 nephrotic syndrome 58 31 occasional (7.5%) Occasional (29-5%) HP:0000100
26 lymphoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0002665
27 sepsis 58 31 occasional (7.5%) Occasional (29-5%) HP:0100806
28 thrombocytopenia 31 HP:0001873
29 hypoplasia of the thymus 31 HP:0000778
30 diarrhea 31 HP:0002014
31 leukocytosis 58 Frequent (79-30%)
32 hypoproteinemia 31 HP:0003075
33 abnormality of lymphocytes 58 Very frequent (99-80%)
34 recurrent bacterial infections 31 HP:0002718
35 recurrent fungal infections 31 HP:0002841
36 recurrent viral infections 31 HP:0004429
37 severe b lymphocytopenia 31 HP:0005365

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Growth Other:
failure to thrive

Skin Nails Hair Hair:
alopecia

Respiratory Lung:
pneumonia

Laboratory Abnormalities:
hypoproteinemia
very low igg
very low iga
very low igm
increased ige

Skin Nails Hair Skin Histology:
lymphocytic infiltrates with occasional histiocytes and eosinophils

Abdomen Liver:
hepatomegaly

Hematology:
anemia
thrombocytopenia
eosinophilia

Immunology:
lymphadenopathy
absent b cells
increased frequency of bacterial, viral, and fungal infections
lymph node architecture severely altered: lack of follicles, depletion of lymphocytes, and increased proportion of interdigitating reticular cells and eosinophils
very low b cells
more
Abdomen Gastrointestinal:
diarrhea

Skin Nails Hair Skin:
pachydermia
generalized erythrodermia

Clinical features from OMIM:

603554

UMLS symptoms related to Omenn Syndrome:


diarrhea

MGI Mouse Phenotypes related to Omenn Syndrome:

45 (show all 18)
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.46 ADA AIRE CARD11 CHD7 DCLRE1C FOXP3
2 endocrine/exocrine gland MP:0005379 10.44 ADA AIRE CHD7 DCLRE1C FOXP3 IFNG
3 immune system MP:0005387 10.43 ADA AIRE CARD11 CHD7 DCLRE1C FOXP3
4 cellular MP:0005384 10.41 ADA CHD7 DCLRE1C FOXP3 IFNG IFNGR1
5 digestive/alimentary MP:0005381 10.39 ADA AIRE CHD7 FOXP3 IFNG IFNGR1
6 homeostasis/metabolism MP:0005376 10.37 ADA AIRE CARD11 CHD7 FOXP3 IFNG
7 growth/size/body region MP:0005378 10.34 ADA AIRE CHD7 DCLRE1C FOXP3 IFNG
8 cardiovascular system MP:0005385 10.27 ADA CHD7 DCLRE1C FOXP3 IFNG IFNGR1
9 mortality/aging MP:0010768 10.22 ADA AIRE CHD7 FOXP3 IFNG IFNGR1
10 liver/biliary system MP:0005370 10.21 ADA AIRE FOXP3 IFNG IFNGR1 IL10
11 craniofacial MP:0005382 10.16 CHD7 FOXP3 IFNG IL10 IL2RG IL4
12 integument MP:0010771 10.11 CARD11 FOXP3 IFNG IFNGR1 IL10 IL4
13 neoplasm MP:0002006 10.11 AIRE IFNG IFNGR1 IL10 IL2RG IL5
14 reproductive system MP:0005389 9.97 ADA AIRE CHD7 FOXP3 IFNG IFNGR1
15 normal MP:0002873 9.96 ADA AIRE FOXP3 IFNG IL10 IL2RG
16 no phenotypic analysis MP:0003012 9.87 AIRE FOXP3 IFNG IL10 IL2RG IL4
17 respiratory system MP:0005388 9.77 ADA AIRE CARD11 CHD7 FOXP3 IFNG
18 skeleton MP:0005390 9.32 ADA CHD7 IFNG IFNGR1 IL10 IL2RG

Drugs & Therapeutics for Omenn Syndrome

Drugs for Omenn Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
2
Hydroxyurea Approved Phase 2 127-07-1 3657
3
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
4
alemtuzumab Approved, Investigational Phase 2 216503-57-0
5
Melphalan Approved Phase 2 148-82-3 460612 4053
6 Immunologic Factors Phase 2
7 Immunosuppressive Agents Phase 2
8 Alkylating Agents Phase 2
9 Antineoplastic Agents, Immunological Phase 2
10
Adenosine Approved, Investigational 58-61-7 60961

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase II Study of Reduced Intensity Conditioning in Pediatric Patients and Young Adults ≤55 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplantation Recruiting NCT01962415 Phase 2 Hydroxyurea;Alemtuzumab;Fludarabine;Melphalan;Thiotepa
2 A Phase 2 Study to Assess the Safety and Efficacy of Cobimetinib in Refractory Langerhans Cell Histiocytosis, LCH-Associated Neurodegenerative Disease, and Other Histiocytic Disorders. Not yet recruiting NCT04079179 Phase 2 Cobimetinib
3 A Pilot Study of Reduced Intensity Conditioning in Pediatric Patients <21 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood Transplantation Completed NCT00744692 Phase 1 Reduced Intensity Conditioning
4 A Retrospective and Cross-Sectional Analysis of Patients Treated for SCID Since January 1,1968 (RDCRN PIDTC-6902) Recruiting NCT01346150
5 A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children With SCID Disorders (RDCRN PIDTC-6901) Recruiting NCT01186913

Search NIH Clinical Center for Omenn Syndrome

Genetic Tests for Omenn Syndrome

Genetic tests related to Omenn Syndrome:

# Genetic test Affiliating Genes
1 Histiocytic Medullary Reticulosis 29 DCLRE1C RAG1 RAG2

Anatomical Context for Omenn Syndrome

MalaCards organs/tissues related to Omenn Syndrome:

40
T Cells, Skin, B Cells, Lymph Node, Bone, Bone Marrow, Thymus

Publications for Omenn Syndrome

Articles related to Omenn Syndrome:

(show top 50) (show all 410)
# Title Authors PMID Year
1
Omenn syndrome due to ARTEMIS mutations. 56 61 54 6
15731174 2005
2
Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B-severe combined immune deficiency or Omenn syndrome. 61 56 6 54
11313270 2001
3
Partial V(D)J recombination activity leads to Omenn syndrome. 61 54 56 6
9630231 1998
4
Biochemical and folding defects in a RAG1 variant associated with Omenn syndrome. 54 6 61
18056378 2007
5
A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection. 6 54 61
16276422 2005
6
AIRE deficiency in thymus of 2 patients with Omenn syndrome. 56 61 54
15696198 2005
7
GvHD-associated cytokine polymorphisms do not associate with Omenn syndrome rather than T-B- SCID in patients with defects in RAG genes. 6 61
17572155 2007
8
A hypomorphic R229Q Rag2 mouse mutant recapitulates human Omenn syndrome. 56 61
17476358 2007
9
Homeostatically proliferating CD4 T cells are involved in the pathogenesis of an Omenn syndrome murine model. 61 56
17476359 2007
10
RAG-dependent primary immunodeficiencies. 6 61
16960852 2006
11
Hematopoietic stem cell transplantation in Omenn syndrome: a single-center experience. 61 6
15908971 2005
12
V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations. 6 61
11133745 2001
13
N-terminal RAG1 frameshift mutations in Omenn's syndrome: internal methionine usage leads to partial V(D)J recombination activity and reveals a fundamental role in vivo for the N-terminal domains. 54 6
11121059 2000
14
Treatment of Omenn syndrome by bone marrow transplantation. 61 56
7608815 1995
15
Mutations in conserved regions of the predicted RAG2 kelch repeats block initiation of V(D)J recombination and result in primary immunodeficiencies. 6
10891502 2000
16
RAG mutations in human B cell-negative SCID. 6
8810255 1996
17
Omenn's reticulosis associated with the nephrotic syndrome. 56
8776375 1996
18
Increased radiosensitivity of granulocyte macrophage colony-forming units and skin fibroblasts in human autosomal recessive severe combined immunodeficiency. 56
8450050 1993
19
Restricted heterogeneity of T lymphocytes in combined immunodeficiency with hypereosinophilia (Omenn's syndrome). 56
2010548 1991
20
Omenn phenotype with short-limbed dwarfism. 56
1986108 1991
21
Transfusion-associated graft-versus-host disease. 56
2248640 1990
22
Omenn's syndrome--pathologic arguments in favor of a graft versus host pathogenesis: a report of nine cases. 56
3679186 1987
23
Omenn disease: termination in lymphoma. 56
3879354 1985
24
Absence of lymphocyte ecto-5'-nucleotidase in infants with reticuloendotheliosis and eosinophilia (Omenn's syndrome). 56
6326896 1984
25
Identification by HLA typing of intrauterine-derived maternal T cells in four patients with severe combined immunodeficiency. 56
7050708 1982
26
Association of a lymphocyte purine enzyme deficiency (5'-nucleotidase) with combined immunodeficiency. 56
6243521 1980
27
Rapidly fatal familial histiocytosis associated with eosinophilia and primary immunological deficiency. 56
4115568 1972
28
Hereditary lymphopenic agammaglobulinemia associated with a distinctive form of short-limbed dwarfism and ectodermal dysplasia. 56
5809843 1969
29
FAMILIAL RETICULOENDOTHELIOSIS WITH EOSINOPHILIA. 56
14328107 1965
30
Analysis of mutations from SCID and Omenn syndrome patients reveals the central role of the Rag2 PHD domain in regulating V(D)J recombination. 61 54
20234091 2010
31
The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events. 61 54
19953608 2010
32
Omenn syndrome due to mutation of the RAG2 gene. 61 54
19470080 2009
33
Molecular analysis of T-B-NK+ severe combined immunodeficiency and Omenn syndrome cases in Saudi Arabia. 61 54
19912631 2009
34
Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome. 54 61
19414857 2009
35
Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency. 54 61
18509675 2009
36
Primary immune deficiencies with aberrant IgE production. 54 61
19084106 2008
37
Omenn syndrome is associated with mutations in DNA ligase IV. 61 54
18845326 2008
38
Lack of nonfunctional B-cell receptor rearrangements in a patient with normal B cell numbers despite partial RAG1 deficiency and atypical SCID/Omenn syndrome. 61 54
18592361 2008
39
Omenn syndrome with mutation in RAG1 gene. 54 61
19011808 2008
40
Adenosine deaminase deficiency can present with features of Omenn syndrome. 54 61
18243287 2008
41
Omenn syndrome: a lack of tolerance on the background of deficient lymphocyte development and maturation. 54 61
16763459 2006
42
Immunodeficiencies with autoimmune consequences. 54 61
16682278 2006
43
Variable phenotypic expression of mutations in genes of the immune system. 61 54
16276411 2005
44
Omenn's syndrome occurring in patients without mutations in recombination activating genes. 61 54
15964782 2005
45
Cardiac thrombus in Omenn syndrome. 61 54
16088419 2005
46
Evolution of a T-B- SCID into an Omenn syndrome phenotype following parainfluenza 3 virus infection. 61 54
15870023 2005
47
Omenn syndrome in the context of other B cell-negative severe combined immunodeficiencies. 61 54
11908269 2002
48
Identification of anti-herpes simplex virus antibody-producing B cells in a patient with an atypical RAG1 immunodeficiency. 54 61
11520796 2001
49
Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders. 54 61
10606976 2000
50
Prenatal diagnosis of RAG-deficient Omenn syndrome. 54 61
10701853 2000

Variations for Omenn Syndrome

ClinVar genetic disease variations for Omenn Syndrome:

6 (show top 50) (show all 300) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RAG1 NM_000448.2(RAG1):c.424C>T (p.Arg142Ter)SNV Pathogenic 626157 rs773929270 11:36595278-36595278 11:36573728-36573728
2 DCLRE1C NM_001033855.3(DCLRE1C):c.241C>T (p.Arg81Ter)SNV Pathogenic 4665 rs121908156 10:14987109-14987109 10:14945110-14945110
3 DCLRE1C NM_001033855.3(DCLRE1C):c.2T>C (p.Met1Thr)SNV Pathogenic 4677 rs121908158 10:14996008-14996008 10:14954009-14954009
4 RAG1 NM_000448.2(RAG1):c.1682G>A (p.Arg561His)SNV Pathogenic 13143 rs104894284 11:36596536-36596536 11:36574986-36574986
5 RAG1 NM_000448.2(RAG1):c.1186C>T (p.Arg396Cys)SNV Pathogenic 13144 rs104894289 11:36596040-36596040 11:36574490-36574490
6 RAG1 NM_000448.2(RAG1):c.2735A>G (p.Tyr912Cys)SNV Pathogenic 13145 rs104894290 11:36597589-36597589 11:36576039-36576039
7 RAG1 NM_000448.2(RAG1):c.1187G>A (p.Arg396His)SNV Pathogenic 13146 rs104894291 11:36596041-36596041 11:36574491-36574491
8 RAG1 NM_000448.2(RAG1):c.1286A>G (p.Asp429Gly)SNV Pathogenic 13147 rs104894292 11:36596140-36596140 11:36574590-36574590
9 RAG1 NM_000448.2(RAG1):c.1681C>T (p.Arg561Cys)SNV Pathogenic 13148 rs104894285 11:36596535-36596535 11:36574985-36574985
10 RAG1 RAG1, 13-BP DEL, NT1723deletion Pathogenic 13150
11 RAG1 RAG1, 2-BP DEL, 368AAdeletion Pathogenic 13151
12 RAG1 RAG1, 1-BP DEL, 887Adeletion Pathogenic 13152
13 RAG1 RAG1, 1-BP DEL, 631Tdeletion Pathogenic 13153
14 RAG1 NM_000448.2(RAG1):c.983G>A (p.Cys328Tyr)SNV Pathogenic 13160 rs121918571 11:36595837-36595837 11:36574287-36574287
15 RAG1 NM_000448.2(RAG1):c.2210G>A (p.Arg737His)SNV Pathogenic/Likely pathogenic 13149 rs104894286 11:36597064-36597064 11:36575514-36575514
16 RAG2 NM_000536.4(RAG2):c.283G>A (p.Gly95Arg)SNV Pathogenic/Likely pathogenic 13133 rs36001797 11:36615436-36615436 11:36593886-36593886
17 RAG1 NM_000448.2(RAG1):c.1303A>G (p.Met435Val)SNV Pathogenic/Likely pathogenic 68680 rs141524540 11:36596157-36596157 11:36574607-36574607
18 RAG1 NM_000448.2(RAG1):c.2348C>G (p.Ser783Ter)SNV Pathogenic/Likely pathogenic 573434 rs754502950 11:36597202-36597202 11:36575652-36575652
19 RAG2 NM_000536.4(RAG2):c.104G>T (p.Gly35Val)SNV Likely pathogenic 496618 rs148508754 11:36615615-36615615 11:36594065-36594065
20 RAG2 NM_000536.4(RAG2):c.1375A>C (p.Met459Leu)SNV Likely pathogenic 496632 rs1204766339 11:36614344-36614344 11:36592794-36592794
21 RAG2 NM_000536.4(RAG2):c.1366G>A (p.Ala456Thr)SNV Likely pathogenic 496631 rs1564995611 11:36614353-36614353 11:36592803-36592803
22 RAG2 NM_000536.4(RAG2):c.1357T>A (p.Trp453Arg)SNV Likely pathogenic 496630 rs1564995627 11:36614362-36614362 11:36592812-36592812
23 RAG2 NM_000536.4(RAG2):c.1329G>T (p.Met443Ile)SNV Likely pathogenic 496627 rs773710101 11:36614390-36614390 11:36592840-36592840
24 RAG2 NM_000536.4(RAG2):c.1320A>C (p.Lys440Asn)SNV Likely pathogenic 496626 rs754413772 11:36614399-36614399 11:36592849-36592849
25 RAG2 NM_000536.4(RAG2):c.470G>T (p.Gly157Val)SNV Likely pathogenic 496622 rs1564997121 11:36615249-36615249 11:36593699-36593699
26 RAG2 NM_000536.4(RAG2):c.115A>G (p.Arg39Gly)SNV Likely pathogenic 13136 rs121917897 11:36615604-36615604 11:36594054-36594054
27 RAG1 NM_000448.2(RAG1):c.2904C>A (p.Asn968Lys)SNV Likely pathogenic 36713 rs193922463 11:36597758-36597758 11:36576208-36576208
28 RAG2 NM_000536.4(RAG2):c.123C>G (p.Cys41Trp)SNV Likely pathogenic 13131 rs121917895 11:36615596-36615596 11:36594046-36594046
29 RAG2 NM_000536.4(RAG2):c.854T>G (p.Met285Arg)SNV Likely pathogenic 13132 rs121917896 11:36614865-36614865 11:36593315-36593315
30 DCLRE1C NM_001033855.3(DCLRE1C):c.103C>G (p.His35Asp)SNV Likely pathogenic 4674 rs121908159 10:14995907-14995907 10:14953908-14953908
31 IL7R NM_002185.5(IL7R):c.265C>T (p.Gln89Ter)SNV Likely pathogenic 804345 5:35867451-35867451 5:35867349-35867349
32 RAG2 NM_000536.4(RAG2):c.367C>T (p.Arg123Cys)SNV Conflicting interpretations of pathogenicity 704774 11:36615352-36615352 11:36593802-36593802
33 RAG2 NM_000536.4(RAG2):c.477C>T (p.Arg159=)SNV Conflicting interpretations of pathogenicity 774545 11:36615242-36615242 11:36593692-36593692
34 RAG1 NM_000448.2(RAG1):c.276C>T (p.His92=)SNV Conflicting interpretations of pathogenicity 733202 11:36595130-36595130 11:36573580-36573580
35 DCLRE1C NM_001033855.3(DCLRE1C):c.1602C>T (p.Ser534=)SNV Conflicting interpretations of pathogenicity 743312 10:14950884-14950884 10:14908885-14908885
36 DCLRE1C NM_001033855.3(DCLRE1C):c.741A>G (p.Thr247=)SNV Conflicting interpretations of pathogenicity 736910 10:14974892-14974892 10:14932893-14932893
37 RAG2 NM_000536.4(RAG2):c.686G>A (p.Arg229Gln)SNV Conflicting interpretations of pathogenicity 13130 rs121917894 11:36615033-36615033 11:36593483-36593483
38 RAG2 NM_000536.4(RAG2):c.644C>T (p.Thr215Ile)SNV Conflicting interpretations of pathogenicity 13135 rs35691292 11:36615075-36615075 11:36593525-36593525
39 RAG1 NM_000448.2(RAG1):c.1346G>A (p.Arg449Lys)SNV Conflicting interpretations of pathogenicity 256188 rs4151031 11:36596200-36596200 11:36574650-36574650
40 RAG2 NM_000536.4(RAG2):c.479C>T (p.Ser160Leu)SNV Conflicting interpretations of pathogenicity 418443 rs756694972 11:36615240-36615240 11:36593690-36593690
41 RAG2 NM_000536.4(RAG2):c.1391G>A (p.Arg464His)SNV Conflicting interpretations of pathogenicity 432772 rs147748696 11:36614328-36614328 11:36592778-36592778
42 RAG2 NM_000536.4(RAG2):c.1504A>G (p.Met502Val)SNV Conflicting interpretations of pathogenicity 440231 rs145614809 11:36614215-36614215 11:36592665-36592665
43 DCLRE1C NM_001033855.3(DCLRE1C):c.1903dup (p.Ser635fs)duplication Conflicting interpretations of pathogenicity 468484 rs760288938 10:14950582-14950583 10:14908583-14908584
44 RAG1 NM_000448.2(RAG1):c.2799A>G (p.Gly933=)SNV Conflicting interpretations of pathogenicity 469114 rs769375583 11:36597653-36597653 11:36576103-36576103
45 RAG1 NM_000448.2(RAG1):c.2571C>T (p.Ala857=)SNV Conflicting interpretations of pathogenicity 469113 rs141560248 11:36597425-36597425 11:36575875-36575875
46 DCLRE1C NM_001033855.3(DCLRE1C):c.350C>T (p.Pro117Leu)SNV Conflicting interpretations of pathogenicity 522770 rs757316102 10:14978549-14978549 10:14936550-14936550
47 RAG2 NM_000536.4(RAG2):c.685C>T (p.Arg229Trp)SNV Conflicting interpretations of pathogenicity 496624 rs765298019 11:36615034-36615034 11:36593484-36593484
48 RAG2 NM_000536.4(RAG2):c.218G>A (p.Arg73His)SNV Conflicting interpretations of pathogenicity 496620 rs762407838 11:36615501-36615501 11:36593951-36593951
49 RAG1 NM_000448.2(RAG1):c.3016A>G (p.Met1006Val)SNV Conflicting interpretations of pathogenicity 536963 rs139113046 11:36597870-36597870 11:36576320-36576320
50 DCLRE1C NM_001033855.3(DCLRE1C):c.1587A>C (p.Ser529=)SNV Conflicting interpretations of pathogenicity 706525 10:14950899-14950899 10:14908900-14908900

UniProtKB/Swiss-Prot genetic disease variations for Omenn Syndrome:

73 (show all 28)
# Symbol AA change Variation ID SNP ID
1 DCLRE1C p.His35Asp VAR_023077 rs121908159
2 RAG1 p.Arg396Cys VAR_008886 rs104894289
3 RAG1 p.Arg396His VAR_008887 rs104894291
4 RAG1 p.Asp429Gly VAR_008888 rs104894292
5 RAG1 p.Arg561His VAR_008889 rs104894284
6 RAG1 p.Arg561Cys VAR_008890 rs104894285
7 RAG1 p.Arg737His VAR_008891 rs104894286
8 RAG1 p.Leu885Arg VAR_008893 rs199474691
9 RAG1 p.Tyr912Cys VAR_008894 rs104894290
10 RAG1 p.Cys328Tyr VAR_025971 rs121918571
11 RAG1 p.Arg396Leu VAR_025972 rs104894291
12 RAG1 p.Ser401Pro VAR_025973 rs199474682
13 RAG1 p.Arg410Gln VAR_025974 rs199474684
14 RAG1 p.Val433Met VAR_025975 rs199474679
15 RAG1 p.Met435Val VAR_025976 rs141524540
16 RAG1 p.Ala444Val VAR_025977 rs199474685
17 RAG1 p.Arg474His VAR_025978 rs199474686
18 RAG1 p.Arg507Trp VAR_025979 rs104894298
19 RAG1 p.Trp522Cys VAR_025980 rs193922461
20 RAG1 p.Arg559Ser VAR_025981 rs199474681
21 RAG1 p.Arg624Cys VAR_025982 rs199474688
22 RAG1 p.Glu669Gly VAR_025983 rs199474689
23 RAG1 p.His753Leu VAR_025984 rs199474687
24 RAG1 p.Arg975Gln VAR_025987 rs150739647
25 RAG1 p.Leu454Gln VAR_067274 rs199474677
26 RAG1 p.Arg699Trp VAR_067276 rs199474676
27 RAG2 p.Cys41Trp VAR_008895 rs121917895
28 RAG2 p.Met285Arg VAR_008896 rs121917896

Expression for Omenn Syndrome

Search GEO for disease gene expression data for Omenn Syndrome.

Pathways for Omenn Syndrome

Pathways related to Omenn Syndrome according to GeneCards Suite gene sharing:

(show all 46)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
14.02 TNFRSF8 TNF RAG2 RAG1 IL7R IL5
2
Show member pathways
13.67 TNFRSF8 TNF IL7R IL5 IL4 IL2RG
3
Show member pathways
13.53 TNF IL7R IL5 IL4 IL2RG IL10
4
Show member pathways
13.39 TNFRSF8 TNF IL7R IL5 IL4 IL2RG
5
Show member pathways
13.29 TNFRSF8 TNF IL7R IL5 IL4 IL2RG
6
Show member pathways
13.14 TNFRSF8 TNF RAG2 RAG1 IL7R IL5
7
Show member pathways
12.85 TNF IL5 IL4 IL10 IFNG FOXP3
8 12.84 IL7R IL5 IL4 IL2RG IFNGR1 IFNG
9
Show member pathways
12.68 TNF IL4 IL10 IGHE IFNGR1 IFNG
10
Show member pathways
12.62 TNF IL5 IL4 IL10 IFNGR1 IFNG
11
Show member pathways
12.57 TNF IL5 IL4 IL2RG IL10 IFNGR1
12
Show member pathways
12.47 IL7R IL5 IL4 IL2RG IL10 IFNGR1
13
Show member pathways
12.32 TNF IL5 IL4 IFNG
14
Show member pathways
12.27 TNF IL4 IL10 IFNGR1 IFNG
15
Show member pathways
12.25 TNF IL5 IL4 IL10 IFNG
16 12.22 TNF IL10 IFNGR1 IFNG
17
Show member pathways
12.17 TNF IL4 IFNGR1 IFNG
18 12.12 TNFRSF8 TNF RAG1 IL4 IL10 IFNG
19
Show member pathways
12.09 IL7R IL4 IL2RG
20
Show member pathways
12.08 RAG2 RAG1 IL7R IL10
21 12.04 TNF IL4 IL2RG IL10 IGHE
22 12 TNF IL7R IL5 IL4 IL10 IFNG
23
Show member pathways
11.95 TNF IL10 IFNGR1 IFNG
24 11.91 TNF IL7R IL5 IL4
25
Show member pathways
11.83 IL4 IL2RG IFNG
26 11.78 IL5 IL4 IFNG
27 11.78 TNF IL7R IL10 IFNG
28
Show member pathways
11.77 TNF IL5 IL4 IFNG FOXP3
29 11.75 TNF IL7R IL5 IL4 IL10 IFNG
30
Show member pathways
11.68 IL4 IL2RG FOXP3
31 11.67 IL5 IL4 IL2RG IL10 IGHE
32 11.65 TNF IL5 IL4
33
Show member pathways
11.63 TNF IL2RG IFNG
34
Show member pathways
11.55 TNF IFNGR1 IFNG
35 11.53 TNF IL10 IFNG
36 11.52 TNF IL4 IL10
37 11.39 IL5 IL4 IL2RG IFNG
38 11.38 TNF IL10 IFNG
39 11.36 TNF IL5 IL4 IFNG
40
Show member pathways
11.36 TNF IL2RG IL10 IFNG FOXP3
41 11.3 RAG2 RAG1 IL7R IL2RG
42 11.3 IL5 IL4 IL2RG IL10 IFNG FOXP3
43 11.23 IL5 IL4 IL10 IFNG
44 11.18 TNF IL5 IL4 IL10 IFNG
45 10.85 IL5 IL4 IL2RG
46 10.75 RAG2 RAG1 IL7R IL2RG DCLRE1C AIRE

GO Terms for Omenn Syndrome

Cellular components related to Omenn Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 external side of plasma membrane GO:0009897 9.35 TNF IL7R IL2RG IGHE ADA
2 nonhomologous end joining complex GO:0070419 9.16 LIG4 DCLRE1C
3 DNA recombinase complex GO:0097519 8.62 RAG2 RAG1

Biological processes related to Omenn Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 51)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 10.13 TNF IL5 IL4 IL10 FOXP3 AIRE
2 positive regulation of gene expression GO:0010628 10.05 TNF IL7R IL4 IFNGR1 IFNG FOXP3
3 defense response to bacterium GO:0042742 10.01 TNF RAG2 IL10 IGHE
4 negative regulation of inflammatory response GO:0050728 9.94 IL4 IL10 FOXP3 ADA
5 response to virus GO:0009615 9.88 TNF IFNGR1 IFNG FOXP3
6 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 9.87 TNF IL4 IFNG
7 DNA recombination GO:0006310 9.87 RAG2 RAG1 LIG4 DCLRE1C
8 humoral immune response GO:0006959 9.86 TNF IFNG AIRE
9 positive regulation of phagocytosis GO:0050766 9.83 TNF IL2RG IFNG
10 T cell differentiation GO:0030217 9.82 RAG2 IL7R CHD7
11 B cell proliferation GO:0042100 9.81 IL7R IL10 CARD11
12 negative regulation of interleukin-6 production GO:0032715 9.8 TNF IL10 FOXP3
13 cytokine-mediated signaling pathway GO:0019221 9.8 TNF IL5 IL4 IL2RG IL10 IGHE
14 T cell differentiation in thymus GO:0033077 9.78 RAG2 RAG1 LIG4
15 positive regulation of cytokine secretion GO:0050715 9.77 TNF IL10 IFNG
16 positive regulation of JAK-STAT cascade GO:0046427 9.77 TNF IL5 IL10
17 regulation of interferon-gamma-mediated signaling pathway GO:0060334 9.71 IFNGR1 IFNG
18 positive regulation of podosome assembly GO:0071803 9.71 TNF IL5
19 positive regulation of T cell differentiation GO:0045582 9.71 RAG1 IL4 ADA
20 T cell activation GO:0042110 9.71 IL4 FOXP3 CARD11 ADA
21 negative regulation of tumor necrosis factor biosynthetic process GO:0042536 9.7 IL4 IL10
22 positive regulation of T cell differentiation in thymus GO:0033089 9.7 IL7R ADA
23 negative regulation of T-helper 17 cell differentiation GO:2000320 9.7 IL4 FOXP3
24 positive regulation of amyloid-beta formation GO:1902004 9.7 TNF IFNGR1 IFNG
25 negative regulation of T cell apoptotic process GO:0070233 9.69 RAG1 IL7R
26 positive regulation of interleukin-1 beta biosynthetic process GO:0050725 9.69 TNF IFNG
27 endothelial cell apoptotic process GO:0072577 9.69 TNF IL10
28 astrocyte activation GO:0048143 9.69 TNF IFNGR1 IFNG
29 negative regulation of thymocyte apoptotic process GO:0070244 9.68 RAG1 ADA
30 positive regulation of mononuclear cell migration GO:0071677 9.68 TNF IL4
31 type 2 immune response GO:0042092 9.68 IL4 IL10
32 negative regulation of cytokine production involved in immune response GO:0002719 9.67 TNF IL10
33 positive regulation of cellular respiration GO:1901857 9.67 IL4 IFNG
34 neuroinflammatory response GO:0150076 9.67 IL4 IFNG
35 regulation of T cell differentiation GO:0045580 9.67 RAG1 CARD11 ADA
36 positive regulation of B cell proliferation GO:0030890 9.67 IL5 IL4 CARD11 ADA
37 negative regulation of cytokine secretion involved in immune response GO:0002740 9.66 TNF IL10
38 regulation of isotype switching GO:0045191 9.65 IL4 IL10
39 negative regulation of chronic inflammatory response GO:0002677 9.65 IL4 FOXP3
40 positive regulation of chemokine biosynthetic process GO:0045080 9.65 TNF IL4 IFNG
41 negative regulation of amyloid-beta clearance GO:1900222 9.63 TNF IFNGR1 IFNG
42 positive regulation of calcidiol 1-monooxygenase activity GO:0060559 9.62 TNF IFNG
43 receptor biosynthetic process GO:0032800 9.62 TNF IL10
44 microglial cell activation GO:0001774 9.62 TNF IL4 IFNGR1 IFNG
45 pre-B cell allelic exclusion GO:0002331 9.61 RAG2 RAG1
46 positive regulation of MHC class II biosynthetic process GO:0045348 9.61 IL4 IL10 IFNG
47 positive regulation of vitamin D biosynthetic process GO:0060557 9.56 TNF IFNG
48 positive regulation of nitrogen compound metabolic process GO:0051173 9.55 TNF IFNG
49 V(D)J recombination GO:0033151 9.46 RAG2 RAG1 LIG4 DCLRE1C
50 B cell differentiation GO:0030183 9.43 RAG2 RAG1 IL4 IL10 DCLRE1C CARD11

Molecular functions related to Omenn Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.21 TNFRSF8 TNF RAG2 RAG1 LIG4 IL7R
2 cytokine receptor activity GO:0004896 9.33 IL7R IL2RG IFNGR1
3 cytokine activity GO:0005125 9.02 TNF IL5 IL4 IL10 IFNG
4 interleukin-7 receptor activity GO:0004917 8.96 IL7R IL2RG

Sources for Omenn Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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