MCID: LYM107
MIFTS: 45

Lymphoproliferative Syndrome 2

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

Aliases & Classifications for Lymphoproliferative Syndrome 2

MalaCards integrated aliases for Lymphoproliferative Syndrome 2:

Name: Lymphoproliferative Syndrome 2 57 12 75 29 13 6 15 73
Cd27 Deficiency 57 12 75
Lpfs2 57 12 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in first months or years of life
variable survival
recurrent acute episodes
favorable response to rituxan (in some patients)


HPO:

32
lymphoproliferative syndrome 2:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Lymphoproliferative Syndrome 2

OMIM : 57 Lymphoproliferative syndrome-2, also known as CD27 deficiency, is an autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impairment in specific antibody function resulting from impaired T cell-dependent B-cell responses and T-cell dysfunction (summary by van Montfrans et al., 2012). The phenotype can vary significantly, from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation (summary by Salzer et al., 2013). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240). (615122)

MalaCards based summary : Lymphoproliferative Syndrome 2, also known as cd27 deficiency, is related to lymphoproliferative syndrome, x-linked, 2 and autosomal recessive lymphoproliferative disease, and has symptoms including fever An important gene associated with Lymphoproliferative Syndrome 2 is CD27 (CD27 Molecule), and among its related pathways/superpathways are Innate Immune System and ERK Signaling. Affiliated tissues include t cells and b cells, and related phenotypes are splenomegaly and hepatomegaly

Disease Ontology : 12 A lymphoproliferative syndrome characterized by autosomal recessive inheritance, persistent symptomatic Epstein-Barr virus-associated viremia, hypogammaglobulinemia, and impairment in specific antibody function and that has material basis in homozygous mutation in the CD27 gene on chromosome 12p13.

UniProtKB/Swiss-Prot : 75 Lymphoproliferative syndrome 2: An autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impaired T-cell-dependent B-cell responses and T-cell dysfunction. The phenotype is highly variable, ranging from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation.

Related Diseases for Lymphoproliferative Syndrome 2

Diseases in the Lymphoproliferative Syndrome family:

Autoimmune Lymphoproliferative Syndrome Autoimmune Lymphoproliferative Syndrome, Type Iia
Lymphoproliferative Syndrome 1 Lymphoproliferative Syndrome 2
Autoimmune Lymphoproliferative Syndrome, Type Iii Autoimmune Lymphoproliferative Syndrome, Type V
Autoimmune Lymphoproliferative Syndrome Due to Ctla4 Haploinsuffiency Autosomal Recessive Lymphoproliferative Disease

Diseases related to Lymphoproliferative Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 29)
# Related Disease Score Top Affiliating Genes
1 lymphoproliferative syndrome, x-linked, 2 11.3
2 autosomal recessive lymphoproliferative disease 10.9
3 selective immunoglobulin deficiency disease 10.4 CD40LG MAGT1
4 lymphoproliferative syndrome 10.4 CD27 IL2RA XIAP
5 monoclonal paraproteinemia 10.4 CD27 CD40LG
6 lymphopenia 10.3 IL2RA MAGT1 PIK3CD
7 opsoclonus-myoclonus syndrome 10.3 CXCL10 CXCR3
8 hemophagocytic lymphohistiocytosis 10.3 CD27 IL2RA XIAP
9 macroglobulinemia 10.3 CD27 CD40LG CD70
10 dysgammaglobulinemia 10.3 CD40LG MAGT1 XIAP
11 solitary osseous plasmacytoma 10.3 CD27 MCL1
12 tetanus 10.2 CD27 CD40LG IL2RA
13 cryoglobulinemia 10.1 CD27 CD40LG CXCL10
14 adult t-cell leukemia 10.1 BCL2L1 IL2RA XIAP
15 japanese spotted fever 10.0 CD40LG CXCL10
16 uveitis 10.0 CXCL10 CXCR3 IL2RA
17 sarcoidosis 1 10.0 CXCL10 CXCR3 IL2RA
18 follicular lymphoma 10.0 BCL2L1 CD27 MCL1
19 mycosis fungoides 10.0 CXCL10 CXCR3 IL2RA
20 secondary progressive multiple sclerosis 9.9 CD40LG CXCL10 CXCR3
21 acute cervicitis 9.9 CD276 CXCL10
22 common variable immunodeficiency 9.9 CD27 CD40LG CD70 IL2RA
23 asymptomatic neurosyphilis 9.8 CD40LG CXCL10
24 alk-negative anaplastic large cell lymphoma 9.6 BCL2L1 CXCR3
25 leukemia, acute myeloid 9.5 BCL2L1 GATA2 MCL1 XIAP
26 mantle cell lymphoma 9.5 BCL2L1 CD40LG MCL1
27 hematologic cancer 9.4 CD40LG GATA2 IL2RA MCL1 XIAP
28 lymphoma, non-hodgkin, familial 8.9 BCL2L1 CD27 CD40LG IL2RA MCL1 XIAP
29 leukemia, chronic lymphocytic 7.5 BCL2L1 CCL19 CD27 CD40LG CD70 CXCR3

Graphical network of the top 20 diseases related to Lymphoproliferative Syndrome 2:



Diseases related to Lymphoproliferative Syndrome 2

Symptoms & Phenotypes for Lymphoproliferative Syndrome 2

Symptoms via clinical synopsis from OMIM:

57
AbdomenSpleen:
splenomegaly

Metabolic Features:
fever

Muscle Soft Tissue:
ascites (in some patients)

Laboratory Abnormalities:
increased susceptibility to ebv infection
persistent ebv viremia
decreased fibrinogen (in some patients)

Abdomen Liver:
hepatomegaly

Immunology:
lymphadenopathy
hypogammaglobulinemia
decreased t cell-dependent antibody production
defective cd8+ t cell function
lack of cd27 expression on lymphocytes
more
Hematology:
pancytopenia (in some patients)
aplastic anemia (in some patients)

Neoplasia:
hemophagocytic lymphohistiocytosis (in some patients)
lymphoproliferative disorder (in some patients)
lymphoma (in some patients)


Clinical features from OMIM:

615122

Human phenotypes related to Lymphoproliferative Syndrome 2:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 32 HP:0001744
2 hepatomegaly 32 HP:0002240
3 fever 32 HP:0001945
4 ascites 32 occasional (7.5%) HP:0001541
5 aplastic anemia 32 occasional (7.5%) HP:0001915
6 decreased antibody level in blood 32 HP:0004313
7 lymphoma 32 occasional (7.5%) HP:0002665
8 lymphadenopathy 32 HP:0002716
9 lymphoproliferative disorder 32 occasional (7.5%) HP:0005523
10 hemophagocytosis 32 occasional (7.5%) HP:0012156

UMLS symptoms related to Lymphoproliferative Syndrome 2:


fever

GenomeRNAi Phenotypes related to Lymphoproliferative Syndrome 2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.72 XIAP BCL2L1 CD40LG CD70 IL2RA MCL1
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.72 MCL1 XIAP BCL2L1 CD27 CD40LG CD70

MGI Mouse Phenotypes related to Lymphoproliferative Syndrome 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.77 BCL2L1 CD27 CD276 CD40LG CD70 CXCL10
2 immune system MP:0005387 9.4 MCL1 PIK3CD XIAP BCL2L1 CD27 CD276

Drugs & Therapeutics for Lymphoproliferative Syndrome 2

Search Clinical Trials , NIH Clinical Center for Lymphoproliferative Syndrome 2

Genetic Tests for Lymphoproliferative Syndrome 2

Genetic tests related to Lymphoproliferative Syndrome 2:

# Genetic test Affiliating Genes
1 Lymphoproliferative Syndrome 2 29 CD27

Anatomical Context for Lymphoproliferative Syndrome 2

MalaCards organs/tissues related to Lymphoproliferative Syndrome 2:

41
T Cells, B Cells

Publications for Lymphoproliferative Syndrome 2

Articles related to Lymphoproliferative Syndrome 2:

# Title Authors Year
1
Immune Dysregulation Syndromes (IPEX, CD27 Deficiency, and Others): Always Doomed from the Start? ( 26661331 )
2016
2
Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency. ( 25843314 )
2015
3
CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. ( 22197273 )
2012

Variations for Lymphoproliferative Syndrome 2

UniProtKB/Swiss-Prot genetic disease variations for Lymphoproliferative Syndrome 2:

75
# Symbol AA change Variation ID SNP ID
1 CD27 p.Cys53Tyr VAR_069793 rs397514667

ClinVar genetic disease variations for Lymphoproliferative Syndrome 2:

6
(show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 CD27 NM_001242.4(CD27): c.24G> A (p.Trp8Ter) single nucleotide variant Pathogenic rs398122933 GRCh37 Chromosome 12, 6554285: 6554285
2 CD27 NM_001242.4(CD27): c.24G> A (p.Trp8Ter) single nucleotide variant Pathogenic rs398122933 GRCh38 Chromosome 12, 6445119: 6445119
3 CD27 NM_001242.4(CD27): c.158G> A (p.Cys53Tyr) single nucleotide variant Pathogenic rs397514667 GRCh37 Chromosome 12, 6554611: 6554611
4 CD27 NM_001242.4(CD27): c.158G> A (p.Cys53Tyr) single nucleotide variant Pathogenic rs397514667 GRCh38 Chromosome 12, 6445445: 6445445
5 CD27 NM_001242.4(CD27): c.30C> T (p.Cys10=) single nucleotide variant Benign rs34540052 GRCh37 Chromosome 12, 6554291: 6554291
6 CD27 NM_001242.4(CD27): c.30C> T (p.Cys10=) single nucleotide variant Benign rs34540052 GRCh38 Chromosome 12, 6445125: 6445125
7 CD27 NM_001242.4(CD27): c.225C> T (p.His75=) single nucleotide variant Likely benign rs745713273 GRCh38 Chromosome 12, 6445512: 6445512
8 CD27 NM_001242.4(CD27): c.225C> T (p.His75=) single nucleotide variant Likely benign rs745713273 GRCh37 Chromosome 12, 6554678: 6554678
9 CD27 NM_001242.4(CD27): c.269-9T> C single nucleotide variant Benign rs11830902 GRCh37 Chromosome 12, 6559330: 6559330
10 CD27 NM_001242.4(CD27): c.269-9T> C single nucleotide variant Benign rs11830902 GRCh38 Chromosome 12, 6450164: 6450164
11 CD27 NM_001242.4(CD27): c.698G> A (p.Arg233His) single nucleotide variant Benign rs2532502 GRCh38 Chromosome 12, 6451307: 6451307
12 CD27 NM_001242.4(CD27): c.698G> A (p.Arg233His) single nucleotide variant Benign rs2532502 GRCh37 Chromosome 12, 6560473: 6560473
13 CD27 NM_001242.4(CD27): c.495C> T (p.Asp165=) single nucleotide variant Likely benign rs375150093 GRCh37 Chromosome 12, 6559753: 6559753
14 CD27 NM_001242.4(CD27): c.495C> T (p.Asp165=) single nucleotide variant Likely benign rs375150093 GRCh38 Chromosome 12, 6450587: 6450587
15 CD27 NM_001242.4(CD27): c.635A> G (p.His212Arg) single nucleotide variant Uncertain significance rs755699729 GRCh37 Chromosome 12, 6560157: 6560157
16 CD27 NM_001242.4(CD27): c.635A> G (p.His212Arg) single nucleotide variant Uncertain significance rs755699729 GRCh38 Chromosome 12, 6450991: 6450991
17 CD27 NM_001242.4(CD27): c.539-9C> T single nucleotide variant Likely benign rs374055287 GRCh38 Chromosome 12, 6450886: 6450886
18 CD27 NM_001242.4(CD27): c.539-9C> T single nucleotide variant Likely benign rs374055287 GRCh37 Chromosome 12, 6560052: 6560052
19 CD27 NM_001242.4(CD27): c.541C> T (p.Gln181Ter) single nucleotide variant Pathogenic rs779092602 GRCh38 Chromosome 12, 6450897: 6450897
20 CD27 NM_001242.4(CD27): c.541C> T (p.Gln181Ter) single nucleotide variant Pathogenic rs779092602 GRCh37 Chromosome 12, 6560063: 6560063

Expression for Lymphoproliferative Syndrome 2

Search GEO for disease gene expression data for Lymphoproliferative Syndrome 2.

Pathways for Lymphoproliferative Syndrome 2

Pathways related to Lymphoproliferative Syndrome 2 according to GeneCards Suite gene sharing:

(show all 24)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.9 BCL2L1 CCL19 CD27 CD40LG CD70 CXCL10
2
Show member pathways
13.71 BCL2L1 CCL19 CCL21 CD27 CD40LG CD70
3
Show member pathways
13.47 BCL2L1 CCL19 CCL21 CD27 CD40LG CD70
4
Show member pathways
13.06 CCL19 CCL21 CD27 CD40LG CD70 CXCL10
5
Show member pathways
12.99 CCL19 CCL21 CD27 CD40LG CD70 CXCL10
6
Show member pathways
12.72 CCL19 CCL21 CXCL10 CXCR3 PIK3CD
7
Show member pathways
12.72 BCL2L1 CCL19 CD27 CD40LG CD70 CXCL10
8
Show member pathways
12.55 BCL2L1 CD27 CD70 MCL1 PIK3CD XIAP
9
Show member pathways
12.48 BCL2L1 IL2RA MCL1 PIK3CD
10 12.35 CD276 CD40LG CXCL10 GATA2 IL2RA
11 12.26 BCL2L1 IL2RA PIK3CD XIAP
12 12.06 BCL2L1 CD40LG MCL1 XIAP
13
Show member pathways
12.01 BCL2L1 IL2RA MCL1
14 11.97 BCL2L1 IL2RA PIK3CD XIAP
15
Show member pathways
11.87 CCL19 CCL21 IL2RA PIK3CD XIAP
16
Show member pathways
11.77 CCL19 CCL21 CXCL10 CXCR3
17 11.72 BCL2L1 PIK3CD XIAP
18
Show member pathways
11.66 BCL2L1 MCL1 XIAP
19
Show member pathways
11.58 BCL2L1 CD40LG XIAP
20 11.56 BCL2L1 PIK3CD XIAP
21 11.22 CD27 CD276 CD40LG CD70
22 11 BCL2L1 CCL19 CCL21 CD40LG XIAP
23 10.96 BCL2L1 MCL1

GO Terms for Lymphoproliferative Syndrome 2

Cellular components related to Lymphoproliferative Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 external side of plasma membrane GO:0009897 9.1 CD27 CD276 CD40LG CXCL10 CXCR3 IL2RA
2 Bcl-2 family protein complex GO:0097136 8.96 BCL2L1 MCL1

Biological processes related to Lymphoproliferative Syndrome 2 according to GeneCards Suite gene sharing:

(show all 33)
# Name GO ID Score Top Affiliating Genes
1 apoptotic process GO:0006915 9.97 BCL2L1 CD27 CXCR3 IL2RA MCL1 XIAP
2 regulation of signaling receptor activity GO:0010469 9.95 CCL19 CCL21 CD40LG CD70 CXCL10
3 cell surface receptor signaling pathway GO:0007166 9.92 CD27 CXCL10 CXCR3 IL2RA
4 tumor necrosis factor-mediated signaling pathway GO:0033209 9.82 CD27 CD40LG CD70
5 T cell costimulation GO:0031295 9.77 CCL19 CCL21 CD40LG
6 cell chemotaxis GO:0060326 9.76 CCL19 CCL21 CXCL10
7 positive regulation of JNK cascade GO:0046330 9.75 CCL19 CCL21 CD27
8 neutrophil chemotaxis GO:0030593 9.73 CCL19 CCL21 PIK3CD
9 response to virus GO:0009615 9.73 BANF1 BCL2L1 CCL19 CXCL10
10 chemotaxis GO:0006935 9.72 CCL19 CCL21 CXCL10 CXCR3 PIK3CD
11 chemokine-mediated signaling pathway GO:0070098 9.71 CCL19 CCL21 CXCL10 CXCR3
12 positive regulation of T cell proliferation GO:0042102 9.67 CCL19 CD276 CD40LG IL2RA
13 negative regulation of intrinsic apoptotic signaling pathway GO:2001243 9.66 BCL2L1 MCL1
14 positive regulation of receptor-mediated endocytosis GO:0048260 9.65 CCL19 CCL21
15 apoptotic mitochondrial changes GO:0008637 9.65 BCL2L1 MCL1
16 cell maturation GO:0048469 9.65 CCL19 CCL21 GATA2
17 positive regulation of T cell differentiation GO:0045582 9.64 CD27 IL2RA
18 cell fate determination GO:0001709 9.64 GATA2 MCL1
19 dendritic cell chemotaxis GO:0002407 9.63 CCL19 CCL21
20 positive regulation of T cell migration GO:2000406 9.63 CCL21 CXCL10
21 cytokine-mediated signaling pathway GO:0019221 9.63 BCL2L1 CCL19 CXCL10 IL2RA MCL1 PIK3CD
22 positive regulation of cell motility GO:2000147 9.62 CCL19 CCL21
23 positive regulation of chemotaxis GO:0050921 9.61 CCL19 CCL21
24 immunological synapse formation GO:0001771 9.6 CCL19 CCL21
25 response to prostaglandin E GO:0034695 9.57 CCL19 CCL21
26 immune response GO:0006955 9.56 CCL19 CCL21 CD27 CD276 CD40LG CD70
27 positive regulation of dendritic cell antigen processing and presentation GO:0002606 9.54 CCL19 CCL21
28 negative regulation of dendritic cell apoptotic process GO:2000669 9.52 CCL19 CCL21
29 establishment of T cell polarity GO:0001768 9.51 CCL19 CCL21
30 positive regulation of glycoprotein biosynthetic process GO:0010560 9.46 CCL19 CCL21
31 T cell chemotaxis GO:0010818 9.43 CXCL10 CXCR3 PIK3CD
32 inflammatory response GO:0006954 9.23 CCL19 CCL21 CD27 CD40LG CXCL10 CXCR3
33 negative regulation of apoptotic process GO:0043066 10.01 BCL2L1 CD27 CD40LG MCL1 XIAP

Molecular functions related to Lymphoproliferative Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chemokine activity GO:0008009 9.43 CCL19 CCL21 CXCL10
2 chemokine receptor binding GO:0042379 9.32 CCL19 CCL21
3 BH3 domain binding GO:0051434 9.16 BCL2L1 MCL1
4 cytokine activity GO:0005125 9.02 CCL19 CCL21 CD40LG CD70 CXCL10
5 CCR7 chemokine receptor binding GO:0031732 8.96 CCL19 CCL21

Sources for Lymphoproliferative Syndrome 2

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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