PSMG2

Chr 18AR

proteasome assembly chaperone 2

Also known as: CLAST3, HCCA3, HsT1707, MDS003, PAC2, PRAAS4, TNFSF5IP1

The PSMG2 protein functions as a chaperone that promotes assembly of the 20S proteasome by forming a heterodimer with PSMG1, which binds to specific proteasome subunits and facilitates alpha ring formation while preventing premature dimerization. Autosomal recessive mutations cause proteasome-associated autoinflammatory syndrome 4, an inflammatory condition resulting from proteasome dysfunction. The gene shows relatively low constraint to loss-of-function variation (LOEUF 1.443), suggesting some tolerance to protein-truncating variants.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?Proteasome-associated autoinflammatory syndrome 4MIM #619183
AR
0
Active trials
1
Pubs (1 yr)
105
P/LP submissions
8%
P/LP missense
1.44
LOEUF
Mechanism
Clinical SummaryPSMG2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
101 unique Pathogenic / Likely Pathogenic· 233 VUS of 461 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.44LOEUF
pLI 0.000
Z-score 0.41
OE 0.87 (0.551.44)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.44Z-score
OE missense 0.90 (0.781.04)
127 obs / 141.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.87 (0.551.44)
00.351.4
Missense OE0.90 (0.781.04)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 11 / 12.6Missense obs/exp: 127 / 141.8Syn Z: -0.62

ClinVar Variant Classifications

461 submitted variants in ClinVar

Classification Summary

Pathogenic88
Likely Pathogenic13
VUS233
Likely Benign82
Benign13
Conflicting3
88
Pathogenic
13
Likely Pathogenic
233
VUS
82
Likely Benign
13
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
85
1
88
Likely Pathogenic
3
7
3
0
13
VUS
15
195
22
1
233
Likely Benign
0
5
33
44
82
Benign
0
6
6
1
13
Conflicting
3
Total1921414947432

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PSMG2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC