Combined Immunodeficiency

Categories: Blood diseases, Immune diseases, Rare diseases

Aliases & Classifications for Combined Immunodeficiency

MalaCards integrated aliases for Combined Immunodeficiency:

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


Orphanet: 58  
Rare immunological diseases

External Ids:

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 70 C0494261

Summaries for Combined Immunodeficiency

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.

Related Diseases for Combined Immunodeficiency

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

(show top 50) (show all 582)
# Related Disease Score Top Affiliating Genes
1 severe combined immunodeficiency 34.1 ZAP70 RAG2 RAG1 RAC2 NHEJ1 LIG4
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 NHEJ1 LIG4 JAK3
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 reticular dysgenesis 33.5 RAG1 NHEJ1 JAK3 IL2RG DCLRE1C ADA
9 severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-positive, nk cell-positive 33.4 IL7R CD3D
10 combined cellular and humoral immune defects with granulomas 33.3 RAG2 RAG1
11 t-b- severe combined immunodeficiency 33.3 RAG2 JAK3 DCLRE1C
12 immunodeficiency 19 33.2 ZAP70 CD3D ADA
13 immunodeficiency 18 33.1 RAG1 CD3D
14 immune deficiency disease 33.0 ZAP70 TFRC STAT1 RAG2 RAG1 RAC2
15 immunodeficiency 14 32.8 DCLRE1C CARMIL2
16 immunodeficiency 11 32.8 MALT1 CARMIL2
17 immunodeficiency 17 32.7 ZAP70 CD3D
18 lig4 syndrome 32.6 RAG2 RAG1 NHEJ1 LIG4 DCLRE1C
19 purine nucleoside phosphorylase deficiency 32.5 ZAP70 RAG1 NHEJ1 DCLRE1C ADA
20 janus kinase-3 deficiency 32.4 LIG4 JAK3 IL2RG
21 recombinase activating gene 1 deficiency 32.3 RAG2 RAG1
22 nijmegen breakage syndrome 32.3 NHEJ1 LIG4 DCLRE1C
23 coronin-1a deficiency 32.3 DCLRE1C CD3D
24 lymphopenia 32.2 RAG1 RAC2 JAK3 IL7R IL2RG ADA
25 immunodeficiency 41 with lymphoproliferation and autoimmunity 31.9 IL7R IL2RG
26 combined t and b cell immunodeficiency 31.7 ZAP70 TFRC STAT1 RAC2 MALT1 CD27-AS1
27 common variable immunodeficiency 31.5 ZAP70 RAG2 RAG1 RAC2 JAK3 CD27
28 t cell deficiency 31.4 ZAP70 RAG2 RAG1 IL7R IL2RG CD27
29 leukemia, acute lymphoblastic 31.3 ZAP70 RAG1 JAK3 IL7R ADA
30 digeorge syndrome 31.3 RAG1 IL2RG DCLRE1C CD27
31 chickenpox 31.2 STAT1 CD27 ADA
32 t-cell acute lymphoblastic leukemia 31.0 STAT1 RAG1 JAK3 IL7R BCL11B
33 chromosomal triplication 31.0 ZAP70 MALT1
34 immunodeficiency with hyper-igm, type 1 31.0 RAG2 RAG1 CD27
35 leukemia, chronic lymphocytic 30.6 ZAP70 TFRC STAT1 CD27 ADA
36 cd40 ligand deficiency 30.6 ZAP70 JAK3 IL2RG DCLRE1C CD27
37 immunodeficiency 31b 30.6 STAT1 RAG1
38 sarcoidosis 1 30.3 STAT1 CD27 ADA
39 severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-negative, due to adenosine deaminase deficiency 11.7
40 severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 11.7
41 combined immunodeficiency, x-linked 11.7
42 short-limb skeletal dysplasia with severe combined immunodeficiency 11.6
43 t-cell immunodeficiency, congenital alopecia, and nail dystrophy 11.6
44 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 11.5
45 immunodeficiency 22 11.5
46 zap70-related severe combined immunodeficiency 11.5
47 immunodeficiency 55 11.5
48 combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia 11.5
49 jak3-deficient severe combined immunodeficiency 11.5
50 immunodeficiency 50 11.5

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

Diseases related to Combined Immunodeficiency

Symptoms & Phenotypes for Combined Immunodeficiency

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

# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 9.23 BCL11B CD27 CD3D DCLRE1C JAK3 STAT1

MGI Mouse Phenotypes related to Combined Immunodeficiency:

# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.35 ADA ARPC1B BCL11B CARMIL2 CD27 CD3D
2 cellular MP:0005384 10.33 ADA BCL11B CD27 DCLRE1C IL2RG IL7R
3 immune system MP:0005387 10.3 ADA ARPC1B BCL11B CARMIL2 CD27 CD3D
4 endocrine/exocrine gland MP:0005379 10.22 ADA BCL11B CARMIL2 DCLRE1C IL2RG IL7R
5 digestive/alimentary MP:0005381 10.03 ADA IL2RG JAK3 LIG4 RAG1 RAG2
6 integument MP:0010771 9.91 ARPC1B BCL11B CARMIL2 MALT1 RAG1 RAG2
7 liver/biliary system MP:0005370 9.7 ADA LIG4 RAC2 RAG1 RAG2 STAT1
8 neoplasm MP:0002006 9.56 BCL11B IL2RG IL7R LIG4 NHEJ1 RAG1
9 normal MP:0002873 9.23 ADA IL2RG IL7R RAG1 RAG2 STAT1

Drugs & Therapeutics for Combined Immunodeficiency

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
Adenosine Approved, Investigational Phase 2, Phase 3 58-61-7 60961
2 Immunoglobulin G Phase 3
3 Rho(D) Immune Globulin Phase 3
4 Immunoglobulins, Intravenous Phase 3
5 gamma-Globulins Phase 3
Mycophenolic acid Approved Phase 2 24280-93-1 446541
Mechlorethamine Approved, Investigational Phase 2 51-75-2 4033
Tacrolimus Approved, Investigational Phase 2 104987-11-3 445643 439492 6473866
Busulfan Approved, Investigational Phase 2 55-98-1 2478
Fludarabine Approved Phase 1, Phase 2 21679-14-1, 75607-67-9 30751
alemtuzumab Approved, Investigational Phase 2 216503-57-0
Thiotepa Approved, Investigational Phase 1, Phase 2 52-24-4 5453
Melphalan Approved Phase 2 148-82-3 4053 460612
Mecasermin Approved, Investigational Phase 1, Phase 2 68562-41-4
Lenograstim Approved, Investigational Phase 2 135968-09-1
Phenylalanine Approved, Investigational, Nutraceutical Phase 2 63-91-2 6140
17 Antitubercular Agents Phase 2
18 Immunosuppressive Agents Phase 2
19 Immunologic Factors Phase 2
20 Alkylating Agents Phase 2
21 Thymoglobulin Phase 1, Phase 2
22 Mitogens Phase 1, Phase 2
23 Hormones Phase 1, Phase 2
24 insulin Phase 1, Phase 2
25 Insulin, Globin Zinc Phase 1, Phase 2
26 Cyclosporins Phase 2
27 Antineoplastic Agents, Immunological Phase 1, Phase 2
28 Antibodies, Monoclonal Phase 1, Phase 2
29 Adjuvants, Immunologic Phase 2
30 Anti-Retroviral Agents Phase 2
31 Plerixafor octahydrochloride Phase 2
32 Antiviral Agents Phase 2
33 Anti-HIV Agents Phase 2
Zidovudine Approved Phase 1 30516-87-1 35370
35 Calcineurin Inhibitors Phase 1
36 Reverse Transcriptase Inhibitors Phase 1
37 Immunoglobulins Phase 1
38 Antibodies Phase 1
Mesna Approved, Investigational 3375-50-6 598
Vidarabine Approved, Investigational 24356-66-9 32326 21704
tannic acid Approved 1401-55-4
Benzocaine Approved, Investigational 1994-09-7, 94-09-7 2337
Methotrexate Approved 1959-05-2, 59-05-2 126941
Levoleucovorin Approved, Investigational 68538-85-2 149436
Cyclophosphamide Approved, Investigational 50-18-0, 6055-19-2 2907
Methylprednisolone Approved, Vet_approved 83-43-2 6741
Methylprednisolone hemisuccinate Approved 2921-57-5
Prednisolone Approved, Vet_approved 50-24-8 5755
Prednisolone acetate Approved, Vet_approved 52-21-1
Prednisone Approved, Vet_approved 53-03-2 5865

Interventional clinical trials:

(show top 50) (show all 69)
# 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 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
3 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
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 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
8 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
9 Phase I Gene Therapy Protocol for Adenosine Deaminase Deficiency Completed NCT01279720 Phase 1, Phase 2
10 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
11 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
12 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
13 Cord Blood Stem Cell Transplantation Study (COBLT) Completed NCT00000603 Phase 2
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 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
16 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
17 Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning Recruiting NCT03311503 Phase 1, Phase 2
18 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
19 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
20 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
21 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
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 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
24 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
25 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
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 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
32 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
33 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
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 Newborn Screening for SCID in a High-Risk Population Completed NCT00845416
47 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
48 Decisions of Female Adolescents About Carrier Testing in Families With X-Linked Severe Combined Immunodeficiency (XSCID) Completed NCT00006335
49 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
50 Gene Therapy for X Linked Severe Combined Immunodeficiency Recruiting NCT04286815

Search NIH Clinical Center for Combined Immunodeficiency

Genetic Tests for Combined Immunodeficiency

Anatomical Context for Combined Immunodeficiency

MalaCards organs/tissues related to Combined Immunodeficiency:

Bone Marrow, T Cells, Skin, Bone, Myeloid, B Cells, Prostate

Publications for Combined Immunodeficiency

Articles related to Combined Immunodeficiency:

(show top 50) (show all 5830)
# Title Authors PMID Year
Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B. 61 6
27959755 2016
Lymphocyte egress signal sphingosine-1-phosphate promotes ERM-guided, bleb-based migration. 61
33764397 2021
Systematic review of literature and analysis of big data from the National Health Insurance System on primary immunodeficiencies in Korea. 61
32683811 2021
Successful living donor liver transplantation for liver failure due to maternal T cell engraftment following cord blood transplantation in X-linked severe combined immunodeficiency disease: case report. 61
33793086 2021
Newborn Screening for Severe Combined Immunodeficiency: 10-Year Experience at a Single Referral Center (2009-2018). 61
33409868 2021
Clinical and Immunological Features of 96 Moroccan Children with SCID Phenotype: Two Decades' Experience. 61
33411152 2021
Proteomic analysis of radio-resistant breast cancer xenografts: Increased TGF-β signaling and metabolism. 61
33325135 2021
Diminished or inversed dose-rate effect on clonogenic ability in Ku-deficient rodent cells. 61
33372229 2021
Gene delivery using AAV8 in vivo for disease stabilization in a bimodal gene therapy approach for the treatment of ADA-deficient SCID. 61
33738330 2021
N-cadherin inhibitor creates a microenvironment that protect TILs from immune checkpoints and Treg cells. 61
33692219 2021
SARS-CoV-2 infection associated with hepatitis in an infant with X-linked severe combined immunodeficiency. 61
33412294 2021
Loss of DIAPH1 causes SCBMS, combined immunodeficiency and mitochondrial dysfunction. 61
33662367 2021
Skin manifestations in pediatric patients with primary immunodeficiency diseases (PIDs) in a tertiary care hospital in Colombia. 61
33747343 2021
Novel ORAI1 Mutation Disrupts Channel Trafficking Resulting in Combined Immunodeficiency. 61
33650027 2021
A Case of Severe Combined Immunodeficiency Missed by Newborn Screening. 61
33712943 2021
Whole-exome sequencing of T- B+ severe combined immunodeficiency in Egyptian infants, JAK3 predominance and novel variants. 61
33040328 2021
Selective IgM deficiency: Follow-up and outcome. 61
33706406 2021
Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects. 61
33231617 2021
Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010. 61
33808002 2021
Development of the Nude Rabbit Model. 61
33606990 2021
Non-viral ex vivo genome-editing in mouse bona fide hematopoietic stem cells with CRISPR/Cas9. 61
33614821 2021
Peripheral immune profile of children with Talaromyces marneffei infections: a retrospective analysis of 21 cases. 61
33743629 2021
Targeted therapy of human leukemia xenografts in immunodeficient zebrafish. 61
33707624 2021
ICOSL in host defense at epithelial barriers: lessons from ICOSLG deficiency. 61
33756276 2021
A novel bi-allelic loss-of-function mutation in STIM1 expands the phenotype of STIM1-related diseases. 61
33733462 2021
Ultrafiltration and Injection of Islet Regenerative Stimuli Secreted by Pancreatic Mesenchymal Stromal Cells. 61
33403929 2021
Severe Fatigue Is Common Among Pediatric Patients with Primary Immunodeficiency and Is Not Related to Disease Activity. 61
33728554 2021
Deuterium Oxide (D2O) Induces Early Stress Response Gene Expression and Impairs Growth and Metastasis of Experimental Malignant Melanoma. 61
33546433 2021
Effects of Phthalate Esters on Human Myometrial and Fibroid Cells: Cell Culture and NOD-SCID Mouse Data. 61
33037561 2021
Novel Variants of DOCK8 Deficiency in a Case Series of Iranian Patients. 61
33634762 2021
Human CD34-negative hematopoietic stem cells: The current understanding of their biological nature. 61
33610645 2021
Humanized NOD/SCID/IL2rγnull mice exhibit functionally augmented human regulatory T cells associated with enzymatic up-regulation of H3K27me3 in comparison with humans. 61
33555619 2021
An appraisal of the Wilson & Jungner criteria in the context of genomic-based newborn screening for inborn errors of immunity. 61
33551024 2021
Lifelong Immune Modulation Versus Hematopoietic Cell Therapy for Inborn Errors of Immunity. 61
33551038 2021
Somatic reversion of pathogenic DOCK8 variants alters lymphocyte differentiation and function to effectively cure DOCK8 deficiency. 61
33290277 2021
Coronavirus disease 2019 in patients with inborn errors of immunity: An international study. 61
32980424 2021
Severe SARS-CoV-2 disease in the context of a NF-κB2 loss-of-function pathogenic variant. 61
33007327 2021
SCID newborn screening: What we've learned. 61
33551023 2021
Down's syndrome and COVID-19: risk or protection factor against infection? A molecular and genetic approach. 61
33231770 2021
A novel zeta-associated protein 70 homozygous mutation causing combined immunodeficiency presenting as neonatal autoimmune hemolytic anemia. 61
33484432 2021
Functional Confirmation of DNA Repair Defect in Ataxia Telangiectasia (AT) Infants Identified by Newborn Screening for Severe Combined Immunodeficiency (NBS SCID). 61
32818697 2021
Trough Concentrations of Specific Antibodies in Primary Immunodeficiency Patients Receiving Intravenous Immunoglobulin Replacement Therapy. 61
33557365 2021
Epidermodysplasia Verruciformis After Hematopoietic Stem Cell Transplantation in a Patient With Severe Combined Immunodeficiency Syndrome. 61
33577180 2021
Newborn screening for severe combined immunodeficiency: clinical and cost-effectiveness approaches. 61
33713100 2021
Hematopoietic Cell Transplantation with Reduced Intensity Conditioning Using Fludarabine/Busulfan or Fludarabine/Melphalan for Primary Immunodeficiency Diseases. 61
33527309 2021
A gain-of-function RAC2 mutation is associated with bone-marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency. 61
31919089 2021
Immunoglobulin therapy for successful management of prolonged, recurrent jaundice in a young adult male with combined immunodeficiency. 61
33527335 2021
A Novel RAC2 Variant Presenting as Severe Combined Immunodeficiency. 61
33188496 2021
When Screening for Severe Combined Immunodeficiency (SCID) with T Cell Receptor Excision Circles Is Not SCID: a Case-Based Review. 61
33411155 2021
Combined immunodeficiency due to a mutation in the γ1 subunit of the coat protein I complex. 61
33529166 2021

Variations for Combined Immunodeficiency

ClinVar genetic disease variations for Combined Immunodeficiency:

6 (show all 22)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MALT1 NM_006785.4(MALT1):c.1060del (p.Arg354fs) Deletion Pathogenic 242616 rs786200954 GRCh37: 18:56390320-56390320
GRCh38: 18:58723088-58723088
2 TFRC NM_001128148.3(TFRC):c.58T>C (p.Tyr20His) SNV Pathogenic 218163 rs863225436 GRCh37: 3:195802210-195802210
GRCh38: 3:196075339-196075339
3 ZAP70 NM_001079.3(ZAP70):c.1079G>C (p.Arg360Pro) SNV Pathogenic 222950 rs869025224 GRCh37: 2:98351172-98351172
GRCh38: 2:97734709-97734709
4 ZAP70 NM_001079.3(ZAP70):c.574C>T (p.Arg192Trp) SNV Pathogenic 222951 rs199840952 GRCh37: 2:98349356-98349356
GRCh38: 2:97732893-97732893
5 BCL11B NM_138576.4(BCL11B):c.1323T>G (p.Asn441Lys) SNV Pathogenic 254673 rs750610248 GRCh37: 14:99641850-99641850
GRCh38: 14:99175513-99175513
6 CARMIL2 NM_001013838.3(CARMIL2):c.490dup (p.Ala164fs) Duplication Pathogenic 266035 rs886041043 GRCh37: 16:67680638-67680639
GRCh38: 16:67646735-67646736
7 CARMIL2 NM_001013838.3(CARMIL2):c.871+1G>T SNV Pathogenic 266036 rs886041044 GRCh37: 16:67681506-67681506
GRCh38: 16:67647603-67647603
8 CARMIL2 NM_001013838.3(CARMIL2):c.1590C>A (p.Asn530Lys) SNV Pathogenic 562177 rs1567629968 GRCh37: 16:67682876-67682876
GRCh38: 16:67648973-67648973
9 STAT1 NM_007315.3(STAT1):c.1154C>T (p.Thr385Met) SNV Pathogenic 144006 rs587777630 GRCh37: 2:191851647-191851647
GRCh38: 2:190986921-190986921
10 ARPC1B NC_000007.14:g.99369754_99378887del Deletion Pathogenic 827686 GRCh37: 7:98967377-98976510
11 ARPC1B NM_005720.4(ARPC1B):c.739_743del (p.Leu247fs) Deletion Pathogenic 827687 rs760191638 GRCh37: 7:98988832-98988836
GRCh38: 7:99391209-99391213
12 CD27-AS1 , CD27 NM_001242.4(CD27):c.250dup (p.Cys84fs) Duplication Pathogenic 827694 rs1592117677 GRCh37: 12:6554702-6554703
GRCh38: 12:6445536-6445537
13 CD27-AS1 , CD27 NM_001242.4(CD27):c.319C>T (p.Arg107Cys) SNV Pathogenic 827695 rs371761387 GRCh37: 12:6559389-6559389
GRCh38: 12:6450223-6450223
14 ZAP70 NM_001079.4(ZAP70):c.283C>T (p.Pro95Ser) SNV Pathogenic 827753 rs1573262398 GRCh37: 2:98340782-98340782
GRCh38: 2:97724319-97724319
15 MYH7 NM_000257.4(MYH7):c.2389G>A (p.Ala797Thr) SNV Likely pathogenic 42901 rs3218716 GRCh37: 14:23894525-23894525
GRCh38: 14:23425316-23425316
16 MYOC NM_000261.2(MYOC):c.1102C>T (p.Gln368Ter) SNV Likely pathogenic 7949 rs74315329 GRCh37: 1:171605478-171605478
GRCh38: 1:171636338-171636338
17 RAC2 NM_002872.5(RAC2):c.184G>A (p.Glu62Lys) SNV Likely pathogenic 464885 rs1555908409 GRCh37: 22:37628882-37628882
GRCh38: 22:37232842-37232842
18 PLAA NM_001031689.3(PLAA):c.1487-1G>A SNV Likely pathogenic 598964 rs1426488816 GRCh37: 9:26913946-26913946
GRCh38: 9:26913948-26913948
19 SCNN1A NM_001038.6(SCNN1A):c.1427G>A (p.Arg476Gln) SNV Uncertain significance 598965 rs72657556 GRCh37: 12:6458505-6458505
GRCh38: 12:6349339-6349339
20 CACNA1A NM_001127222.2(CACNA1A):c.6125C>T (p.Thr2042Met) SNV Uncertain significance 386521 rs563345694 GRCh37: 19:13323262-13323262
GRCh38: 19:13212448-13212448
21 COL6A2 NM_001849.3(COL6A2):c.2008A>G (p.Thr670Ala) SNV Uncertain significance 598977 rs753298014 GRCh37: 21:47545737-47545737
GRCh38: 21:46125823-46125823
22 ADAR NM_001111.5(ADAR):c.1646C>A (p.Ala549Asp) SNV Uncertain significance 598987 rs1557882064 GRCh37: 1:154571017-154571017
GRCh38: 1:154598541-154598541

Expression for Combined Immunodeficiency

Search GEO for disease gene expression data for Combined Immunodeficiency.

Pathways for Combined Immunodeficiency

Pathways related to Combined Immunodeficiency according to KEGG:

# Name Kegg Source Accession
1 Primary immunodeficiency hsa05340

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

(show all 18)
# Super pathways Score Top Affiliating Genes
Show member pathways
Show member pathways
Show member pathways
4 12.63 STAT1 RAC2 JAK3 IL7R IL2RG
Show member pathways
Show member pathways
12.25 ZAP70 RAC2 MALT1 CD3D
Show member pathways
Show member pathways
10 11.81 STAT1 JAK3 IL2RG
Show member pathways
Show member pathways
11.77 ZAP70 MALT1 CD3D
13 11.72 TFRC IL7R CD3D
Show member pathways
11.67 STAT1 JAK3 IL2RG
15 11.48 STAT1 JAK3 IL7R IL2RG
Show member pathways
17 10.86 ZAP70 RAG2 RAG1 JAK3 IL7R IL2RG
18 10.8 RAG2 RAG1 JAK3 IL7R IL2RG

GO Terms for Combined Immunodeficiency

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 IL7R IL2RG CD3D CD27 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 26)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 10.02 TFRC MALT1 CD27 BCL11B ADA
2 adaptive immune response GO:0002250 9.97 ZAP70 RAG1 JAK3 DCLRE1C CD3D
3 DNA recombination GO:0006310 9.78 RAG2 RAG1 LIG4 DCLRE1C
4 double-strand break repair via nonhomologous end joining GO:0006303 9.74 NHEJ1 LIG4 DCLRE1C
5 double-strand break repair GO:0006302 9.73 NHEJ1 LIG4 DCLRE1C
6 response to ionizing radiation GO:0010212 9.72 NHEJ1 LIG4 DCLRE1C
7 interleukin-7-mediated signaling pathway GO:0038111 9.67 JAK3 IL7R IL2RG
8 positive regulation of calcium-mediated signaling GO:0050850 9.63 ZAP70 ADA
9 negative regulation of T cell apoptotic process GO:0070233 9.63 RAG1 IL7R CD27
10 regulation of T cell differentiation GO:0045580 9.62 RAG1 ADA
11 T cell differentiation GO:0030217 9.62 ZAP70 RAG2 NHEJ1 IL7R
12 interleukin-15-mediated signaling pathway GO:0035723 9.61 JAK3 IL2RG
13 positive thymic T cell selection GO:0045059 9.61 ZAP70 CD3D
14 interleukin-9-mediated signaling pathway GO:0038113 9.61 STAT1 JAK3 IL2RG
15 interleukin-2-mediated signaling pathway GO:0038110 9.6 JAK3 IL2RG
16 positive regulation of alpha-beta T cell differentiation GO:0046638 9.59 ZAP70 ADA
17 positive regulation of T cell differentiation in thymus GO:0033089 9.58 IL7R ADA
18 negative regulation of thymocyte apoptotic process GO:0070244 9.58 RAG1 JAK3 ADA
19 T cell differentiation in thymus GO:0033077 9.56 RAG2 RAG1 LIG4 BCL11B
20 B cell differentiation GO:0030183 9.55 RAG2 RAG1 NHEJ1 JAK3 DCLRE1C
21 T cell receptor V(D)J recombination GO:0033153 9.54 LIG4 BCL11B
22 interleukin-21-mediated signaling pathway GO:0038114 9.54 STAT1 JAK3 IL2RG
23 interleukin-4-mediated signaling pathway GO:0035771 9.52 JAK3 IL2RG
24 pre-B cell allelic exclusion GO:0002331 9.51 RAG2 RAG1
25 positive regulation of T cell differentiation GO:0045582 9.26 ZAP70 RAG1 CD27 ADA
26 V(D)J recombination GO:0033151 8.92 RAG2 RAG1 LIG4 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 for Combined Immunodeficiency

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
69 Tocris
71 UMLS via Orphanet
Loading form....