XCID
MCID: CMB081
MIFTS: 43

Combined Immunodeficiency, X-Linked (XCID)

Categories: Genetic diseases, Immune diseases

Aliases & Classifications for Combined Immunodeficiency, X-Linked

MalaCards integrated aliases for Combined Immunodeficiency, X-Linked:

Name: Combined Immunodeficiency, X-Linked 58 30 6
Combined Immunodeficiency, X-Linked, Moderate 58 13
Xcid 58 76
X-Linked Combined Immunodeficiency Diseases 74
X-Linked Combined Immunodeficiency 76
Combined Immunodeficiency 74
Immunodeficiency 6; Imd6 58
Immunodeficiency 6 58
Cidx 58
Imd6 58

Characteristics:

OMIM:

58
Inheritance:
x-linked recessive

Miscellaneous:
reduced life expectancy


HPO:

33
combined immunodeficiency, x-linked:
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Combined Immunodeficiency, X-Linked

UniProtKB/Swiss-Prot : 76 X-linked combined immunodeficiency: Less severe form of X-linked immunodeficiency with a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.

MalaCards based summary : Combined Immunodeficiency, X-Linked, also known as combined immunodeficiency, x-linked, moderate, is related to combined t cell and b cell immunodeficiency and severe combined immunodeficiency. An important gene associated with Combined Immunodeficiency, X-Linked is IL2RG (Interleukin 2 Receptor Subunit Gamma), and among its related pathways/superpathways are Th17 cell differentiation and NF-kappaB Signaling. The drugs Pharmaceutical Solutions and Busulfan have been mentioned in the context of this disorder. Affiliated tissues include t cells, bone and bone marrow, and related phenotypes are sinusitis and otitis media

Description from OMIM: 312863

Related Diseases for Combined Immunodeficiency, X-Linked

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

# Related Disease Score Top Affiliating Genes
1 combined t cell and b cell immunodeficiency 29.8 IL2RG ZAP70
2 severe combined immunodeficiency 29.6 BCL11B IL2RG ZAP70
3 severe combined immunodeficiency, x-linked 13.0
4 immunodeficiency 50 11.4
5 immunodeficiency, common variable, 6 11.2

Graphical network of the top 20 diseases related to Combined Immunodeficiency, X-Linked:



Diseases related to Combined Immunodeficiency, X-Linked

Symptoms & Phenotypes for Combined Immunodeficiency, X-Linked

Human phenotypes related to Combined Immunodeficiency, X-Linked:

33 (show all 8)
# Description HPO Frequency HPO Source Accession
1 sinusitis 33 HP:0000246
2 otitis media 33 HP:0000388
3 pneumonia 33 HP:0002090
4 recurrent bronchitis 33 HP:0002837
5 decreased circulating igg level 33 HP:0004315
6 decreased proportion of cd4-positive t cells 33 HP:0005407
7 combined immunodeficiency 33 HP:0005387
8 decreased proportion of cd8-positive t cells 33 HP:0005415

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Head:
sinusitis

Respiratory Lung:
pneumonia

Respiratory Airways:
bronchitis

Head And Neck Ears:
otitis media

Immunology:
decreased number of cd4+ t cells
normal number of natural killer cells
normal number of b cells
paucity of lymphoid tissue
decreased number of cd8+ t cells
more
Laboratory Abnormalities:
reduced igg levels

Clinical features from OMIM:

312863

GenomeRNAi Phenotypes related to Combined Immunodeficiency, X-Linked according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Upregulation of Wnt/beta-catenin pathway after WNT3A stimulation GR00016-A 8.8 RAC2 STAT1 TFRC

MGI Mouse Phenotypes related to Combined Immunodeficiency, X-Linked:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.7 BCL11B CARMIL2 IL2RG RAC2 STAT1 TFRC
2 immune system MP:0005387 9.5 BCL11B CARMIL2 IL2RG RAC2 STAT1 TFRC
3 integument MP:0010771 9.02 BCL11B CARMIL2 STAT1 TFRC ZAP70

Drugs & Therapeutics for Combined Immunodeficiency, X-Linked

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

(show all 50)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Pharmaceutical Solutions Phase 2, Phase 3
2
Busulfan Approved, Investigational Phase 1, Phase 2,Phase 2 55-98-1 2478
3
Amiloride Approved Phase 2 2016-88-8, 2609-46-3 16231
4
Teriparatide Approved, Investigational Phase 2 52232-67-4 16133850
5
Parathyroid hormone Approved, Investigational Phase 2 9002-64-6
6
Hydrochlorothiazide Approved, Vet_approved Phase 2 58-93-5 3639
7
Mecasermin Approved, Investigational Phase 1, Phase 2 68562-41-4
8
Calcium Approved, Nutraceutical Phase 2 7440-70-2 271
9
Vitamin D Approved, Nutraceutical, Vet_approved Phase 2 1406-16-2
10
Alfacalcidol Approved, Nutraceutical Phase 2 41294-56-8 5282181
11 Alkylating Agents Phase 1, Phase 2,Phase 2
12 Antineoplastic Agents, Alkylating Phase 1, Phase 2,Phase 2
13 Immunosuppressive Agents Phase 1, Phase 2,Phase 2
14 Immunologic Factors Phase 1, Phase 2,Phase 2
15 Hormones Phase 2,Phase 1
16 Micronutrients Phase 2
17 Hydroxycholecalciferols Phase 2
18 Sodium Chloride Symporter Inhibitors Phase 2
19 Nutrients Phase 2
20 Trace Elements Phase 2
21 Sodium Channel Blockers Phase 2
22 Vitamins Phase 2
23 Calcium, Dietary Phase 2
24 diuretics Phase 2
25 Natriuretic Agents Phase 2
26 Antihypertensive Agents Phase 2
27 Bone Density Conservation Agents Phase 2
28 Diuretics, Potassium Sparing Phase 2
29 Calciferol Phase 2
30 Mitogens Phase 1, Phase 2
31 Insulin, Globin Zinc Phase 1, Phase 2
32 Hypoglycemic Agents Phase 1, Phase 2
33 insulin Phase 1, Phase 2
34
Miconazole Approved, Investigational, Vet_approved Phase 1 22916-47-8 4189
35
Mycophenolic acid Approved Phase 1 24280-93-1 446541
36 Antirheumatic Agents Phase 1
37 Dermatologic Agents Phase 1
38 Antifungal Agents Phase 1
39 Anti-Bacterial Agents Phase 1
40 Calcineurin Inhibitors Phase 1
41 Antibiotics, Antitubercular Phase 1
42 Anti-Infective Agents Phase 1
43 Cyclosporins Phase 1
44 Antitubercular Agents Phase 1
45
Acetylcholine Approved, Investigational 51-84-3 187
46
Nitroprusside Approved, Investigational 15078-28-1 11963622
47
Adenosine Approved, Investigational 58-61-7 60961
48 Coagulants Not Applicable
49 Factor VIII Not Applicable
50 Estrogens

Interventional clinical trials:

(show all 32)
# Name Status NCT ID Phase Drugs
1 Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Idursulfase Completed NCT00630747 Phase 2, Phase 3
2 Gene Therapy for X-linked Severe Combined Immunodeficiency Unknown status NCT01410019 Phase 1, Phase 2
3 Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Duchenne Muscular Dystrophy Unknown status NCT01610440 Phase 1, Phase 2
4 An Open-Label Clinical Trial of Replagal Enzyme Therapy in Children Ages 7-17 Years With Fabry Disease Completed NCT00071877 Phase 2 Replagal
5 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
6 Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID) Recruiting NCT01306019 Phase 1, Phase 2 Busulfan
7 Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants Recruiting NCT01512888 Phase 1, Phase 2 Busulfan
8 Gene Transfer for SCID-X1 Using a Self-inactivating Lentiviral Vector (TYF-IL-2Rg) Recruiting NCT03217617 Phase 1, Phase 2
9 Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning Recruiting NCT03311503 Phase 1, Phase 2
10 Recombinant Human rhPTH(1-34) VS Association Alfacalcidol/Hydrochlorothiazide in Severe Primary Hypoparathyroidism Recruiting NCT02824718 Phase 2 Teriparatide;Thiazide;Potassium sparing diuretic;Alfacalcidol
11 Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector Active, not recruiting NCT01129544 Phase 1, Phase 2
12 Treatment for Growth Failure in Patients With X-Linked Severe Combined Immunodeficiency: Phase 2 Study of Insulin-Like Growth Factor-1 Terminated NCT00490100 Phase 1, Phase 2 Increlex
13 Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID) Completed NCT00028236 Phase 1 Gene-Transduced Autologous CD34+ Stem Cells
14 An Open-Label Maintenance Study of the Enzyme Replacement Therapy Replagal in Patients With Fabry Disease Completed NCT00357786 Phase 1 Replagal agalsidase alfa;Replagal
15 Gene Therapy for Gaucher's and Fabry Disease Using Viruses and Blood-Forming Cells Completed NCT00001234 Phase 1
16 Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant Active, not recruiting NCT00008450 Phase 1 Cyclosporine;Mycophenolate Mofetil
17 Lentiviral Gene Therapy for X-linked Severe Combined Immunodeficiency Not yet recruiting NCT03601286 Phase 1 Lentiviral vector transduced CD34+ cells
18 Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Unknown status NCT01175239 Not Applicable
19 Efficacy and Safety of ADVATE Standard Prophylaxis to Hemophilia A Unknown status NCT02280265 Not Applicable Recombinant Human Coagulation Factor VIII for injection
20 Genome-wide Single Cell Haplotyping as a Generic Method for Preimplantation Genetic Diagnosis Unknown status NCT01336400
21 Influences on Female Adolescents' Decisions Regarding Testing for Carrier Status of XSCID Completed NCT00006335
22 Establishment of Biomarkers for Fabry Disease Completed NCT01165697
23 Vasodilation in Patients With Fabry's Disease Completed NCT00001774
24 Analysis of the Nervous System in Patients With Fabry's Disease Completed NCT00001491
25 Genetic Studies Spermatogenic Failure Completed NCT00548977
26 Natural History of the Progression of Choroideremia Study Recruiting NCT03359551
27 Evaluation of Patients With Immune Function Abnormalities Recruiting NCT00128973
28 Patients Treated for SCID (1968-Present) Recruiting NCT01346150
29 Natural History Study of SCID Disorders Recruiting NCT01186913
30 Molecular and Clinical Studies of Primary Immunodeficiency Diseases Active, not recruiting NCT00006319
31 Platelet Function in Patients With Hemophilia A Enrolling by invitation NCT02093065
32 cliniMACs HUD for T Cell Depletion No longer available NCT02915406

Search NIH Clinical Center for Combined Immunodeficiency, X-Linked

Genetic Tests for Combined Immunodeficiency, X-Linked

Genetic tests related to Combined Immunodeficiency, X-Linked:

# Genetic test Affiliating Genes
1 Combined Immunodeficiency, X-Linked 30 IL2RG

Anatomical Context for Combined Immunodeficiency, X-Linked

MalaCards organs/tissues related to Combined Immunodeficiency, X-Linked:

42
T Cells, Bone, Bone Marrow, Testes, B Cells

Publications for Combined Immunodeficiency, X-Linked

Articles related to Combined Immunodeficiency, X-Linked:

# Title Authors Year
1
Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. ( 7883965 )
1995
2
Repertoire of V alpha and V beta regions of T cell antigen receptors on CD4+ and CD8+ peripheral blood T cells in a novel X-linked combined immunodeficiency disease. ( 1348030 )
1992
3
A novel X-linked combined immunodeficiency disease. ( 2243135 )
1990
4
Immunoglobulin classes, IgC subclasses, Gm genetic markers, and Clq following bone marrow transplantation in X-linked combined immunodeficiency. ( 4589842 )
1974
5
Transfer factor induced delayed hypersensitivity in X-linked combined immunodeficiency. ( 4356606 )
1973

Variations for Combined Immunodeficiency, X-Linked

UniProtKB/Swiss-Prot genetic disease variations for Combined Immunodeficiency, X-Linked:

76
# Symbol AA change Variation ID SNP ID
1 IL2RG p.Arg222Cys VAR_002688 rs111033618
2 IL2RG p.Leu293Gln VAR_002702 rs137852510

ClinVar genetic disease variations for Combined Immunodeficiency, X-Linked:

6 (show all 32)
# Gene Variation Type Significance SNP ID Assembly Location
1 TFRC NM_003234.3(TFRC): c.58T> C (p.Tyr20His) single nucleotide variant Pathogenic rs863225436 GRCh37 Chromosome 3, 195802210: 195802210
2 TFRC NM_003234.3(TFRC): c.58T> C (p.Tyr20His) single nucleotide variant Pathogenic rs863225436 GRCh38 Chromosome 3, 196075339: 196075339
3 MYOC NM_000261.1(MYOC): c.1102C> T (p.Gln368Ter) single nucleotide variant Likely pathogenic rs74315329 GRCh37 Chromosome 1, 171605478: 171605478
4 MYOC NM_000261.1(MYOC): c.1102C> T (p.Gln368Ter) single nucleotide variant Likely pathogenic rs74315329 GRCh38 Chromosome 1, 171636338: 171636338
5 IL2RG NM_000206.2(IL2RG): c.878T> A (p.Leu293Gln) single nucleotide variant Pathogenic rs137852510 GRCh37 Chromosome X, 70328173: 70328173
6 IL2RG NM_000206.2(IL2RG): c.878T> A (p.Leu293Gln) single nucleotide variant Pathogenic rs137852510 GRCh38 Chromosome X, 71108323: 71108323
7 IL2RG NM_000206.2(IL2RG): c.664C> T (p.Arg222Cys) single nucleotide variant Pathogenic rs111033618 GRCh37 Chromosome X, 70329171: 70329171
8 IL2RG NM_000206.2(IL2RG): c.664C> T (p.Arg222Cys) single nucleotide variant Pathogenic rs111033618 GRCh38 Chromosome X, 71109321: 71109321
9 MYH7 NM_000257.3(MYH7): c.2389G> A (p.Ala797Thr) single nucleotide variant Pathogenic/Likely pathogenic rs3218716 GRCh37 Chromosome 14, 23894525: 23894525
10 MYH7 NM_000257.3(MYH7): c.2389G> A (p.Ala797Thr) single nucleotide variant Pathogenic/Likely pathogenic rs3218716 GRCh38 Chromosome 14, 23425316: 23425316
11 STAT1 NM_007315.3(STAT1): c.1154C> T (p.Thr385Met) single nucleotide variant Pathogenic rs587777630 GRCh37 Chromosome 2, 191851647: 191851647
12 STAT1 NM_007315.3(STAT1): c.1154C> T (p.Thr385Met) single nucleotide variant Pathogenic rs587777630 GRCh38 Chromosome 2, 190986921: 190986921
13 ZAP70 NM_001079.3(ZAP70): c.574C> T (p.Arg192Trp) single nucleotide variant Pathogenic rs199840952 GRCh37 Chromosome 2, 98349356: 98349356
14 ZAP70 NM_001079.3(ZAP70): c.574C> T (p.Arg192Trp) single nucleotide variant Pathogenic rs199840952 GRCh38 Chromosome 2, 97732893: 97732893
15 ZAP70 NM_001079.3(ZAP70): c.1079G> C (p.Arg360Pro) single nucleotide variant Pathogenic rs869025224 GRCh38 Chromosome 2, 97734709: 97734709
16 ZAP70 NM_001079.3(ZAP70): c.1079G> C (p.Arg360Pro) single nucleotide variant Pathogenic rs869025224 GRCh37 Chromosome 2, 98351172: 98351172
17 BCL11B NM_138576.3(BCL11B): c.1323T> G (p.Asn441Lys) single nucleotide variant Pathogenic rs750610248 GRCh38 Chromosome 14, 99175513: 99175513
18 BCL11B NM_138576.3(BCL11B): c.1323T> G (p.Asn441Lys) single nucleotide variant Pathogenic rs750610248 GRCh37 Chromosome 14, 99641850: 99641850
19 CACNA1A NM_001127221.1(CACNA1A): c.6128C> T (p.Thr2043Met) single nucleotide variant Uncertain significance rs563345694 GRCh37 Chromosome 19, 13323262: 13323262
20 CACNA1A NM_001127221.1(CACNA1A): c.6128C> T (p.Thr2043Met) single nucleotide variant Uncertain significance rs563345694 GRCh38 Chromosome 19, 13212448: 13212448
21 RAC2 NM_002872.4(RAC2): c.184G> A (p.Glu62Lys) single nucleotide variant Pathogenic/Likely pathogenic rs1555908409 GRCh37 Chromosome 22, 37628882: 37628882
22 RAC2 NM_002872.4(RAC2): c.184G> A (p.Glu62Lys) single nucleotide variant Pathogenic/Likely pathogenic rs1555908409 GRCh38 Chromosome 22, 37232842: 37232842
23 CARMIL2 NM_001013838.2(CARMIL2): c.1590C> A (p.Asn530Lys) single nucleotide variant Pathogenic GRCh38 Chromosome 16, 67648973: 67648973
24 CARMIL2 NM_001013838.2(CARMIL2): c.1590C> A (p.Asn530Lys) single nucleotide variant Pathogenic GRCh37 Chromosome 16, 67682876: 67682876
25 ADAR NM_001193495.2(ADAR): c.761C> A (p.Ala254Asp) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 154571017: 154571017
26 ADAR NM_001193495.2(ADAR): c.761C> A (p.Ala254Asp) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 154598541: 154598541
27 PLAA NM_001031689.3(PLAA): c.1487-1G> A single nucleotide variant Likely pathogenic GRCh37 Chromosome 9, 26913946: 26913946
28 PLAA NM_001031689.3(PLAA): c.1487-1G> A single nucleotide variant Likely pathogenic GRCh38 Chromosome 9, 26913948: 26913948
29 SCNN1A NM_001159576.1(SCNN1A): c.1604G> A (p.Arg535Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 6458505: 6458505
30 SCNN1A NM_001159576.1(SCNN1A): c.1604G> A (p.Arg535Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 6349339: 6349339
31 COL6A2 NM_001849.3(COL6A2): c.2008A> G (p.Thr670Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 21, 47545737: 47545737
32 COL6A2 NM_001849.3(COL6A2): c.2008A> G (p.Thr670Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 21, 46125823: 46125823

Expression for Combined Immunodeficiency, X-Linked

Search GEO for disease gene expression data for Combined Immunodeficiency, X-Linked.

Pathways for Combined Immunodeficiency, X-Linked

GO Terms for Combined Immunodeficiency, X-Linked

Biological processes related to Combined Immunodeficiency, X-Linked according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of lamellipodium assembly GO:0010592 9.16 CARMIL2 RAC2
2 interleukin-9-mediated signaling pathway GO:0038113 8.96 IL2RG STAT1
3 interleukin-21-mediated signaling pathway GO:0038114 8.62 IL2RG STAT1

Sources for Combined Immunodeficiency, X-Linked

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....