CASP8D
MCID: CSP005
MIFTS: 44

Caspase 8 Deficiency (CASP8D)

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

Aliases & Classifications for Caspase 8 Deficiency

MalaCards integrated aliases for Caspase 8 Deficiency:

Name: Caspase 8 Deficiency 58 12 54
Caspase-8 Deficiency 54 76 30 6 41
Autoimmune Lymphoproliferative Syndrome Type 2b 12 54 15 74
Alps2b 58 12 54
Ceds 58 12 60
Autoimmune Lymphoproliferative Syndrome with Recurrent Viral Infections 12 60
Alps with Recurrent Viral Infections 12 60
Caspase 8 Deficiency Syndrome 12 60
Autoimmune Lymphoproliferative Syndrome, Type Iib; Alps2b 58
Autoimmune Lymphoproliferative Syndrome, Type Iib 58
Autoimmune Lymphoproliferative Syndrome Type Iib 12
Caspase Eight Deficiency State 12
Casp8d 76

Characteristics:

Orphanet epidemiological data:

60
autoimmune lymphoproliferative syndrome with recurrent viral infections
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive


HPO:

33
caspase 8 deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0110116
OMIM 58 607271
ICD10 34 D47.9
ICD10 via Orphanet 35 D47.9
UMLS via Orphanet 75 C1846545
Orphanet 60 ORPHA275517
MedGen 43 C1846545
UMLS 74 C1846545

Summaries for Caspase 8 Deficiency

UniProtKB/Swiss-Prot : 76 Caspase-8 deficiency: Disorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95- induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization.

MalaCards based summary : Caspase 8 Deficiency, also known as caspase-8 deficiency, is related to classic ehlers-danlos syndrome and cranioectodermal dysplasia 1. An important gene associated with Caspase 8 Deficiency is CASP8 (Caspase 8), and among its related pathways/superpathways are ERK Signaling and TNFR1 Pathway. Affiliated tissues include t cells, nk cells and b cells, and related phenotypes are failure to thrive and splenomegaly

Disease Ontology : 12 An autoimmune lymphoproliferative syndrome that has material basis in homozygous mutation in the CASP8 gene on chromosome 2q33.

OMIM : 58 Caspase 8 deficiency is a syndrome of lymphadenopathy and splenomegaly, marginal elevation of 'double-negative T cells' (DNT; T-cell receptor alpha/beta+, CD4-/CD8-), defective FAS-induced apoptosis, and defective T-, B-, and natural killer (NK)-cell activation, with recurrent bacterial and viral infections (summary by Madkaikar et al., 2011). (607271)

Wikipedia : 77 Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8... more...

Related Diseases for Caspase 8 Deficiency

Graphical network of the top 20 diseases related to Caspase 8 Deficiency:



Diseases related to Caspase 8 Deficiency

Symptoms & Phenotypes for Caspase 8 Deficiency

Human phenotypes related to Caspase 8 Deficiency:

33 (show all 11)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 33 HP:0001508
2 splenomegaly 33 HP:0001744
3 short stature 33 HP:0004322
4 asthma 33 HP:0002099
5 chronic diarrhea 33 HP:0002028
6 eczema 33 HP:0000964
7 pneumonia 33 HP:0002090
8 lymphadenopathy 33 HP:0002716
9 decreased t cell activation 33 HP:0005419
10 recurrent sinopulmonary infections 33 HP:0005425
11 defective b cell activation 33 HP:0005384

Symptoms via clinical synopsis from OMIM:

58
Growth Other:
failure to thrive

Growth Height:
short stature

Skin Nails Hair Skin:
eczema

Immunology:
lymphadenopathy
recurrent sinopulmonary infections
herpes simplex virus infection, mucocutaneous
defective cd95-induced apoptosis of peripheral blood lymphocytes
no response to pneumococcal vaccination
more
Abdomen Spleen:
splenomegaly

Respiratory Airways:
asthma
reactive airway disease

Respiratory Lung:
pneumonia

Abdomen Gastrointestinal:
diarrhea, chronic

Clinical features from OMIM:

607271

Drugs & Therapeutics for Caspase 8 Deficiency

Search Clinical Trials , NIH Clinical Center for Caspase 8 Deficiency

Genetic Tests for Caspase 8 Deficiency

Genetic tests related to Caspase 8 Deficiency:

# Genetic test Affiliating Genes
1 Caspase-8 Deficiency 30 CASP8

Anatomical Context for Caspase 8 Deficiency

MalaCards organs/tissues related to Caspase 8 Deficiency:

42
T Cells, Nk Cells, B Cells, Skin, Bone, Bone Marrow

Publications for Caspase 8 Deficiency

Articles related to Caspase 8 Deficiency:

# Title Authors Year
1
Intestinal Inflammation and Dysregulated Immunity in Patients With Inherited Caspase-8 Deficiency. ( 30267714 )
2019
2
Caspase-8 deficiency in mouse embryos triggers chronic RIPK1-dependent activation of inflammatory genes, independently of RIPK3. ( 29666472 )
2018
3
Caspase-8 Deficiency Presenting as Late-Onset Multi-Organ Lymphocytic Infiltration with Granulomas in two Adult Siblings. ( 25814141 )
2015
4
Th-MYCN mice with caspase-8 deficiency develop advanced neuroblastoma with bone marrow metastasis. ( 23536557 )
2013
5
Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease. ( 19720838 )
2009
6
Caspase-8 deficiency facilitates cellular transformation in vitro. ( 18566604 )
2008
7
Caspase-8 deficiency in T cells leads to a lethal lymphoinfiltrative immune disorder. ( 16157684 )
2005
8
Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. ( 12353035 )
2002

Variations for Caspase 8 Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Caspase 8 Deficiency:

76
# Symbol AA change Variation ID SNP ID
1 CASP8 p.Arg248Trp VAR_014204 rs17860424

ClinVar genetic disease variations for Caspase 8 Deficiency:

6 (show top 50) (show all 84)
# Gene Variation Type Significance SNP ID Assembly Location
1 CASP8 NM_001228.4(CASP8): c.793C> T (p.Arg265Trp) single nucleotide variant Pathogenic rs17860424 GRCh37 Chromosome 2, 202141631: 202141631
2 CASP8 NM_001228.4(CASP8): c.793C> T (p.Arg265Trp) single nucleotide variant Pathogenic rs17860424 GRCh38 Chromosome 2, 201276908: 201276908
3 CASP8 NM_001228.4(CASP8): c.904G> C (p.Asp302His) single nucleotide variant protective rs1045485 GRCh37 Chromosome 2, 202149589: 202149589
4 CASP8 NM_001228.4(CASP8): c.904G> C (p.Asp302His) single nucleotide variant protective rs1045485 GRCh38 Chromosome 2, 201284866: 201284866
5 CASP8 NM_001228.4(CASP8): c.528A> G (p.Ile176Met) single nucleotide variant Uncertain significance rs149933993 GRCh38 Chromosome 2, 201272658: 201272658
6 CASP8 NM_001228.4(CASP8): c.528A> G (p.Ile176Met) single nucleotide variant Uncertain significance rs149933993 GRCh37 Chromosome 2, 202137381: 202137381
7 CASP8 NM_001228.4(CASP8): c.970A> G (p.Met324Val) single nucleotide variant Uncertain significance rs148960588 GRCh37 Chromosome 2, 202149655: 202149655
8 CASP8 NM_001228.4(CASP8): c.970A> G (p.Met324Val) single nucleotide variant Uncertain significance rs148960588 GRCh38 Chromosome 2, 201284932: 201284932
9 CASP8 NM_001228.4(CASP8): c.1355+12C> T single nucleotide variant Uncertain significance rs375465590 GRCh37 Chromosome 2, 202150052: 202150052
10 CASP8 NM_001228.4(CASP8): c.1355+12C> T single nucleotide variant Uncertain significance rs375465590 GRCh38 Chromosome 2, 201285329: 201285329
11 CASP8 NM_001228.4(CASP8): c.*98C> T single nucleotide variant Uncertain significance rs36155452 GRCh37 Chromosome 2, 202151415: 202151415
12 CASP8 NM_001228.4(CASP8): c.*98C> T single nucleotide variant Uncertain significance rs36155452 GRCh38 Chromosome 2, 201286692: 201286692
13 CASP8 NM_001228.4(CASP8): c.*316C> T single nucleotide variant Uncertain significance rs35419671 GRCh37 Chromosome 2, 202151633: 202151633
14 CASP8 NM_001228.4(CASP8): c.*316C> T single nucleotide variant Uncertain significance rs35419671 GRCh38 Chromosome 2, 201286910: 201286910
15 CASP8 NM_001228.4(CASP8): c.*464T> C single nucleotide variant Benign rs1045494 GRCh38 Chromosome 2, 201287058: 201287058
16 CASP8 NM_001228.4(CASP8): c.*464T> C single nucleotide variant Benign rs1045494 GRCh37 Chromosome 2, 202151781: 202151781
17 CASP8 NM_001228.4(CASP8): c.*578C> A single nucleotide variant Uncertain significance rs886055434 GRCh38 Chromosome 2, 201287172: 201287172
18 CASP8 NM_001228.4(CASP8): c.*578C> A single nucleotide variant Uncertain significance rs886055434 GRCh37 Chromosome 2, 202151895: 202151895
19 CASP8 NM_001228.4(CASP8): c.435C> T (p.Ser145=) single nucleotide variant Conflicting interpretations of pathogenicity rs17860422 GRCh38 Chromosome 2, 201271549: 201271549
20 CASP8 NM_001228.4(CASP8): c.435C> T (p.Ser145=) single nucleotide variant Conflicting interpretations of pathogenicity rs17860422 GRCh37 Chromosome 2, 202136272: 202136272
21 CASP8 NM_001228.4(CASP8): c.840A> G (p.Thr280=) single nucleotide variant Likely benign rs35142591 GRCh38 Chromosome 2, 201276955: 201276955
22 CASP8 NM_001228.4(CASP8): c.840A> G (p.Thr280=) single nucleotide variant Likely benign rs35142591 GRCh37 Chromosome 2, 202141678: 202141678
23 CASP8 NM_001228.4(CASP8): c.1011G> A (p.Lys337=) single nucleotide variant Benign rs1045487 GRCh37 Chromosome 2, 202149696: 202149696
24 CASP8 NM_001228.4(CASP8): c.1011G> A (p.Lys337=) single nucleotide variant Benign rs1045487 GRCh38 Chromosome 2, 201284973: 201284973
25 CASP8 NM_001228.4(CASP8): c.1089T> C (p.Pro363=) single nucleotide variant Uncertain significance rs768360449 GRCh37 Chromosome 2, 202149774: 202149774
26 CASP8 NM_001228.4(CASP8): c.1089T> C (p.Pro363=) single nucleotide variant Uncertain significance rs768360449 GRCh38 Chromosome 2, 201285051: 201285051
27 CASP8 NM_001228.4(CASP8): c.*60C> T single nucleotide variant Likely benign rs13425113 GRCh37 Chromosome 2, 202151377: 202151377
28 CASP8 NM_001228.4(CASP8): c.*60C> T single nucleotide variant Likely benign rs13425113 GRCh38 Chromosome 2, 201286654: 201286654
29 CASP8 NM_001228.4(CASP8): c.*83G> A single nucleotide variant Likely benign rs17860428 GRCh37 Chromosome 2, 202151400: 202151400
30 CASP8 NM_001228.4(CASP8): c.*83G> A single nucleotide variant Likely benign rs17860428 GRCh38 Chromosome 2, 201286677: 201286677
31 CASP8 NM_001228.4(CASP8): c.*99G> A single nucleotide variant Likely benign rs13425383 GRCh37 Chromosome 2, 202151416: 202151416
32 CASP8 NM_001228.4(CASP8): c.*99G> A single nucleotide variant Likely benign rs13425383 GRCh38 Chromosome 2, 201286693: 201286693
33 CASP8 NM_001228.4(CASP8): c.*122G> C single nucleotide variant Benign rs3185378 GRCh38 Chromosome 2, 201286716: 201286716
34 CASP8 NM_001228.4(CASP8): c.*122G> C single nucleotide variant Benign rs3185378 GRCh37 Chromosome 2, 202151439: 202151439
35 CASP8 NM_001228.4(CASP8): c.*124C> T single nucleotide variant Uncertain significance rs886055432 GRCh37 Chromosome 2, 202151441: 202151441
36 CASP8 NM_001228.4(CASP8): c.*124C> T single nucleotide variant Uncertain significance rs886055432 GRCh38 Chromosome 2, 201286718: 201286718
37 CASP8 NM_001228.4(CASP8): c.*175C> T single nucleotide variant Likely benign rs2141331 GRCh37 Chromosome 2, 202151492: 202151492
38 CASP8 NM_001228.4(CASP8): c.*175C> T single nucleotide variant Likely benign rs2141331 GRCh38 Chromosome 2, 201286769: 201286769
39 CASP8 NM_001228.4(CASP8): c.*429A> G single nucleotide variant Likely benign rs17860433 GRCh38 Chromosome 2, 201287023: 201287023
40 CASP8 NM_001228.4(CASP8): c.*429A> G single nucleotide variant Likely benign rs17860433 GRCh37 Chromosome 2, 202151746: 202151746
41 CASP8 NM_001228.4(CASP8): c.*935_*936dupAT duplication Benign rs397897264 GRCh38 Chromosome 2, 201287529: 201287530
42 CASP8 NM_001228.4(CASP8): c.*935_*936dupAT duplication Benign rs397897264 GRCh37 Chromosome 2, 202152252: 202152253
43 CASP8 NM_001228.4(CASP8): c.1359C> T (p.Gly453=) single nucleotide variant Uncertain significance rs777463099 GRCh38 Chromosome 2, 201286462: 201286462
44 CASP8 NM_001228.4(CASP8): c.1359C> T (p.Gly453=) single nucleotide variant Uncertain significance rs777463099 GRCh37 Chromosome 2, 202151185: 202151185
45 CASP8 NM_001228.4(CASP8): c.*411G> C single nucleotide variant Likely benign rs17860432 GRCh38 Chromosome 2, 201287005: 201287005
46 CASP8 NM_001228.4(CASP8): c.*411G> C single nucleotide variant Likely benign rs17860432 GRCh37 Chromosome 2, 202151728: 202151728
47 CASP8 NM_001228.4(CASP8): c.*591T> C single nucleotide variant Uncertain significance rs187758494 GRCh38 Chromosome 2, 201287185: 201287185
48 CASP8 NM_001228.4(CASP8): c.*591T> C single nucleotide variant Uncertain significance rs187758494 GRCh37 Chromosome 2, 202151908: 202151908
49 CASP8 NM_001228.4(CASP8): c.*812T> A single nucleotide variant Uncertain significance rs538987233 GRCh38 Chromosome 2, 201287406: 201287406
50 CASP8 NM_001228.4(CASP8): c.*812T> A single nucleotide variant Uncertain significance rs538987233 GRCh37 Chromosome 2, 202152129: 202152129

Expression for Caspase 8 Deficiency

Search GEO for disease gene expression data for Caspase 8 Deficiency.

Pathways for Caspase 8 Deficiency

Pathways related to Caspase 8 Deficiency according to GeneCards Suite gene sharing:

(show all 28)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.53 CASP10 CASP8 COL5A1 COL5A2 FADD RIPK1
2
Show member pathways
12.67 CASP10 CASP8 FADD RIPK1
3
Show member pathways
12.67 CASP10 CASP8 FADD RIPK1
4
Show member pathways
12.63 CASP10 CASP8 FADD RIPK1
5
Show member pathways
12.51 CASP10 CASP8 FADD RIPK1
6
Show member pathways
12.46 CASP10 CASP8 FADD RIPK1
7
Show member pathways
12.4 CASP8 FADD RIPK1
8
Show member pathways
12.39 CASP10 CASP8 FADD RIPK1
9
Show member pathways
12.29 CASP10 CASP8 FADD RIPK1
10
Show member pathways
12.24 CASP10 CASP8 FADD
11 12 CASP8 FADD RIPK1
12
Show member pathways
12 CASP10 CASP8 FADD RIPK1
13 11.97 CASP10 CASP8 FADD
14
Show member pathways
11.97 CASP10 CASP8 FADD RIPK1
15
Show member pathways
11.94 CASP8 FADD RIPK1
16
Show member pathways
11.87 CASP8 FADD RIPK1
17
Show member pathways
11.86 CASP10 CASP8 FADD RIPK1
18
Show member pathways
11.56 CASP10 CASP8
19
Show member pathways
11.55 CASP10 CASP8 FADD RIPK1
20
Show member pathways
11.53 CASP8 FADD RIPK1
21 11.49 CASP8 FADD
22 11.48 FADD RIPK1
23 11.3 CASP10 CASP8 FADD RIPK1
24 11.25 CASP8 FADD
25 11.24 COL5A1 COL5A2
26 11.2 CASP10 CASP8
27 11.14 CASP8 FADD RIPK1
28 10.66 CASP10 CASP8 FADD RIPK1

GO Terms for Caspase 8 Deficiency

Cellular components related to Caspase 8 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane raft GO:0045121 9.5 CASP8 FADD RIPK1
2 death-inducing signaling complex GO:0031264 9.33 CASP8 FADD RIPK1
3 collagen type V trimer GO:0005588 9.26 COL5A1 COL5A2
4 CD95 death-inducing signaling complex GO:0031265 9.13 CASP10 CASP8 FADD
5 ripoptosome GO:0097342 8.92 CASP10 CASP8 FADD RIPK1

Biological processes related to Caspase 8 Deficiency according to GeneCards Suite gene sharing:

(show all 30)
# Name GO ID Score Top Affiliating Genes
1 apoptotic process GO:0006915 9.9 CASP10 CASP8 FADD RIPK1
2 cell surface receptor signaling pathway GO:0007166 9.8 CASP10 CASP8 FADD
3 regulation of apoptotic process GO:0042981 9.8 CASP10 CASP8 FADD
4 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 9.76 CASP10 CASP8 FADD RIPK1
5 extrinsic apoptotic signaling pathway GO:0097191 9.67 CASP8 FADD RIPK1
6 positive regulation of tumor necrosis factor production GO:0032760 9.65 FADD RIPK1
7 collagen fibril organization GO:0030199 9.64 COL5A1 COL5A2
8 skin development GO:0043588 9.64 COL5A1 COL5A2
9 negative regulation of I-kappaB kinase/NF-kappaB signaling GO:0043124 9.63 CASP8 RIPK1
10 extrinsic apoptotic signaling pathway via death domain receptors GO:0008625 9.62 CASP8 FADD
11 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 9.62 CASP10 CASP8 FADD RIPK1
12 response to tumor necrosis factor GO:0034612 9.61 CASP8 RIPK1
13 regulation of tumor necrosis factor-mediated signaling pathway GO:0010803 9.61 CASP8 RIPK1
14 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902042 9.61 CASP8 FADD RIPK1
15 positive regulation of interleukin-8 production GO:0032757 9.59 FADD RIPK1
16 positive regulation of extrinsic apoptotic signaling pathway GO:2001238 9.58 FADD RIPK1
17 execution phase of apoptosis GO:0097194 9.58 CASP10 CASP8
18 TRIF-dependent toll-like receptor signaling pathway GO:0035666 9.58 CASP8 FADD RIPK1
19 positive regulation of proteolysis GO:0045862 9.57 CASP8 FADD
20 activation of cysteine-type endopeptidase activity GO:0097202 9.56 CASP8 FADD
21 regulation of necroptotic process GO:0060544 9.55 CASP8 FADD
22 necroptotic signaling pathway GO:0097527 9.54 FADD RIPK1
23 regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902041 9.54 CASP8 FADD RIPK1
24 TRAIL-activated apoptotic signaling pathway GO:0036462 9.52 CASP8 FADD
25 eye morphogenesis GO:0048592 9.51 COL5A1 COL5A2
26 negative regulation of endodermal cell differentiation GO:1903225 9.48 COL5A1 COL5A2
27 positive regulation of macrophage differentiation GO:0045651 9.43 CASP8 FADD RIPK1
28 toll-like receptor 3 signaling pathway GO:0034138 9.33 CASP8 FADD RIPK1
29 apoptotic signaling pathway GO:0097190 9.26 CASP10 CASP8 FADD RIPK1
30 death-inducing signaling complex assembly GO:0071550 8.8 CASP8 FADD RIPK1

Molecular functions related to Caspase 8 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein-containing complex binding GO:0044877 9.61 CASP8 FADD RIPK1
2 ubiquitin protein ligase binding GO:0031625 9.58 CASP10 CASP8 RIPK1
3 extracellular matrix structural constituent conferring tensile strength GO:0030020 9.37 COL5A1 COL5A2
4 tumor necrosis factor receptor binding GO:0005164 9.32 CASP8 FADD
5 cysteine-type endopeptidase activity involved in apoptotic process GO:0097153 9.26 CASP10 CASP8
6 cysteine-type endopeptidase activity involved in apoptotic signaling pathway GO:0097199 9.16 CASP10 CASP8
7 death receptor binding GO:0005123 9.13 CASP8 FADD RIPK1
8 death effector domain binding GO:0035877 8.8 CASP10 CASP8 FADD

Sources for Caspase 8 Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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