T B NK SCID
MCID: SVR096
MIFTS: 45

Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative (T B NK SCID)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Severe Combined Immunodeficiency, Autosomal Recessive, T...

MalaCards integrated aliases for Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative:

Name: Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative 57 29 6 40
Severe Immunodeficiency, Autosomal Recessive, T-Cell Negative, B-Cell Negative, Nk Cell-Positive 53 29 6 40
Severe Combined Immunodeficiency, B Cell-Negative 57 13 6
Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Positive 57 12
Severe Combined Immunodeficiency Due to Complete Rag1/2 Deficiency 53 59
Scid, Autosomal Recessive, T-Negative/b-Positive Type 57 13
Scid Due to Complete Rag1/2 Deficiency 53 59
Severe Combined Immunodeficiency Autosomal Recessive T-Cell-Negative/b-Cell-Negative/nk-Cell-Positive 75
Severe Combined Immunodeficiency Autosomal Recessive T Cell-Negative/b Cell-Negative/nk Cell-Positive 75
Severe Combined Immunodeficiency Autosomal Recessive T-Cell Negative/b-Cell Negative/nk-Cell Positive 75
Severe Combined Immunodeficiency Autosomal Recessive T-Cell-Negative/b-Cell-Positive/nk-Cell-Negative 75
Severe Combined Immunodeficiency Autosomal Recessive T Cell-Negative/b Cell-Positive/nk Cell-Negative 75
Severe Combined Immunodeficiency Autosomal Recessive T-Cell Negative/b-Cell Positive/nk-Cell Negative 75
Autosomal Recessive T Cell-Negative, B-Cell Negative, Nk Cell-Positive Scid 12
Severe Combined Immunodeficiency Due to Complete Rag1-2 Deficiency 12
Scid, Ar, T-Cell Negative, B-Cell Negative, Nk Cell-Positive 53
T-B+ Severe Combined Immunodeficiency Due to Jak3 Deficiency 59
Scid, T Cell-Negative, B Cell-Positive, Nk Cell-Negative 57
Scid, T Cell-Negative, B Cell-Negative, Nk Cell-Positive 57
Scid T Cell-Negative B Cell-Negative Nk Cell-Positive 75
Scid Due to Complete Rag1-2 Deficiency 12
T-B+ Scid Due to Jak3 Deficiency 59
T B Nk Scid 75

Characteristics:

Orphanet epidemiological data:

59
t-b+ severe combined immunodeficiency due to jak3 deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-positive, nk cell-negative:
Inheritance autosomal recessive inheritance

severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0090013
ICD10 33 D81.1
UMLS via Orphanet 74 C1832322
ICD10 via Orphanet 34 D81.1 D81.2
MeSH 44 D016511

Summaries for Severe Combined Immunodeficiency, Autosomal Recessive, T...

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 331206Disease definitionSevere combined immunodeficiency due to complete RAG1/2 deficiency is a rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia.Visit the Orphanet disease page for more resources.

MalaCards based summary : Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative, also known as severe immunodeficiency, autosomal recessive, t-cell negative, b-cell negative, nk cell-positive, is related to severe combined immunodeficiency and combined t cell and b cell immunodeficiency. An important gene associated with Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative is JAK3 (Janus Kinase 3), and among its related pathways/superpathways are Cytokine Signaling in Immune system and NF-kappaB Signaling. Affiliated tissues include b cells, t cells and nk cells, and related phenotypes are failure to thrive and arthritis

Disease Ontology : 12 A severe combined immunodeficiency characterized by being T cell-negative, B cell-negative and natural killer cell-positive and that has material basis in mutation in the RAG1 and RAG2 genes on chromosome 11p12.

UniProtKB/Swiss-Prot : 75 Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.

Description from OMIM: 600802 601457

Related Diseases for Severe Combined Immunodeficiency, Autosomal Recessive, T...

Graphical network of the top 20 diseases related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative:



Diseases related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative

Symptoms & Phenotypes for Severe Combined Immunodeficiency, Autosomal Recessive, T...

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive

Abdomen Gastrointestinal:
intestinal obstruction
diarrhea

Respiratory Lung:
pneumonia

Immunology:
absent natural killer cell cytotoxicity
undetectable/absent peripheral lymph nodes
markedly reduced cd3+ proportion
increased proportion of cd19+ b cells
intrinsic b cell defect
more
Respiratory Airways:
recurrent upper respiratory tract infections

Neurologic Central Nervous System:
meningitis

Laboratory Abnormalities:
panhypogammaglobulinemia


Clinical features from OMIM:

600802 601457

Human phenotypes related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative:

32 (show all 18)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 arthritis 32 HP:0001369
3 recurrent upper respiratory tract infections 32 HP:0002788
4 intestinal obstruction 32 HP:0005214
5 diarrhea 32 HP:0002014
6 otitis media 32 HP:0000388
7 conjunctivitis 32 HP:0000509
8 meningitis 32 HP:0001287
9 decrease in t cell count 32 HP:0005403
10 b lymphocytopenia 32 HP:0010976
11 pneumonia 32 HP:0002090
12 abnormality of the lymph nodes 32 HP:0002733
13 severe combined immunodeficiency 32 HP:0004430
14 panhypogammaglobulinemia 32 HP:0003139
15 recurrent opportunistic infections 32 HP:0005390
16 cutaneous anergy 32 HP:0002965
17 mastoiditis 32 HP:0000265
18 failure to thrive secondary to recurrent infections 32 HP:0008866

MGI Mouse Phenotypes related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.13 JAK3 RAG1 RAG2
2 endocrine/exocrine gland MP:0005379 8.8 JAK3 RAG1 RAG2

Drugs & Therapeutics for Severe Combined Immunodeficiency, Autosomal Recessive, T...

Search Clinical Trials , NIH Clinical Center for Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative

Genetic Tests for Severe Combined Immunodeficiency, Autosomal Recessive, T...

Genetic tests related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative:

# Genetic test Affiliating Genes
1 Severe Immunodeficiency, Autosomal Recessive, T-Cell Negative, B-Cell Negative, Nk Cell-Positive 29 RAG1 RAG2
2 Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative 29 JAK3

Anatomical Context for Severe Combined Immunodeficiency, Autosomal Recessive, T...

MalaCards organs/tissues related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative:

41
B Cells, T Cells, Nk Cells, Skin, Lymph Node, Testes, Bone Marrow

Publications for Severe Combined Immunodeficiency, Autosomal Recessive, T...

Articles related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative:

# Title Authors Year
1
A novel pathogenic frameshift variant of CD3E gene in two T-B+ NK+ SCID patients from Turkey. ( 28597365 )
2017
2
Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID. ( 21883749 )
2011
3
A novel missense RAG-1 mutation results in T-B-NK+ SCID in Athabascan-speaking Dine Indians from the Canadian Northwest Territories. ( 18701881 )
2009
4
A novel DKC1 mutation, severe combined immunodeficiency (T+B-NK-SCID) and bone marrow transplantation in an infant with Hoyeraal-Hreidarsson syndrome. ( 12437656 )
2002

Variations for Severe Combined Immunodeficiency, Autosomal Recessive, T...

UniProtKB/Swiss-Prot genetic disease variations for Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative:

75 (show all 14)
# Symbol AA change Variation ID SNP ID
1 JAK3 p.Tyr100Cys VAR_006284 rs137852624
2 JAK3 p.Pro151Arg VAR_010492 rs55778349
3 JAK3 p.Glu481Gly VAR_010493
4 JAK3 p.Arg582Trp VAR_010494 rs193922361
5 JAK3 p.Cys759Arg VAR_010497
6 JAK3 p.Leu910Ser VAR_010498
7 JAK3 p.Asp169Glu VAR_019338 rs147181709
8 JAK3 p.Gly589Ser VAR_019339 rs886039394
9 RAG1 p.Arg624His VAR_007803 rs199474680
10 RAG1 p.Glu722Lys VAR_007804 rs28933392
11 RAG1 p.Val433Met VAR_025975 rs199474679
12 RAG1 p.Arg559Ser VAR_025981 rs199474681
13 RAG2 p.Arg229Gln VAR_005570 rs121917894
14 RAG2 p.Cys478Tyr VAR_005571 rs121918573

ClinVar genetic disease variations for Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative:

6 (show top 50) (show all 265)
# Gene Variation Type Significance SNP ID Assembly Location
1 JAK3 NM_000215.3(JAK3): c.299A> G (p.Tyr100Cys) single nucleotide variant Pathogenic rs137852624 GRCh37 Chromosome 19, 17954595: 17954595
2 JAK3 NM_000215.3(JAK3): c.299A> G (p.Tyr100Cys) single nucleotide variant Pathogenic rs137852624 GRCh38 Chromosome 19, 17843786: 17843786
3 JAK3 JAK3, 151-BP DEL deletion Pathogenic
4 JAK3 JAK3, 1-BP INS, 1172G insertion Pathogenic
5 JAK3 NM_000215.3(JAK3): c.1695C> A (p.Cys565Ter) single nucleotide variant Pathogenic rs137852625 GRCh37 Chromosome 19, 17948747: 17948747
6 JAK3 NM_000215.3(JAK3): c.1695C> A (p.Cys565Ter) single nucleotide variant Pathogenic rs137852625 GRCh38 Chromosome 19, 17837938: 17837938
7 JAK3 NM_000215.3(JAK3): c.1333C> T (p.Arg445Ter) single nucleotide variant Pathogenic rs137852626 GRCh37 Chromosome 19, 17950394: 17950394
8 JAK3 NM_000215.3(JAK3): c.1333C> T (p.Arg445Ter) single nucleotide variant Pathogenic rs137852626 GRCh38 Chromosome 19, 17839585: 17839585
9 JAK3 JAK3, ASP169GLU undetermined variant Pathogenic
10 JAK3 NM_000215.3(JAK3): c.172_174delGCC (p.Ala58del) deletion Pathogenic rs137852627 GRCh37 Chromosome 19, 17955053: 17955055
11 JAK3 NM_000215.3(JAK3): c.172_174delGCC (p.Ala58del) deletion Pathogenic rs137852627 GRCh38 Chromosome 19, 17844244: 17844246
12 RAG2 NM_000536.3(RAG2): c.1433G> A (p.Cys478Tyr) single nucleotide variant Uncertain significance rs121918573 GRCh37 Chromosome 11, 36614286: 36614286
13 RAG2 NM_000536.3(RAG2): c.1433G> A (p.Cys478Tyr) single nucleotide variant Uncertain significance rs121918573 GRCh38 Chromosome 11, 36592736: 36592736
14 RAG2 NM_000536.3(RAG2): c.686G> A (p.Arg229Gln) single nucleotide variant Uncertain significance rs121917894 GRCh37 Chromosome 11, 36615033: 36615033
15 RAG2 NM_000536.3(RAG2): c.686G> A (p.Arg229Gln) single nucleotide variant Uncertain significance rs121917894 GRCh38 Chromosome 11, 36593483: 36593483
16 RAG2 NM_000536.3(RAG2): c.123C> G (p.Cys41Trp) single nucleotide variant Likely pathogenic rs121917895 GRCh37 Chromosome 11, 36615596: 36615596
17 RAG2 NM_000536.3(RAG2): c.123C> G (p.Cys41Trp) single nucleotide variant Likely pathogenic rs121917895 GRCh38 Chromosome 11, 36594046: 36594046
18 RAG2 NM_001243785.1(RAG2): c.283G> A (p.Gly95Arg) single nucleotide variant Likely pathogenic rs36001797 GRCh37 Chromosome 11, 36615436: 36615436
19 RAG2 NM_001243785.1(RAG2): c.283G> A (p.Gly95Arg) single nucleotide variant Likely pathogenic rs36001797 GRCh38 Chromosome 11, 36593886: 36593886
20 RAG2 RAG2, 3-BP DEL, NT2018 deletion Pathogenic
21 RAG2 NM_000536.3(RAG2): c.644C> T (p.Thr215Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs35691292 GRCh37 Chromosome 11, 36615075: 36615075
22 RAG2 NM_000536.3(RAG2): c.644C> T (p.Thr215Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs35691292 GRCh38 Chromosome 11, 36593525: 36593525
23 RAG2 NM_000536.3(RAG2): c.115A> G (p.Arg39Gly) single nucleotide variant Likely pathogenic rs121917897 GRCh37 Chromosome 11, 36615604: 36615604
24 RAG2 NM_000536.3(RAG2): c.115A> G (p.Arg39Gly) single nucleotide variant Likely pathogenic rs121917897 GRCh38 Chromosome 11, 36594054: 36594054
25 RAG1 NM_000448.2(RAG1): c.2164G> A (p.Glu722Lys) single nucleotide variant Pathogenic rs28933392 GRCh37 Chromosome 11, 36597018: 36597018
26 RAG1 NM_000448.2(RAG1): c.2164G> A (p.Glu722Lys) single nucleotide variant Pathogenic rs28933392 GRCh38 Chromosome 11, 36575468: 36575468
27 RAG1 NM_000448.2(RAG1): c.2320G> T (p.Glu774Ter) single nucleotide variant Pathogenic rs104894282 GRCh37 Chromosome 11, 36597174: 36597174
28 RAG1 NM_000448.2(RAG1): c.2320G> T (p.Glu774Ter) single nucleotide variant Pathogenic rs104894282 GRCh38 Chromosome 11, 36575624: 36575624
29 RAG1 NM_000448.2(RAG1): c.2814T> G (p.Tyr938Ter) single nucleotide variant Pathogenic rs104894283 GRCh37 Chromosome 11, 36597668: 36597668
30 RAG1 NM_000448.2(RAG1): c.2814T> G (p.Tyr938Ter) single nucleotide variant Pathogenic rs104894283 GRCh38 Chromosome 11, 36576118: 36576118
31 RAG1 NM_000448.2(RAG1): c.1187G> A (p.Arg396His) single nucleotide variant Pathogenic rs104894291 GRCh37 Chromosome 11, 36596041: 36596041
32 RAG1 NM_000448.2(RAG1): c.1187G> A (p.Arg396His) single nucleotide variant Pathogenic rs104894291 GRCh38 Chromosome 11, 36574491: 36574491
33 RAG1 NM_000448.2(RAG1): c.1681C> T (p.Arg561Cys) single nucleotide variant Pathogenic rs104894285 GRCh37 Chromosome 11, 36596535: 36596535
34 RAG1 NM_000448.2(RAG1): c.1681C> T (p.Arg561Cys) single nucleotide variant Pathogenic rs104894285 GRCh38 Chromosome 11, 36574985: 36574985
35 RAG1 RAG1, 1-BP DEL, 631T deletion Pathogenic
36 RAG1 NM_000448.2(RAG1): c.2326C> T (p.Arg776Trp) single nucleotide variant Pathogenic rs121918572 GRCh37 Chromosome 11, 36597180: 36597180
37 RAG1 NM_000448.2(RAG1): c.2326C> T (p.Arg776Trp) single nucleotide variant Pathogenic rs121918572 GRCh38 Chromosome 11, 36575630: 36575630
38 JAK3 NM_000215.3(JAK3): c.2259C> T (p.Ala753=) single nucleotide variant Benign rs35458530 GRCh37 Chromosome 19, 17945471: 17945471
39 JAK3 NM_000215.3(JAK3): c.2259C> T (p.Ala753=) single nucleotide variant Benign rs35458530 GRCh38 Chromosome 19, 17834662: 17834662
40 JAK3 NM_000215.3(JAK3): c.2625C> T (p.Leu875=) single nucleotide variant Benign rs2230589 GRCh37 Chromosome 19, 17943383: 17943383
41 JAK3 NM_000215.3(JAK3): c.2625C> T (p.Leu875=) single nucleotide variant Benign rs2230589 GRCh38 Chromosome 19, 17832574: 17832574
42 JAK3 NM_000215.3(JAK3): c.452C> G (p.Pro151Arg) single nucleotide variant Benign/Likely benign rs55778349 GRCh37 Chromosome 19, 17953950: 17953950
43 JAK3 NM_000215.3(JAK3): c.452C> G (p.Pro151Arg) single nucleotide variant Benign/Likely benign rs55778349 GRCh38 Chromosome 19, 17843141: 17843141
44 RAG1 NM_000448.2(RAG1): c.1566G> T (p.Trp522Cys) single nucleotide variant Pathogenic rs193922461 GRCh37 Chromosome 11, 36596420: 36596420
45 RAG1 NM_000448.2(RAG1): c.1566G> T (p.Trp522Cys) single nucleotide variant Pathogenic rs193922461 GRCh38 Chromosome 11, 36574870: 36574870
46 RAG1 NM_000448.2(RAG1): c.189A> G (p.Pro63=) single nucleotide variant Benign/Likely benign rs34357808 GRCh37 Chromosome 11, 36595043: 36595043
47 RAG1 NM_000448.2(RAG1): c.189A> G (p.Pro63=) single nucleotide variant Benign/Likely benign rs34357808 GRCh38 Chromosome 11, 36573493: 36573493
48 RAG1 NM_000448.2(RAG1): c.322C> T (p.Arg108Ter) single nucleotide variant Pathogenic/Likely pathogenic rs193922464 GRCh37 Chromosome 11, 36595176: 36595176
49 RAG1 NM_000448.2(RAG1): c.322C> T (p.Arg108Ter) single nucleotide variant Pathogenic/Likely pathogenic rs193922464 GRCh38 Chromosome 11, 36573626: 36573626
50 RAG1 NM_000448.2(RAG1): c.906C> A (p.Asp302Glu) single nucleotide variant Benign/Likely benign rs4151030 GRCh37 Chromosome 11, 36595760: 36595760

Expression for Severe Combined Immunodeficiency, Autosomal Recessive, T...

Search GEO for disease gene expression data for Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative.

Pathways for Severe Combined Immunodeficiency, Autosomal Recessive, T...

Pathways related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.54 JAK3 RAG1 RAG2
2 11.84 JAK3 RAG1
3
Show member pathways
11.3 RAG1 RAG2
4 10.7 JAK3 RAG1 RAG2
5 10.25 JAK3 RAG1 RAG2

GO Terms for Severe Combined Immunodeficiency, Autosomal Recessive, T...

Biological processes related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin organization GO:0006325 9.46 RAG1 RAG2
2 adaptive immune response GO:0002250 9.43 JAK3 RAG1
3 DNA recombination GO:0006310 9.4 RAG1 RAG2
4 T cell differentiation in thymus GO:0033077 9.37 RAG1 RAG2
5 T cell homeostasis GO:0043029 9.32 JAK3 RAG1
6 V(D)J recombination GO:0033151 9.26 RAG1 RAG2
7 negative regulation of thymocyte apoptotic process GO:0070244 9.16 JAK3 RAG1
8 pre-B cell allelic exclusion GO:0002331 8.96 RAG1 RAG2
9 B cell differentiation GO:0030183 8.8 JAK3 RAG1 RAG2

Molecular functions related to Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ubiquitin protein ligase activity GO:0061630 8.62 RAG1 RAG2

Sources for Severe Combined Immunodeficiency, Autosomal Recessive, T...

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10 dbSNP
11 DGIdb
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69 SNOMED-CT via HPO
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74 UMLS via Orphanet
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