ALPS3
MCID: ATM083
MIFTS: 35

Autoimmune Lymphoproliferative Syndrome, Type Iii (ALPS3)

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

Aliases & Classifications for Autoimmune Lymphoproliferative Syndrome, Type Iii

MalaCards integrated aliases for Autoimmune Lymphoproliferative Syndrome, Type Iii:

Name: Autoimmune Lymphoproliferative Syndrome, Type Iii 57 75 29 6 73
Alps3 57 12 75
Autoimmune Lymphoproliferative Syndrome Type 3 12 15
Cvid9 12 75
Immunodeficiency, Common Variable, 9, Formerly; Cvid9, Formerly 57
Autoimmune Lymphoproliferative Syndrome Type Iii 12
Immunodeficiency, Common Variable, 9, Formerly 57
Immunodeficiency, Variable, Common, Type 9 40
Autoimmune Lymphoproliferative Syndrome 3 75
Immunodeficiency, Common Variable, 9 75
Common Variable Immunodeficiency 9 12
Cvid9, Formerly 57

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or childhood
variable manifestations


HPO:

32
autoimmune lymphoproliferative syndrome, type iii:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Autoimmune Lymphoproliferative Syndrome, Type Iii

OMIM : 57 Autoimmune lymphoproliferative syndrome type III is an autosomal recessive disorder of immune dysregulation. The phenotype is variable, but most patients have significant lymphadenopathy associated with variable autoimmune manifestations. Some patients may have recurrent infections. Lymphocyte accumulation results from a combination of impaired apoptosis and excessive proliferation (summary by Oliveira, 2013). For a general description and a discussion of genetic heterogeneity of ALPS, see 601859. (615559)

MalaCards based summary : Autoimmune Lymphoproliferative Syndrome, Type Iii, also known as alps3, is related to autoimmune lymphoproliferative syndrome and lymphoproliferative syndrome, and has symptoms including arthralgia An important gene associated with Autoimmune Lymphoproliferative Syndrome, Type Iii is PRKCD (Protein Kinase C Delta), and among its related pathways/superpathways are PEDF Induced Signaling and PAK Pathway. Affiliated tissues include b cells and t cells, and related phenotypes are splenomegaly and hepatomegaly

Disease Ontology : 12 An autoimmune lymphoproliferative syndrome that has material basis in homozygous mutation in the PRKCD gene on chromosome 3p21.

UniProtKB/Swiss-Prot : 75 Autoimmune lymphoproliferative syndrome 3: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. CVID9 patients have B-cell deficiency and severe autoimmunity.

Related Diseases for Autoimmune Lymphoproliferative Syndrome, Type Iii

Symptoms & Phenotypes for Autoimmune Lymphoproliferative Syndrome, Type Iii

Symptoms via clinical synopsis from OMIM:

57
Abdomen Spleen:
splenomegaly

Skeletal:
arthralgia
polychondritis, autoimmune

Hematology:
autoimmune thrombocytopenia
antiphospholipid syndrome hemolytic anemia

Skin Nails Hair Skin:
erythematous rash (in some patients)

Abdomen Liver:
hepatomegaly

Immunology:
recurrent infections
lymphadenopathy
autoimmune disorders
decreased igg
b-cell lymphocytosis
more
Genitourinary Kidneys:
nephrotic syndrome (in some patients)
membranous glomerulonephritis (in some patients)
deposition of igg and complement seen on renal biopsy (in some patients)


Clinical features from OMIM:

615559

Human phenotypes related to Autoimmune Lymphoproliferative Syndrome, Type Iii:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 32 HP:0001744
2 hepatomegaly 32 HP:0002240
3 arthralgia 32 HP:0002829
4 hemolytic anemia 32 HP:0001878
5 nephrotic syndrome 32 HP:0000100
6 recurrent infections 32 HP:0002719
7 lymphadenopathy 32 HP:0002716
8 autoimmune thrombocytopenia 32 HP:0001973
9 lymphocytosis 32 HP:0100827
10 membranous nephropathy 32 HP:0012578

UMLS symptoms related to Autoimmune Lymphoproliferative Syndrome, Type Iii:


arthralgia

Drugs & Therapeutics for Autoimmune Lymphoproliferative Syndrome, Type Iii

Search Clinical Trials , NIH Clinical Center for Autoimmune Lymphoproliferative Syndrome, Type Iii

Genetic Tests for Autoimmune Lymphoproliferative Syndrome, Type Iii

Genetic tests related to Autoimmune Lymphoproliferative Syndrome, Type Iii:

# Genetic test Affiliating Genes
1 Autoimmune Lymphoproliferative Syndrome, Type Iii 29 PRKCD

Anatomical Context for Autoimmune Lymphoproliferative Syndrome, Type Iii

MalaCards organs/tissues related to Autoimmune Lymphoproliferative Syndrome, Type Iii:

41
B Cells, T Cells

Publications for Autoimmune Lymphoproliferative Syndrome, Type Iii

Articles related to Autoimmune Lymphoproliferative Syndrome, Type Iii:

# Title Authors Year
1
Autoimmune lymphoproliferative syndrome type III: an indefinite disorder. ( 11342357 )
2001
2
Autoimmune lymphoproliferative syndrome type III, an indefinite disorder. ( 11378568 )
2001

Variations for Autoimmune Lymphoproliferative Syndrome, Type Iii

ClinVar genetic disease variations for Autoimmune Lymphoproliferative Syndrome, Type Iii:

6 (show all 50)
# Gene Variation Type Significance SNP ID Assembly Location
1 PRKCD NM_006254.3(PRKCD): c.1352+1G> A single nucleotide variant Pathogenic rs398122958 GRCh37 Chromosome 3, 53220712: 53220712
2 PRKCD NM_006254.3(PRKCD): c.1352+1G> A single nucleotide variant Pathogenic rs398122958 GRCh38 Chromosome 3, 53186696: 53186696
3 PRKCD NM_006254.3(PRKCD): c.1528G> A (p.Gly510Ser) single nucleotide variant Pathogenic rs606231296 GRCh38 Chromosome 3, 53188832: 53188832
4 PRKCD NM_006254.3(PRKCD): c.1528G> A (p.Gly510Ser) single nucleotide variant Pathogenic rs606231296 GRCh37 Chromosome 3, 53222848: 53222848
5 PRKCD NM_006254.3(PRKCD): c.1840C> T (p.Arg614Trp) single nucleotide variant Pathogenic rs606231297 GRCh38 Chromosome 3, 53189969: 53189969
6 PRKCD NM_006254.3(PRKCD): c.1840C> T (p.Arg614Trp) single nucleotide variant Pathogenic rs606231297 GRCh37 Chromosome 3, 53223985: 53223985
7 PRKCD NM_006254.3(PRKCD): c.1043A> G (p.Asn348Ser) single nucleotide variant Uncertain significance rs33911937 GRCh37 Chromosome 3, 53220000: 53220000
8 PRKCD NM_006254.3(PRKCD): c.1043A> G (p.Asn348Ser) single nucleotide variant Uncertain significance rs33911937 GRCh38 Chromosome 3, 53185984: 53185984
9 PRKCD NM_006254.3(PRKCD): c.945T> C (p.Gly315=) single nucleotide variant Likely benign rs781846856 GRCh38 Chromosome 3, 53185660: 53185660
10 PRKCD NM_006254.3(PRKCD): c.945T> C (p.Gly315=) single nucleotide variant Likely benign rs781846856 GRCh37 Chromosome 3, 53219676: 53219676
11 PRKCD NM_006254.3(PRKCD): c.1926G> A (p.Ala642=) single nucleotide variant Benign rs56338517 GRCh37 Chromosome 3, 53226177: 53226177
12 PRKCD NM_006254.3(PRKCD): c.1926G> A (p.Ala642=) single nucleotide variant Benign rs56338517 GRCh38 Chromosome 3, 53192161: 53192161
13 PRKCD NM_006254.3(PRKCD): c.214G> C (p.Val72Leu) single nucleotide variant Benign rs151061939 GRCh38 Chromosome 3, 53179675: 53179675
14 PRKCD NM_006254.3(PRKCD): c.214G> C (p.Val72Leu) single nucleotide variant Benign rs151061939 GRCh37 Chromosome 3, 53213691: 53213691
15 PRKCD NM_006254.3(PRKCD): c.715A> G (p.Met239Val) single nucleotide variant Uncertain significance rs369236318 GRCh38 Chromosome 3, 53183509: 53183509
16 PRKCD NM_006254.3(PRKCD): c.715A> G (p.Met239Val) single nucleotide variant Uncertain significance rs369236318 GRCh37 Chromosome 3, 53217525: 53217525
17 PRKCD NM_006254.3(PRKCD): c.741C> T (p.Cys247=) single nucleotide variant Benign rs55709737 GRCh37 Chromosome 3, 53217551: 53217551
18 PRKCD NM_006254.3(PRKCD): c.741C> T (p.Cys247=) single nucleotide variant Benign rs55709737 GRCh38 Chromosome 3, 53183535: 53183535
19 PRKCD NM_006254.3(PRKCD): c.890G> A (p.Arg297Lys) single nucleotide variant Uncertain significance rs782243565 GRCh38 Chromosome 3, 53185605: 53185605
20 PRKCD NM_006254.3(PRKCD): c.890G> A (p.Arg297Lys) single nucleotide variant Uncertain significance rs782243565 GRCh37 Chromosome 3, 53219621: 53219621
21 PRKCD NM_006254.3(PRKCD): c.1260+6C> T single nucleotide variant Benign rs180706867 GRCh37 Chromosome 3, 53220362: 53220362
22 PRKCD NM_006254.3(PRKCD): c.1260+6C> T single nucleotide variant Benign rs180706867 GRCh38 Chromosome 3, 53186346: 53186346
23 PRKCD NM_006254.3(PRKCD): c.1176G> A (p.Glu392=) single nucleotide variant Likely benign rs782735766 GRCh38 Chromosome 3, 53186256: 53186256
24 PRKCD NM_006254.3(PRKCD): c.1176G> A (p.Glu392=) single nucleotide variant Likely benign rs782735766 GRCh37 Chromosome 3, 53220272: 53220272
25 PRKCD NM_006254.3(PRKCD): c.1743+8C> T single nucleotide variant Benign rs182290450 GRCh38 Chromosome 3, 53189254: 53189254
26 PRKCD NM_006254.3(PRKCD): c.1743+8C> T single nucleotide variant Benign rs182290450 GRCh37 Chromosome 3, 53223270: 53223270
27 PRKCD NM_006254.3(PRKCD): c.788-2A> G single nucleotide variant Likely pathogenic GRCh38 Chromosome 3, 53184872: 53184872
28 PRKCD NM_006254.3(PRKCD): c.788-2A> G single nucleotide variant Likely pathogenic GRCh37 Chromosome 3, 53218888: 53218888
29 PRKCD NM_006254.3(PRKCD): c.584C> T (p.Ala195Val) single nucleotide variant Uncertain significance rs977894332 GRCh37 Chromosome 3, 53217149: 53217149
30 PRKCD NM_006254.3(PRKCD): c.584C> T (p.Ala195Val) single nucleotide variant Uncertain significance rs977894332 GRCh38 Chromosome 3, 53183133: 53183133
31 PRKCD NM_006254.3(PRKCD): c.1086+9T> C single nucleotide variant Likely benign GRCh38 Chromosome 3, 53186036: 53186036
32 PRKCD NM_006254.3(PRKCD): c.1086+9T> C single nucleotide variant Likely benign GRCh37 Chromosome 3, 53220052: 53220052
33 PRKCD NM_006254.3(PRKCD): c.1981G> A (p.Ala661Thr) single nucleotide variant Uncertain significance rs149202171 GRCh38 Chromosome 3, 53192216: 53192216
34 PRKCD NM_006254.3(PRKCD): c.1981G> A (p.Ala661Thr) single nucleotide variant Uncertain significance rs149202171 GRCh37 Chromosome 3, 53226232: 53226232
35 PRKCD NM_006254.3(PRKCD): c.1362C> T (p.Ala454=) single nucleotide variant Likely benign rs41295962 GRCh38 Chromosome 3, 53187349: 53187349
36 PRKCD NM_006254.3(PRKCD): c.1362C> T (p.Ala454=) single nucleotide variant Likely benign rs41295962 GRCh37 Chromosome 3, 53221365: 53221365
37 PRKCD NM_006254.3(PRKCD): c.1036A> G (p.Ile346Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 3, 53185977: 53185977
38 PRKCD NM_006254.3(PRKCD): c.1036A> G (p.Ile346Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 3, 53219993: 53219993
39 PRKCD NM_006254.3(PRKCD): c.1081G> A (p.Gly361Arg) single nucleotide variant Uncertain significance rs369078144 GRCh38 Chromosome 3, 53186022: 53186022
40 PRKCD NM_006254.3(PRKCD): c.1081G> A (p.Gly361Arg) single nucleotide variant Uncertain significance rs369078144 GRCh37 Chromosome 3, 53220038: 53220038
41 PRKCD NM_006254.3(PRKCD): c.22G> A (p.Ala8Thr) single nucleotide variant Uncertain significance rs368029897 GRCh37 Chromosome 3, 53212460: 53212460
42 PRKCD NM_006254.3(PRKCD): c.22G> A (p.Ala8Thr) single nucleotide variant Uncertain significance rs368029897 GRCh38 Chromosome 3, 53178444: 53178444
43 PRKCD NM_006254.3(PRKCD): c.928G> A (p.Val310Ile) single nucleotide variant Uncertain significance rs773144753 GRCh37 Chromosome 3, 53219659: 53219659
44 PRKCD NM_006254.3(PRKCD): c.928G> A (p.Val310Ile) single nucleotide variant Uncertain significance rs773144753 GRCh38 Chromosome 3, 53185643: 53185643
45 PRKCD NM_006254.3(PRKCD): c.604G> A (p.Asp202Asn) single nucleotide variant Uncertain significance rs149165175 GRCh37 Chromosome 3, 53217169: 53217169
46 PRKCD NM_006254.3(PRKCD): c.604G> A (p.Asp202Asn) single nucleotide variant Uncertain significance rs149165175 GRCh38 Chromosome 3, 53183153: 53183153
47 PRKCD NM_006254.3(PRKCD): c.940C> G (p.Gln314Glu) single nucleotide variant Uncertain significance GRCh38 Chromosome 3, 53185655: 53185655
48 PRKCD NM_006254.3(PRKCD): c.940C> G (p.Gln314Glu) single nucleotide variant Uncertain significance GRCh37 Chromosome 3, 53219671: 53219671
49 PRKCD NM_006254.3(PRKCD): c.1352+4C> T single nucleotide variant Uncertain significance rs202155309 GRCh38 Chromosome 3, 53186699: 53186699
50 PRKCD NM_006254.3(PRKCD): c.1352+4C> T single nucleotide variant Uncertain significance rs202155309 GRCh37 Chromosome 3, 53220715: 53220715

Expression for Autoimmune Lymphoproliferative Syndrome, Type Iii

Search GEO for disease gene expression data for Autoimmune Lymphoproliferative Syndrome, Type Iii.

Pathways for Autoimmune Lymphoproliferative Syndrome, Type Iii

Pathways related to Autoimmune Lymphoproliferative Syndrome, Type Iii according to GeneCards Suite gene sharing:

(show all 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.05 CASP10 FASLG PRKCD
2
Show member pathways
12.61 CASP10 FASLG PRKCD
3
Show member pathways
12.22 CASP10 FASLG PRKCD
4
Show member pathways
12.01 CASP10 PRKCD
5
Show member pathways
11.97 CASP10 FASLG
6
Show member pathways
11.92 CASP10 PRKCD
7
Show member pathways
11.89 CASP10 FASLG PRKCD
8
Show member pathways
11.79 CASP10 FASLG
9
Show member pathways
11.74 CASP10 FASLG
10
Show member pathways
11.74 CASP10 FASLG
11
Show member pathways
11.68 CASP10 FASLG
12
Show member pathways
11.41 CASP10 PRKCD
13
Show member pathways
11.33 CASP10 FASLG PRKCD
14
Show member pathways
11.07 CASP10 PRKCD

GO Terms for Autoimmune Lymphoproliferative Syndrome, Type Iii

Biological processes related to Autoimmune Lymphoproliferative Syndrome, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 9.26 CASP10 FASLG
2 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 9.16 CASP10 FASLG
3 apoptotic process GO:0006915 9.13 CASP10 FASLG PRKCD
4 apoptotic signaling pathway GO:0097190 8.62 CASP10 FASLG

Sources for Autoimmune Lymphoproliferative Syndrome, Type Iii

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
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44 MeSH
45 MESH via Orphanet
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50 NCIt
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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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