Rare genetic inflammatory skin disorders

Gene: PSMB10

Green List (high evidence)

Comment on list classification: There are now more than 3 cases reported with both mono- and bi- allelic PSMB10 variants, presenting with a chronic inflammatory skin rash. Hence, this gene should be promoted to Green with MOI BOTH monoallelic and biallelic, autosomal or pseudoautosomal.

Created: 10 Mar 2026, 3:09 p.m. | Last Modified: 10 Mar 2026, 3:09 p.m.

Panel Version: 4.18

MONOALLELIC CASES:
PMID: 36250618 Hebert et al., 2022
Patient 1 - severe combined immunodeficiency (SCID), ectodermal dysplasia, alopecia, hypodontia and anonychia; het de novo PSMB10 NM_002801.3: c.601G>A p.(Gly201Arg) variant.

PMID: 38503300 van der Made et al., 2024
Identified de novo PSMB10 mutations in 6 infants with SCID-Omenn syndrome. The syndromic presentation includes severe combined immunodeficiency (SCID), as well as diarrhea (6/6), alopecia (4/5), and desquamating erythematous rash (6/6). Reported variants: PSMB10: c.166G>C, p.Asp56His and c.601G>A/c.601G>C, p.Gly201Arg.

PMID: 39734035 Kuehn et al., 2025
Case report: white female with SCID, failure to thrive, diarrhea, and pruritic rash - symptom onset at 5-9 months. Trio WES identified a de novo PSMB10 variant in the proband: c.601G>A, p.Gly201Arg.

https://doi.org/10.70962/jhi.20250096 Fournier et al., 2025
Report of 3 patients with WES detected de novo heterozygous PSMB10 variants: c.614A>C p.Asp205Ala for PI and c.623C>T p.Ser208Phe for PII and PIII. Presentation: combined immunodeficiency (3/3), generalized erythroderma with desquamation (1/3), chronic diarrhea (2/3), severe liver disease (2/3).
Functional evidence: PSMB10 constructs were expressed in HEK293T cells prior to SDS-PAGE/western blotting analysis. The p.Asp205Ala and p.Ser208Phe PSMB10 variants were shown to impair proteasome assembly and exert dominant-negative effects on PSMB9 expression.

BIALLELIC CASES:
PMID: 31783057 Sarrabay et al., 2020
3yo girl with a proteasome-associated autoinflammatory syndrome, homozygous for a PSMB10 c.41T>C, p.Phe14Ser variant. She presented with failure to thrive, cutaneous rash, and hepatosplenomegaly. No immunodeficiency.

PMID: 37600812 Papendorf et al., 2023
Three unrelated Brazilian patients present with four novel PSMB10 variants. All share the p.Phe14del variant plus a different novel variant: p.Gly167Asp, p.Cys83Leufs*123, and c.710+1G>C. All 3 patients had skin lesions, recurrent fevers, failure to thrive; microcytic anemia ascertained in 2/3.

PSMB10 is now associated with AD Immunodeficiency 121 with autoinflammation, MIM:620807 & AR Proteasome-associated autoinflammatory syndrome 5, MIM:619175 (OMIM accessed 10th Mar 2026).
Sources: Literature

Created: 10 Mar 2026, 3:05 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency 121 with autoinflammation, OMIM:620807; Proteasome-associated autoinflammatory syndrome 5, OMIM:619175

Publications

• 31783057
• 36250618
• 37600812
• 38503300
• 39734035