Proteasome-associated autoinflammatory syndrome 5

Summary

Proteasome-associated autoinflammatory syndrome 5 (MONDO:0030924) is a disease caused by PSMB10 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PSMB10 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	proteasome-associated autoinflammatory syndrome 5
Mondo ID	MONDO:0030924
OMIM	619175
DOID	DOID:0060919
UMLS	C5543027
MedGen	1779962
GARD	0018448
Is cancer (heuristic)	no

Also known as: PRAAS5 · proteasome-associated autoinflammatory syndrome 5

Data availability: 8 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › proteosome-associated autoinflammatory syndrome › proteasome-associated autoinflammatory syndrome 5

Related subtypes (5): proteasome-associated autoinflammatory syndrome 4, proteasome-associated autoinflammatory syndrome 1, proteasome-associated autoinflammatory syndrome 3, proteasome-associated autoinflammatory syndrome 2, proteasome-associated autoinflammatory syndrome 6

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

5 pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3241965	NM_002801.4(PSMB10):c.500G>A (p.Gly167Asp)	LOC130059250	Pathogenic	no assertion criteria provided
3241964	NM_002801.4(PSMB10):c.40_42del (p.Phe14del)	PSMB10	Pathogenic	no assertion criteria provided
3241966	NM_002801.4(PSMB10):c.247dup (p.Cys83fs)	PSMB10	Pathogenic	no assertion criteria provided
3241967	NM_002801.4(PSMB10):c.710+1G>C	PSMB10	Pathogenic	no assertion criteria provided
997016	NM_002801.4(PSMB10):c.41T>C (p.Phe14Ser)	PSMB10	Pathogenic	no assertion criteria provided
3780496	NM_002801.4(PSMB10):c.56+1G>A	PSMB10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2435273	NM_002801.4(PSMB10):c.629G>A (p.Gly210Asp)	PSMB10	Uncertain significance	criteria provided, single submitter
2435274	NM_002801.4(PSMB10):c.736G>A (p.Gly246Arg)	PSMB10	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PSMB10	Strong	Autosomal recessive	proteasome-associated autoinflammatory syndrome 5	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PSMB10	Orphanet:39041	Omenn syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PSMB10	HGNC:9538	ENSG00000205220	P40306	Proteasome subunit beta type-10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PSMB10	Proteasome subunit beta type-10	The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PSMB10	Other/Unknown	no		Pept_T1A_subB, Proteasome_sua/b, Proteasome_bsu_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PSMB10	134	ubiquitous	marker	granulocyte, leukocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PSMB10	2,588

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSMB10	P40306	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Antigen processing: Ub, ATP-independent proteasomal degradation	1	571.0×	0.007	PSMB10
Cross-presentation of soluble exogenous antigens (endosomes)	1	253.8×	0.007	PSMB10
Proteasome assembly	1	203.9×	0.007	PSMB10
ER-Phagosome pathway	1	129.8×	0.008	PSMB10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	1	4213.0×	0.001	PSMB10
proteasomal ubiquitin-independent protein catabolic process	1	2808.7×	0.001	PSMB10
T cell proliferation	1	383.0×	0.005	PSMB10
humoral immune response	1	280.9×	0.005	PSMB10
cell morphogenesis	1	157.5×	0.008	PSMB10
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.019	PSMB10

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PSMB10	BORTEZOMIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PSMB10	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BORTEZOMIB	4	PSMB10
CARFILZOMIB	4	PSMB10
IXAZOMIB	3	PSMB10
MARIZOMIB	3	PSMB10
DELANZOMIB	2	PSMB10
ZETOMIPZOMIB	2	PSMB10
OPROZOMIB	2	PSMB10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PSMB10	206	Binding:195, ADMET:8, Functional:3

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PSMB10	206

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

7 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
BORTEZOMIB	4	PSMB10
CARFILZOMIB	4	PSMB10
IXAZOMIB	3	PSMB10
MARIZOMIB	3	PSMB10
DELANZOMIB	2	PSMB10
ZETOMIPZOMIB	2	PSMB10
OPROZOMIB	2	PSMB10

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PSMB10
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.