Proteasome-associated autoinflammatory syndrome 4

Summary

Proteasome-associated autoinflammatory syndrome 4 (MONDO:0030931) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	proteasome-associated autoinflammatory syndrome 4
Mondo ID	MONDO:0030931
OMIM	619183
DOID	DOID:0060915
UMLS	C5543053
MedGen	1780127
GARD	0018449
Is cancer (heuristic)	no

Also known as: PRAAS4 · proteasome-associated autoinflammatory syndrome 4

Data availability: 5 ClinVar variants · 2 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 4

Related subtypes (5): proteasome-associated autoinflammatory syndrome 5, 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

5 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
997018	NM_020232.5(PSMG2):c.666_667del (p.Tyr223fs)	PSMG2	Pathogenic	no assertion criteria provided
1342492	NM_020232.5(PSMG2):c.582-1G>A	PSMG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1391289	NM_020232.5(PSMG2):c.784G>A (p.Ala262Thr)	PSMG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435276	NM_020232.5(PSMG2):c.377C>G (p.Ser126Ter)	PSMG2	Uncertain significance	criteria provided, single submitter
997019	NM_020232.5(PSMG2):c.675T>G (p.Asn225Lys)	PSMG2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
PSMG2	Limited	Unknown	proteasome-associated autoinflammatory syndrome 4	2

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
PSMG2	HGNC:24929	ENSG00000128789	Q969U7	Proteasome assembly chaperone 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PSMG2	Proteasome assembly chaperone 2	Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG1.

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)
PSMG2	Other/Unknown	no		Proteasome_assmbl_chp_2_euk, Proteasome_assmbl_chaperone_2, PSMG2_sf

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
adult organism	1
gingival epithelium	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PSMG2	288	ubiquitous	marker	primordial germ cell in gonad, adult organism, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PSMG2	1,344

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSMG2	Q969U7	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Proteasome assembly	1	203.9×	0.005	PSMG2

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
proteasome assembly	1	1532.0×	0.002	PSMG2
chaperone-mediated protein complex assembly	1	702.2×	0.002	PSMG2
mitotic spindle assembly checkpoint signaling	1	561.7×	0.002	PSMG2
negative regulation of apoptotic process	1	34.8×	0.029	PSMG2

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PSMG2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PSMG2	5	Binding:5

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	PSMG2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PSMG2	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.