CCHIDG
MCID: CMB022
MIFTS: 35

Combined Cellular and Humoral Immune Defects with Granulomas (CCHIDG)

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

Aliases & Classifications for Combined Cellular and Humoral Immune Defects with Granulomas

MalaCards integrated aliases for Combined Cellular and Humoral Immune Defects with Granulomas:

Name: Combined Cellular and Humoral Immune Defects with Granulomas 56 52 73 29 13 6 71
Combined Immunodeficiency Due to Rag 1/2 Deficiency 52 58
Combined Immunodeficiency with Skin Granulomas 52 6
Combined Immunodeficiency with Granulomatosis 52 58
Cid Due to Rag 1/2 Deficiency 52 58
Immune Defects, Combined Cellular and Humoral with Granulomas 39
Cchidg 56
Chidg 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood
allelic disorder to t cell-negative, b cell-negative, nk cell- negative scid , which is more severe


HPO:

31
combined cellular and humoral immune defects with granulomas:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare skin diseases
Rare immunological diseases


External Ids:

OMIM 56 233650
ICD10 via Orphanet 33 D81.1
UMLS via Orphanet 72 C2673536
Orphanet 58 ORPHA157949
MedGen 41 C2673536
SNOMED-CT via HPO 68 123785006 190981001 258211005
UMLS 71 C2673536

Summaries for Combined Cellular and Humoral Immune Defects with Granulomas

NIH Rare Diseases : 52 Combined immunodeficiency with skin granulomas is characterized by recurrent viral infections and the presence of granulomas in the skin, mucous membranes and/or internal organs . There is a gradual reduction in the number and function of B cells (a type of white blood cell that makes antibodies ), and T lymphocytes (a type of white blood cell , that protect the body from infection attacking the infected cells directly), hypogammaglobulinemia (reduction in all types of gamma globulins, including antibodies that help fight infection.) and defective autoinmunity where the immune system attacks the body itself. Some people may develop associated auto-immune diseases such as myasthenia gravis , vitiligo , low blood red and white cells, psoriasis , and Guillain-Barre syndrome . It is caused by mutations in the RAG1 and/or RAG2 genes . These genes provide instructions for making a member of a group of proteins called the RAG complex, which is involved in the process, known as V(D)J recombination , needed for maintaining the diversity of the B and T cells so they can be able to recognize diverse foreign agents allowing the body to fight infections. The mutations can impair RAG complex formation and function, resulting in an impaired B and T cells' function. Depending on the residual activity of the RAG proteins the disease can be more or less severe. In less severe cases symptoms are milder and may appear later in life. Treatment is with bone marrow transplantation .

MalaCards based summary : Combined Cellular and Humoral Immune Defects with Granulomas, also known as combined immunodeficiency due to rag 1/2 deficiency, is related to recombinase activating gene 1 deficiency and inflammatory bowel disease 18. An important gene associated with Combined Cellular and Humoral Immune Defects with Granulomas is RAG1 (Recombination Activating 1), and among its related pathways/superpathways are FoxO signaling pathway and Primary immunodeficiency. Affiliated tissues include skin, b cells and t cells, and related phenotypes are recurrent respiratory infections and decreased circulating igg level

UniProtKB/Swiss-Prot : 73 Combined cellular and humoral immune defects with granulomas: Immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. Other characteristics include hypogammaglobulinemia, a diminished number of T and B-cells, and sparse thymic tissue on ultrasonography.

More information from OMIM: 233650

Related Diseases for Combined Cellular and Humoral Immune Defects with Granulomas

Graphical network of the top 20 diseases related to Combined Cellular and Humoral Immune Defects with Granulomas:



Diseases related to Combined Cellular and Humoral Immune Defects with Granulomas

Symptoms & Phenotypes for Combined Cellular and Humoral Immune Defects with Granulomas

Human phenotypes related to Combined Cellular and Humoral Immune Defects with Granulomas:

31
# Description HPO Frequency HPO Source Accession
1 recurrent respiratory infections 31 HP:0002205
2 decreased circulating igg level 31 HP:0004315
3 decrease in t cell count 31 HP:0005403
4 b lymphocytopenia 31 HP:0010976
5 combined immunodeficiency 31 HP:0005387

Symptoms via clinical synopsis from OMIM:

56
Immunology:
hypogammaglobulinemia
granulomas, non-infectious
granulomas can appear on skin, tongue, lungs, or other tissues
lack of thymus on ultrasound
decreased numbers of b cells
more

Clinical features from OMIM:

233650

Drugs & Therapeutics for Combined Cellular and Humoral Immune Defects with Granulomas

Search Clinical Trials , NIH Clinical Center for Combined Cellular and Humoral Immune Defects with Granulomas

Genetic Tests for Combined Cellular and Humoral Immune Defects with Granulomas

Genetic tests related to Combined Cellular and Humoral Immune Defects with Granulomas:

# Genetic test Affiliating Genes
1 Combined Cellular and Humoral Immune Defects with Granulomas 29 RAG1 RAG2

Anatomical Context for Combined Cellular and Humoral Immune Defects with Granulomas

MalaCards organs/tissues related to Combined Cellular and Humoral Immune Defects with Granulomas:

40
Skin, B Cells, T Cells, Bone, Bone Marrow, Thymus, Lung

Publications for Combined Cellular and Humoral Immune Defects with Granulomas

Articles related to Combined Cellular and Humoral Immune Defects with Granulomas:

# Title Authors PMID Year
1
Hypomorphic Rag mutations can cause destructive midline granulomatous disease. 56 6
20489056 2010
2
An immunodeficiency disease with RAG mutations and granulomas. 56 6
18463379 2008
3
Familial combined cellular and humoral immune defect with multisystem granulomata. 56
644530 1978

Variations for Combined Cellular and Humoral Immune Defects with Granulomas

ClinVar genetic disease variations for Combined Cellular and Humoral Immune Defects with Granulomas:

6 (show top 50) (show all 94) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RAG1 NM_000448.2(RAG1):c.1187G>A (p.Arg396His)SNV Pathogenic 13146 rs104894291 11:36596041-36596041 11:36574491-36574491
2 RAG1 NM_000448.2(RAG1):c.2210G>A (p.Arg737His)SNV Pathogenic 13149 rs104894286 11:36597064-36597064 11:36575514-36575514
3 RAG1 NM_000448.2(RAG1):c.940C>T (p.Arg314Trp)SNV Pathogenic 13156 rs121918568 11:36595794-36595794 11:36574244-36574244
4 RAG1 NM_000448.2(RAG1):c.2333G>A (p.Arg778Gln)SNV Pathogenic 13158 rs121918569 11:36597187-36597187 11:36575637-36575637
5 RAG1 NM_000448.2(RAG1):c.983G>A (p.Cys328Tyr)SNV Pathogenic 13160 rs121918571 11:36595837-36595837 11:36574287-36574287
6 RAG1 NM_000448.2(RAG1):c.1621del (p.Leu541fs)deletion Pathogenic 29867 11:36596475-36596475 11:36574925-36574925
7 RAG1 NM_000448.2(RAG1):c.1566G>T (p.Trp522Cys)SNV Pathogenic 36710 rs193922461 11:36596420-36596420 11:36574870-36574870
8 RAG1 NM_000448.2(RAG1):c.1421G>A (p.Arg474His)SNV Pathogenic 68684 rs199474686 11:36596275-36596275 11:36574725-36574725
9 RAG1 NM_000448.2(RAG1):c.2974A>G (p.Lys992Glu)SNV Pathogenic 372488 rs539590514 11:36597828-36597828 11:36576278-36576278
10 RAG2 NM_000536.4(RAG2):c.595G>T (p.Glu199Ter)SNV Pathogenic 463972 rs748727021 11:36615124-36615124 11:36593574-36593574
11 RAG1 NM_000448.2(RAG1):c.1180C>T (p.Arg394Trp)SNV Pathogenic 660211 11:36596034-36596034 11:36574484-36574484
12 RAG1 NM_000448.2(RAG1):c.994C>T (p.Arg332Ter)SNV Pathogenic 649706 11:36595848-36595848 11:36574298-36574298
13 RAG1 NM_000448.2(RAG1):c.424C>T (p.Arg142Ter)SNV Pathogenic 626157 rs773929270 11:36595278-36595278 11:36573728-36573728
14 RAG1 NC_000011.10:g.36573664_36573671deldeletion Pathogenic 802671 11:36595210-36595217 11:36573660-36573667
15 RAG1 NC_000011.10:g.36575636C>TSNV Pathogenic 802672 11:36597186-36597186 11:36575636-36575636
16 RAG1 NM_000448.2(RAG1):c.2348C>G (p.Ser783Ter)SNV Pathogenic/Likely pathogenic 573434 rs754502950 11:36597202-36597202 11:36575652-36575652
17 RAG1 NM_000448.2(RAG1):c.1210C>T (p.Arg404Trp)SNV Pathogenic/Likely pathogenic 636824 11:36596064-36596064 11:36574514-36574514
18 RAG1 NM_000448.2(RAG1):c.322C>T (p.Arg108Ter)SNV Pathogenic/Likely pathogenic 36714 rs193922464 11:36595176-36595176 11:36573626-36573626
19 RAG1 NM_000448.2(RAG1):c.1303A>G (p.Met435Val)SNV Pathogenic/Likely pathogenic 68680 rs141524540 11:36596157-36596157 11:36574607-36574607
20 RAG1 NM_000448.2(RAG1):c.2326C>T (p.Arg776Trp)SNV Likely pathogenic 13161 rs121918572 11:36597180-36597180 11:36575630-36575630
21 RAG2 NM_000536.4(RAG2):c.283G>A (p.Gly95Arg)SNV Likely pathogenic 13133 rs36001797 11:36615436-36615436 11:36593886-36593886
22 RAG2 NM_000536.4(RAG2):c.230C>A (p.Thr77Asn)SNV Likely pathogenic 13137 rs121918574 11:36615489-36615489 11:36593939-36593939
23 RAG2 NM_000536.4(RAG2):c.1375A>C (p.Met459Leu)SNV Likely pathogenic 496632 rs1204766339 11:36614344-36614344 11:36592794-36592794
24 RAG2 NM_000536.4(RAG2):c.186C>A (p.Phe62Leu)SNV Likely pathogenic 496619 rs1564997563 11:36615533-36615533 11:36593983-36593983
25 RAG2 NM_000536.4(RAG2):c.1352G>C (p.Gly451Ala)SNV Conflicting interpretations of pathogenicity 13138 rs121918575 11:36614367-36614367 11:36592817-36592817
26 RAG1 NM_000448.2(RAG1):c.2603C>T (p.Ala868Val)SNV Conflicting interpretations of pathogenicity 36712 rs193922462 11:36597457-36597457 11:36575907-36575907
27 RAG2 NM_000536.4(RAG2):c.104G>C (p.Gly35Ala)SNV Conflicting interpretations of pathogenicity 36716 rs148508754 11:36615615-36615615 11:36594065-36594065
28 RAG1 NM_000448.2(RAG1):c.2981A>G (p.His994Arg)SNV Conflicting interpretations of pathogenicity 372489 rs775412266 11:36597835-36597835 11:36576285-36576285
29 RAG1 NM_000448.2(RAG1):c.335G>A (p.Arg112His)SNV Conflicting interpretations of pathogenicity 427093 rs749223640 11:36595189-36595189 11:36573639-36573639
30 RAG2 NM_000536.4(RAG2):c.1504A>G (p.Met502Val)SNV Conflicting interpretations of pathogenicity 440231 rs145614809 11:36614215-36614215 11:36592665-36592665
31 RAG1 NM_000448.2(RAG1):c.527G>T (p.Cys176Phe)SNV Conflicting interpretations of pathogenicity 372487 rs149229197 11:36595381-36595381 11:36573831-36573831
32 RAG1 NM_000448.2(RAG1):c.549G>A (p.Met183Ile)SNV Uncertain significance 626003 rs750394886 11:36595403-36595403 11:36573853-36573853
33 RAG1 NM_000448.2(RAG1):c.997T>C (p.Tyr333His)SNV Uncertain significance 644561 11:36595851-36595851 11:36574301-36574301
34 RAG1 NM_000448.2(RAG1):c.1012A>C (p.Thr338Pro)SNV Uncertain significance 646474 11:36595866-36595866 11:36574316-36574316
35 RAG1 NM_000448.2(RAG1):c.1154T>C (p.Ile385Thr)SNV Uncertain significance 656205 11:36596008-36596008 11:36574458-36574458
36 RAG1 NM_000448.2(RAG1):c.1256A>G (p.Lys419Arg)SNV Uncertain significance 641925 11:36596110-36596110 11:36574560-36574560
37 RAG1 NM_000448.2(RAG1):c.1468A>G (p.Thr490Ala)SNV Uncertain significance 662733 11:36596322-36596322 11:36574772-36574772
38 RAG1 NM_000448.2(RAG1):c.1559T>C (p.Phe520Ser)SNV Uncertain significance 641796 11:36596413-36596413 11:36574863-36574863
39 RAG1 NM_000448.2(RAG1):c.2060G>A (p.Ser687Asn)SNV Uncertain significance 646600 11:36596914-36596914 11:36575364-36575364
40 RAG1 NM_000448.2(RAG1):c.2140C>T (p.Leu714Phe)SNV Uncertain significance 652982 11:36596994-36596994 11:36575444-36575444
41 RAG1 NM_000448.2(RAG1):c.2204C>T (p.Ala735Val)SNV Uncertain significance 653876 11:36597058-36597058 11:36575508-36575508
42 RAG1 NM_000448.2(RAG1):c.2516A>T (p.His839Leu)SNV Uncertain significance 645889 11:36597370-36597370 11:36575820-36575820
43 RAG2 NM_000536.4(RAG2):c.1516C>T (p.Arg506Cys)SNV Uncertain significance 663452 11:36614203-36614203 11:36592653-36592653
44 RAG2 NM_000536.4(RAG2):c.1396C>T (p.Leu466Phe)SNV Uncertain significance 650904 11:36614323-36614323 11:36592773-36592773
45 RAG2 NM_000536.4(RAG2):c.1253C>T (p.Thr418Ile)SNV Uncertain significance 660163 11:36614466-36614466 11:36592916-36592916
46 RAG2 NM_000536.4(RAG2):c.1092C>G (p.Asn364Lys)SNV Uncertain significance 665506 11:36614627-36614627 11:36593077-36593077
47 RAG2 NM_000536.4(RAG2):c.830A>G (p.Tyr277Cys)SNV Uncertain significance 639778 11:36614889-36614889 11:36593339-36593339
48 RAG2 NM_000536.4(RAG2):c.242A>G (p.Lys81Arg)SNV Uncertain significance 662108 11:36615477-36615477 11:36593927-36593927
49 RAG2 NM_000536.4(RAG2):c.68A>G (p.Asn23Ser)SNV Uncertain significance 658239 11:36615651-36615651 11:36594101-36594101
50 RAG1 NM_000448.2(RAG1):c.1060C>A (p.Leu354Met)SNV Uncertain significance 469110 rs753165042 11:36595914-36595914 11:36574364-36574364

UniProtKB/Swiss-Prot genetic disease variations for Combined Cellular and Humoral Immune Defects with Granulomas:

73
# Symbol AA change Variation ID SNP ID
1 RAG1 p.Arg737His VAR_008891 rs104894286
2 RAG1 p.Arg507Trp VAR_025979 rs104894298
3 RAG1 p.Arg314Trp VAR_045957 rs121918568
4 RAG1 p.Arg778Gln VAR_045958 rs121918569
5 RAG1 p.Arg975Trp VAR_045959 rs121918570
6 RAG2 p.Thr77Asn VAR_045960 rs121918574
7 RAG2 p.Gly451Ala VAR_045962 rs121918575

Expression for Combined Cellular and Humoral Immune Defects with Granulomas

Search GEO for disease gene expression data for Combined Cellular and Humoral Immune Defects with Granulomas.

Pathways for Combined Cellular and Humoral Immune Defects with Granulomas

Pathways related to Combined Cellular and Humoral Immune Defects with Granulomas according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.29 RAG2 RAG1
2 10.54 RAG2 RAG1
3 10.07 RAG2 RAG1

GO Terms for Combined Cellular and Humoral Immune Defects with Granulomas

Cellular components related to Combined Cellular and Humoral Immune Defects with Granulomas according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA recombinase complex GO:0097519 8.62 RAG2 RAG1

Biological processes related to Combined Cellular and Humoral Immune Defects with Granulomas according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin organization GO:0006325 9.37 RAG2 RAG1
2 DNA recombination GO:0006310 9.32 RAG2 RAG1
3 B cell differentiation GO:0030183 9.26 RAG2 RAG1
4 T cell differentiation in thymus GO:0033077 9.16 RAG2 RAG1
5 V(D)J recombination GO:0033151 8.96 RAG2 RAG1
6 pre-B cell allelic exclusion GO:0002331 8.62 RAG2 RAG1

Molecular functions related to Combined Cellular and Humoral Immune Defects with Granulomas according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sequence-specific DNA binding GO:0043565 8.96 RAG2 RAG1
2 ubiquitin protein ligase activity GO:0061630 8.62 RAG2 RAG1

Sources for Combined Cellular and Humoral Immune Defects with Granulomas

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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