IMD48
MCID: IMM143
MIFTS: 36

Immunodeficiency 48 (IMD48)

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

Aliases & Classifications for Immunodeficiency 48

MalaCards integrated aliases for Immunodeficiency 48:

Name: Immunodeficiency 48 57 12 72 15
Combined Immunodeficiency Due to Zap70 Deficiency 12 58 29 6
Selective T-Cell Defect 57 72 13
Imd48 57 12 72
Zeta-Associated-Protein 70 Deficiency 12 58
Stcd 57 72
Severe Combined Immunodeficiency, Atypical 44
Selective T-Cell Defect; Stcd 57
Immunodeficiency, Type 48 39
Zap70 Deficiency 70

Characteristics:

Orphanet epidemiological data:

58
combined immunodeficiency due to zap70 deficiency
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
immunodeficiency 48:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


Summaries for Immunodeficiency 48

Disease Ontology : 12 A T cell deficiency characterized by a selective T cell defect where circulating T cells exclusively express CD4, CD3, and T-cell receptor-alpha/beta and not CD8 on their surfaces that has material basis in homozygous or compound heterozygous mutation in ZAP70 on chromosome 2q11.2.

MalaCards based summary : Immunodeficiency 48, also known as combined immunodeficiency due to zap70 deficiency, is related to severe combined immunodeficiency, atypical and zap-70 deficiency, and has symptoms including diarrhea An important gene associated with Immunodeficiency 48 is ZAP70 (Zeta Chain Of T Cell Receptor Associated Protein Kinase 70). Affiliated tissues include t cells and b cells, and related phenotypes are recurrent viral infections and recurrent opportunistic infections

UniProtKB/Swiss-Prot : 72 Immunodeficiency 48: A form of severe immunodeficiency characterized by a selective absence of CD8+ T-cells.

More information from OMIM: 269840 PS300755

Related Diseases for Immunodeficiency 48

Diseases related to Immunodeficiency 48 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 severe combined immunodeficiency, atypical 11.5
2 zap-70 deficiency 11.5
3 zap70-related severe combined immunodeficiency 11.3
4 purine nucleoside phosphorylase deficiency 10.0

Symptoms & Phenotypes for Immunodeficiency 48

Human phenotypes related to Immunodeficiency 48:

58 31 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 recurrent viral infections 58 31 hallmark (90%) Very frequent (99-80%) HP:0004429
2 recurrent opportunistic infections 58 31 hallmark (90%) Very frequent (99-80%) HP:0005390
3 decreased lymphocyte proliferation in response to mitogen 58 31 hallmark (90%) Very frequent (99-80%) HP:0031381
4 failure to thrive 58 31 frequent (33%) Frequent (79-30%) HP:0001508
5 chronic diarrhea 58 31 frequent (33%) Frequent (79-30%) HP:0002028
6 pneumonia 58 31 frequent (33%) Frequent (79-30%) HP:0002090
7 recurrent infection of the gastrointestinal tract 58 31 frequent (33%) Frequent (79-30%) HP:0004798
8 recurrent upper and lower respiratory tract infections 58 31 frequent (33%) Frequent (79-30%) HP:0200117
9 chronic oral candidiasis 58 31 frequent (33%) Frequent (79-30%) HP:0009098
10 absence of cd8-positive t cells 58 31 frequent (33%) Frequent (79-30%) HP:0005422
11 nephrotic syndrome 58 31 occasional (7.5%) Occasional (29-5%) HP:0000100
12 stroke 58 31 occasional (7.5%) Occasional (29-5%) HP:0001297
13 skin rash 58 31 occasional (7.5%) Occasional (29-5%) HP:0000988
14 eosinophilia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001880
15 recurrent bacterial skin infections 58 31 occasional (7.5%) Occasional (29-5%) HP:0005406
16 lymphadenopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002716
17 hepatosplenomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001433
18 colitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002583
19 lymphocytosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0100827
20 recurrent mycobacterial infections 58 31 occasional (7.5%) Occasional (29-5%) HP:0011274
21 stomatitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0010280
22 lymphadenitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002840
23 lymphoma 58 31 very rare (1%) Very rare (<4-1%) HP:0002665
24 autoimmune hemolytic anemia 58 31 very rare (1%) Very rare (<4-1%) HP:0001890
25 autoimmune thrombocytopenia 58 31 very rare (1%) Very rare (<4-1%) HP:0001973
26 lymphoproliferative disorder 58 31 very rare (1%) Very rare (<4-1%) HP:0005523
27 splenomegaly 31 HP:0001744
28 hepatomegaly 31 HP:0002240
29 diarrhea 31 HP:0002014
30 eczematoid dermatitis 31 HP:0000976
31 chronic mucocutaneous candidiasis 58 Occasional (29-5%)
32 recurrent bacterial infections 58 Very frequent (99-80%)
33 recurrent candida infections 31 HP:0005401
34 abnormality of the lymph nodes 58 Occasional (29-5%)
35 panhypogammaglobulinemia 31 HP:0003139
36 decreased proportion of cd8-positive t cells 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Growth Other:
failure to thrive

Abdomen Liver:
hepatomegaly

Laboratory Abnormalities:
panhypogammaglobulinemia
defective (ca2+) mobilization in t cells

Respiratory Lung:
pneumonia, particularly pneumocystis carinii
parainfluenza pneumonitis

Abdomen Spleen:
splenomegaly

Abdomen Gastrointestinal:
diarrhea

Skin Nails Hair Skin:
candidiasis
chronic eczematoid rash

Immunology:
normal number of circulating lymphocytes
increased number of circulating lymphocytes
absent cd8+ t cells
abundant cd4+ t cells
normal number of natural killer cells
more

Clinical features from OMIM®:

269840 (Updated 05-Apr-2021)

UMLS symptoms related to Immunodeficiency 48:


diarrhea

Drugs & Therapeutics for Immunodeficiency 48

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 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

Search NIH Clinical Center for Immunodeficiency 48

Cochrane evidence based reviews: severe combined immunodeficiency, atypical

Genetic Tests for Immunodeficiency 48

Genetic tests related to Immunodeficiency 48:

# Genetic test Affiliating Genes
1 Combined Immunodeficiency Due to Zap70 Deficiency 29

Anatomical Context for Immunodeficiency 48

MalaCards organs/tissues related to Immunodeficiency 48:

40
T Cells, B Cells

Publications for Immunodeficiency 48

Articles related to Immunodeficiency 48:

# Title Authors PMID Year
1
Specific immunoglobulin E responses in ZAP-70-deficient patients are mediated by Syk-dependent T-cell receptor signalling. 57 6
11412303 2001
2
Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. 6 57
8202712 1994
3
Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. 6 57
8124727 1994
4
ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. 6
8202713 1994
5
A hereditary immunodeficiency characterized by CD8+ T lymphocyte deficiency and impaired lymphocyte activation. 57
1333922 1992
6
Depletion of CD8+ cells in human thymic medulla results in selective immune deficiency. 57
2511270 1989
7
First report on the Moroccan registry of primary immunodeficiencies: 15 years of experience (1998-2012). 61
24619622 2014

Variations for Immunodeficiency 48

ClinVar genetic disease variations for Immunodeficiency 48:

6 (show top 50) (show all 174)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ZAP70 NM_001079.4(ZAP70):c.261C>G (p.Tyr87Ter) SNV Pathogenic 954252 GRCh37: 2:98340760-98340760
GRCh38: 2:97724297-97724297
2 ZAP70 NM_001079.3(ZAP70):c.1247dup (p.Met416fs) Duplication Pathogenic 567226 rs1559328006 GRCh37: 2:98351876-98351877
GRCh38: 2:97735413-97735414
3 ZAP70 NM_001079.3(ZAP70):c.1624-11G>A SNV Pathogenic 13253 rs730880318 GRCh37: 2:98354447-98354447
GRCh38: 2:97737984-97737984
4 ZAP70 NM_001079.3(ZAP70):c.1510_1522del (p.Lys504fs) Deletion Pathogenic 13256 rs730880319 GRCh37: 2:98354246-98354258
GRCh38: 2:97737783-97737795
5 ZAP70 NM_001079.3(ZAP70):c.1393C>T (p.Arg465Cys) SNV Pathogenic 38912 rs113994174 GRCh37: 2:98354039-98354039
GRCh38: 2:97737576-97737576
6 ZAP70 NM_001079.3(ZAP70):c.1554C>A (p.Ser518Arg) SNV Pathogenic 13255 rs104893674 GRCh37: 2:98354291-98354291
GRCh38: 2:97737828-97737828
7 ZAP70 NM_001079.3(ZAP70):c.838-80G>A SNV Pathogenic 41039 rs113994173 GRCh37: 2:98349927-98349927
GRCh38: 2:97733464-97733464
8 ZAP70 NM_001079.3(ZAP70):c.1394G>A (p.Arg465His) SNV Pathogenic 13257 rs137853201 GRCh37: 2:98354040-98354040
GRCh38: 2:97737577-97737577
9 ZAP70 NM_001079.4(ZAP70):c.791-1G>A SNV Likely pathogenic 861386 GRCh37: 2:98349759-98349759
GRCh38: 2:97733296-97733296
10 ZAP70 NM_001079.3(ZAP70):c.7G>C (p.Asp3His) SNV Uncertain significance 538567 rs1009114725 GRCh37: 2:98340506-98340506
GRCh38: 2:97724043-97724043
11 ZAP70 NM_001079.3(ZAP70):c.1415G>A (p.Arg472Gln) SNV Uncertain significance 538568 rs758807149 GRCh37: 2:98354061-98354061
GRCh38: 2:97737598-97737598
12 ZAP70 NM_001079.3(ZAP70):c.1490C>T (p.Ser497Leu) SNV Uncertain significance 576771 rs149765220 GRCh37: 2:98354227-98354227
GRCh38: 2:97737764-97737764
13 ZAP70 NC_000002.12:g.(?_97737453)_(97739518_?)del Deletion Uncertain significance 831747 GRCh37: 2:98353916-98355981
GRCh38:
14 ZAP70 NM_001079.4(ZAP70):c.203C>G (p.Thr68Ser) SNV Uncertain significance 839560 GRCh37: 2:98340702-98340702
GRCh38: 2:97724239-97724239
15 ZAP70 NM_001079.4(ZAP70):c.1290-5C>A SNV Uncertain significance 842117 GRCh37: 2:98353931-98353931
GRCh38: 2:97737468-97737468
16 ZAP70 NM_001079.4(ZAP70):c.1094A>G (p.Asp365Gly) SNV Uncertain significance 847196 GRCh37: 2:98351724-98351724
GRCh38: 2:97735261-97735261
17 ZAP70 NM_001079.3(ZAP70):c.827C>T (p.Thr276Met) SNV Uncertain significance 565808 rs199502727 GRCh37: 2:98349796-98349796
GRCh38: 2:97733333-97733333
18 ZAP70 NM_001079.3(ZAP70):c.1591G>A (p.Glu531Lys) SNV Uncertain significance 567678 rs1559329735 GRCh37: 2:98354328-98354328
GRCh38: 2:97737865-97737865
19 ZAP70 NM_001079.3(ZAP70):c.1757T>C (p.Phe586Ser) SNV Uncertain significance 569200 rs1559330813 GRCh37: 2:98355858-98355858
GRCh38: 2:97739395-97739395
20 ZAP70 NM_001079.3(ZAP70):c.914C>T (p.Pro305Leu) SNV Uncertain significance 572188 rs762428344 GRCh37: 2:98351007-98351007
GRCh38: 2:97734544-97734544
21 ZAP70 NM_001079.3(ZAP70):c.1429A>G (p.Ile477Val) SNV Uncertain significance 573039 rs1559329401 GRCh37: 2:98354075-98354075
GRCh38: 2:97737612-97737612
22 ZAP70 NM_001079.3(ZAP70):c.973C>T (p.Leu325Phe) SNV Uncertain significance 640017 rs200511463 GRCh37: 2:98351066-98351066
GRCh38: 2:97734603-97734603
23 ZAP70 NM_001079.3(ZAP70):c.935C>T (p.Thr312Met) SNV Uncertain significance 640029 rs903840321 GRCh37: 2:98351028-98351028
GRCh38: 2:97734565-97734565
24 ZAP70 NM_001079.3(ZAP70):c.1018G>A (p.Ala340Thr) SNV Uncertain significance 640510 rs1559327232 GRCh37: 2:98351111-98351111
GRCh38: 2:97734648-97734648
25 ZAP70 NM_001079.3(ZAP70):c.1753G>A (p.Asp585Asn) SNV Uncertain significance 642248 rs200648080 GRCh37: 2:98355854-98355854
GRCh38: 2:97739391-97739391
26 ZAP70 NM_001079.3(ZAP70):c.1190A>G (p.Tyr397Cys) SNV Uncertain significance 642687 rs200097002 GRCh37: 2:98351820-98351820
GRCh38: 2:97735357-97735357
27 ZAP70 NM_001079.3(ZAP70):c.1765G>A (p.Val589Met) SNV Uncertain significance 646832 rs149605945 GRCh37: 2:98355866-98355866
GRCh38: 2:97739403-97739403
28 ZAP70 NM_001079.3(ZAP70):c.302C>A (p.Pro101Gln) SNV Uncertain significance 651969 rs1573262435 GRCh37: 2:98340801-98340801
GRCh38: 2:97724338-97724338
29 ZAP70 NM_001079.3(ZAP70):c.1139C>T (p.Thr380Met) SNV Uncertain significance 654054 rs1573284696 GRCh37: 2:98351769-98351769
GRCh38: 2:97735306-97735306
30 ZAP70 NM_001079.3(ZAP70):c.791-3C>T SNV Uncertain significance 658581 rs200430850 GRCh37: 2:98349757-98349757
GRCh38: 2:97733294-97733294
31 ZAP70 NM_001079.3(ZAP70):c.1115A>C (p.Lys372Thr) SNV Uncertain significance 662568 rs1573284622 GRCh37: 2:98351745-98351745
GRCh38: 2:97735282-97735282
32 ZAP70 NM_001079.3(ZAP70):c.1468G>A (p.Asp490Asn) SNV Uncertain significance 662682 rs56059280 GRCh37: 2:98354114-98354114
GRCh38: 2:97737651-97737651
33 ZAP70 NM_001079.3(ZAP70):c.940G>A (p.Val314Met) SNV Uncertain significance 636456 rs200679935 GRCh37: 2:98351033-98351033
GRCh38: 2:97734570-97734570
34 ZAP70 NM_001079.3(ZAP70):c.1737-3C>T SNV Uncertain significance 337638 rs56249179 GRCh37: 2:98355835-98355835
GRCh38: 2:97739372-97739372
35 ZAP70 NM_001079.3(ZAP70):c.1529_1532dup (p.Ile511fs) Duplication Uncertain significance 659957 rs770985198 GRCh37: 2:98354263-98354264
GRCh38: 2:97737800-97737801
36 ZAP70 NM_001079.3(ZAP70):c.109C>G (p.Arg37Gly) SNV Uncertain significance 659958 rs1573261820 GRCh37: 2:98340608-98340608
GRCh38: 2:97724145-97724145
37 ZAP70 NM_001079.4(ZAP70):c.711G>C (p.Glu237Asp) SNV Uncertain significance 945253 GRCh37: 2:98349596-98349596
GRCh38: 2:97733133-97733133
38 ZAP70 NM_001079.3(ZAP70):c.*161G>A SNV Uncertain significance 337641 rs886056486 GRCh37: 2:98356122-98356122
GRCh38: 2:97739659-97739659
39 ZAP70 NM_001079.3(ZAP70):c.156C>T (p.His52=) SNV Uncertain significance 337627 rs138447206 GRCh37: 2:98340655-98340655
GRCh38: 2:97724192-97724192
40 ZAP70 NM_001079.3(ZAP70):c.1083-3C>A SNV Uncertain significance 337635 rs199890589 GRCh37: 2:98351710-98351710
GRCh38: 2:97735247-97735247
41 ZAP70 NM_001079.3(ZAP70):c.606C>T (p.Leu202=) SNV Uncertain significance 337630 rs199943332 GRCh37: 2:98349388-98349388
GRCh38: 2:97732925-97732925
42 ZAP70 NM_001079.3(ZAP70):c.*328C>T SNV Uncertain significance 337643 rs201790312 GRCh37: 2:98356289-98356289
GRCh38: 2:97739826-97739826
43 ZAP70 NM_001079.3(ZAP70):c.516G>A (p.Glu172=) SNV Uncertain significance 337629 rs886056485 GRCh37: 2:98341668-98341668
GRCh38: 2:97725205-97725205
44 ZAP70 NM_001079.3(ZAP70):c.1617C>T (p.Pro539=) SNV Uncertain significance 337636 rs189807102 GRCh37: 2:98354354-98354354
GRCh38: 2:97737891-97737891
45 ZAP70 NM_001079.3(ZAP70):c.1025T>C (p.Ile342Thr) SNV Uncertain significance 337634 rs142702703 GRCh37: 2:98351118-98351118
GRCh38: 2:97734655-97734655
46 ZAP70 NM_001079.3(ZAP70):c.1737-3C>T SNV Uncertain significance 337638 rs56249179 GRCh37: 2:98355835-98355835
GRCh38: 2:97739372-97739372
47 ZAP70 NM_001079.3(ZAP70):c.-133C>T SNV Uncertain significance 337622 rs201616095 GRCh37: 2:98330105-98330105
GRCh38: 2:97713642-97713642
48 ZAP70 NM_001079.3(ZAP70):c.981C>G (p.Asp327Glu) SNV Uncertain significance 583386 rs201605654 GRCh37: 2:98351074-98351074
GRCh38: 2:97734611-97734611
49 ZAP70 NM_001079.3(ZAP70):c.1082+8C>T SNV Uncertain significance 471240 rs55933862 GRCh37: 2:98351183-98351183
GRCh38: 2:97734720-97734720
50 ZAP70 NM_001079.3(ZAP70):c.80C>A (p.Ala27Glu) SNV Uncertain significance 646277 rs373708142 GRCh37: 2:98340579-98340579
GRCh38: 2:97724116-97724116

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency 48:

72
# Symbol AA change Variation ID SNP ID
1 ZAP70 p.Ser518Arg VAR_006351 rs104893674
2 ZAP70 p.Arg465His VAR_015538 rs137853201
3 ZAP70 p.Leu337Arg VAR_065623 rs125442800
4 ZAP70 p.Arg465Cys VAR_065624 rs113994174
5 ZAP70 p.Ala507Val VAR_065625
6 ZAP70 p.Cys564Arg VAR_065626

Expression for Immunodeficiency 48

Search GEO for disease gene expression data for Immunodeficiency 48.

Pathways for Immunodeficiency 48

GO Terms for Immunodeficiency 48

Cellular components related to Immunodeficiency 48 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell-cell junction GO:0005911 8.62 ZAP70 DES

Sources for Immunodeficiency 48

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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