PRAAS3
MCID: PRT134
MIFTS: 34

Proteasome-Associated Autoinflammatory Syndrome 3 (PRAAS3)

Categories: Bone diseases, Endocrine diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases

Aliases & Classifications for Proteasome-Associated Autoinflammatory Syndrome 3

MalaCards integrated aliases for Proteasome-Associated Autoinflammatory Syndrome 3:

Name: Proteasome-Associated Autoinflammatory Syndrome 3 57 72 29 6
Proteasome-Associated Autoinflammatory Syndrome 3, Digenic 57 72 29
Proteasome-Associated Autoinflammatory Syndrome 3 and Digenic Forms 57 29
Praas3 57 72

Characteristics:

OMIM®:

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

Miscellaneous:
onset in early infancy
one patient with only psmb4 mutations has been reported (last curated july 2018)
digenic inheritance (mutation in psmb4 and psmb9) has been reported in 1 family (last curated july 2018)


HPO:

31
proteasome-associated autoinflammatory syndrome 3:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Proteasome-Associated Autoinflammatory Syndrome 3

OMIM® : 57 Proteasome-associated autoinflammatory syndrome-3 is an autosomal recessive syndrome with onset in early infancy. Affected individuals present with nodular dermatitis, recurrent fever, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and dysregulation of the immune response, particularly associated with abnormal type I interferon-induced gene expression patterns. Additional features are highly variable, but may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications (summary by Brehm et al., 2015). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040). (617591) (Updated 20-May-2021)

MalaCards based summary : Proteasome-Associated Autoinflammatory Syndrome 3, also known as proteasome-associated autoinflammatory syndrome 3, digenic, is related to panniculitis. An important gene associated with Proteasome-Associated Autoinflammatory Syndrome 3 is PSMB9 (Proteasome 20S Subunit Beta 9), and among its related pathways/superpathways are fMLP Pathway and Signaling by Wnt. Affiliated tissues include liver, and related phenotypes are failure to thrive and splenomegaly

UniProtKB/Swiss-Prot : 72 Proteasome-associated autoinflammatory syndrome 3: An autoinflammatory disorder characterized by onset in early infancy and recurrent fever, nodular dermatitis, myositis, panniculitis- induced lipodystrophy, lymphadenopathy, and immune dysregulation. Variable accompanying features may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications. PRAAS3 inheritance is autosomal recessive or digenic.

Related Diseases for Proteasome-Associated Autoinflammatory Syndrome 3

Diseases in the Proteasome-Associated Autoinflammatory Syndrome 1 family:

Proteasome-Associated Autoinflammatory Syndrome 3 Proteasome-Associated Autoinflammatory Syndrome 2
Proteasome-Associated Autoinflammatory Syndrome 5 Proteasome-Associated Autoinflammatory Syndrome 4

Diseases related to Proteasome-Associated Autoinflammatory Syndrome 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 panniculitis 9.5 PSMB9 PSMB4

Symptoms & Phenotypes for Proteasome-Associated Autoinflammatory Syndrome 3

Human phenotypes related to Proteasome-Associated Autoinflammatory Syndrome 3:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 31 HP:0001508
2 splenomegaly 31 HP:0001744
3 hepatomegaly 31 HP:0002240
4 arthritis 31 HP:0001369
5 flexion contracture 31 HP:0001371
6 hypertriglyceridemia 31 HP:0002155
7 anemia 31 HP:0001903
8 sinusitis 31 HP:0000246
9 elevated hepatic transaminase 31 HP:0002910
10 thrombocytopenia 31 HP:0001873
11 lipodystrophy 31 HP:0009125
12 arthralgia 31 HP:0002829
13 lymphopenia 31 HP:0001888
14 periorbital edema 31 HP:0100539
15 conjunctivitis 31 HP:0000509
16 skin rash 31 HP:0000988
17 acanthosis nigricans 31 HP:0000956
18 recurrent infections 31 HP:0002719
19 lymphadenopathy 31 HP:0002716
20 myositis 31 HP:0100614
21 elevated erythrocyte sedimentation rate 31 HP:0003565
22 recurrent fever 31 HP:0001954
23 panniculitis 31 HP:0012490
24 finger swelling 31 HP:0025131
25 increased circulating antibody level 31 HP:0010702

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive
poor overall growth

Abdomen Liver:
hepatomegaly

Hematology:
anemia
thrombocytopenia
lymphopenia

Muscle Soft Tissue:
lipodystrophy
myositis
panniculitis
intraabdominal fat
peripheral calcinosis

Head And Neck Eyes:
conjunctivitis
periorbital swelling
periorbital erythema
violaceous eyelids

Head And Neck Face:
facial edema

Laboratory Abnormalities:
increased erythrocyte sedimentation rate
increased acute phase reactants
elevated liver enzymes
increased c-reactive protein
increased triglycerides
more
Head And Neck Ears:
otitis

Neurologic Central Nervous System:
aseptic meningitis

Abdomen Spleen:
splenomegaly

Skeletal:
arthritis
arthralgia
joint contractures

Head And Neck Head:
sinusitis

Immunology:
lymphopenia
recurrent infections
lymphadenopathy
hypergammaglobulinemia
autoantibodies
more
Skin Nails Hair Skin:
skin rash
acanthosis nigricans
skin lesions
neutrophilic dermatosis
annular plaques

Skeletal Hands:
finger swelling

Metabolic Features:
fever, recurrent
metabolic syndrome

Skeletal Feet:
toe swelling

Clinical features from OMIM®:

617591 (Updated 20-May-2021)

Drugs & Therapeutics for Proteasome-Associated Autoinflammatory Syndrome 3

Search Clinical Trials , NIH Clinical Center for Proteasome-Associated Autoinflammatory Syndrome 3

Genetic Tests for Proteasome-Associated Autoinflammatory Syndrome 3

Genetic tests related to Proteasome-Associated Autoinflammatory Syndrome 3:

# Genetic test Affiliating Genes
1 Proteasome-Associated Autoinflammatory Syndrome 3 29 PSMB4 PSMB9
2 Proteasome-Associated Autoinflammatory Syndrome 3, Digenic 29
3 Proteasome-Associated Autoinflammatory Syndrome 3 and Digenic Forms 29

Anatomical Context for Proteasome-Associated Autoinflammatory Syndrome 3

MalaCards organs/tissues related to Proteasome-Associated Autoinflammatory Syndrome 3:

40
Liver

Publications for Proteasome-Associated Autoinflammatory Syndrome 3

Articles related to Proteasome-Associated Autoinflammatory Syndrome 3:

# Title Authors PMID Year
1
Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. 57 6
26524591 2015
2
Mutations in proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. 6 57
21953331 2012

Variations for Proteasome-Associated Autoinflammatory Syndrome 3

ClinVar genetic disease variations for Proteasome-Associated Autoinflammatory Syndrome 3:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PSMB4 NM_002796.3(PSMB4):c.636_644del (p.Asp212_Val214del) Deletion Pathogenic 548955 rs1553209362 GRCh37: 1:151373772-151373780
GRCh38: 1:151401296-151401304
2 PSMB4 NM_002796.3(PSMB4):c.-9G>A SNV Pathogenic 548956 rs200946642 GRCh37: 1:151372055-151372055
GRCh38: 1:151399579-151399579
3 PSMB4 NM_002796.3(PSMB4):c.44dup (p.Pro16fs) Duplication Pathogenic 548957 rs1235715459 GRCh37: 1:151372101-151372102
GRCh38: 1:151399625-151399626
4 PSMB9 NM_002800.5(PSMB9):c.494G>A (p.Gly165Asp) SNV Pathogenic 548995 rs369359789 GRCh37: 6:32826244-32826244
GRCh38: 6:32858467-32858467
5 PSMB4 NM_002796.3(PSMB4):c.472G>A (p.Gly158Arg) SNV Uncertain significance 1032848 GRCh37: 1:151373042-151373042
GRCh38: 1:151400566-151400566

UniProtKB/Swiss-Prot genetic disease variations for Proteasome-Associated Autoinflammatory Syndrome 3:

72
# Symbol AA change Variation ID SNP ID
1 PSMB9 p.Gly165Asp VAR_075258 rs369359789

Expression for Proteasome-Associated Autoinflammatory Syndrome 3

Search GEO for disease gene expression data for Proteasome-Associated Autoinflammatory Syndrome 3.

Pathways for Proteasome-Associated Autoinflammatory Syndrome 3

Pathways related to Proteasome-Associated Autoinflammatory Syndrome 3 according to GeneCards Suite gene sharing:

(show all 16)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.41 PSMB9 PSMB4
2
Show member pathways
12.31 PSMB9 PSMB4
3
Show member pathways
12.26 PSMB9 PSMB4
4
Show member pathways
12.24 PSMB9 PSMB4
5
Show member pathways
12.21 PSMB9 PSMB4
6
Show member pathways
12.12 PSMB9 PSMB4
7
Show member pathways
12.1 PSMB9 PSMB4
8
Show member pathways
12.03 PSMB9 PSMB4
9
Show member pathways
11.97 PSMB9 PSMB4
10
Show member pathways
11.92 PSMB9 PSMB4
11
Show member pathways
11.82 PSMB9 PSMB4
12 11.72 PSMB9 PSMB4
13
Show member pathways
11.67 PSMB9 PSMB4
14
Show member pathways
11.5 PSMB9 PSMB4
15 10.78 PSMB9 PSMB4
16 10.69 PSMB9 PSMB4

GO Terms for Proteasome-Associated Autoinflammatory Syndrome 3

Cellular components related to Proteasome-Associated Autoinflammatory Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 proteasome complex GO:0000502 9.16 PSMB9 PSMB4
2 proteasome core complex GO:0005839 8.96 PSMB9 PSMB4
3 proteasome core complex, beta-subunit complex GO:0019774 8.62 PSMB9 PSMB4

Biological processes related to Proteasome-Associated Autoinflammatory Syndrome 3 according to GeneCards Suite gene sharing:

(show all 28)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.64 PSMB9 PSMB4
2 proteolysis GO:0006508 9.63 PSMB9 PSMB4
3 viral process GO:0016032 9.63 PSMB9 PSMB4
4 post-translational protein modification GO:0043687 9.62 PSMB9 PSMB4
5 MAPK cascade GO:0000165 9.62 PSMB9 PSMB4
6 protein polyubiquitination GO:0000209 9.61 PSMB9 PSMB4
7 protein deubiquitination GO:0016579 9.61 PSMB9 PSMB4
8 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043161 9.6 PSMB9 PSMB4
9 negative regulation of canonical Wnt signaling pathway GO:0090090 9.59 PSMB9 PSMB4
10 T cell receptor signaling pathway GO:0050852 9.58 PSMB9 PSMB4
11 Fc-epsilon receptor signaling pathway GO:0038095 9.58 PSMB9 PSMB4
12 positive regulation of canonical Wnt signaling pathway GO:0090263 9.57 PSMB9 PSMB4
13 tumor necrosis factor-mediated signaling pathway GO:0033209 9.56 PSMB9 PSMB4
14 regulation of mRNA stability GO:0043488 9.55 PSMB9 PSMB4
15 stimulatory C-type lectin receptor signaling pathway GO:0002223 9.54 PSMB9 PSMB4
16 interleukin-1-mediated signaling pathway GO:0070498 9.52 PSMB9 PSMB4
17 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process GO:0031146 9.51 PSMB9 PSMB4
18 Wnt signaling pathway, planar cell polarity pathway GO:0060071 9.49 PSMB9 PSMB4
19 anaphase-promoting complex-dependent catabolic process GO:0031145 9.48 PSMB9 PSMB4
20 regulation of mitotic cell cycle phase transition GO:1901990 9.46 PSMB9 PSMB4
21 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent GO:0002479 9.43 PSMB9 PSMB4
22 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0061418 9.4 PSMB9 PSMB4
23 NIK/NF-kappaB signaling GO:0038061 9.37 PSMB9 PSMB4
24 regulation of hematopoietic stem cell differentiation GO:1902036 9.32 PSMB9 PSMB4
25 negative regulation of G2/M transition of mitotic cell cycle GO:0010972 9.26 PSMB9 PSMB4
26 proteolysis involved in cellular protein catabolic process GO:0051603 9.16 PSMB9 PSMB4
27 regulation of cellular amino acid metabolic process GO:0006521 8.96 PSMB9 PSMB4
28 proteasomal ubiquitin-independent protein catabolic process GO:0010499 8.62 PSMB9 PSMB4

Molecular functions related to Proteasome-Associated Autoinflammatory Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptidase activity GO:0008233 9.16 PSMB9 PSMB4
2 endopeptidase activity GO:0004175 8.96 PSMB9 PSMB4
3 threonine-type endopeptidase activity GO:0004298 8.62 PSMB9 PSMB4

Sources for Proteasome-Associated Autoinflammatory Syndrome 3

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
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