LPFS2
MCID: LYM107
MIFTS: 47

Lymphoproliferative Syndrome 2 (LPFS2)

Categories: Blood diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Rare 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 40 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, b cells and lung, 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 26)
# Related Disease Score Top Affiliating Genes
1 lymphoproliferative syndrome, x-linked, 2 11.4
2 autosomal recessive lymphoproliferative disease 11.1
3 htlv-1 associated myelopathy/tropical spastic paraparesis 10.1 CXCR3 IL2RA
4 macroglobulinemia 10.1 CD27 CD40LG CD70
5 dysgammaglobulinemia 10.1 MAGT1 XIAP
6 lymphopenia 10.1 IL2RA MAGT1 PIK3CD
7 waldenstrom macroglobulinemia 10.1 CD27 CD40LG CD70
8 acrodermatitis chronica atrophicans 10.1 CD40LG CXCL10
9 opsoclonus-myoclonus syndrome 10.1 CXCL10 CXCR3
10 hemophagocytic lymphohistiocytosis 10.0 CD27 IL2RA XIAP
11 tetanus 10.0 CD27 CD40LG IL2RA
12 adult t-cell leukemia 10.0 BCL2L1 IL2RA XIAP
13 uveitis 10.0 CXCL10 CXCR3 IL2RA
14 solitary osseous plasmacytoma 10.0 CD27 MCL1
15 secondary progressive multiple sclerosis 10.0 CD40LG CXCL10 CXCR3
16 common variable immunodeficiency 10.0 CD27 CD40LG CD70 IL2RA
17 follicular lymphoma 9.9 BCL2L1 CD27 MCL1
18 hematologic cancer 9.9 GATA2 IL2RA MCL1 XIAP
19 mycosis fungoides 9.9 CXCL10 CXCR3 IL2RA
20 myeloma, multiple 9.9 BCL2L1 CD27 MCL1 XIAP
21 cryoglobulinemia 9.9 CD27 CD40LG CXCL10 CXCR3
22 immunodeficiency with hyper-igm, type 2 9.9 CD276 CD40LG CXCL10
23 combined t cell and b cell immunodeficiency 9.9
24 leukemia, acute myeloid 9.8 BCL2L1 GATA2 MCL1 XIAP
25 lymphoma, non-hodgkin, familial 9.7 BCL2L1 CD27 CD70 IL2RA MCL1 XIAP
26 leukemia, chronic lymphocytic 9.2 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
Abdomen Spleen:
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 BCL2L1 CD40LG CD70 IL2RA MCL1 XIAP
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.72 BCL2L1 CD40LG CD70 IL2RA MCL1 XIAP

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 BCL2L1 CD27 CD276 CD40LG CD70 CXCL10

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, Lung, Myeloid

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 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 CD27 NM_001242.4(CD27): c.24G> A (p.Trp8Ter) single nucleotide variant Pathogenic rs398122933 GRCh38 Chromosome 12, 6445119: 6445119
2 CD27 NM_001242.4(CD27): c.24G> A (p.Trp8Ter) single nucleotide variant Pathogenic rs398122933 GRCh37 Chromosome 12, 6554285: 6554285
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 GRCh37 Chromosome 12, 6554678: 6554678
8 CD27 NM_001242.4(CD27): c.225C> T (p.His75=) single nucleotide variant Likely benign rs745713273 GRCh38 Chromosome 12, 6445512: 6445512
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
21 CD27 NM_001242.4(CD27): c.239dup (p.His80Glnfs) duplication Pathogenic GRCh38 Chromosome 12, 6445526: 6445526
22 CD27 NM_001242.4(CD27): c.239dup (p.His80Glnfs) duplication Pathogenic GRCh37 Chromosome 12, 6554692: 6554692
23 CD27 NM_001242.4(CD27): c.122A> G (p.Gln41Arg) single nucleotide variant Uncertain significance rs752259578 GRCh38 Chromosome 12, 6445217: 6445217
24 CD27 NM_001242.4(CD27): c.122A> G (p.Gln41Arg) single nucleotide variant Uncertain significance rs752259578 GRCh37 Chromosome 12, 6554383: 6554383
25 CD27 NM_001242.4(CD27): c.277G> A (p.Val93Ile) single nucleotide variant Uncertain significance rs761113232 GRCh37 Chromosome 12, 6559347: 6559347
26 CD27 NM_001242.4(CD27): c.277G> A (p.Val93Ile) single nucleotide variant Uncertain significance rs761113232 GRCh38 Chromosome 12, 6450181: 6450181

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 29)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.92 BCL2L1 CCL19 CD27 CD40LG CD70 CXCL10
2
Show member pathways
13.75 BCL2L1 CCL19 CCL21 CD27 CD40LG CD70
3
Show member pathways
13.49 BCL2L1 CCL19 CCL21 CD27 CD40LG CD70
4
Show member pathways
13.06 CCL19 CCL21 CD27 CD40LG CD70 CXCL10
5
Show member pathways
13.04 CCL19 CCL21 CD27 CD40LG CD70 CXCL10
6
Show member pathways
12.76 CCL19 CCL21 CXCL10 CXCR3 PIK3CD
7
Show member pathways
12.72 BCL2L1 CCL19 CD27 CD40LG CD70 CXCL10
8
Show member pathways
12.58 BCL2L1 CD27 CD70 MCL1 PIK3CD XIAP
9
Show member pathways
12.53 BCL2L1 CD27 CD40LG CD70 MCL1
10
Show member pathways
12.5 BCL2L1 CD40LG IL2RA PIK3CD
11 12.37 CD276 CD40LG CXCL10 GATA2 IL2RA
12
Show member pathways
12.28 BCL2L1 IL2RA MCL1 PIK3CD
13 12.27 BCL2L1 IL2RA PIK3CD XIAP
14
Show member pathways
12.1 CCL19 CCL21 CXCL10 CXCR3 PIK3CD
15 12.08 BCL2L1 CD40LG MCL1 XIAP
16
Show member pathways
12.07 BCL2L1 IL2RA PIK3CD XIAP
17 11.98 BCL2L1 IL2RA PIK3CD XIAP
18
Show member pathways
11.89 CCL19 CCL21 IL2RA PIK3CD XIAP
19
Show member pathways
11.8 CCL19 CCL21 CXCL10 CXCR3
20 11.76 BCL2L1 PIK3CD XIAP
21
Show member pathways
11.68 BCL2L1 MCL1 XIAP
22
Show member pathways
11.6 BCL2L1 CD40LG XIAP
23 11.59 BCL2L1 PIK3CD XIAP
24 11.22 CD27 CD276 CD40LG CD70
25 11 BCL2L1 CCL19 CCL21 CD40LG XIAP
26 10.98 BCL2L1 MCL1
28 10.95 CCL19 CCL21 CD40LG CD70 CXCL10
29 10.89 CCL19 CCL21 CD40LG CD70 CXCL10

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 35)
# Name GO ID Score Top Affiliating Genes
1 regulation of signaling receptor activity GO:0010469 9.97 CCL19 CCL21 CD40LG CD70 CXCL10
2 cell proliferation GO:0008283 9.96 BCL2L1 CD276 CD70 IL2RA
3 cell surface receptor signaling pathway GO:0007166 9.91 CD27 CXCL10 CXCR3 IL2RA
4 inflammatory response GO:0006954 9.85 CCL19 CCL21 CD40LG CXCL10 CXCR3 PIK3CD
5 positive regulation of JNK cascade GO:0046330 9.78 CCL19 CCL21 CD27
6 response to virus GO:0009615 9.78 BANF1 BCL2L1 CCL19 CXCL10
7 tumor necrosis factor-mediated signaling pathway GO:0033209 9.77 CD27 CD40LG CD70
8 cell chemotaxis GO:0060326 9.76 CCL19 CCL21 CXCL10 CXCR3
9 neutrophil chemotaxis GO:0030593 9.73 CCL19 CCL21 CXCL10 PIK3CD
10 T cell costimulation GO:0031295 9.71 CCL19 CCL21 CD40LG
11 chemokine-mediated signaling pathway GO:0070098 9.71 CCL19 CCL21 CXCL10 CXCR3
12 cell maturation GO:0048469 9.69 CCL19 CCL21 GATA2
13 positive regulation of interleukin-12 production GO:0032735 9.67 CCL19 CD40LG
14 negative regulation of intrinsic apoptotic signaling pathway GO:2001243 9.66 BCL2L1 MCL1
15 positive regulation of neutrophil chemotaxis GO:0090023 9.66 CCL19 CCL21
16 positive regulation of receptor-mediated endocytosis GO:0048260 9.65 CCL19 CCL21
17 positive regulation of T cell differentiation GO:0045582 9.65 CD27 IL2RA
18 cell fate determination GO:0001709 9.64 GATA2 MCL1
19 dendritic cell chemotaxis GO:0002407 9.64 CCL19 CCL21
20 positive regulation of cell motility GO:2000147 9.63 CCL19 CCL21
21 positive regulation of T cell migration GO:2000406 9.63 CCL21 CXCL10
22 positive regulation of chemotaxis GO:0050921 9.62 CCL19 CCL21
23 positive regulation of T cell proliferation GO:0042102 9.62 CCL19 CD276 CD40LG IL2RA
24 immunological synapse formation GO:0001771 9.6 CCL19 CCL21
25 response to prostaglandin E GO:0034695 9.58 CCL19 CCL21
26 negative regulation of dendritic cell apoptotic process GO:2000669 9.57 CCL19 CCL21
27 positive regulation of dendritic cell antigen processing and presentation GO:0002606 9.56 CCL19 CCL21
28 establishment of T cell polarity GO:0001768 9.55 CCL19 CCL21
29 chemotaxis GO:0006935 9.55 CCL19 CCL21 CXCL10 CXCR3 PIK3CD
30 positive regulation of glycoprotein biosynthetic process GO:0010560 9.49 CCL19 CCL21
31 T cell chemotaxis GO:0010818 9.43 CXCL10 CXCR3 PIK3CD
32 cytokine-mediated signaling pathway GO:0019221 9.43 BCL2L1 CCL19 CXCL10 IL2RA MCL1 PIK3CD
33 immune response GO:0006955 9.23 CCL19 CCL21 CD276 CD40LG CD70 CXCL10
34 negative regulation of apoptotic process GO:0043066 10.02 BCL2L1 CD27 CD40LG MCL1 XIAP
35 apoptotic process GO:0006915 10 BCL2L1 CD27 CXCR3 IL2RA 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 cysteine-type endopeptidase inhibitor activity involved in apoptotic process GO:0043027 9.37 CD27 XIAP
3 chemokine receptor binding GO:0042379 9.32 CCL19 CCL21
4 BH3 domain binding GO:0051434 9.16 BCL2L1 MCL1
5 cytokine activity GO:0005125 9.02 CCL19 CCL21 CD40LG CD70 CXCL10
6 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
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45 MESH via Orphanet
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49 NCI
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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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