MCID: SVR096
MIFTS: 44

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

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

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.

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 combined immunodeficiency, x-linked and severe combined 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.

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, Lymph Node, Skin, Testes, Bone

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 155)
# 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 Pathogenic rs121918573 GRCh37 Chromosome 11, 36614286: 36614286
13 RAG2 NM_000536.3(RAG2): c.1433G> A (p.Cys478Tyr) single nucleotide variant Pathogenic rs121918573 GRCh38 Chromosome 11, 36592736: 36592736
14 RAG2 NM_000536.3(RAG2): c.686G> A (p.Arg229Gln) single nucleotide variant Pathogenic rs121917894 GRCh37 Chromosome 11, 36615033: 36615033
15 RAG2 NM_000536.3(RAG2): c.686G> A (p.Arg229Gln) single nucleotide variant Pathogenic rs121917894 GRCh38 Chromosome 11, 36593483: 36593483
16 RAG2 RAG2, 3-BP DEL, NT2018 deletion Pathogenic
17 RAG2 NM_000536.3(RAG2): c.115A> G (p.Arg39Gly) single nucleotide variant Pathogenic rs121917897 GRCh37 Chromosome 11, 36615604: 36615604
18 RAG2 NM_000536.3(RAG2): c.115A> G (p.Arg39Gly) single nucleotide variant Pathogenic rs121917897 GRCh38 Chromosome 11, 36594054: 36594054
19 RAG1 NM_000448.2(RAG1): c.2164G> A (p.Glu722Lys) single nucleotide variant Pathogenic rs28933392 GRCh37 Chromosome 11, 36597018: 36597018
20 RAG1 NM_000448.2(RAG1): c.2164G> A (p.Glu722Lys) single nucleotide variant Pathogenic rs28933392 GRCh38 Chromosome 11, 36575468: 36575468
21 RAG1 NM_000448.2(RAG1): c.2320G> T (p.Glu774Ter) single nucleotide variant Pathogenic rs104894282 GRCh37 Chromosome 11, 36597174: 36597174
22 RAG1 NM_000448.2(RAG1): c.2320G> T (p.Glu774Ter) single nucleotide variant Pathogenic rs104894282 GRCh38 Chromosome 11, 36575624: 36575624
23 RAG1 NM_000448.2(RAG1): c.2814T> G (p.Tyr938Ter) single nucleotide variant Pathogenic rs104894283 GRCh37 Chromosome 11, 36597668: 36597668
24 RAG1 NM_000448.2(RAG1): c.2814T> G (p.Tyr938Ter) single nucleotide variant Pathogenic rs104894283 GRCh38 Chromosome 11, 36576118: 36576118
25 RAG1 NM_000448.2(RAG1): c.1681C> T (p.Arg561Cys) single nucleotide variant Pathogenic rs104894285 GRCh37 Chromosome 11, 36596535: 36596535
26 RAG1 NM_000448.2(RAG1): c.1681C> T (p.Arg561Cys) single nucleotide variant Pathogenic rs104894285 GRCh38 Chromosome 11, 36574985: 36574985
27 RAG1 RAG1, 1-BP DEL, 631T deletion Pathogenic
28 RAG1 NM_000448.2(RAG1): c.2326C> T (p.Arg776Trp) single nucleotide variant Pathogenic rs121918572 GRCh37 Chromosome 11, 36597180: 36597180
29 RAG1 NM_000448.2(RAG1): c.2326C> T (p.Arg776Trp) single nucleotide variant Pathogenic rs121918572 GRCh38 Chromosome 11, 36575630: 36575630
30 RAG1 NM_000448.2(RAG1): c.322C> T (p.Arg108Ter) single nucleotide variant Pathogenic/Likely pathogenic rs193922464 GRCh37 Chromosome 11, 36595176: 36595176
31 RAG1 NM_000448.2(RAG1): c.322C> T (p.Arg108Ter) single nucleotide variant Pathogenic/Likely pathogenic rs193922464 GRCh38 Chromosome 11, 36573626: 36573626
32 RAG1 NM_000448.2(RAG1): c.1331C> T (p.Ala444Val) single nucleotide variant Pathogenic rs199474685 GRCh37 Chromosome 11, 36596185: 36596185
33 RAG1 NM_000448.2(RAG1): c.1331C> T (p.Ala444Val) single nucleotide variant Pathogenic rs199474685 GRCh38 Chromosome 11, 36574635: 36574635
34 RAG1 NM_000448.2(RAG1): c.2095C> T (p.Arg699Trp) single nucleotide variant Likely pathogenic rs199474676 GRCh37 Chromosome 11, 36596949: 36596949
35 RAG1 NM_000448.2(RAG1): c.2095C> T (p.Arg699Trp) single nucleotide variant Likely pathogenic rs199474676 GRCh38 Chromosome 11, 36575399: 36575399
36 JAK3 NM_000215.3(JAK3): c.187A> G (p.Ile63Val) single nucleotide variant Conflicting interpretations of pathogenicity rs144405201 GRCh37 Chromosome 19, 17954707: 17954707
37 JAK3 NM_000215.3(JAK3): c.187A> G (p.Ile63Val) single nucleotide variant Conflicting interpretations of pathogenicity rs144405201 GRCh38 Chromosome 19, 17843898: 17843898
38 RAG1 NM_000448.2(RAG1): c.1346G> A (p.Arg449Lys) single nucleotide variant Benign rs4151031 GRCh37 Chromosome 11, 36596200: 36596200
39 RAG1 NM_000448.2(RAG1): c.1346G> A (p.Arg449Lys) single nucleotide variant Benign rs4151031 GRCh38 Chromosome 11, 36574650: 36574650
40 RAG2 NM_000536.3(RAG2): c.878A> G (p.Glu293Gly) single nucleotide variant Benign/Likely benign rs16929093 GRCh38 Chromosome 11, 36593291: 36593291
41 RAG2 NM_000536.3(RAG2): c.878A> G (p.Glu293Gly) single nucleotide variant Benign/Likely benign rs16929093 GRCh37 Chromosome 11, 36614841: 36614841
42 RAG1 NM_000448.2(RAG1): c.256_257delAA (p.Lys86Valfs) deletion Pathogenic rs772962160 GRCh37 Chromosome 11, 36595110: 36595111
43 RAG1 NM_000448.2(RAG1): c.256_257delAA (p.Lys86Valfs) deletion Pathogenic rs772962160 GRCh38 Chromosome 11, 36573560: 36573561
44 RAG1 NM_000448.2(RAG1): c.2659G> A (p.Asp887Asn) single nucleotide variant Benign/Likely benign rs4151034 GRCh38 Chromosome 11, 36575963: 36575963
45 RAG1 NM_000448.2(RAG1): c.2659G> A (p.Asp887Asn) single nucleotide variant Benign/Likely benign rs4151034 GRCh37 Chromosome 11, 36597513: 36597513
46 RAG1 NM_000448.2(RAG1): c.577G> A (p.Glu193Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs34841221 GRCh37 Chromosome 11, 36595431: 36595431
47 RAG1 NM_000448.2(RAG1): c.577G> A (p.Glu193Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs34841221 GRCh38 Chromosome 11, 36573881: 36573881
48 RAG2 NM_000536.3(RAG2): c.1095T> C (p.Ser365=) single nucleotide variant Conflicting interpretations of pathogenicity rs140519815 GRCh38 Chromosome 11, 36593074: 36593074
49 RAG2 NM_000536.3(RAG2): c.1095T> C (p.Ser365=) single nucleotide variant Conflicting interpretations of pathogenicity rs140519815 GRCh37 Chromosome 11, 36614624: 36614624
50 JAK3 NM_000215.3(JAK3): c.2451C> T (p.Phe817=) single nucleotide variant Conflicting interpretations of pathogenicity rs201576913 GRCh38 Chromosome 19, 17832829: 17832829

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...

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
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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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