XCID
MCID: CMB081
MIFTS: 35

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 57 29 6
Combined Immunodeficiency, X-Linked, Moderate 57 13
Xcid 57 75
X-Linked Combined Immunodeficiency Diseases 73
X-Linked Combined Immunodeficiency 75
Combined Immunodeficiency 73
Immunodeficiency 6; Imd6 57
Immunodeficiency 6 57
Cidx 57
Imd6 57

Characteristics:

OMIM:

57
Inheritance:
x-linked recessive

Miscellaneous:
reduced life expectancy


HPO:

32
combined immunodeficiency, x-linked:
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Combined Immunodeficiency, X-Linked

UniProtKB/Swiss-Prot : 75 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 Primary immunodeficiency and Inflammatory Response Pathway. The drugs Pharmaceutical Solutions and Busulfan have been mentioned in the context of this disorder. Affiliated tissues include t cells, bone and b cells, 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 29.7 IL2RG ZAP70
2 severe combined immunodeficiency 29.7 BCL11B IL2RG ZAP70
3 severe combined immunodeficiency, x-linked 12.9
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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Combined Immunodeficiency, X-Linked:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 sinusitis 32 HP:0000246
2 otitis media 32 HP:0000388
3 pneumonia 32 HP:0002090
4 igg deficiency 32 HP:0004315
5 recurrent bronchitis 32 HP:0002837
6 decreased proportion of cd4-positive t cells 32 HP:0005407
7 combined immunodeficiency 32 HP:0005387
8 decreased proportion of cd8-positive t cells 32 HP:0005415

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

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.56 BCL11B CARMIL2 IL2RG ZAP70
2 hematopoietic system MP:0005397 9.55 BCL11B CARMIL2 IL2RG TFRC ZAP70
3 immune system MP:0005387 9.35 BCL11B CARMIL2 IL2RG TFRC ZAP70
4 integument MP:0010771 8.92 BCL11B CARMIL2 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 46)
# 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
Teriparatide Approved, Investigational Phase 2 52232-67-4 16133850
4
Hydrochlorothiazide Approved, Vet_approved Phase 2 58-93-5 3639
5
Amiloride Approved Phase 2 2016-88-8, 2609-46-3 16231
6
Mecasermin Approved, Investigational Phase 1, Phase 2 68562-41-4
7
Alfacalcidol Approved, Nutraceutical Phase 2 41294-56-8 5282181
8
Vitamin D Approved, Nutraceutical, Vet_approved Phase 2 1406-16-2
9 Antineoplastic Agents, Alkylating Phase 1, Phase 2,Phase 2
10 Immunologic Factors Phase 1, Phase 2,Phase 2
11 Immunosuppressive Agents Phase 1, Phase 2,Phase 2
12 Alkylating Agents Phase 1, Phase 2,Phase 2
13 Sodium Channel Blockers Phase 2
14 Antihypertensive Agents Phase 2
15 Micronutrients Phase 2
16 Trace Elements Phase 2
17 diuretics Phase 2
18 Natriuretic Agents Phase 2
19 Calcium, Dietary Phase 2
20 Vitamins Phase 2
21 Hydroxycholecalciferols Phase 2
22 Calciferol Phase 2
23 Sodium Chloride Symporter Inhibitors Phase 2
24 Bone Density Conservation Agents Phase 2
25 Diuretics, Potassium Sparing Phase 2
26 insulin Phase 1, Phase 2
27 Mitogens Phase 1, Phase 2
28 Insulin, Globin Zinc Phase 1, Phase 2
29 Hypoglycemic Agents Phase 1, Phase 2
30 Hormones Phase 1, Phase 2
31
Mycophenolic acid Approved Phase 1 24280-93-1 446541
32
Miconazole Approved, Investigational, Vet_approved Phase 1 22916-47-8 4189
33 Antibiotics, Antitubercular Phase 1
34 Dermatologic Agents Phase 1
35 Calcineurin Inhibitors Phase 1
36 Antirheumatic Agents Phase 1
37 Antifungal Agents Phase 1
38 Anti-Infective Agents Phase 1
39 Cyclosporins Phase 1
40 Anti-Bacterial Agents Phase 1
41 Antitubercular Agents Phase 1
42
Nitroprusside Approved, Investigational 15078-28-1 11963622
43
Acetylcholine Approved 51-84-3 187
44 Coagulants Not Applicable
45 Factor VIII Not Applicable
46 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 29 IL2RG

Anatomical Context for Combined Immunodeficiency, X-Linked

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

41
T Cells, Bone, B Cells, Lung, Myeloid, Bone Marrow, Nk 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

Variations for Combined Immunodeficiency, X-Linked

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

75
# 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 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 IL2RG NM_000206.2(IL2RG): c.878T> A (p.Leu293Gln) single nucleotide variant Pathogenic rs137852510 GRCh37 Chromosome X, 70328173: 70328173
2 IL2RG NM_000206.2(IL2RG): c.878T> A (p.Leu293Gln) single nucleotide variant Pathogenic rs137852510 GRCh38 Chromosome X, 71108323: 71108323
3 IL2RG NM_000206.2(IL2RG): c.664C> T (p.Arg222Cys) single nucleotide variant Pathogenic rs111033618 GRCh37 Chromosome X, 70329171: 70329171
4 IL2RG NM_000206.2(IL2RG): c.664C> T (p.Arg222Cys) single nucleotide variant Pathogenic rs111033618 GRCh38 Chromosome X, 71109321: 71109321
5 TFRC NM_003234.3(TFRC): c.58T> C (p.Tyr20His) single nucleotide variant Pathogenic rs863225436 GRCh37 Chromosome 3, 195802210: 195802210
6 TFRC NM_003234.3(TFRC): c.58T> C (p.Tyr20His) single nucleotide variant Pathogenic rs863225436 GRCh38 Chromosome 3, 196075339: 196075339
7 ZAP70 NM_001079.3(ZAP70): c.574C> T (p.Arg192Trp) single nucleotide variant Pathogenic rs199840952 GRCh37 Chromosome 2, 98349356: 98349356
8 ZAP70 NM_001079.3(ZAP70): c.574C> T (p.Arg192Trp) single nucleotide variant Pathogenic rs199840952 GRCh38 Chromosome 2, 97732893: 97732893
9 ZAP70 NM_001079.3(ZAP70): c.1079G> C (p.Arg360Pro) single nucleotide variant Pathogenic rs869025224 GRCh38 Chromosome 2, 97734709: 97734709
10 ZAP70 NM_001079.3(ZAP70): c.1079G> C (p.Arg360Pro) single nucleotide variant Pathogenic rs869025224 GRCh37 Chromosome 2, 98351172: 98351172
11 BCL11B NM_138576.3(BCL11B): c.1323T> G (p.Asn441Lys) single nucleotide variant Pathogenic rs750610248 GRCh38 Chromosome 14, 99175513: 99175513
12 BCL11B NM_138576.3(BCL11B): c.1323T> G (p.Asn441Lys) single nucleotide variant Pathogenic rs750610248 GRCh37 Chromosome 14, 99641850: 99641850
13 CARMIL2 NM_001013838.2(CARMIL2): c.1590C> A (p.Asn530Lys) single nucleotide variant Pathogenic GRCh38 Chromosome 16, 67648973: 67648973
14 CARMIL2 NM_001013838.2(CARMIL2): c.1590C> A (p.Asn530Lys) single nucleotide variant Pathogenic GRCh37 Chromosome 16, 67682876: 67682876

Expression for Combined Immunodeficiency, X-Linked

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

Pathways for Combined Immunodeficiency, X-Linked

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

# Super pathways Score Top Affiliating Genes
1 10.52 IL2RG ZAP70
2 10.14 IL2RG ZAP70

GO Terms for Combined Immunodeficiency, X-Linked

Sources for Combined Immunodeficiency, X-Linked

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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