Lymphoproliferative Syndrome 2 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

LPFS2 MCID: LYM107 MIFTS: 48	Lymphoproliferative Syndrome 2 (LPFS2) Categories: Blood diseases, Cancer diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Rare diseases
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Aliases & Classifications for Lymphoproliferative Syndrome 2

MalaCards integrated aliases for Lymphoproliferative Syndrome 2:

Name: Lymphoproliferative Syndrome 2 ⁵⁷ ¹² ⁷³ ²⁹ ¹³ ⁶ ¹⁵ ³⁹ ⁷¹

Cd27 Deficiency ⁵⁷ ¹² ⁵⁸ ⁷³

Lpfs2 ⁵⁷ ¹² ⁷³

Autosomal Recessive Lymphoproliferative Disease Due to Cd27 Deficiency ⁵⁸

Combined Immunodeficiency Due to Cd27 Deficiency ⁵⁸

Characteristics:

Orphanet epidemiological data:

⁵⁸

combined immunodeficiency due to cd27 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

⁵⁷ (Updated 05-Mar-2021)

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:

³¹

lymphoproliferative syndrome 2:
Inheritance autosomal recessive inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Cancer diseases
Anatomical: Blood diseases Immune diseases Gastrointestinal diseases

See all MalaCards categories (disease lists)

ICD10: ³² ³³

Neoplasms

Neoplasms of uncertain or unknown behaviour

Other neoplasms of uncertain or unknown behaviour of lymphoid, haematopoietic and related tissue

Neoplasm of uncertain or unknown behaviour of lymphoid, haematopoietic and related tissue, unspecified

Orphanet: ⁵⁸

Rare immunological diseases

External Ids:

Disease Ontology ¹² DOID:0060708

OMIM® ⁵⁷ 615122

OMIM Phenotypic Series ⁵⁷ PS308240

MeSH ⁴⁴ D008232

ICD10 ³² D47.9

ICD10 via Orphanet ³³ D47.9

Orphanet ⁵⁸ ORPHA238505

MedGen ⁴¹ C3554540 CN168059

UMLS ⁷¹ C3554540

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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) (Updated 05-Mar-2021)

MalaCards based summary : Lymphoproliferative Syndrome 2, also known as cd27 deficiency, is related to lymphoproliferative syndrome, x-linked, 2 and immunodysregulation, polyendocrinopathy, and enteropathy, x-linked, and has symptoms including fever An important gene associated with Lymphoproliferative Syndrome 2 is CD27 (CD27 Molecule), and among its related pathways/superpathways are Akt Signaling and NF-kappaB Signaling. Related phenotypes are ascites and splenomegaly

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 : ⁷³ 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.

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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
Lymphoproliferative Syndrome 3

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

(show top 50) (show all 132)

#	Related Disease	Score	Top Affiliating Genes
1	lymphoproliferative syndrome, x-linked, 2	32.0	XIAP STXBP2 SLAMF1 SH2D1A LYST ITK
2	immunodysregulation, polyendocrinopathy, and enteropathy, x-linked	30.1	CD8A CD4 CD28
3	agammaglobulinemia	30.0	TNFRSF13B SH2D1A ITK CR2
4	lymphoproliferative syndrome	29.9	XIAP SLAMF1 SH2D1A ITK CD70 CD27
5	aplastic anemia	29.8	SH2D1A CD70 CD4 CD28 CD27
6	lymphoproliferative syndrome, x-linked, 1	29.4	XIAP STXBP2 SLAMF1 SH2D1A MAGT1 LYST
7	hemophagocytic lymphohistiocytosis	29.4	XIAP STXBP2 SH2D1A LYST ITK CR2
8	combined immunodeficiency	29.2	TNFRSF4 MAGT1 CORO1A CD8A CD70 CD4
9	immune deficiency disease	29.1	TNFRSF13B SLAMF1 SH2D1A CR2 CD8A CD4
10	transient hypogammaglobulinemia	10.4	TNFRSF13B CD27
11	systemic epstein-barr virus-positive t-cell lymphoma of childhood	10.4	SH2D1A CR2
12	cork-handlers' disease	10.4	CD8A CD4
13	necrotic uveal melanoma	10.4	CD8A CD4
14	early yaws	10.4	CD8A CD4
15	ventilation pneumonitis	10.4	CD8A CD4
16	diffuse infiltrative lymphocytosis syndrome	10.3	CD8A CD4
17	latent syphilis	10.3	CD8A CD4
18	type 1 diabetes mellitus 23	10.3	CD8A CD4
19	autoimmune lymphoproliferative syndrome, type iia	10.3	CD8A CD4
20	parapsoriasis	10.3	CD8A CD4
21	gastroduodenitis	10.3	CD8A CD4
22	primary syphilis	10.3	CD8A CD4
23	norwegian scabies	10.3	CD8A CD4
24	bird fancier's lung	10.3	CD8A CD4
25	skin sarcoidosis	10.3	CD8A CD4
26	metal allergy	10.3	CD8A CD4
27	variola major	10.3	CD8A CD4
28	follicular mucinosis	10.3	CD8A CD4
29	african histoplasmosis	10.3	CD4 AP3B1
30	tertiary syphilis	10.3	CD8A CD4
31	spongiotic dermatitis	10.3	CD8A CD4
32	acute retinal necrosis syndrome	10.3	CD8A CD4
33	cerebral lymphoma	10.3	CD8A CD4
34	oral tuberculosis	10.3	CD8A CD4
35	cerebritis	10.3	CD8A CD4
36	invasive malignant thymoma	10.3	CD8A CD4
37	west nile encephalitis	10.3	CD8A CD4
38	lobomycosis	10.3	CR2 CD4
39	exanthema subitum	10.3	CD8A CD4
40	immunodeficiency 36	10.3	CD8A CD4
41	viral exanthem	10.3	CD8A CD4
42	secondary syphilis	10.3	CD8A CD4
43	glanders	10.3	CD8A CD4
44	subacute lymphocytic thyroiditis	10.3	CR2 CD4
45	superficial basal cell carcinoma	10.3	CD8A CD4
46	esophageal candidiasis	10.3	CD8A CD4
47	macroglobulinemia	10.3	TNFRSF13B CD70 CD27
48	immunodeficiency 13	10.3	STK4 MAGT1 CD4
49	dermatomycosis	10.3	CR2 CD4
50	parotid disease	10.3	CD8A CD4

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

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Symptoms & Phenotypes for Lymphoproliferative Syndrome 2

Human phenotypes related to Lymphoproliferative Syndrome 2:

³¹ (show all 18)

#	Description	HPO Frequency	HPO Source Accession
1	ascites ³¹	occasional (7.5%)	HP:0001541
2	splenomegaly ³¹	very rare (1%)	HP:0001744
3	hepatomegaly ³¹	very rare (1%)	HP:0002240
4	fever ³¹	very rare (1%)	HP:0001945
5	uveitis ³¹	very rare (1%)	HP:0000554
6	recurrent pneumonia ³¹	very rare (1%)	HP:0006532
7	sepsis ³¹	very rare (1%)	HP:0100806
8	lymphadenopathy ³¹	very rare (1%)	HP:0002716
9	hepatosplenomegaly ³¹	very rare (1%)	HP:0001433
10	oral ulcer ³¹	very rare (1%)	HP:0000155
11	lymphoproliferative disorder ³¹	very rare (1%)	HP:0005523
12	hodgkin lymphoma ³¹	very rare (1%)	HP:0012189
13	hemophagocytosis ³¹	very rare (1%)	HP:0012156
14	aplastic anemia ³¹	very rare (1%)	HP:0001915
15	severe varicella zoster infection ³¹	very rare (1%)	HP:0032170
16	decreased circulating antibody level ³¹	very rare (1%)	HP:0004313
17	persistent ebv viremia ³¹	very rare (1%)	HP:0020072
18	decreased lymphocyte proliferation in response to mitogen ³¹		HP:0031381

Symptoms via clinical synopsis from OMIM®:

⁵⁷ (Updated 05-Mar-2021)

Abdomen Spleen:
splenomegaly

Metabolic Features:
fever

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

Hematology:
pancytopenia (in some patients)
aplastic anemia (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

Muscle Soft Tissue:
ascites (in some patients)

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

Clinical features from OMIM®:

615122 (Updated 05-Mar-2021)

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	Reduced mammosphere formation	GR00396-S	9.17	AP3B1 CD27 CD28 CTPS1 ITK TNFRSF13B

MGI Mouse Phenotypes related to Lymphoproliferative Syndrome 2:

⁴⁶

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	cellular	MP:0005384	9.97	AP3B1 CD27 CD28 CD4 CD8A CORO1A
2	hematopoietic system	MP:0005397	9.91	AP3B1 CD27 CD28 CD4 CD70 CD8A
3	immune system	MP:0005387	9.58	AP3B1 CD27 CD28 CD4 CD70 CD8A

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Drugs & Therapeutics for Lymphoproliferative Syndrome 2

Search Clinical Trials , NIH Clinical Center for Lymphoproliferative Syndrome 2

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Genetic Tests for Lymphoproliferative Syndrome 2

Genetic tests related to Lymphoproliferative Syndrome 2:

#	Genetic test	Affiliating Genes
1	Lymphoproliferative Syndrome 2 ²⁹	CD27

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Anatomical Context for Lymphoproliferative Syndrome 2

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Publications for Lymphoproliferative Syndrome 2

Articles related to Lymphoproliferative Syndrome 2:

(show all 11)

#	Title	Authors	PMID	Year
1	Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27. ⁵⁷ ⁶	Salzer E...Seidel MG	22801960	2013
2	CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. ⁵⁷ ⁶	van Montfrans JM...Tesselaar K	22197273	2012
3	Loss-of-function mutations within the IL-2 inducible kinase ITK in patients with EBV-associated lymphoproliferative diseases. ⁶	Linka RM...Borkhardt A	22289921	2012
4	CD27: a new player in the field of common variable immunodeficiency and EBV-associated lymphoproliferative disorder? ⁵⁷	Seidel MG	22365582	2012
5	IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach. ⁶	Stepensky P...Resnick IB	21109689	2011
6	Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation. ⁶	Huck K...Borkhardt A	19425169	2009
7	Expanding clinical spectrum of female X-linked lymphoproliferative syndrome 2. ⁶¹	Suryaprakash S...Savasan S	32686289	2021
8	Unique BIR domain sets determine inhibitor of apoptosis protein-driven cell death and NOD2 complex signal specificity. ⁶¹	Chirieleison SM...Abbott DW	30018081	2018
9	Nucleotide-binding oligomerization domain (NOD) signaling defects and cell death susceptibility cannot be uncoupled in X-linked inhibitor of apoptosis (XIAP)-driven inflammatory disease. ⁶¹	Chirieleison SM...Abbott DW	28404814	2017
10	Human X-linked variable immunodeficiency caused by a hypomorphic mutation in XIAP in association with a rare polymorphism in CD40LG. ⁶¹	Rigaud S...Latour S	21543760	2011
11	Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies. ⁶¹	Diaz de Heredia C...Sanchez de Toledo J	18084339	2008

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Genes for Lymphoproliferative Syndrome 2

Genes related to Lymphoproliferative Syndrome 2 (4 elite genes):

(show all 27)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	CD27	CD27 Molecule	Protein Coding	1275.33	Molecular basis known ⁵⁷ Causative germline mutation ⁵⁸ Causative variation ⁷³ Genetic Tests ²⁹ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)
2	XIAP	X-Linked Inhibitor Of Apoptosis	Protein Coding	414.57	Pathogenic ⁶ DISEASES inferred ¹⁵ GeneCards inferred via : Variants (show sections)
3	CD27-AS1	CD27 Antisense RNA 1	RNA Gene	408.87	Pathogenic ⁶ GeneCards inferred via : Variants (show sections)	22197273
4	ITK	IL2 Inducible T Cell Kinase	Protein Coding	406.17	Pathogenic ⁶ DISEASES inferred ¹⁵	19425169 22289921
5	CD70	CD70 Molecule	Protein Coding	7.3	DISEASES inferred ¹⁵
6	MAGT1	Magnesium Transporter 1	Protein Coding	6.82	DISEASES inferred ¹⁵
7	SH2D1A	SH2 Domain Containing 1A	Protein Coding	5.95	DISEASES inferred ¹⁵
8	STK4	Serine/Threonine Kinase 4	Protein Coding	5.6	DISEASES inferred ¹⁵
9	CORO1A	Coronin 1A	Protein Coding	5.5	DISEASES inferred ¹⁵
10	STXBP2	Syntaxin Binding Protein 2	Protein Coding	5.44	DISEASES inferred ¹⁵
11	CD8A	CD8a Molecule	Protein Coding	5.28	DISEASES inferred ¹⁵
12	SLAMF1	Signaling Lymphocytic Activation Molecule Family Member 1	Protein Coding	5.28	DISEASES inferred ¹⁵
13	TNFRSF4	TNF Receptor Superfamily Member 4	Protein Coding	5.27	DISEASES inferred ¹⁵
14	CTPS1	CTP Synthase 1	Protein Coding	5.14	DISEASES inferred ¹⁵
15	AP3B1	Adaptor Related Protein Complex 3 Subunit Beta 1	Protein Coding	5.12	DISEASES inferred ¹⁵
16	CR2	Complement C3d Receptor 2	Protein Coding	5.11	DISEASES inferred ¹⁵
17	CD28	CD28 Molecule	Protein Coding	5.1	DISEASES inferred ¹⁵
18	CD4	CD4 Molecule	Protein Coding	5	DISEASES inferred ¹⁵
19	TNFRSF13B	TNF Receptor Superfamily Member 13B	Protein Coding	4.94	DISEASES inferred ¹⁵
20	LYST	Lysosomal Trafficking Regulator	Protein Coding	4.91	DISEASES inferred ¹⁵
21	ZNF302	Zinc Finger Protein 302	Protein Coding	4.84	DISEASES inferred ¹⁵
22	KLRK1	Killer Cell Lectin Like Receptor K1	Protein Coding	4.81	DISEASES inferred ¹⁵
23	FAAP24	FA Core Complex Associated Protein 24	Protein Coding	4.76	DISEASES inferred ¹⁵
24	STX11	Syntaxin 11	Protein Coding	4.74	DISEASES inferred ¹⁵
25	CTLA4	Cytotoxic T-Lymphocyte Associated Protein 4	Protein Coding	4.72	DISEASES inferred ¹⁵
26	SLAMF6	SLAM Family Member 6	Protein Coding	4.72	DISEASES inferred ¹⁵
27	CARMIL3	Capping Protein Regulator And Myosin 1 Linker 3	Protein Coding	4.72	DISEASES inferred ¹⁵

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Variations for Lymphoproliferative Syndrome 2

ClinVar genetic disease variations for Lymphoproliferative Syndrome 2:

⁶ (show top 50) (show all 197)

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	GRCh37 Pos	GRCh38 Pos
1	ITK	NM_005546.3(ITK):c.1003C>T (p.Arg335Trp)	SNV	Pathogenic	12741	rs121908191	5:156668673-156668673	5:157241663-157241663
2	CD27-AS1	NM_001242.4(CD27):c.24G>A (p.Trp8Ter)	SNV	Pathogenic	40889	rs398122933	12:6554285-6554285	12:6445119-6445119
3	CD27-AS1	NM_001242.4(CD27):c.158G>A (p.Cys53Tyr)	SNV	Pathogenic	40890	rs397514667	12:6554611-6554611	12:6445445-6445445
4	ITK	NM_005546.3(ITK):c.1764C>G (p.Tyr588Ter)	SNV	Pathogenic	64371	rs397514260	5:156675990-156675990	5:157248980-157248980
5	ITK	NM_005546.3(ITK):c.86G>A (p.Arg29His)	SNV	Pathogenic	64372	rs397514261	5:156608074-156608074	5:157181063-157181063
6	CD27-AS1	NM_001242.4(CD27):c.239dup (p.His80fs)	Duplication	Pathogenic	578414	rs748418658	12:6554691-6554692	12:6445525-6445526
7	CD27-AS1	NM_001242.4(CD27):c.541C>T (p.Gln181Ter)	SNV	Pathogenic	540910	rs779092602	12:6560063-6560063	12:6450897-6450897
8	XIAP	NM_001167.4(XIAP):c.-10_977+11del	Deletion	Pathogenic	973578		X:123019498-123022574	X:123885648-123888724
9	ITK	NM_005546.3(ITK):c.150G>A (p.Thr50=)	SNV	Conflicting interpretations of pathogenicity	352457	rs61743239	5:156635911-156635911	5:157208900-157208900
10	ITK	NM_005546.3(ITK):c.237G>A (p.Pro79=)	SNV	Conflicting interpretations of pathogenicity	352458	rs201403794	5:156635998-156635998	5:157208987-157208987
11	ITK	NM_005546.3(ITK):c.1276C>T (p.Leu426=)	SNV	Conflicting interpretations of pathogenicity	352473	rs145991142	5:156671315-156671315	5:157244305-157244305
12	ITK	NM_005546.3(ITK):c.1455C>T (p.Ala485=)	SNV	Conflicting interpretations of pathogenicity	352474	rs201568204	5:156672741-156672741	5:157245731-157245731
13	ITK	NM_005546.3(ITK):c.1510A>T (p.Thr504Ser)	SNV	Uncertain significance	540355	rs151046132	5:156672796-156672796	5:157245786-157245786
14	ITK	NM_005546.3(ITK):c.725A>G (p.Lys242Arg)	SNV	Uncertain significance	540356	rs761513530	5:156659361-156659361	5:157232351-157232351
15	ITK	NM_005546.3(ITK):c.767C>T (p.Thr256Ile)	SNV	Uncertain significance	540357	rs115751349	5:156659403-156659403	5:157232393-157232393
16	ITK	NM_005546.3(ITK):c.631G>C (p.Val211Leu)	SNV	Uncertain significance	540358	rs142038079	5:156650008-156650008	5:157222998-157222998
17	ITK	NM_005546.3(ITK):c.1829G>A (p.Arg610His)	SNV	Uncertain significance	540359	rs138438785	5:156679654-156679654	5:157252644-157252644
18	ITK	NM_005546.3(ITK):c.*706G>C	SNV	Uncertain significance	352484	rs886060329	5:156680394-156680394	5:157253384-157253384
19	ITK	NM_005546.3(ITK):c.*1928G>A	SNV	Uncertain significance	352501	rs886060334	5:156681616-156681616	5:157254606-157254606
20	ITK	NM_005546.3(ITK):c.1492G>T (p.Val498Leu)	SNV	Uncertain significance	473141	rs758820629	5:156672778-156672778	5:157245768-157245768
21	ITK	NM_005546.3(ITK):c.1715G>A (p.Ser572Asn)	SNV	Uncertain significance	473142	rs140542010	5:156675941-156675941	5:157248931-157248931
22	ITK	NM_005546.3(ITK):c.1685G>A (p.Arg562Gln)	SNV	Uncertain significance	578820	rs142618425	5:156675911-156675911	5:157248901-157248901
23	ITK	NM_005546.3(ITK):c.1153A>G (p.Lys385Glu)	SNV	Uncertain significance	579298	rs767083015	5:156670725-156670725	5:157243715-157243715
24	ITK	NM_005546.3(ITK):c.539A>G (p.Tyr180Cys)	SNV	Uncertain significance	579957	rs1561657402	5:156649916-156649916	5:157222906-157222906
25	CD27-AS1	NM_001242.4(CD27):c.122A>G (p.Gln41Arg)	SNV	Uncertain significance	581569	rs752259578	12:6554383-6554383	12:6445217-6445217
26	ITK	NM_005546.3(ITK):c.82G>T (p.Val28Phe)	SNV	Uncertain significance	638898	rs1580869283	5:156608070-156608070	5:157181059-157181059
27	ITK	NM_005546.3(ITK):c.1282C>A (p.Gln428Lys)	SNV	Uncertain significance	641419	rs150270557	5:156671321-156671321	5:157244311-157244311
28	ITK	NM_005546.3(ITK):c.674A>G (p.Tyr225Cys)	SNV	Uncertain significance	642717	rs201567966	5:156655332-156655332	5:157228322-157228322
29	CD27-AS1	NM_001242.4(CD27):c.353C>A (p.Thr118Asn)	SNV	Uncertain significance	644090	rs373598636	12:6559423-6559423	12:6450257-6450257
30	ITK	NM_005546.3(ITK):c.1791+5G>A	SNV	Uncertain significance	644968	rs1288043073	5:156676022-156676022	5:157249012-157249012
31	ITK	NM_005546.3(ITK):c.1411G>A (p.Ala471Thr)	SNV	Uncertain significance	646233	rs368438364	5:156671450-156671450	5:157244440-157244440
32	ITK	NM_005546.3(ITK):c.571G>A (p.Ala191Thr)	SNV	Uncertain significance	352463	rs534229766	5:156649948-156649948	5:157222938-157222938
33	ITK	NM_005546.3(ITK):c.1034C>T (p.Ala345Val)	SNV	Uncertain significance	647566	rs1421908099	5:156668704-156668704	5:157241694-157241694
34	ITK	NM_005546.3(ITK):c.1601G>A (p.Arg534His)	SNV	Uncertain significance	649542	rs745561238	5:156672977-156672977	5:157245967-157245967
35	CD27-AS1	NM_001242.4(CD27):c.233G>A (p.Arg78Gln)	SNV	Uncertain significance	649825	rs145433356	12:6554686-6554686	12:6445520-6445520
36	ITK	NM_005546.3(ITK):c.495G>T (p.Arg165Ser)	SNV	Uncertain significance	654225	rs533252659	5:156644917-156644917	5:157217907-157217907
37	CD27-AS1	NM_001242.4(CD27):c.206T>C (p.Val69Ala)	SNV	Uncertain significance	655342	rs749266346	12:6554659-6554659	12:6445493-6445493
38	CD27-AS1	NM_001242.4(CD27):c.721G>A (p.Glu241Lys)	SNV	Uncertain significance	656240	rs759504816	12:6560496-6560496	12:6451330-6451330
39	ITK	NC_000005.9:g.(?_156607793)_(156650044_?)dup	Duplication	Uncertain significance	656285		5:156607793-156650044
40	CD27-AS1	NM_001242.4(CD27):c.488T>C (p.Leu163Pro)	SNV	Uncertain significance	656369	rs958102669	12:6559746-6559746	12:6450580-6450580
41	ITK	NM_005546.3(ITK):c.873G>T (p.Lys291Asn)	SNV	Uncertain significance	657763	rs1580905431	5:156667093-156667093	5:157240083-157240083
42	ITK	NM_005546.3(ITK):c.667A>G (p.Ser223Gly)	SNV	Uncertain significance	658392	rs200825710	5:156655325-156655325	5:157228315-157228315
43	CD27-AS1	NM_001242.4(CD27):c.712A>G (p.Arg238Gly)	SNV	Uncertain significance	662511	rs376329676	12:6560487-6560487	12:6451321-6451321
44	CD27-AS1	NM_001242.4(CD27):c.7C>T (p.Arg3Trp)	SNV	Uncertain significance	663095	rs755775043	12:6554268-6554268	12:6445102-6445102
45	CD27-AS1	NM_001242.4(CD27):c.546A>T (p.Arg182Ser)	SNV	Uncertain significance	663562	rs746393687	12:6560068-6560068	12:6450902-6450902
46	ITK	NM_005546.3(ITK):c.526G>A (p.Val176Ile)	SNV	Uncertain significance	665307	rs1452423111	5:156649903-156649903	5:157222893-157222893
47	ITK	NM_005546.3(ITK):c.1828C>T (p.Arg610Cys)	SNV	Uncertain significance	665754	rs763559802	5:156679653-156679653	5:157252643-157252643
48	CD27-AS1	NM_001242.4(CD27):c.254G>A (p.Arg85Gln)	SNV	Uncertain significance	666185	rs1404955716	12:6554707-6554707	12:6445541-6445541
49	ITK	NM_005546.3(ITK):c.*140C>T	SNV	Uncertain significance	352479	rs536343015	5:156679828-156679828	5:157252818-157252818
50	ITK	NM_005546.3(ITK):c.*1767C>A	SNV	Uncertain significance	352499	rs184917807	5:156681455-156681455	5:157254445-157254445

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

⁷³

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

Sources

Expression for Lymphoproliferative Syndrome 2

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

Sources

Pathways for Lymphoproliferative Syndrome 2

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

(show all 13)

#	Super pathways	Score	Top Affiliating Genes
1	Akt Signaling ⁶³ Show member pathways p38 Signaling ⁶³ Tec Kinases Signaling ⁶³	13.18	XIAP TNFRSF4 TNFRSF13B ITK CD70 CD4
2	NF-kappaB Signaling ⁴	12.32	TNFRSF4 SH2D1A ITK CD8A CD28
3	Hematopoietic cell lineage ³⁶	11.7	CR2 CD8A CD4
4	Hematopoietic Stem Cell Differentiation Pathways and Lineage-specific Markers ⁶⁴	11.62	SLAMF1 CD8A CD4 CD28
5	Dendritic Cells Developmental Lineage Pathway ⁶⁴	11.56	SLAMF1 CD8A CD4
6	Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway ²³ Show member pathways Apoptosis and survival Anti-apoptotic TNFs/NF-kB/IAP pathway ²³	11.53	XIAP TNFRSF4 TNFRSF13B
7	CTLA4 Signaling ⁶³	11.5	CD8A CD4 CD28
8	TCR signaling in naive CD4+ T cells ¹ Show member pathways TCR signaling in naive CD8+ T cells ¹	11.49	ITK CD8A CD4 CD28
9	Th2 Differentiation Pathway ⁶⁴	11.3	TNFRSF4 CD4 CD28
10	TNF Superfamily Pathway: Human Ligand-Receptor Interactions and their Associated Functions ⁶⁴ Show member pathways TNFs bind their physiological receptors ⁶⁵	11.17	TNFRSF4 TNFRSF13B CD70 CD27
11	Primary immunodeficiency ³⁶	11.12	TNFRSF13B CD8A CD4
12	T-Cell Receptor and Co-stimulatory Signaling ¹	10.99	ITK CD8A CD28
13	IgA-Producing B Cells in the Intestine ⁶⁴	10.84	TNFRSF4 TNFRSF13B SLAMF1 CR2 CD28

Sources

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	plasma membrane	GO:0005886	9.97	TNFRSF4 TNFRSF13B STXBP2 SLAMF1 MAGT1 ITK
2	cell surface	GO:0009986	9.65	TNFRSF4 SLAMF1 CD4 CD28 CD27
3	external side of plasma membrane	GO:0009897	9.35	TNFRSF4 CD8A CD4 CD28 CD27
4	integral component of plasma membrane	GO:0005887	9.23	TNFRSF4 TNFRSF13B MAGT1 CD8A CD70 CD4

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

(show all 12)

#	Name	GO ID	Score	Top Affiliating Genes
1	cell surface receptor signaling pathway	GO:0007166	9.83	TNFRSF13B CD8A CD4 CD28 CD27
2	immune response	GO:0006955	9.8	TNFRSF4 CR2 CD8A CD70 CD4 CD28
3	adaptive immune response	GO:0002250	9.73	TNFRSF13B SLAMF1 SH2D1A ITK CD8A CD4
4	viral entry into host cell	GO:0046718	9.67	TNFRSF4 SLAMF1 CR2
5	tumor necrosis factor-mediated signaling pathway	GO:0033209	9.67	TNFRSF4 TNFRSF13B CD70 CD27
6	phagocytosis	GO:0006909	9.63	SLAMF1 LYST CORO1A
7	B cell proliferation	GO:0042100	9.58	CTPS1 CR2 CD70
8	immune system process	GO:0002376	9.56	TNFRSF13B SLAMF1 SH2D1A ITK CTPS1 CR2
9	leukocyte chemotaxis	GO:0030595	9.51	LYST CORO1A
10	T cell mediated immunity	GO:0002456	9.48	CD8A CD70
11	positive regulation of T cell proliferation	GO:0042102	9.46	CORO1A CD70 CD4 CD28
12	T cell activation	GO:0042110	8.92	ITK CD8A CD4 CD28

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

#	Name	GO ID	Score	Top Affiliating Genes
1	transmembrane signaling receptor activity	GO:0004888	9.46	SLAMF1 CR2 CD4 CD27
2	coreceptor activity	GO:0015026	9.13	CD8A CD4 CD28
3	virus receptor activity	GO:0001618	8.92	TNFRSF4 SLAMF1 CR2 CD4

Sources

Sources for Lymphoproliferative Syndrome 2

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

⁵ ClinicalTrials

⁶ ClinVar

⁷ CNVD

⁸ Cochrane Library

⁹ Cosmic

¹⁰ dbSNP

¹¹ DGIdb

¹² Disease Ontology

¹³ diseasecard

¹⁴ DiseaseEnhancer

¹⁵ DISEASES

¹⁶ DrugBank

¹⁷ EFO

¹⁸ ExPASy

¹⁹ FMA

²⁰ GARD

²¹ GeneAnalytics

²² GeneCards

²³ GeneGo (Thomson Reuters)

²⁴ GeneHancer via GeneCards

²⁵ GeneReviews

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HMDB

³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

⁴² MedlinePlus

⁴³ MedlinePlus Genetics

⁴⁴ MeSH

⁴⁵ MESH via Orphanet

⁴⁶ MGI

⁴⁷ miR2Disease

⁴⁸ NCBI Bookshelf

⁴⁹ NCI

⁵⁰ NCIt

⁵¹ NDF-RT

⁵² NIH Clinical Center

⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 05-Mar-2021)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

⁶² PubMed Health

⁶³ QIAGEN

⁶⁴ R&D Systems

⁶⁵ Reactome

⁶⁶ Sino Biological

⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia

Lymphoproliferative Syndrome 2 (LPFS2)

Aliases & Classifications for Lymphoproliferative Syndrome 2

MalaCards integrated aliases for Lymphoproliferative Syndrome 2:

Characteristics:

Orphanet epidemiological data:

OMIM®:

HPO:

Classifications:

External Ids:

Summaries for Lymphoproliferative Syndrome 2

Related Diseases for Lymphoproliferative Syndrome 2

Diseases in the Lymphoproliferative Syndrome family:

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

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

Symptoms & Phenotypes for Lymphoproliferative Syndrome 2

Human phenotypes related to Lymphoproliferative Syndrome 2:

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

UMLS symptoms related to Lymphoproliferative Syndrome 2:

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

MGI Mouse Phenotypes related to Lymphoproliferative Syndrome 2:

Drugs & Therapeutics for Lymphoproliferative Syndrome 2

Genetic Tests for Lymphoproliferative Syndrome 2

Genetic tests related to Lymphoproliferative Syndrome 2:

Anatomical Context for Lymphoproliferative Syndrome 2

Publications for Lymphoproliferative Syndrome 2

Articles related to Lymphoproliferative Syndrome 2:

Genes for Lymphoproliferative Syndrome 2

Genes related to Lymphoproliferative Syndrome 2 (4 elite genes):

Variations for Lymphoproliferative Syndrome 2

ClinVar genetic disease variations for Lymphoproliferative Syndrome 2:

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

Expression for Lymphoproliferative Syndrome 2

Pathways for Lymphoproliferative Syndrome 2

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

GO Terms for Lymphoproliferative Syndrome 2

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

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

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

Sources for Lymphoproliferative Syndrome 2