ALPS3
MCID: ATM083
MIFTS: 37

Autoimmune Lymphoproliferative Syndrome, Type Iii (ALPS3)

Categories: Blood diseases, Cancer 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 72 29 6 70
Alps3 57 12 72
Autoimmune Lymphoproliferative Syndrome Type 3 12 15
Autoimmune Lymphoproliferative Syndrome 3 72 29
Cvid9 12 72
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 39
Immunodeficiency, Common Variable, 9 72
Common Variable Immunodeficiency 9 12
Cvid9, Formerly 57

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or childhood
variable manifestations


HPO:

31
autoimmune lymphoproliferative syndrome, type iii:
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) (Updated 20-May-2021)

MalaCards based summary : Autoimmune Lymphoproliferative Syndrome, Type Iii, also known as alps3, is related to lymphoproliferative syndrome and autoimmune 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 Ceramide Pathway and VEGF Pathway (Tocris). Affiliated tissues include b cells, t cells and kidney, 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 : 72 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

Graphical network of the top 20 diseases related to Autoimmune Lymphoproliferative Syndrome, Type Iii:



Diseases related to Autoimmune Lymphoproliferative Syndrome, Type Iii

Symptoms & Phenotypes for Autoimmune Lymphoproliferative Syndrome, Type Iii

Human phenotypes related to Autoimmune Lymphoproliferative Syndrome, Type Iii:

31 (show all 37)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 31 very rare (1%) HP:0001744
2 hepatomegaly 31 very rare (1%) HP:0002240
3 arthritis 31 very rare (1%) HP:0001369
4 recurrent otitis media 31 very rare (1%) HP:0000403
5 alopecia 31 very rare (1%) HP:0001596
6 nephrotic syndrome 31 very rare (1%) HP:0000100
7 recurrent urinary tract infections 31 very rare (1%) HP:0000010
8 mediastinal lymphadenopathy 31 very rare (1%) HP:0100721
9 elevated c-reactive protein level 31 very rare (1%) HP:0011227
10 hepatosplenomegaly 31 very rare (1%) HP:0001433
11 elevated erythrocyte sedimentation rate 31 very rare (1%) HP:0003565
12 recurrent fever 31 very rare (1%) HP:0001954
13 stage 5 chronic kidney disease 31 very rare (1%) HP:0003774
14 autoimmune hemolytic anemia 31 very rare (1%) HP:0001890
15 generalized lymphadenopathy 31 very rare (1%) HP:0008940
16 follicular hyperplasia 31 very rare (1%) HP:0002729
17 autoimmune thrombocytopenia 31 very rare (1%) HP:0001973
18 decreased serum complement c3 31 very rare (1%) HP:0005421
19 antinuclear antibody positivity 31 very rare (1%) HP:0003493
20 recurrent sinusitis 31 very rare (1%) HP:0011108
21 lymphoproliferative disorder 31 very rare (1%) HP:0005523
22 erythematous macule 31 very rare (1%) HP:0025475
23 recurrent lower respiratory tract infections 31 very rare (1%) HP:0002783
24 decreased serum complement c4 31 very rare (1%) HP:0045042
25 obstruction of the superior vena cava 31 very rare (1%) HP:0031041
26 membranous nephropathy 31 very rare (1%) HP:0012578
27 increased b cell count 31 very rare (1%) HP:0005404
28 elevated serum alanine aminotransferase 31 very rare (1%) HP:0031964
29 elevated serum aspartate aminotransferase 31 very rare (1%) HP:0031956
30 anticardiolipin igg antibody positivity 31 very rare (1%) HP:0020136
31 increased circulating antibody level 31 very rare (1%) HP:0010702
32 reduced natural killer cell activity 31 very rare (1%) HP:0012178
33 persistent ebv viremia 31 very rare (1%) HP:0020072
34 decreased proportion of class-switched memory b cells 31 very rare (1%) HP:0030388
35 increased proportion autoreactive unresponsive cd21-/low b cells 31 very rare (1%) HP:0033207
36 absent isohemagglutinin level 31 very rare (1%) HP:0410293
37 autoimmunity 31 HP:0002960

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Abdomen Spleen:
splenomegaly

Hematology:
hemolytic anemia
autoimmune thrombocytopenia
antiphospholipid syndrome

Immunology:
recurrent infections
lymphadenopathy
autoimmune disorders
decreased igg
b-cell lymphocytosis
more
Skin Nails Hair Skin:
erythematous rash (in some patients)

Abdomen Liver:
hepatomegaly

Skeletal:
arthralgia
polychondritis, autoimmune

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 (Updated 20-May-2021)

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 3 29
2 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:

40
B Cells, T Cells, Kidney

Publications for Autoimmune Lymphoproliferative Syndrome, Type Iii

Articles related to Autoimmune Lymphoproliferative Syndrome, Type Iii:

# Title Authors PMID Year
1
Protein kinase cδ deficiency causes mendelian systemic lupus erythematosus with B cell-defective apoptosis and hyperproliferation. 6 57
23666743 2013
2
B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ. 57 6
23319571 2013
3
Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans. 6 57
23430113 2013
4
Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta. 6 57
11976687 2002
5
The expanding spectrum of the autoimmune lymphoproliferative syndromes. 57
24240292 2013
6
Overexpression of the antiapoptotic gene Bfl-1 in B cells from patients with familial systemic lupus erythematosus. 57
17402365 2007
7
Autoimmune lymphoproliferative syndrome type III, an indefinite disorder. 61
11378568 2001
8
Autoimmune lymphoproliferative syndrome type III: an indefinite disorder. 61
11342357 2001

Variations for Autoimmune Lymphoproliferative Syndrome, Type Iii

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

6 (show top 50) (show all 133)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PRKCD NM_006254.4(PRKCD):c.1352+1G>A SNV Pathogenic 89076 rs398122958 GRCh37: 3:53220712-53220712
GRCh38: 3:53186696-53186696
2 PRKCD NM_006254.4(PRKCD):c.1528G>A (p.Gly510Ser) SNV Pathogenic 157674 rs606231296 GRCh37: 3:53222848-53222848
GRCh38: 3:53188832-53188832
3 PRKCD NM_006254.4(PRKCD):c.1840C>T (p.Arg614Trp) SNV Pathogenic 157675 rs606231297 GRCh37: 3:53223985-53223985
GRCh38: 3:53189969-53189969
4 PRKCD NM_006254.4(PRKCD):c.571C>T (p.Gln191Ter) SNV Pathogenic 958249 GRCh37: 3:53215748-53215748
GRCh38: 3:53181732-53181732
5 PRKCD NM_006254.4(PRKCD):c.788-2A>G SNV Likely pathogenic 541623 rs1295207359 GRCh37: 3:53218888-53218888
GRCh38: 3:53184872-53184872
6 PRKCD NM_006254.4(PRKCD):c.1447C>T (p.Arg483Trp) SNV Conflicting interpretations of pathogenicity 798180 rs35891605 GRCh37: 3:53222767-53222767
GRCh38: 3:53188751-53188751
7 PRKCD NM_006254.4(PRKCD):c.949G>A (p.Glu317Lys) SNV Uncertain significance 618335 rs55929201 GRCh37: 3:53219680-53219680
GRCh38: 3:53185664-53185664
8 PRKCD NM_006254.4(PRKCD):c.742G>A (p.Gly248Ser) SNV Uncertain significance 973660 GRCh37: 3:53217552-53217552
GRCh38: 3:53183536-53183536
9 PRKCD NM_006254.4(PRKCD):c.703G>A (p.Val235Ile) SNV Uncertain significance 995601 GRCh37: 3:53217513-53217513
GRCh38: 3:53183497-53183497
10 PRKCD NM_006254.4(PRKCD):c.1211C>G (p.Ala404Gly) SNV Uncertain significance 864015 GRCh37: 3:53220307-53220307
GRCh38: 3:53186291-53186291
11 PRKCD NM_006254.4(PRKCD):c.1051T>G (p.Phe351Val) SNV Uncertain significance 964363 GRCh37: 3:53220008-53220008
GRCh38: 3:53185992-53185992
12 PRKCD NM_006254.4(PRKCD):c.1637C>T (p.Ser546Phe) SNV Uncertain significance 967865 GRCh37: 3:53223156-53223156
GRCh38: 3:53189140-53189140
13 PRKCD NM_006254.4(PRKCD):c.584C>T (p.Ala195Val) SNV Uncertain significance 541621 rs977894332 GRCh37: 3:53217149-53217149
GRCh38: 3:53183133-53183133
14 PRKCD NM_006254.4(PRKCD):c.1036A>G (p.Ile346Val) SNV Uncertain significance 541622 rs1434557148 GRCh37: 3:53219993-53219993
GRCh38: 3:53185977-53185977
15 PRKCD NM_006254.4(PRKCD):c.604G>A (p.Asp202Asn) SNV Uncertain significance 569464 rs149165175 GRCh37: 3:53217169-53217169
GRCh38: 3:53183153-53183153
16 PRKCD NM_006254.4(PRKCD):c.940C>G (p.Gln314Glu) SNV Uncertain significance 569535 rs1553668823 GRCh37: 3:53219671-53219671
GRCh38: 3:53185655-53185655
17 PRKCD NM_006254.4(PRKCD):c.22G>A (p.Ala8Thr) SNV Uncertain significance 571838 rs368029897 GRCh37: 3:53212460-53212460
GRCh38: 3:53178444-53178444
18 PRKCD NM_006254.4(PRKCD):c.928G>A (p.Val310Ile) SNV Uncertain significance 573919 rs773144753 GRCh37: 3:53219659-53219659
GRCh38: 3:53185643-53185643
19 PRKCD NM_006254.4(PRKCD):c.1781_1782delinsTG (p.Thr594Met) Indel Uncertain significance 660505 rs1575545467 GRCh37: 3:53223926-53223927
GRCh38: 3:53189910-53189911
20 PRKCD NM_006254.4(PRKCD):c.1927C>T (p.Arg643Cys) SNV Uncertain significance 945701 GRCh37: 3:53226178-53226178
GRCh38: 3:53192162-53192162
21 PRKCD NM_006254.4(PRKCD):c.1081G>A (p.Gly361Arg) SNV Uncertain significance 541624 rs369078144 GRCh37: 3:53220038-53220038
GRCh38: 3:53186022-53186022
22 PRKCD NM_006254.4(PRKCD):c.1981G>A (p.Ala661Thr) SNV Uncertain significance 541625 rs149202171 GRCh37: 3:53226232-53226232
GRCh38: 3:53192216-53192216
23 PRKCD NM_006254.4(PRKCD):c.889-9C>T SNV Uncertain significance 626154 rs782612523 GRCh37: 3:53219611-53219611
GRCh38: 3:53185595-53185595
24 PRKCD NM_006254.4(PRKCD):c.1294G>A (p.Gly432Arg) SNV Uncertain significance 845822 GRCh37: 3:53220653-53220653
GRCh38: 3:53186637-53186637
25 PRKCD NM_006254.4(PRKCD):c.890G>A (p.Arg297Lys) SNV Uncertain significance 474771 rs782243565 GRCh37: 3:53219621-53219621
GRCh38: 3:53185605-53185605
26 PRKCD NM_006254.4(PRKCD):c.1060G>C (p.Val354Leu) SNV Uncertain significance 642881 rs782601434 GRCh37: 3:53220017-53220017
GRCh38: 3:53186001-53186001
27 PRKCD NM_006254.4(PRKCD):c.580G>A (p.Ala194Thr) SNV Uncertain significance 643195 rs782475090 GRCh37: 3:53217145-53217145
GRCh38: 3:53183129-53183129
28 PRKCD NM_006254.4(PRKCD):c.549C>A (p.Asn183Lys) SNV Uncertain significance 645396 rs1378624159 GRCh37: 3:53215726-53215726
GRCh38: 3:53181710-53181710
29 PRKCD NM_006254.4(PRKCD):c.1296G>T (p.Gly432=) SNV Uncertain significance 650951 rs781784839 GRCh37: 3:53220655-53220655
GRCh38: 3:53186639-53186639
30 PRKCD NM_006254.4(PRKCD):c.280C>T (p.Arg94Cys) SNV Uncertain significance 653371 rs963574725 GRCh37: 3:53213757-53213757
GRCh38: 3:53179741-53179741
31 PRKCD NM_006254.4(PRKCD):c.1707C>G (p.Arg569=) SNV Uncertain significance 653831 rs1575544912 GRCh37: 3:53223226-53223226
GRCh38: 3:53189210-53189210
32 PRKCD NM_006254.4(PRKCD):c.1345C>T (p.Arg449Cys) SNV Uncertain significance 655541 rs1575542392 GRCh37: 3:53220704-53220704
GRCh38: 3:53186688-53186688
33 PRKCD NM_006254.4(PRKCD):c.1060G>A (p.Val354Ile) SNV Uncertain significance 658787 rs782601434 GRCh37: 3:53220017-53220017
GRCh38: 3:53186001-53186001
34 PRKCD NM_006254.4(PRKCD):c.610A>T (p.Ile204Phe) SNV Uncertain significance 659131 rs1575537929 GRCh37: 3:53217175-53217175
GRCh38: 3:53183159-53183159
35 PRKCD NM_006254.4(PRKCD):c.1872+1G>A SNV Uncertain significance 663401 rs782367516 GRCh37: 3:53224018-53224018
GRCh38: 3:53190002-53190002
36 PRKCD NM_006254.4(PRKCD):c.1844G>T (p.Arg615Met) SNV Uncertain significance 871253 GRCh37: 3:53223989-53223989
GRCh38: 3:53189973-53189973
37 PRKCD NM_006254.4(PRKCD):c.1003G>A (p.Gly335Ser) SNV Uncertain significance 999564 GRCh37: 3:53219960-53219960
GRCh38: 3:53185944-53185944
38 PRKCD NM_006254.4(PRKCD):c.1801C>G (p.Pro601Ala) SNV Uncertain significance 1003064 GRCh37: 3:53223946-53223946
GRCh38: 3:53189930-53189930
39 PRKCD NM_006254.4(PRKCD):c.826G>T (p.Val276Leu) SNV Uncertain significance 1005060 GRCh37: 3:53218928-53218928
GRCh38: 3:53184912-53184912
40 PRKCD NM_006254.4(PRKCD):c.1743+10CTGGG[4] Microsatellite Uncertain significance 1008549 GRCh37: 3:53223271-53223272
GRCh38: 3:53189255-53189256
41 PRKCD NM_006254.4(PRKCD):c.1873-3T>C SNV Uncertain significance 1009655 GRCh37: 3:53226121-53226121
GRCh38: 3:53192105-53192105
42 overlap with 2 genes NC_000003.11:g.(?_53125899)_(53215768_?)dup Duplication Uncertain significance 1011310 GRCh37: 3:53125899-53215768
GRCh38:
43 PRKCD NM_006254.4(PRKCD):c.1352+4C>T SNV Uncertain significance 576675 rs202155309 GRCh37: 3:53220715-53220715
GRCh38: 3:53186699-53186699
44 PRKCD NM_006254.4(PRKCD):c.657+3G>A SNV Uncertain significance 642091 rs199785209 GRCh37: 3:53217225-53217225
GRCh38: 3:53183209-53183209
45 PRKCD NM_006254.4(PRKCD):c.1957G>A (p.Asp653Asn) SNV Uncertain significance 845746 GRCh37: 3:53226208-53226208
GRCh38: 3:53192192-53192192
46 PRKCD NM_006254.4(PRKCD):c.458T>C (p.Ile153Thr) SNV Uncertain significance 849910 GRCh37: 3:53215541-53215541
GRCh38: 3:53181525-53181525
47 PRKCD NM_006254.4(PRKCD):c.925C>G (p.Pro309Ala) SNV Uncertain significance 851463 GRCh37: 3:53219656-53219656
GRCh38: 3:53185640-53185640
48 PRKCD NM_006254.4(PRKCD):c.373G>A (p.Val125Met) SNV Uncertain significance 853731 GRCh37: 3:53215280-53215280
GRCh38: 3:53181264-53181264
49 PRKCD NM_006254.4(PRKCD):c.1040A>G (p.Asn347Ser) SNV Uncertain significance 855612 GRCh37: 3:53219997-53219997
GRCh38: 3:53185981-53185981
50 PRKCD NM_006254.4(PRKCD):c.1450G>A (p.Asp484Asn) SNV Uncertain significance 859393 GRCh37: 3:53222770-53222770
GRCh38: 3:53188754-53188754

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:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.05 PRKCD CASP10
2
Show member pathways
10.54 PRKCD CASP10

GO Terms for Autoimmune Lymphoproliferative Syndrome, Type Iii

Sources for Autoimmune Lymphoproliferative Syndrome, Type Iii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....