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MCID: CMB007
MIFTS: 57

Combined Immunodeficiency

Categories: Blood diseases, Immune diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Drugs
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Aliases & Classifications for Combined Immunodeficiency

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MalaCards integrated aliases for Combined Immunodeficiency:

Name: Combined Immunodeficiency 12 12 36 15
Combined T Cell and B Cell Immunodeficiency 12 15
Congenital Combined Immunodeficiency 12 6
Syndrome with Combined Immunodeficiency 58

Classifications:

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


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Disease Ontology 12 DOID:0111962 DOID:628
KEGG 36 H00093
ICD9CM 34 279.2
NCIt 50 C27871
SNOMED-CT 67 191003005
ICD10 32 D81 D81.9
Orphanet 58 ORPHA331217
UMLS 71 C0494261
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Summaries for Combined Immunodeficiency

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KEGG : 36 The term combined immunodeficiency (CID) is used to distinguish patients with low, but not absent, T-cell function from those with severe CID (SCID) characterized by profound deficiencies of T- and B-cell (and sometimes NK- cell) function. Hyper-IgM syndrome (HIM) represents a group of distinct entities characterized by defective normal or elevated IgM in the presence of diminished IgG and IgA levels. The genetic anomaly in X-linked hyper-IgM syndrome has been mapped to Xq26, and resides in mutations of the CD40 ligand gene. Missense mutation in exon 7 of the common gamma chain (IL2RG) causes a moderate form of X-linked CID. This point mutation in IL2RG leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID. Two related deficiencies of recombination activating genes, RAG1 and RAG2 result in a spectrum of SCID called RAG1/RAG2 deficiency and Omenn syndrome. Mutations that lead to total absence of RAG1 or RAG2 gene product (null mutations) are known to lead to SCID without mature lymphoid cells, whereas mutations that result in partial V(D)J recombinase activity due to missense mutation on at least one allele lead to Omenn syndrome. Mutations of both TAP1 and TAP2 genes result in deficient expression of class I HLA proteins on the cell surface with defects in natural killer cell cytotoxicity. Defective expression of major histocompatibility complex (MHC) class II molecules account for 5% of SCID. The genetic lesions responsible for this syndrome do not lie within the MHC-II locus itself, but reside instead in genes encoding transcription factors, RFX5, RFXAP, RFXANK(B), and CIITA, controlling MHC-II expression. ZAP-70 deficiency is inherited in an autosomal recessive manner. Recurrent and opportunistic infections occur within the first year of life. The mutations in genes responsible for CRAC channel function, ORAI1 and STIM1, cause the defect in Ca2+ influx.

MalaCards based summary : Combined Immunodeficiency, also known as combined t cell and b cell immunodeficiency, is related to severe combined immunodeficiency and severe combined immunodeficiency, x-linked. An important gene associated with Combined Immunodeficiency is ZAP70 (Zeta Chain Of T Cell Receptor Associated Protein Kinase 70), and among its related pathways/superpathways are Primary immunodeficiency and Innate Immune System. The drugs Adenosine and Immunoglobulin G have been mentioned in the context of this disorder. Affiliated tissues include bone marrow, t cells and skin, and related phenotypes are Reduced mammosphere formation and hematopoietic system

Disease Ontology : 12 A primary immunodeficiency disease that involves multiple components of the immune system.

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Related Diseases for Combined Immunodeficiency

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Diseases related to Combined Immunodeficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 580)
# Related Disease Score Top Affiliating Genes
1 severe combined immunodeficiency 34.0 ZAP70 RAG2 RAG1 RAC2 PTPRC NHEJ1
2 severe combined immunodeficiency, x-linked 33.9 JAK3 IL7R IL2RG ADA
3 severe combined immunodeficiency with sensitivity to ionizing radiation 33.8 RAG2 RAG1 NHEJ1 LIG4 DCLRE1C
4 severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-positive, nk cell-negative 33.8 RAG2 RAG1 JAK3 ADA
5 omenn syndrome 33.7 ZAP70 RAG2 RAG1 PTPRC NHEJ1 LIG4
6 adenosine deaminase deficiency 33.7 RAG2 RAG1 JAK3 IL2RG CD3D ADA
7 bare lymphocyte syndrome, type ii 33.6 ZAP70 RAG2 RAG1 NHEJ1 LIG4 JAK3
8 severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-positive, nk cell-positive 33.6 PTPRC IL7R CD3D
9 reticular dysgenesis 33.4 NHEJ1 JAK3 IL2RG DCLRE1C CD3D ADA
10 t-b- severe combined immunodeficiency 33.3 RAG2 JAK3 DCLRE1C
11 immunodeficiency 19 33.2 ZAP70 CD3D ADA
12 combined cellular and humoral immune defects with granulomas 33.1 RAG2 RAG1
13 immunodeficiency 18 33.1 RAG1 CD3D
14 immune deficiency disease 33.0 ZAP70 TFRC STAT1 RAG2 RAG1 RAC2
15 immunodeficiency 11 32.7 MALT1 CARMIL2
16 lig4 syndrome 32.6 RAG2 RAG1 NHEJ1 LIG4 DCLRE1C
17 purine nucleoside phosphorylase deficiency 32.5 ZAP70 RAG1 NHEJ1 DCLRE1C ADA
18 janus kinase-3 deficiency 32.4 LIG4 JAK3 IL2RG
19 recombinase activating gene 1 deficiency 32.3 RAG2 RAG1
20 cd45 deficiency 32.3 ZAP70 PTPRC
21 coronin-1a deficiency 32.2 DCLRE1C CD3D
22 nijmegen breakage syndrome 32.2 NHEJ1 LIG4 DCLRE1C
23 lymphopenia 32.1 RAG1 RAC2 JAK3 IL7R IL2RG ADA
24 common variable immunodeficiency 31.5 ZAP70 RAG2 RAG1 RAC2 JAK3 ADA
25 leukemia, acute lymphoblastic 31.4 ZAP70 RAG1 PTPRC JAK3 IL7R ADA
26 t cell deficiency 31.3 ZAP70 RAG2 RAG1 PTPRC IL7R IL2RG
27 t-cell acute lymphoblastic leukemia 31.1 STAT1 RAG1 PTPRC JAK3 IL7R BCL11B
28 t-cell lymphoblastic leukemia/lymphoma 31.0 ZAP70 RAG1 PTPRC ADA
29 chromosomal triplication 31.0 ZAP70 MALT1
30 leukemia, chronic lymphocytic 30.6 ZAP70 TFRC STAT1 PTPRC ADA
31 cd40 ligand deficiency 30.5 ZAP70 JAK3 IL2RG DCLRE1C
32 severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-negative, due to adenosine deaminase deficiency 11.7
33 severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 11.7
34 combined immunodeficiency, x-linked 11.7
35 short-limb skeletal dysplasia with severe combined immunodeficiency 11.6
36 t-cell immunodeficiency, congenital alopecia, and nail dystrophy 11.6
37 immunodeficiency 22 11.5
38 zap70-related severe combined immunodeficiency 11.5
39 immunodeficiency 55 11.5
40 combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia 11.5
41 jak3-deficient severe combined immunodeficiency 11.5
42 immunodeficiency 50 11.5
43 immunodeficiency 16 11.5
44 immunodeficiency 52 11.4
45 immunodeficiency 49 11.4
46 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 11.4
47 immunodeficiency 21 11.4
48 immunodeficiency 14 11.4
49 immunodeficiency 36 11.4
50 immunodeficiency 53 11.4

Graphical network of the top 20 diseases related to Combined Immunodeficiency:



Diseases related to Combined Immunodeficiency
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Symptoms & Phenotypes for Combined Immunodeficiency

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GenomeRNAi Phenotypes related to Combined Immunodeficiency according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 9.23 BCL11B CD3D DCLRE1C JAK3 PTPRC STAT1

MGI Mouse Phenotypes related to Combined Immunodeficiency:

46 (show all 13)
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.45 ADA ARPC1B BCL11B CARMIL2 CD3D DCLRE1C
2 immune system MP:0005387 10.41 ADA ARPC1B BCL11B CARMIL2 CD3D DCLRE1C
3 cellular MP:0005384 10.4 ADA BCL11B DCLRE1C IL2RG IL7R JAK3
4 endocrine/exocrine gland MP:0005379 10.34 ADA BCL11B CARMIL2 DCLRE1C IL2RG IL7R
5 homeostasis/metabolism MP:0005376 10.27 ADA ARPC1B BCL11B CARMIL2 IL2RG LIG4
6 digestive/alimentary MP:0005381 10.16 ADA IL2RG JAK3 LIG4 PTPRC RAG1
7 mortality/aging MP:0010768 10.13 ADA BCL11B IL2RG JAK3 LIG4 MALT1
8 integument MP:0010771 10.1 ARPC1B BCL11B CARMIL2 MALT1 PTPRC RAG1
9 liver/biliary system MP:0005370 9.97 ADA LIG4 PTPRC RAC2 RAG1 RAG2
10 neoplasm MP:0002006 9.91 BCL11B IL2RG IL7R LIG4 NHEJ1 PTPRC
11 normal MP:0002873 9.81 ADA IL2RG IL7R PTPRC RAG1 RAG2
12 respiratory system MP:0005388 9.5 ADA IL2RG PTPRC RAG1 RAG2 STAT1
13 skeleton MP:0005390 9.28 ADA ARPC1B BCL11B IL2RG PTPRC RAG1
Sources

Drugs & Therapeutics for Combined Immunodeficiency

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Drugs for Combined Immunodeficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 78)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational Phase 2, Phase 3 58-61-7 60961
2 Immunoglobulin G Phase 3
3 gamma-Globulins Phase 3
4 Immunoglobulins, Intravenous Phase 3
5 Rho(D) Immune Globulin Phase 3
6
Mycophenolic acid Approved Phase 2 24280-93-1 446541
7
Methotrexate Approved Phase 2 1959-05-2, 59-05-2 126941
8
Levoleucovorin Approved, Investigational Phase 2 68538-85-2 149436
9
Tacrolimus Approved, Investigational Phase 2 104987-11-3 445643 439492 6473866
10
Mechlorethamine Approved, Investigational Phase 2 51-75-2 4033
11
Busulfan Approved, Investigational Phase 2 55-98-1 2478
12
alemtuzumab Approved, Investigational Phase 2 216503-57-0
13
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
14
Thiotepa Approved, Investigational Phase 1, Phase 2 52-24-4 5453
15
Melphalan Approved Phase 2 148-82-3 4053 460612
16
Mecasermin Approved, Investigational Phase 1, Phase 2 68562-41-4
17
Lenograstim Approved, Investigational Phase 2 135968-09-1
18
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
19
Phenylalanine Approved, Investigational, Nutraceutical Phase 2 63-91-2 6140
20 Antitubercular Agents Phase 2
21 Dermatologic Agents Phase 2
22 Calcineurin Inhibitors Phase 2
23 Vitamin B Complex Phase 2
24 Folic Acid Antagonists Phase 2
25 Vitamin B9 Phase 2
26 Folate Phase 2
27 Immunosuppressive Agents Phase 2
28 Immunologic Factors Phase 2
29 Alkylating Agents Phase 2
30 Thymoglobulin Phase 1, Phase 2
31 Mitogens Phase 1, Phase 2
32 Cyclosporins Phase 2
33 Insulin, Globin Zinc Phase 1, Phase 2
34 Hormones Phase 1, Phase 2
35 insulin Phase 1, Phase 2
36 Anti-HIV Agents Phase 2
37 Antineoplastic Agents, Immunological Phase 2
38 Adjuvants, Immunologic Phase 2
39 Antiviral Agents Phase 2
40 Anti-Retroviral Agents Phase 2
41 Plerixafor octahydrochloride Phase 2
42 Antibodies, Monoclonal Phase 1, Phase 2
43
Zidovudine Approved Phase 1 30516-87-1 35370
44 Reverse Transcriptase Inhibitors Phase 1
45 Antibodies Phase 1
46 Immunoglobulins Phase 1
47
Cyclophosphamide Approved, Investigational 50-18-0, 6055-19-2 2907
48
Mesna Approved, Investigational 3375-50-6 598
49
Vidarabine Approved, Investigational 24356-66-9 32326 21704
50
tannic acid Approved 1401-55-4

Interventional clinical trials:

(show top 50) (show all 68)
# Name Status NCT ID Phase Drugs
1 Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Selected Non-Malignant Diseases Unknown status NCT01019876 Phase 2, Phase 3 Fludarabine;Cyclophosphamide;Cyclophosphamide 40;Cyclophosphamide 30
2 IGIV-C 10% Rapid Infusion Trial in Primary Immune Deficient Patients Completed NCT00220766 Phase 3 Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified;Dextrose, 5% in Water
3 A Study of EZN-2279 (Polyethylene Glycol Recombinant Adenosine Deaminase [PEG-rADA]) Administered as a Weekly Intramuscular Injection in Patients With Adenosine Deaminase (ADA)-Deficient Combined Immunodeficiency Completed NCT01420627 Phase 3
4 A Single Arm, Open Label Clinical Study to Enable Process Validation of Commercial Grade Ex Vivo Hematopoietic Stem Cell Gene Therapy (OTL-101) in Subjects With Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID) Suspended NCT04140539 Phase 2, Phase 3
5 Protocol No. 2 of Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Using a Self Retroviral Vector - SCID2 Unknown status NCT01410019 Phase 1, Phase 2
6 Treatment of ADA-SCID by Gene Therapy on Somatic Cells Completed NCT00599781 Phase 1, Phase 2
7 Efficacy and Safety of Cryopreserved Formulation of Autologous CD34+ Hematopoietic Stem Cells Transduced Ex Vivo With EFS Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency Due to ADA Deficiency Completed NCT02999984 Phase 1, Phase 2 busulfan;PEG-ADA ERT
8 MND-ADA Transduction of CD34+ Cells From the Bone Marrow Of Children With Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID): Effect of Discontinuation of PEG-ADA and Marrow Cytoreduction With Busulfan Completed NCT00794508 Phase 2
9 Phase I/II Trial of De-Escalation of Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency Completed NCT00228852 Phase 1, Phase 2 Busulfan, Fludarabine and ATG
10 Phase I/II, Historical Controlled, Open-label, Non-randomised, Single-centre Trial to Assess the Safety and Efficacy of EF1αS-ADA Lentiviral Vector Mediated Gene Modification of Autologous CD34+ Cells From ADA-deficient Individuals Completed NCT01380990 Phase 1, Phase 2 Busulfan;Peg-Ada
11 Phase I Gene Therapy Protocol for Adenosine Deaminase Deficiency Completed NCT01279720 Phase 1, Phase 2
12 Cord Blood Stem Cell Transplantation Study (COBLT) Completed NCT00000603 Phase 2
13 A Phase II Trial of Reduced Intensity Allogeneic Stem Cell Transplantation With Fludarabine, Melphalan and Low Dose Total Body Irradiation Completed NCT01529827 Phase 2 fludarabine phosphate;melphalan;tacrolimus;mycophenolate mofetil;methotrexate
14 Autologous Transplantation of Bone Marrow CD34+ Stem/Progenitor Cells After Addition of a Normal Human ADA cDNA by the EFS-ADA Lentiviral Vector for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID) Completed NCT01852071 Phase 1, Phase 2 busulfan;PEG-ADA ERT
15 Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency Recruiting NCT03315078 Phase 1, Phase 2 Palifermin;Busulfan
16 Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning Recruiting NCT03311503 Phase 1, Phase 2
17 Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency Recruiting NCT01306019 Phase 1, Phase 2 Palifermin;Busulfan
18 A Pilot Feasibility Study of Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants Using a Self-Inactivating Lentiviral Vector to Transduce Autologous CD34+ Hematopoietic Cells Recruiting NCT01512888 Phase 1, Phase 2 Busulfan
19 Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID) Recruiting NCT03597594 Phase 1, Phase 2 Anti-thymocyte globulin (rabbit);Busulfan;Fludarabine;Thiotepa
20 A Phase I/II Feasibility Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency (ART-SCID) Using a Self-Inactivating Lentiviral Vector (AProArt) to Transduce Autologous CD34 Hematopoietic Cells Recruiting NCT03538899 Phase 1, Phase 2 AProArt;Busulfan
21 Efficacy and Safety of a Cryopreserved Formulation of Autologous CD34+ Haematopoietic Stem Cells Transduced ex Vivo With Elongation Factor 1α Short Form (EFS) Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency (SCID) Due to Adenosine Deaminase Deficiency Recruiting NCT03765632 Phase 1, Phase 2 Busulfan;Peg-Ada
22 PEDS024, Phase I/II Feasibility Study of Busulfan Fludarabine and Thiotepa Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation (HSCT) for Children With Non-Malignant Disorders Recruiting NCT03513328 Phase 1, Phase 2 Thiotepa--single daily dose;Thiotepa--escalated dose
23 A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Immune Function Disorders Using a Reduced Intensity Preparatory Regime Recruiting NCT01821781 Phase 2 Transplant preparative regimen of alemtuzumab, fludarabine, thiotepa, and melphalan
24 Gene Transfer for X-linked Severe Combined Immunodeficiency (SCID-X1) Using a Self-inactivating Lentiviral Vector （TYF-IL-2Rg） Recruiting NCT03217617 Phase 1, Phase 2
25 A Phase I/II Study Evaluating the Safety and the Efficacy of Human T Lymphoid Progenitor (HTLP) Injection to Accelerate Immune Reconstitution After Partially HLA Compatible Allogeneic Hematopoietic Stem Cell Transplantation in SCID Patients Recruiting NCT03879876 Phase 1, Phase 2
26 A Randomized Trial of Low Versus Moderate Exposure Busulfan for Infants With Severe Combined Immunodeficiency (SCID) Receiving TCRαβ+/CD19+ Depleted Transplantation: A Phase II Study by the Primary Immune Deficiency Treatment Consortium (PIDTC) and Pediatric Blood and Marrow Transplant Consortium (PBMTC) Recruiting NCT03619551 Phase 2 Busulfan
27 Multi-institutional Phase I/II Trial Evaluating the Treatment of SCID-X1 Patients With Retrovirus-mediated Gene Transfer Active, not recruiting NCT01129544 Phase 1, Phase 2
28 Matched Related and Unrelated Donor Stem Cell Transplantation for Severe Combined Immune Deficiency (SCID): Busulfan-based Conditioning With h-ATG, Radiation, and Sirolimus Enrolling by invitation NCT04370795 Phase 1, Phase 2 Sirolimus;Busulfan;Horse -Anti-thymocyte;G-CSF
29 Bilateral Orthotopic Lung Transplant in Tandem With CD3+ and CD19+ Cell Depleted Bone Marrow Transplant From Partially HLA-Matched Cadaveric Donors Enrolling by invitation NCT01852370 Phase 1, Phase 2
30 Treatment for Growth Failure in Patients With X-Linked Severe Combined Immunodeficiency (XSCID): A Phase 2 Study Assessing Safety and Clinical Response to Treatment With Insulin-like Growth Factor-1 (IGF-1) Terminated NCT00490100 Phase 1, Phase 2 Increlex
31 Hematopoietic Stem Cell Transplantation for Children With Severe Combined Immunodeficiency Disease Utilizing Alemtuzumab and Mobilization With Plerixafor & Filgrastim Terminated NCT01182675 Phase 2 Transplant Conditioning with Mobilization Only;Transplant Conditioning with Mobilization and Alemtuzumab
32 Phase I/II Trial of Hematopoietic Stem Cell Transplant (HSCT) for Children With Severe Combined Immune Deficiency (SCID) and Without an HLA-Matched Sibling Donor Terminated NCT02127892 Phase 1, Phase 2
33 CD45 and Alemtuzumab Monoclonal Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Severe Combined Immunodeficiency Disease (SCID) And Other Primary Immunodeficiency Disorders Terminated NCT00579137 Phase 1, Phase 2 Fludarabine
34 Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID): Selective Depletion of Naive Cells From the Graft Terminated NCT02737384 Phase 2
35 Sirolimus in Prevention of aGVHD in Maternally Engrafted (TME) Severe Combined Immunodeficiency (SCID) Infants Receiving Unconditioned Hematopoietic Stem Cell Transplant (HSCT) Withdrawn NCT02177760 Phase 2 Sirolimus
36 Ex Vivo Retroviral Gene Transfer For Treatment of X-Linked Severe Combined Immunodeficiency (XSCID) Completed NCT00028236 Phase 1 Gene-Transduced Autologous CD34+ Stem Cells
37 Induction of Mixed Hematopoietic Chimerism in Patients With Severe Combined Immunodeficiency Disorders Using Allogeneic Bone Marrow and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil Completed NCT00008450 Phase 1 Cyclosporine;Mycophenolate Mofetil
38 Treatment of SCID Due to ADA Deficiency With Autologous Cord Blood or Bone Marrow CD34+ Cells Transduced With a Human ADA Gene Completed NCT00018018 Phase 1 CD34+ cells transduced with ADA retrovir
39 Transplantation of Highly Purified Haploidentical CD133 Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome Completed NCT00152100 Phase 1 Filgrastim, Alemtuzumab
40 Neurotrophic Effects of Immunophilin Ligands on Human Hair Follicles Grafted Onto Service Combined Immunodeficient (SCID) Mice Completed NCT00177099 Phase 1 FK506, GP11046, GP11511
41 Phase I/II Study of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Recruiting NCT03601286 Phase 1 Lentiviral vector transduced CD34+ cells
42 A Phase I Study To Evaluate The Safety And Tolerability of JSP191 For Hematopoietic Cell Transplantation Conditioning To Achieve Engraftment And Immune Reconstitution In Subjects With SCID Recruiting NCT02963064 Phase 1
43 Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency Not yet recruiting NCT02860559 Phase 1
44 Gene Therapy for SCID-X1 Using a Self-inactivating (SIN) Gammaretroviral Vector Unknown status NCT01175239
45 Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China Unknown status NCT02231983
46 Decisions of Female Adolescents About Carrier Testing in Families With X-Linked Severe Combined Immunodeficiency (XSCID) Completed NCT00006335
47 Treatment of Severe Combined Immunodeficiency Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency With Autologous Lymphocytes of CD34+ Cells Transduced With a Human ADA Gene: A Natural History Study Completed NCT00001255 ADA PBSC;ADA Umbilical Cord Blood Cells;Transduced Lymphocytes
48 Evaluation of the Clinical Utility and Cost Effectiveness Ratio of Generalized Neonatal Screening for Severe Combined Immunodeficiencies (SCID) by Quantification of TRECs on Guthrie Cards Completed NCT02244450
49 Newborn Screening for SCID in a High-Risk Population Completed NCT00845416
50 Gene Therapy for X Linked Severe Combined Immunodeficiency Recruiting NCT04286815

Search NIH Clinical Center for Combined Immunodeficiency

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Genetic Tests for Combined Immunodeficiency

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Anatomical Context for Combined Immunodeficiency

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MalaCards organs/tissues related to Combined Immunodeficiency:

40
Bone Marrow, T Cells, Skin, Bone, Breast, B Cells, Prostate
Sources

Publications for Combined Immunodeficiency

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Articles related to Combined Immunodeficiency:

(show top 50) (show all 5782)
# Title Authors PMID Year
1
SARS-CoV-2 infection associated with hepatitis in an infant with X-linked severe combined immunodeficiency. 61
33412294 2021
2
Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects. 61
33231617 2021
3
Severe SARS-CoV-2 disease in the context of a NF-κB2 loss-of-function pathogenic variant. 61
33007327 2021
4
Coronavirus disease 2019 in patients with inborn errors of immunity: An international study. 61
32980424 2021
5
SCID newborn screening: What we've learned. 61
33551023 2021
6
Lifelong Immune Modulation Versus Hematopoietic Cell Therapy for Inborn Errors of Immunity. 61
33551038 2021
7
Deuterium Oxide (D2O) Induces Early Stress Response Gene Expression and Impairs Growth and Metastasis of Experimental Malignant Melanoma. 61
33546433 2021
8
An appraisal of the Wilson & Jungner criteria in the context of genomic-based newborn screening for inborn errors of immunity. 61
33551024 2021
9
Effects of Phthalate Esters on Human Myometrial and Fibroid Cells: Cell Culture and NOD-SCID Mouse Data. 61
33037561 2021
10
Somatic reversion of pathogenic DOCK8 variants alters lymphocyte differentiation and function to effectively cure DOCK8 deficiency. 61
33290277 2021
11
Current Clinical Applications of In Vivo Gene Therapy with AAVs. 61
33309881 2021
12
Development of the nude rabbit model. 61
33606990 2021
13
Utility of 211At-trastuzumab for the Treatment of Metastatic Gastric Cancer in the Liver: Evaluation of a Preclinical α-Radioimmunotherapy Approach in a Clinically-relevant Mouse Model. 61
33547212 2021
14
Adenylate kinase 2 expression and addiction in T-ALL. 61
33560378 2021
15
Hematopoietic Stem Cell Transplantation Is a Curative Therapy for Transferrin Receptor 1 (TFRC) Deficiency. 61
33096268 2021
16
Overview of STING-Associated Vasculopathy with Onset in Infancy (SAVI) Among 21 Patients. 61
33217613 2021
17
Emapalumab treatment in an ADA-SCID patient with refractory hemophagocytic lymphohistiocytosis-related graft failure and disseminated bacillus Calmette-Guérin infection. 61
32817285 2021
18
Ultrafiltration and Injection of Islet Regenerative Stimuli Secreted by Pancreatic Mesenchymal Stromal Cells. 61
33403929 2021
19
Targeting human plasmacytoid dendritic cells through BDCA2 prevents skin inflammation and fibrosis in a novel xenotransplant mouse model of scleroderma. 61
33542104 2021
20
The regulation of DOCK family proteins on T and B cells. 61
32542827 2021
21
Down's syndrome and COVID-19: risk or protection factor against infection? A molecular and genetic approach. 61
33231770 2021
22
Immunoglobulin therapy for successful management of prolonged, recurrent jaundice in a young adult male with combined immunodeficiency. 61
33527335 2021
23
A gain-of-function RAC2 mutation is associated with bone-marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency. 61
31919089 2021
24
Combined immunodeficiency due to a mutation in the γ1 subunit of the coat protein I complex. 61
33529166 2021
25
Ten Years of Newborn Screening for Severe Combined Immunodeficiency (SCID) in Massachusetts. 61
33607339 2021
26
Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency. 61
33263173 2021
27
Functional Confirmation of DNA Repair Defect in Ataxia Telangiectasia (AT) Infants Identified by Newborn Screening for Severe Combined Immunodeficiency (NBS SCID). 61
32818697 2021
28
Trough Concentrations of Specific Antibodies in Primary Immunodeficiency Patients Receiving Intravenous Immunoglobulin Replacement Therapy. 61
33557365 2021
29
Epidermodysplasia Verruciformis After Hematopoietic Stem Cell Transplantation in a Patient With Severe Combined Immunodeficiency Syndrome. 61
33577180 2021
30
Two Novel Homozygous Mutations in Phosphoglucomutase 3 Leading to Severe Combined Immunodeficiency, Skeletal Dysplasia, and Malformations. 61
33534079 2021
31
A Novel RAC2 Variant Presenting as Severe Combined Immunodeficiency. 61
33188496 2021
32
Complete Absence of CD3γ Protein Expression Is Responsible for Combined Immunodeficiency with Autoimmunity Rather than SCID. 61
33215322 2021
33
Hematopoietic Cell Transplantation with Reduced Intensity Conditioning Using Fludarabine/Busulfan or Fludarabine/Melphalan for Primary Immunodeficiency Diseases. 61
33527309 2021
34
When Screening for Severe Combined Immunodeficiency (SCID) with T Cell Receptor Excision Circles Is Not SCID: a Case-Based Review. 61
33411155 2021
35
Combined immunodeficiency caused by a novel homozygous NFKB1 mutation. 61
32980423 2021
36
[Newborn screening for severe T and B lymphocyte deficiencies in Switzerland]. 61
33443835 2021
37
Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency. 61
32387109 2021
38
Functional inhibition or genetic deletion of acid sphingomyelinase bacteriostatically inhibits Anaplasma phagocytophilum infection in vivo. 61
33220685 2021
39
Neural crest-derived mesenchymal progenitor cells enhance cranial allograft integration. 61
33512772 2021
40
Novel genetic variants of inborn errors of immunity. 61
33481921 2021
41
Parents' Perspectives and Societal Acceptance of Implementation of Newborn Screening for SCID in the Netherlands. 61
33070266 2021
42
Bacillus Calmette-Guérin vaccine-related complications in children in Oman. 61
33550906 2021
43
Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers. 61
33006109 2021
44
Failure of Viral-Specific T Cells Administered in Pre-transplant Settings in Children with Inborn Errors of Immunity. 61
33462728 2021
45
In Vivo Gene Therapy for Canine SCID-X1 Using Cocal-Pseudotyped Lentiviral Vector. 61
32741228 2021
46
Diagnosis of Hyper IgM syndrome in a Previously Healthy Adolescent Boy Presented with Cutaneous and Cerebral Cryptococcosis. 61
33060515 2021
47
Chondrodysplasia and growth failure in children after early hematopoietic stem cell transplantation for non-oncologic disorders. 61
33398909 2021
48
Clinical and Immunological Features of 96 Moroccan Children with SCID Phenotype: Two Decades' Experience. 61
33411152 2021
49
Diagnosing Omenn syndrome. 61
33511666 2021
50
IKAROS-Associated Diseases in 2020: Genotypes, Phenotypes, and Outcomes in Primary Immune Deficiency/Inborn Errors of Immunity. 61
33392855 2021
Sources

Variations for Combined Immunodeficiency

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ClinVar genetic disease variations for Combined Immunodeficiency:

6 (show all 20)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MALT1 NM_006785.4(MALT1):c.1060del (p.Arg354fs) Deletion Pathogenic 242616 rs786200954 18:56390320-56390320 18:58723088-58723088
2 TFRC NM_001128148.3(TFRC):c.58T>C (p.Tyr20His) SNV Pathogenic 218163 rs863225436 3:195802210-195802210 3:196075339-196075339
3 ZAP70 NM_001079.3(ZAP70):c.1079G>C (p.Arg360Pro) SNV Pathogenic 222950 rs869025224 2:98351172-98351172 2:97734709-97734709
4 ZAP70 NM_001079.3(ZAP70):c.574C>T (p.Arg192Trp) SNV Pathogenic 222951 rs199840952 2:98349356-98349356 2:97732893-97732893
5 BCL11B NM_138576.4(BCL11B):c.1323T>G (p.Asn441Lys) SNV Pathogenic 254673 rs750610248 14:99641850-99641850 14:99175513-99175513
6 CARMIL2 NM_001013838.3(CARMIL2):c.1590C>A (p.Asn530Lys) SNV Pathogenic 562177 rs1567629968 16:67682876-67682876 16:67648973-67648973
7 STAT1 NM_007315.3(STAT1):c.1154C>T (p.Thr385Met) SNV Pathogenic 144006 rs587777630 2:191851647-191851647 2:190986921-190986921
8 ARPC1B NC_000007.14:g.99369754_99378887del Deletion Pathogenic 827686 7:98967377-98976510
9 ARPC1B NM_005720.4(ARPC1B):c.739_743del (p.Leu247fs) Deletion Pathogenic 827687 rs760191638 7:98988832-98988836 7:99391209-99391213
10 CD27-AS1 NM_001242.4(CD27):c.250dup (p.Cys84fs) Duplication Pathogenic 827694 rs1592117677 12:6554702-6554703 12:6445536-6445537
11 CD27-AS1 NM_001242.4(CD27):c.319C>T (p.Arg107Cys) SNV Pathogenic 827695 rs371761387 12:6559389-6559389 12:6450223-6450223
12 ZAP70 NM_001079.4(ZAP70):c.283C>T (p.Pro95Ser) SNV Pathogenic 827753 rs1573262398 2:98340782-98340782 2:97724319-97724319
13 MYH7 NM_000257.4(MYH7):c.2389G>A (p.Ala797Thr) SNV Likely pathogenic 42901 rs3218716 14:23894525-23894525 14:23425316-23425316
14 MYOC NM_000261.2(MYOC):c.1102C>T (p.Gln368Ter) SNV Likely pathogenic 7949 rs74315329 1:171605478-171605478 1:171636338-171636338
15 RAC2 NM_002872.5(RAC2):c.184G>A (p.Glu62Lys) SNV Likely pathogenic 464885 rs1555908409 22:37628882-37628882 22:37232842-37232842
16 PLAA NM_001031689.3(PLAA):c.1487-1G>A SNV Likely pathogenic 598964 rs1426488816 9:26913946-26913946 9:26913948-26913948
17 SCNN1A NM_001038.6(SCNN1A):c.1427G>A (p.Arg476Gln) SNV Uncertain significance 598965 rs72657556 12:6458505-6458505 12:6349339-6349339
18 CACNA1A NM_001127222.2(CACNA1A):c.6125C>T (p.Thr2042Met) SNV Uncertain significance 386521 rs563345694 19:13323262-13323262 19:13212448-13212448
19 COL6A2 NM_001849.3(COL6A2):c.2008A>G (p.Thr670Ala) SNV Uncertain significance 598977 rs753298014 21:47545737-47545737 21:46125823-46125823
20 ADAR NM_001111.5(ADAR):c.1646C>A (p.Ala549Asp) SNV Uncertain significance 598987 rs1557882064 1:154571017-154571017 1:154598541-154598541
Sources

Expression for Combined Immunodeficiency

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Search GEO for disease gene expression data for Combined Immunodeficiency.
Sources

Pathways for Combined Immunodeficiency

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Pathways related to Combined Immunodeficiency according to KEGG:

36
# Name Kegg Source Accession
1 Primary immunodeficiency hsa05340

Pathways related to Combined Immunodeficiency according to GeneCards Suite gene sharing:

(show all 25)
# Super pathways Score Top Affiliating Genes
1
Innate Immune System 65
Show member pathways
 13.89 ZAP70 STAT1 RAG2 RAG1 PTPRC MALT1
2
Akt Signaling 63
Show member pathways
 13.28 ZAP70 STAT1 RAC2 JAK3 IL7R IL2RG
3
TCR Signaling (Qiagen) 63
Show member pathways
 12.73 ZAP70 STAT1 RAC2 PTPRC MALT1 JAK3
4
Pathways in cancer 36
12.7 STAT1 RAC2 JAK3 IL7R IL2RG
5
Immune response NFAT in immune response 23
Show member pathways
 12.48 ZAP70 PTPRC MALT1 CD3D ARPC1B
6
T cell receptor signaling pathway 36
Show member pathways
 12.43 ZAP70 STAT1 PTPRC MALT1 CD3D
7
Th17 cell differentiation 36
Show member pathways
 12.41 ZAP70 STAT1 JAK3 IL2RG CD3D
8
B Cell Receptor Signaling Pathway (sino) 66
Show member pathways
 12.28 ZAP70 RAC2 PTPRC MALT1 CD3D
9
JAK-STAT signaling pathway 36
Show member pathways
 12.27 STAT1 JAK3 IL7R IL2RG
10
NF-kappaB Signaling 4
12.27 ZAP70 STAT1 RAG1 PTPRC MALT1 JAK3
11
TCR signaling (REACTOME) 65
Show member pathways
 12.19 ZAP70 PTPRC MALT1 CD3D
12
ICos-ICosL Pathway in T-Helper Cell 63
Show member pathways
 12.18 ZAP70 RAC2 PTPRC MALT1 IL2RG CD3D
13
Interleukin-4 and 13 signaling 65
11.86 STAT1 JAK3 IL2RG
14
IL12-mediated signaling events 1
Show member pathways
 11.85 STAT1 IL2RG CD3D
15
Translocation of ZAP-70 to Immunological synapse 65
Show member pathways
 11.82 ZAP70 PTPRC CD3D
16
Hematopoietic cell lineage 36
11.78 TFRC IL7R CD3D
17
TCR signaling in naive CD4+ T cells 1
Show member pathways
 11.77 ZAP70 PTPRC MALT1 CD3D
18
Fc gamma R-mediated phagocytosis 36
11.76 RAC2 PTPRC ARPC1B
19
Th17 Differentiation Pathway 64
Show member pathways
 11.72 STAT1 JAK3 IL2RG
20
CXCR4-mediated signaling events 1
11.6 STAT1 PTPRC CD3D
21
Commom Cytokine Receptor G Chain Siganaling Pathway 66
11.51 STAT1 PTPRC JAK3 IL7R IL2RG
22
Interferon type I signaling pathways 1
11.43 ZAP70 STAT1 PTPRC
23
IL-7 Signaling Pathway 1
Show member pathways
 11.31 STAT1 JAK3 IL7R IL2RG
24
Primary immunodeficiency 36
10.9 ZAP70 RAG2 RAG1 PTPRC JAK3 IL7R
25
Interleukin-7 signaling 65
10.8 RAG2 RAG1 JAK3 IL7R IL2RG
Sources

GO Terms for Combined Immunodeficiency

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Cellular components related to Combined Immunodeficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 clathrin-coated vesicle membrane GO:0030665 9.5 TFRC IL7R CD3D
2 external side of plasma membrane GO:0009897 9.43 TFRC PTPRC IL7R IL2RG CD3D ADA
3 DNA ligase IV complex GO:0032807 9.26 NHEJ1 LIG4
4 DNA recombinase complex GO:0097519 9.16 RAG2 RAG1
5 nonhomologous end joining complex GO:0070419 8.8 NHEJ1 LIG4 DCLRE1C

Biological processes related to Combined Immunodeficiency according to GeneCards Suite gene sharing:

(show all 33)
# Name GO ID Score Top Affiliating Genes
1 adaptive immune response GO:0002250 10.02 ZAP70 RAG1 JAK3 DCLRE1C CD3D
2 T cell receptor signaling pathway GO:0050852 9.88 ZAP70 PTPRC MALT1 CD3D
3 double-strand break repair via nonhomologous end joining GO:0006303 9.78 NHEJ1 LIG4 DCLRE1C
4 DNA recombination GO:0006310 9.78 RAG2 RAG1 LIG4 DCLRE1C
5 double-strand break repair GO:0006302 9.77 NHEJ1 LIG4 DCLRE1C
6 positive regulation of T cell proliferation GO:0042102 9.76 TFRC PTPRC JAK3
7 response to ionizing radiation GO:0010212 9.74 NHEJ1 LIG4 DCLRE1C
8 T cell activation GO:0042110 9.72 ZAP70 PTPRC ADA
9 positive regulation of B cell proliferation GO:0030890 9.7 TFRC PTPRC ADA
10 interleukin-7-mediated signaling pathway GO:0038111 9.67 JAK3 IL7R IL2RG
11 positive regulation of calcium-mediated signaling GO:0050850 9.66 ZAP70 ADA
12 regulation of T cell differentiation GO:0045580 9.65 RAG1 ADA
13 interleukin-15-mediated signaling pathway GO:0035723 9.65 JAK3 IL2RG
14 negative thymic T cell selection GO:0045060 9.65 ZAP70 PTPRC
15 interleukin-2-mediated signaling pathway GO:0038110 9.64 JAK3 IL2RG
16 positive regulation of alpha-beta T cell differentiation GO:0046638 9.64 ZAP70 ADA
17 regulation of JAK-STAT cascade GO:0046425 9.63 PTPRC JAK3
18 positive regulation of T cell differentiation in thymus GO:0033089 9.63 IL7R ADA
19 positive thymic T cell selection GO:0045059 9.63 ZAP70 PTPRC CD3D
20 negative regulation of T cell apoptotic process GO:0070233 9.62 RAG1 IL7R
21 T cell differentiation in thymus GO:0033077 9.62 RAG2 RAG1 LIG4 BCL11B
22 positive regulation of alpha-beta T cell proliferation GO:0046641 9.61 ZAP70 PTPRC
23 interleukin-9-mediated signaling pathway GO:0038113 9.61 STAT1 JAK3 IL2RG
24 negative regulation of T cell mediated cytotoxicity GO:0001915 9.6 PTPRC IL7R
25 negative regulation of thymocyte apoptotic process GO:0070244 9.58 RAG1 JAK3 ADA
26 T cell receptor V(D)J recombination GO:0033153 9.56 LIG4 BCL11B
27 positive regulation of T cell differentiation GO:0045582 9.56 ZAP70 RAG1 PTPRC ADA
28 interleukin-4-mediated signaling pathway GO:0035771 9.54 JAK3 IL2RG
29 interleukin-21-mediated signaling pathway GO:0038114 9.54 STAT1 JAK3 IL2RG
30 pre-B cell allelic exclusion GO:0002331 9.51 RAG2 RAG1
31 V(D)J recombination GO:0033151 9.46 RAG2 RAG1 LIG4 DCLRE1C
32 T cell differentiation GO:0030217 9.35 ZAP70 RAG2 PTPRC NHEJ1 IL7R
33 B cell differentiation GO:0030183 9.1 RAG2 RAG1 PTPRC NHEJ1 JAK3 DCLRE1C

Molecular functions related to Combined Immunodeficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.93 ZAP70 TFRC STAT1 RAG2 RAG1 RAC2
2 interleukin-7 receptor activity GO:0004917 8.62 IL7R IL2RG
Sources

Sources for Combined Immunodeficiency

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
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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