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OS
MCID: OMN001
MIFTS: 66

Omenn Syndrome (OS)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Omenn Syndrome

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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:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Blood diseases Immune diseases
See all MalaCards categories (disease lists)
ICD10: 32 33
Orphanet: 58  
Rare immunological diseases


Sources

Summaries for Omenn Syndrome

About this section
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 RAG1 (Recombination Activating 1), and among its related pathways/superpathways are Innate Immune System and Cytokine Signaling in Immune system. The drugs Hydroxyurea and Melphalan have been mentioned in the context of this disorder. Affiliated tissues include t cells, b cells and bone, and related phenotypes are failure to thrive and hepatomegaly

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.

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...

More information from OMIM: 603554
Sources

Related Diseases for Omenn Syndrome

About this section

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

(show top 50) (show all 744)
# Related Disease Score Top Affiliating Genes
1 combined t cell and b cell immunodeficiency 33.1 RAG2 RAG1 LIG4 IL7R IL4 IL2RG
2 hypereosinophilic syndrome 31.9 IL5 IL4 IL10 IGHE IFNG
3 alopecia 31.9 TNF IL4 IFNG AIRE
4 thyroiditis 31.8 TNF IL4 IL10 FOXP3
5 exanthem 31.7 TNF IL10 H2AC18
6 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 31.6 RAG1 IL10 IFNG FOXP3 AIRE
7 hashimoto thyroiditis 31.6 TNF IL5 IL4 IL10 IFNG FOXP3
8 severe combined immunodeficiency 31.5 RMRP RAG2 RAG1 LIG4 IL7R IL5
9 graft-versus-host disease 31.4 TNF IL10 IFNG
10 adenosine deaminase deficiency 31.4 RAG2 RAG1 IL2RG ADA
11 reticular dysgenesis 31.4 RAG1 IL2RG DCLRE1C ADA
12 osteomyelitis 31.3 TNF IL4 IL10 IFNG
13 thrombocytopenia 31.3 TNF IL4 IL10 IFNG FOXP3
14 acute graft versus host disease 31.2 TNF IL4 IL10 IFNG
15 polyendocrinopathy 31.2 FOXP3 AIRE
16 lymphopenia 31.2 RAG1 IL7R IL4 IL2RG IL10 IFNG
17 severe combined immunodeficiency, x-linked 31.2 IL7R IL4 IL2RG ADA
18 t-b- severe combined immunodeficiency 31.1 RAG2 DCLRE1C
19 peritonitis 31.1 TNF IL4 IL10 IFNG ADA
20 immune deficiency disease 31.1 TNF RAG2 RAG1 LIG4 IL7R IL4
21 stomatitis 31.1 TNF IL4 IL10 IFNG
22 t cell deficiency 31.0 RAG1 IL7R IL2RG DOCK8
23 myocarditis 31.0 TNF IL4 IL10 IFNG
24 bronchiolitis 31.0 TNF IL5 IL4 IL10 IFNG
25 candidiasis 31.0 TNF IL4 IL10 IFNG AIRE
26 ige responsiveness, atopic 30.9 IL5 IL4 IL10 IGHE IFNG
27 autoimmune disease 30.9 TNF IL7R IL5 IL4 IL10 IFNG
28 chronic graft versus host disease 30.9 IL10 IFNG
29 purpura 30.9 TNF IL4 IL10
30 gastroenteritis 30.9 TNF IL5 IL4 IL10 IFNG
31 diarrhea 30.8 TNF IL5 IL10 IFNG FOXP3
32 ileus 30.8 TNF IL10 IFNG
33 bacterial infectious disease 30.8 TNF IL10 IFNG H2AC18
34 neuritis 30.8 TNF IL4 IL10 IFNG
35 diphtheria 30.7 TNF IL5 IL4 IFNG
36 arthritis 30.7 TNF IL4 IL10 IFNG FOXP3
37 toxoplasmosis 30.7 TNF IL5 IL4 IL10 IFNG
38 silicosis 30.7 TNF IL4 IL10
39 dermatitis 30.7 TNF IL5 IL4 IL10 IGHE IFNG
40 allergic hypersensitivity disease 30.6 TNF IL5 IL4 IL10 IGHE IFNG
41 pulmonary disease, chronic obstructive 30.6 TNF IL5 IL4 IL10 H2AC18
42 uveitis 30.6 TNF IL4 IL10 IFNG
43 rhinitis 30.6 TNF IL5 IL4 IL10 IGHE IFNG
44 appendicitis 30.5 TNF IL10 IFNG
45 keratopathy 30.5 TNF IL4 AIRE
46 neuromyelitis optica 30.5 IL7R IL5 IL4
47 chagas disease 30.5 TNF IL4 IL10 IFNG
48 acute cystitis 30.5 TNF IL10 H2AC18
49 bacterial pneumonia 30.5 TNF IL10 H2AC18 ADA
50 severe acute respiratory syndrome 30.5 TNF IL10 IFNG

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



Diseases related to Omenn Syndrome
Sources

Symptoms & Phenotypes for Omenn Syndrome

About this section

Human phenotypes related to Omenn Syndrome:

58 31 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
2 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
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 edema 58 31 frequent (33%) Frequent (79-30%) HP:0000969
12 pruritus 58 31 frequent (33%) Frequent (79-30%) HP:0000989
13 dry skin 58 31 frequent (33%) Frequent (79-30%) HP:0000958
14 thickened skin 58 31 frequent (33%) Frequent (79-30%) HP:0001072
15 pneumonia 58 31 frequent (33%) Frequent (79-30%) HP:0002090
16 aplasia/hypoplasia of the eyebrow 58 31 frequent (33%) Frequent (79-30%) HP:0100840
17 eosinophilia 58 31 frequent (33%) Frequent (79-30%) HP:0001880
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 leukocytosis 58 Frequent (79-30%)
31 diarrhea 31 HP:0002014
32 recurrent bacterial infections 31 HP:0002718
33 recurrent viral infections 31 HP:0004429
34 recurrent fungal infections 31 HP:0002841
35 hypoproteinemia 31 HP:0003075
36 abnormality of lymphocytes 58 Very frequent (99-80%)
37 severe b lymphocytopenia 31 HP:0005365

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive

Abdomen Liver:
hepatomegaly

Hematology:
anemia
thrombocytopenia
eosinophilia

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 Spleen:
splenomegaly

Skin Nails Hair Hair:
alopecia

Abdomen Gastrointestinal:
diarrhea

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
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 14)
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.39 ADA AIRE CARD11 CHD7 DCLRE1C DOCK8
2 cellular MP:0005384 10.38 ADA CHD7 DCLRE1C DOCK8 FOXP3 IFNG
3 endocrine/exocrine gland MP:0005379 10.34 ADA AIRE CHD7 DCLRE1C FOXP3 IFNG
4 immune system MP:0005387 10.33 ADA AIRE CARD11 CHD7 DCLRE1C DOCK8
5 digestive/alimentary MP:0005381 10.32 ADA AIRE CHD7 FOXP3 IFNG IL10
6 growth/size/body region MP:0005378 10.29 ADA AIRE CHD7 DCLRE1C FOXP3 IFNG
7 homeostasis/metabolism MP:0005376 10.28 ADA AIRE CARD11 CHD7 FOXP3 IFNG
8 craniofacial MP:0005382 10.13 CHD7 FOXP3 IFNG IL10 IL2RG IL4
9 liver/biliary system MP:0005370 10.11 ADA AIRE FOXP3 IFNG IL10 IL4
10 neoplasm MP:0002006 10.02 AIRE IFNG IL10 IL2RG IL5 IL7R
11 normal MP:0002873 9.85 ADA AIRE FOXP3 IFNG IL10 IL2RG
12 no phenotypic analysis MP:0003012 9.8 AIRE FOXP3 IFNG IL10 IL2RG IL4
13 reproductive system MP:0005389 9.73 ADA AIRE CHD7 FOXP3 IFNG IL10
14 respiratory system MP:0005388 9.44 ADA AIRE CARD11 CHD7 FOXP3 IFNG
Sources

Drugs & Therapeutics for Omenn Syndrome

About this section

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

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Hydroxyurea Approved Phase 2 127-07-1 3657
2
Melphalan Approved Phase 2 148-82-3 4053 460612
3
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
4
alemtuzumab Approved, Investigational Phase 2 216503-57-0
5
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
6 Immunologic Factors Phase 2
7 Alkylating Agents Phase 2
8 Antineoplastic Agents, Immunological Phase 2
9 Antimetabolites Phase 2
10 Immunosuppressive Agents Phase 2
11
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 ≤40 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

Sources

Genetic Tests for Omenn Syndrome

About this section

Genetic tests related to Omenn Syndrome:

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

Anatomical Context for Omenn Syndrome

About this section

MalaCards organs/tissues related to Omenn Syndrome:

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

Publications for Omenn Syndrome

About this section

Articles related to Omenn Syndrome:

(show top 50) (show all 398)
# Title Authors PMID Year
1
Omenn syndrome due to ARTEMIS mutations. 54 61 56 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. 54 61 56 6
11313270 2001
3
Partial V(D)J recombination activity leads to Omenn syndrome. 54 61 56 6
9630231 1998
4
Biochemical and folding defects in a RAG1 variant associated with Omenn syndrome. 54 61 6
18056378 2007
5
A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection. 54 61 6
16276422 2005
6
AIRE deficiency in thymus of 2 patients with Omenn syndrome. 54 61 56
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. 61 6
17572155 2007
8
A hypomorphic R229Q Rag2 mouse mutant recapitulates human Omenn syndrome. 61 56
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. 61 6
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. 61 6
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. 54 61
20234091 2010
31
The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events. 54 61
19953608 2010
32
Omenn syndrome due to mutation of the RAG2 gene. 54 61
19470080 2009
33
Molecular analysis of T-B-NK+ severe combined immunodeficiency and Omenn syndrome cases in Saudi Arabia. 54 61
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. 54 61
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. 54 61
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. 54 61
16276411 2005
44
Omenn's syndrome occurring in patients without mutations in recombination activating genes. 54 61
15964782 2005
45
Cardiac thrombus in Omenn syndrome. 54 61
16088419 2005
46
Evolution of a T-B- SCID into an Omenn syndrome phenotype following parainfluenza 3 virus infection. 54 61
15870023 2005
47
Omenn syndrome in the context of other B cell-negative severe combined immunodeficiencies. 54 61
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
Sources

Variations for Omenn Syndrome

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ClinVar genetic disease variations for Omenn Syndrome:

6 (show top 50) (show all 198) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DCLRE1C NM_001033855.3(DCLRE1C):c.241C>T (p.Arg81Ter)SNV Pathogenic 4665 rs121908156 10:14987109-14987109 10:14945110-14945110
2 DCLRE1C NM_001033855.3(DCLRE1C):c.2T>C (p.Met1Thr)SNV Pathogenic 4677 rs121908158 10:14996008-14996008 10:14954009-14954009
3 RAG1 NM_000448.2(RAG1):c.1682G>A (p.Arg561His)SNV Pathogenic 13143 rs104894284 11:36596536-36596536 11:36574986-36574986
4 RAG1 NM_000448.2(RAG1):c.1186C>T (p.Arg396Cys)SNV Pathogenic 13144 rs104894289 11:36596040-36596040 11:36574490-36574490
5 RAG1 NM_000448.2(RAG1):c.2735A>G (p.Tyr912Cys)SNV Pathogenic 13145 rs104894290 11:36597589-36597589 11:36576039-36576039
6 RAG1 NM_000448.2(RAG1):c.1187G>A (p.Arg396His)SNV Pathogenic 13146 rs104894291 11:36596041-36596041 11:36574491-36574491
7 RAG1 NM_000448.2(RAG1):c.1286A>G (p.Asp429Gly)SNV Pathogenic 13147 rs104894292 11:36596140-36596140 11:36574590-36574590
8 RAG1 NM_000448.2(RAG1):c.1681C>T (p.Arg561Cys)SNV Pathogenic 13148 rs104894285 11:36596535-36596535 11:36574985-36574985
9 RAG1 NM_000448.2(RAG1):c.2210G>A (p.Arg737His)SNV Pathogenic 13149 rs104894286 11:36597064-36597064 11:36575514-36575514
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.424C>T (p.Arg142Ter)SNV Pathogenic 626157 rs773929270 11:36595278-36595278 11:36573728-36573728
16 RAG1 NM_000448.2(RAG1):c.2348C>G (p.Ser783Ter)SNV Pathogenic/Likely pathogenic 573434 rs754502950 11:36597202-36597202 11:36575652-36575652
17 RAG1 NM_000448.2(RAG1):c.1303A>G (p.Met435Val)SNV Pathogenic/Likely pathogenic 68680 rs141524540 11:36596157-36596157 11:36574607-36574607
18 RAG2 NM_000536.4(RAG2):c.115A>G (p.Arg39Gly)SNV Likely pathogenic 13136 rs121917897 11:36615604-36615604 11:36594054-36594054
19 RAG1 NM_000448.2(RAG1):c.2904C>A (p.Asn968Lys)SNV Likely pathogenic 36713 rs193922463 11:36597758-36597758 11:36576208-36576208
20 DCLRE1C NM_001033855.3(DCLRE1C):c.103C>G (p.His35Asp)SNV Likely pathogenic 4674 rs121908159 10:14995907-14995907 10:14953908-14953908
21 RAG2 NM_000536.4(RAG2):c.123C>G (p.Cys41Trp)SNV Likely pathogenic 13131 rs121917895 11:36615596-36615596 11:36594046-36594046
22 RAG2 NM_000536.4(RAG2):c.854T>G (p.Met285Arg)SNV Likely pathogenic 13132 rs121917896 11:36614865-36614865 11:36593315-36593315
23 RAG2 NM_000536.4(RAG2):c.283G>A (p.Gly95Arg)SNV Likely pathogenic 13133 rs36001797 11:36615436-36615436 11:36593886-36593886
24 RAG2 NM_000536.4(RAG2):c.104G>T (p.Gly35Val)SNV Likely pathogenic 496618 rs148508754 11:36615615-36615615 11:36594065-36594065
25 IL7R NM_002185.5(IL7R):c.265C>T (p.Gln89Ter)SNV Likely pathogenic 804345 5:35867451-35867451 5:35867349-35867349
26 RAG2 NM_000536.4(RAG2):c.1375A>C (p.Met459Leu)SNV Likely pathogenic 496632 rs1204766339 11:36614344-36614344 11:36592794-36592794
27 RAG2 NM_000536.4(RAG2):c.1366G>A (p.Ala456Thr)SNV Likely pathogenic 496631 rs1564995611 11:36614353-36614353 11:36592803-36592803
28 RAG2 NM_000536.4(RAG2):c.1357T>A (p.Trp453Arg)SNV Likely pathogenic 496630 rs1564995627 11:36614362-36614362 11:36592812-36592812
29 RAG2 NM_000536.4(RAG2):c.1329G>T (p.Met443Ile)SNV Likely pathogenic 496627 rs773710101 11:36614390-36614390 11:36592840-36592840
30 RAG2 NM_000536.4(RAG2):c.1320A>C (p.Lys440Asn)SNV Likely pathogenic 496626 rs754413772 11:36614399-36614399 11:36592849-36592849
31 RAG2 NM_000536.4(RAG2):c.470G>T (p.Gly157Val)SNV Likely pathogenic 496622 rs1564997121 11:36615249-36615249 11:36593699-36593699
32 RAG2 NM_000536.4(RAG2):c.479C>T (p.Ser160Leu)SNV Conflicting interpretations of pathogenicity 418443 rs756694972 11:36615240-36615240 11:36593690-36593690
33 RAG2 NM_000536.4(RAG2):c.1504A>G (p.Met502Val)SNV Conflicting interpretations of pathogenicity 440231 rs145614809 11:36614215-36614215 11:36592665-36592665
34 DCLRE1C NM_001033855.3(DCLRE1C):c.1903dup (p.Ser635fs)duplication Conflicting interpretations of pathogenicity 468484 rs760288938 10:14950582-14950583 10:14908583-14908584
35 RAG2 NM_000536.4(RAG2):c.*52T>ASNV Conflicting interpretations of pathogenicity 304549 rs546979744 11:36614083-36614083 11:36592533-36592533
36 RAG2 NM_000536.4(RAG2):c.63G>A (p.Leu21=)SNV Conflicting interpretations of pathogenicity 304559 rs142797325 11:36615656-36615656 11:36594106-36594106
37 DCLRE1C NM_001033855.3(DCLRE1C):c.350C>T (p.Pro117Leu)SNV Conflicting interpretations of pathogenicity 522770 rs757316102 10:14978549-14978549 10:14936550-14936550
38 RAG2 NM_000536.4(RAG2):c.218G>A (p.Arg73His)SNV Conflicting interpretations of pathogenicity 496620 rs762407838 11:36615501-36615501 11:36593951-36593951
39 RAG2 NM_000536.4(RAG2):c.644C>T (p.Thr215Ile)SNV Conflicting interpretations of pathogenicity 13135 rs35691292 11:36615075-36615075 11:36593525-36593525
40 DCLRE1C NM_001033855.3(DCLRE1C):c.2001A>G (p.Leu667=)SNV Conflicting interpretations of pathogenicity 194347 rs61749163 10:14950485-14950485 10:14908486-14908486
41 RAG2 NM_000536.4(RAG2):c.1247G>T (p.Trp416Leu)SNV Conflicting interpretations of pathogenicity 36717 rs193922572 11:36614472-36614472 11:36592922-36592922
42 RAG2 NM_000536.4(RAG2):c.22G>A (p.Val8Ile)SNV Conflicting interpretations of pathogenicity 138885 rs150762709 11:36615697-36615697 11:36594147-36594147
43 DCLRE1C NM_001033855.3(DCLRE1C):c.1101A>G (p.Pro367=)SNV Conflicting interpretations of pathogenicity 286957 rs143782439 10:14961792-14961792 10:14919793-14919793
44 DCLRE1C NM_001033855.3(DCLRE1C):c.1491T>C (p.Asp497=)SNV Conflicting interpretations of pathogenicity 299314 rs114767681 10:14950995-14950995 10:14908996-14908996
45 RAG1 NM_000448.2(RAG1):c.577G>A (p.Glu193Lys)SNV Conflicting interpretations of pathogenicity 304495 rs34841221 11:36595431-36595431 11:36573881-36573881
46 DCLRE1C NM_001033855.3(DCLRE1C):c.915G>A (p.Val305=)SNV Conflicting interpretations of pathogenicity 299317 rs774772480 10:14970017-14970017 10:14928018-14928018
47 DCLRE1C NM_001033855.3(DCLRE1C):c.1545A>G (p.Gly515=)SNV Conflicting interpretations of pathogenicity 299313 rs41300672 10:14950941-14950941 10:14908942-14908942
48 DCLRE1C NM_001033855.3(DCLRE1C):c.1368C>T (p.Asn456=)SNV Conflicting interpretations of pathogenicity 299315 rs144654282 10:14951118-14951118 10:14909119-14909119
49 RAG1 NM_000448.2(RAG1):c.2751G>A (p.Gln917=)SNV Conflicting interpretations of pathogenicity 304506 rs150721661 11:36597605-36597605 11:36576055-36576055
50 DCLRE1C NM_001033855.3(DCLRE1C):c.169G>T (p.Val57Phe)SNV Conflicting interpretations of pathogenicity 299322 rs138077101 10:14987181-14987181 10:14945182-14945182

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

Sources

Expression for Omenn Syndrome

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Search GEO for disease gene expression data for Omenn Syndrome.
Sources

Pathways for Omenn Syndrome

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

(show all 36)
# Super pathways Score Top Affiliating Genes
1
Innate Immune System 65
Show member pathways
 14 TNF RAG2 RAG1 IL7R IL5 IL4
2
Cytokine Signaling in Immune system 65
Show member pathways
 13.35 TNF RAG2 RAG1 IL7R IL5 IL4
3
Allograft rejection 1 36
Show member pathways
 12.82 TNF IL5 IL4 IL10 IFNG FOXP3
4
Pathways in cancer 36
12.79 IL7R IL5 IL4 IL2RG IFNG
5
Immune response NFAT in immune response 22
Show member pathways
 12.63 TNF IL4 IL10 IGHE IFNG CARD11
6
T cell receptor signaling pathway 36
Show member pathways
 12.59 TNF IL5 IL4 IL10 IFNG CARD11
7
Th17 cell differentiation 36
Show member pathways
 12.58 TNF IL5 IL4 IL2RG IL10 IFNG
8
NF-kappaB Signaling 4
12.44 TNF RAG1 IL4 IL10 IFNG FOXP3
9
IL-17 Family Signaling Pathways 64
Show member pathways
 12.29 TNF IL5 IL4 IFNG
10
JAK-STAT signaling pathway (KEGG) 36
Show member pathways
 12.28 IL7R IL5 IL4 IL2RG IL10 IFNG
11
Immune response IFN alpha/beta signaling pathway 22
Show member pathways
 12.24 TNF IL5 IL4 IL10 IFNG
12
Toxoplasmosis 36
Show member pathways
 12.22 TNF IL4 IL10 IFNG
13
FoxO signaling pathway 36
Show member pathways
 12.06 RAG2 RAG1 IL7R IL10
14
Th1 Differentiation Pathway 64
Show member pathways
 12.03 TNF IL2RG IL10 IFNG
15
Interleukin-4 and 13 signaling 65
12.01 TNF IL4 IL2RG IL10 IGHE
16
Hematopoietic Stem Cell Differentiation Pathways and Lineage-specific Markers 64
11.91 TNF IL7R IL5 IL4 IL10 IFNG
17
Hematopoietic cell lineage 36
11.9 TNF IL7R IL5 IL4
18
Glucocorticoid receptor regulatory network 1
11.75 IL5 IL4 IFNG
19
Dendritic Cells Developmental Lineage Pathway 64
11.75 TNF IL7R IL10 IFNG
20
Calcineurin-regulated NFAT-dependent transcription in lymphocytes 1
Show member pathways
 11.74 TNF IL5 IL4 IFNG FOXP3
21
Microglia Activation During Neuroinflammation: Microglia Polarization 64
11.73 TNF IL4 IL10 IFNG
22
IL2 signaling events mediated by PI3K 1
Show member pathways
 11.66 IL4 IL2RG FOXP3
23
Innate Lymphoid Cell Differentiation Pathways 64
11.64 TNF IL7R IL5 IL4 IL10 IFNG
24
Lung fibrosis 1
11.63 TNF IL5 IL4
25
Downstream signaling in naive CD8+ T cells 1
Show member pathways
 11.61 TNF IL2RG IFNG
26
IL4-mediated signaling events 1
11.6 IL5 IL4 IL2RG IL10 IGHE
27
Malaria 36
11.51 TNF IL10 IFNG
28
Interleukin-10 signaling 65
11.5 TNF IL4 IL10
29
Inflammatory Response Pathway 1
11.37 IL5 IL4 IL2RG IFNG
30
African trypanosomiasis 36
11.36 TNF IL10 IFNG
31
Development and heterogeneity of the ILC family 1
11.33 TNF IL5 IL4 IFNG
32
Interleukin-7 signaling 65
11.26 RAG2 RAG1 IL7R IL2RG
33
OX40 Pathway 63
11.19 IL5 IL4 IL10 IFNG
34
Th2 Differentiation Pathway 64
11.1 IL5 IL4 IL2RG IL10 IFNG FOXP3
35
Cytokines and Inflammatory Response 1
11.02 TNF IL5 IL4 IL10 IFNG
36
Primary immunodeficiency 36
10.75 RAG2 RAG1 IL7R IL2RG DCLRE1C AIRE
Sources

GO Terms for Omenn Syndrome

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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 all 39)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 10.09 TNF IL5 IL4 IL10 FOXP3 AIRE
2 positive regulation of gene expression GO:0010628 10.05 TNF IL7R IL4 IFNG FOXP3
3 defense response to bacterium GO:0042742 9.98 TNF RAG2 IL10 IGHE
4 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 9.83 TNF IL4 IFNG
5 DNA recombination GO:0006310 9.83 RAG2 RAG1 LIG4 DCLRE1C
6 humoral immune response GO:0006959 9.82 TNF IFNG AIRE
7 positive regulation of phagocytosis GO:0050766 9.8 TNF IL2RG IFNG
8 cytokine-mediated signaling pathway GO:0019221 9.8 TNF IL7R IL5 IL4 IL2RG IL10
9 T cell differentiation GO:0030217 9.77 RAG2 IL7R CHD7
10 negative regulation of interleukin-6 production GO:0032715 9.77 TNF IL10 FOXP3
11 B cell proliferation GO:0042100 9.76 IL7R IL10 CARD11
12 T cell differentiation in thymus GO:0033077 9.72 RAG2 RAG1 LIG4
13 positive regulation of JAK-STAT cascade GO:0046427 9.71 TNF IL5 IL10
14 T cell activation GO:0042110 9.71 IL4 FOXP3 CARD11 ADA
15 positive regulation of podosome assembly GO:0071803 9.68 TNF IL5
16 positive regulation of chemokine biosynthetic process GO:0045080 9.67 TNF IFNG
17 negative regulation of amyloid-beta clearance GO:1900222 9.67 TNF IFNG
18 negative regulation of tumor necrosis factor biosynthetic process GO:0042536 9.67 IL4 IL10
19 positive regulation of T cell differentiation in thymus GO:0033089 9.66 IL7R ADA
20 endothelial cell apoptotic process GO:0072577 9.65 TNF IL10
21 negative regulation of thymocyte apoptotic process GO:0070244 9.65 RAG1 ADA
22 positive regulation of T cell differentiation GO:0045582 9.65 RAG1 IL4 ADA
23 negative regulation of cytokine secretion involved in immune response GO:0002740 9.64 TNF IL10
24 neuroinflammatory response GO:0150076 9.63 IL4 IFNG
25 type 2 immune response GO:0042092 9.63 IL4 IL10
26 regulation of T cell differentiation GO:0045580 9.63 RAG1 CARD11 ADA
27 positive regulation of B cell proliferation GO:0030890 9.62 IL5 IL4 CARD11 ADA
28 positive regulation of cellular respiration GO:1901857 9.61 IL4 IFNG
29 regulation of isotype switching GO:0045191 9.61 IL4 IL10
30 positive regulation of MHC class II biosynthetic process GO:0045348 9.61 IL4 IL10 IFNG
31 positive regulation of calcidiol 1-monooxygenase activity GO:0060559 9.58 TNF IFNG
32 receptor biosynthetic process GO:0032800 9.57 TNF IL10
33 pre-B cell allelic exclusion GO:0002331 9.56 RAG2 RAG1
34 negative regulation of T cell apoptotic process GO:0070233 9.54 RAG1 IL7R DOCK8
35 positive regulation of vitamin D biosynthetic process GO:0060557 9.51 TNF IFNG
36 positive regulation of nitrogen compound metabolic process GO:0051173 9.49 TNF IFNG
37 V(D)J recombination GO:0033151 9.46 RAG2 RAG1 LIG4 DCLRE1C
38 B cell differentiation GO:0030183 9.43 RAG2 RAG1 IL4 IL10 DCLRE1C CARD11
39 immune response GO:0006955 9.32 TNF RAG1 IL7R IL5 IL4 IL2RG

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

# Name GO ID Score Top Affiliating Genes
1 cytokine activity GO:0005125 9.02 TNF IL5 IL4 IL10 IFNG
2 interleukin-7 receptor activity GO:0004917 8.96 IL7R IL2RG
Sources

Sources for Omenn Syndrome

About this section
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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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