Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: PSMB10

Green List (high evidence)

Comment on mode of inheritance: There are now more than 3 cases reported with both mono- and bi- allelic PSMB10 variants - presenting with a proteasome-associated autoinflammatory syndrome (with or without recurrent infections and chronic diarrhea). Hence, the MOI should be updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.

Created: 10 Mar 2026, 3:17 p.m. | Last Modified: 10 Mar 2026, 3:17 p.m.

Panel Version: 8.80

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).

Created: 10 Mar 2026, 2:39 p.m. | Last Modified: 10 Mar 2026, 3:02 p.m.

Panel Version: 8.78

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

Green List (high evidence)

In addition to its behaviour as an AR disease gene for PRAAS (ie an autoinflammatory disorder), de novo, heterozygous variants in PSMB10 are now recognised to cause a distinct phenotype, sometimes known as "PRAAS-ID", characterised by profound lymphopenia, combined immunodeficiency and inflammatory phenomena resembling Omenn's syndrome. A total of 10 cases have been reported at time of writing (summarised in doi:10.70962/jhi.20250096), of whom six bore p.Gly201Arg, two p.Ser208Phe and one each p.Asp205Ala and p.Asp56His. Recognised as a monoallelic form of combined immunodeficiency in Table 1 of the 2024 IUIS classification of inborn errors of immunity.

Created: 23 Feb 2026, 12:31 p.m. | Last Modified: 23 Feb 2026, 12:41 p.m.

Panel Version: 8.78

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
SCID; Omenn syndrome; liver disease

Publications

• 38503300
• 39734035
• doi:10.70962/jhi.20250096

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence for the promotion of this gene to green rating in this panel.

Created: 30 Oct 2023, 6:13 p.m. | Last Modified: 30 Oct 2023, 6:13 p.m.

Panel Version: 4.67

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Proteasome-associated autoinflammatory syndrome 5, OMIM:619175

Green List (high evidence)

Now associated with a phenotype in OMIM - Proteasome-associated autoinflammatory syndrome 5

PMID: 37600812 reported three new, unrelated patients with compound het LOF variants in this gene, confirmed in trans

Created: 18 Oct 2023, 12:50 p.m. | Last Modified: 18 Oct 2023, 12:50 p.m.

Panel Version: 4.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Proteasome-associated autoinflammatory syndrome 5

Publications

• PMID: 37600812

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 8:36 p.m. | Last Modified: 3 May 2024, 8:36 p.m.

Panel Version: 5.3

Comment on list classification: Not associated with phenotype in OMIM (last edited on 06/25/2007) or in Gen2Phen. PMID 31783057 reports a case of Proteasome-associated autoinflammatory syndrome in an infant with a biallelic variant (c.41T>C, p.Phe14Ser), together with supporting functional studies.

Created: 14 Apr 2020, 1:51 p.m. | Last Modified: 14 Apr 2020, 1:51 p.m.

Panel Version: 2.55

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: New gene for review. Single case recommend Red rating

Created: 26 Feb 2020, 4:32 p.m. | Last Modified: 26 Feb 2020, 4:32 p.m.

Panel Version: 2.6

New gene suggested by expert reviewer- unable to do a full curational review (Green rating recommended) as we are waiting for new PanelApp features before this gene can be added to this GMS panel.

Created: 22 Jan 2020, 11:37 a.m. | Last Modified: 22 Jan 2020, 11:37 a.m.

Panel Version: 2.0

I don't know

Single case, homozygous missense variant, good functional experimental support.
Sources: Literature

Created: 18 Jan 2020, 7:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Proteasome-associated autoinflammatory syndrome

Publications

• 31783057