Autoinflammatory disorders

Gene: OTULIN

Green List (high evidence)

Comment on phenotypes: OMIM phenotype updated 22nd May 2026.

Created: 22 May 2026, 11:43 a.m. | Last Modified: 22 May 2026, 11:43 a.m.

Panel Version: 3.9

Comment on mode of inheritance: There are now 3 unrelated individuals reported with heterozygous missense (putative dominant-negative) variants in OTULIN, and an ORAS-like autoinflammatory syndrome. Hence, the MOI should be changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal on Autoinflammatory disorders.

Created: 22 May 2026, 11:42 a.m. | Last Modified: 22 May 2026, 11:42 a.m.

Panel Version: 3.7

PMID: 38630025 Davidson et al., 2024
Report of 2 patients (unrelated, 1 Caucasian and 1 Saudi family) with het p.Cys129Ser (stemming from c.385T>A or c.386G>C) change in OTULIN and a presentation consistent with OTULIN-related autoinflammatory syndrome. Authors observed accumulation of linear ubiquitin chains, increased sensitivity to TNF-induced death, and dysregulation of inflammatory signaling in patient cells. Patients presented with very early onset chronic inflammation, sterlie pustulosis, wound dehiscence. Variant is posed to have a dominant-negative effect.

PMID: 38914362 Caballero-Oteyza et al., 2024
Novel homozygous missense mutation OTULIN c.595T>A; p.(Trp199Arg) detected in a Moroccan infant with an ORAS phenotype of severe, sterile systemic inflammation, panniculitis. Method: WES + Sanger. Literature review in the paper includes 9 AR ORAS, 17 OTULIN Haploinsufficiency (AR Immunodeficiency) and 3 Dominant negative ORAS cases (including one from this study).

OMIM has associations for OTULIN-related Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive, OMIM:617099 and Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant, OMIM:621030 (accessed 22nd May 2026).

Created: 22 May 2026, 11:41 a.m. | Last Modified: 22 May 2026, 1:14 p.m.

Panel Version: 3.9

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive, OMIM:617099; Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant, OMIM:621030

Publications

• 38630025
• 38914362

Green List (high evidence)

This gene has been added to the panel on the recommendation of the NHS Genomic Medicine Service and should be rated green.

Created: 16 Feb 2022, 11:44 a.m. | Last Modified: 16 Feb 2022, 11:44 a.m.

Panel Version: 0.36