Proteasome-Associated Autoinflammatory Syndrome 3 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

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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:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Bone diseases Skin diseases Endocrine diseases Immune diseases

See all MalaCards categories (disease lists)

External Ids:

OMIM® ⁵⁷ 617591

OMIM Phenotypic Series ⁵⁷ PS256040

MeSH ⁴⁴ D056660

MedGen ⁴¹ C4747850 CN252341

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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.

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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

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Symptoms & Phenotypes for Proteasome-Associated Autoinflammatory Syndrome 3

Human phenotypes related to Proteasome-Associated Autoinflammatory Syndrome 3:

³¹ (show all 25)

#	Description	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)

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Drugs & Therapeutics for Proteasome-Associated Autoinflammatory Syndrome 3

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

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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

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Anatomical Context for Proteasome-Associated Autoinflammatory Syndrome 3

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

⁴⁰

Liver

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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	Brehm A...Goldbach-Mansky R	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	Liu Y...Zlotogorski A	21953331	2012

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Genes for Proteasome-Associated Autoinflammatory Syndrome 3

Genes related to Proteasome-Associated Autoinflammatory Syndrome 3 (2 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	PSMB9	Proteasome 20S Subunit Beta 9	Protein Coding	1367.29	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative variation ⁷² Genetic Tests ²⁹ Unconfirmed association ⁵⁷ GeneCards inferred via : Disorders Variants (show sections)	26524591
2	PSMB4	Proteasome 20S Subunit Beta 4	Protein Coding	1067.66	Molecular basis known ⁵⁷ Pathogenic ⁶ Genetic Tests ²⁹ Unconfirmed association ⁵⁷ GeneCards inferred via : Disorders Variants (show sections)	26524591 21953331

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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

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Expression for Proteasome-Associated Autoinflammatory Syndrome 3

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

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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	fMLP Pathway ⁶³ Show member pathways Alpha-Adrenergic Signaling ⁶³ CCR3 Pathway in Eosinophils ⁶³ CXCR4 Pathway ⁶³ Huntington's Disease Pathway ⁶³ Internalin Pathway ⁶³ Signal transduction Activation of PKC via G-Protein coupled receptor ²³ VEGF and S-1P Signaling ⁶³	12.41	PSMB9 PSMB4
2	Signaling by Wnt ⁶⁵ Show member pathways TCF dependent signaling in response to WNT ⁶⁵	12.31	PSMB9 PSMB4
3	Mitotic Metaphase and Anaphase ⁶⁵ Show member pathways Mitotic Anaphase ⁶⁵ Separation of Sister Chromatids ⁶⁵	12.26	PSMB9 PSMB4
4	Deubiquitination ⁶⁵ Show member pathways Ub-specific processing proteases ⁶⁵	12.24	PSMB9 PSMB4
5	Beta-Adrenergic Signaling ⁶³ Show member pathways CDK5 Pathway ⁶³ Erythropoietin Pathway ⁶³ Insulin Receptor Pathway ⁶³	12.21	PSMB9 PSMB4
6	Downstream signaling events of B Cell Receptor (BCR) ⁶⁵ Show member pathways Activation of RAS in B cells ⁶⁵ Signaling by the B Cell Receptor (BCR) ⁶⁵	12.12	PSMB9 PSMB4
7	Chks in Checkpoint Regulation ⁶³ Show member pathways DNA Repair Mechanisms ⁶³ Estrogen-mediated S-Phase Entry ⁶³ G2-M Phase Transition ⁶³ Parkinson's Disease Pathway ⁶³ SREBP Proteolysis ⁶³	12.1	PSMB9 PSMB4
8	Cell Cycle Checkpoints ⁶⁵ Show member pathways G2/M Checkpoints ⁶⁵	12.03	PSMB9 PSMB4
9	Signaling by Hedgehog ⁶⁵ Show member pathways Activation of SMO ⁶⁵ Hedgehog off' state ⁶⁵ Hedgehog on' state ⁶⁵	11.97	PSMB9 PSMB4
10	Mitotic G1-G1/S phases ⁶⁵ Show member pathways G1 to S cell cycle control ¹ G1/S Transition ⁶⁵	11.92	PSMB9 PSMB4
11	Antigen processing-Cross presentation ⁶⁵ Show member pathways Cross-presentation of particulate exogenous antigens (phagosomes) ⁶⁵ Endosomal/Vacuolar pathway ⁶⁵ ER-Phagosome pathway ⁶⁵ Immune response Antigen presentation by MHC class I ²³	11.82	PSMB9 PSMB4
12	WNT Signaling ⁶³	11.72	PSMB9 PSMB4
13	CLEC7A (Dectin-1) signaling ⁶⁵ Show member pathways Alternative NF-kappaB pathway ¹ CLEC7A/inflammasome pathway ⁶⁵ C-type lectin receptors (CLRs) ⁶⁵	11.67	PSMB9 PSMB4
14	TCR signaling ⁶⁵ Show member pathways Downstream TCR signaling ⁶⁵	11.5	PSMB9 PSMB4
15	Presenilin-Mediated Signaling ⁶³	10.78	PSMB9 PSMB4
16	Transcription_P53 signaling pathway ²³	10.69	PSMB9 PSMB4

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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

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Sources for Proteasome-Associated Autoinflammatory Syndrome 3

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⁵⁴ Novoseek

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⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 20-May-2021)

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⁶⁷ SNOMED-CT

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⁶⁹ Tocris

⁷⁰ UMLS

⁷¹ UMLS via Orphanet

⁷² UniProtKB/Swiss-Prot

⁷³ Wikipedia

Proteasome-Associated Autoinflammatory Syndrome 3 (PRAAS3)

Aliases & Classifications for Proteasome-Associated Autoinflammatory Syndrome 3

MalaCards integrated aliases for Proteasome-Associated Autoinflammatory Syndrome 3:

Characteristics:

OMIM®:

HPO:

Classifications:

External Ids:

Summaries for Proteasome-Associated Autoinflammatory Syndrome 3

Related Diseases for Proteasome-Associated Autoinflammatory Syndrome 3

Diseases in the Proteasome-Associated Autoinflammatory Syndrome 1 family:

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

Symptoms & Phenotypes for Proteasome-Associated Autoinflammatory Syndrome 3

Human phenotypes related to Proteasome-Associated Autoinflammatory Syndrome 3:

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

Drugs & Therapeutics for Proteasome-Associated Autoinflammatory Syndrome 3

Genetic Tests for Proteasome-Associated Autoinflammatory Syndrome 3

Genetic tests related to Proteasome-Associated Autoinflammatory Syndrome 3:

Anatomical Context for Proteasome-Associated Autoinflammatory Syndrome 3

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

Publications for Proteasome-Associated Autoinflammatory Syndrome 3

Articles related to Proteasome-Associated Autoinflammatory Syndrome 3:

Genes for Proteasome-Associated Autoinflammatory Syndrome 3

Genes related to Proteasome-Associated Autoinflammatory Syndrome 3 (2 elite genes):

Variations for Proteasome-Associated Autoinflammatory Syndrome 3

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

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

Expression 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:

GO Terms for Proteasome-Associated Autoinflammatory Syndrome 3

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

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

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

Sources for Proteasome-Associated Autoinflammatory Syndrome 3