Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: KARS

Green List (high evidence)

KARS1 encodes lysyl-tRNA synthetase, an enzyme crucial for protein translation in both the cytoplasm and mitochondria.

Classically associated with a multisystemic condition involving progressive leukoencephalopathy, peripheral neuropathy, and deafness, recent evidence establishes KARS1 defects as an Inborn Error of Immunity (IEI) characterized by B cell metabolic impairment and antibody deficiency.

Saettini et al. identified 1 patient from 1 family carrying pathogenic biallelic KARS1 variants (p.Phe291Val/p.Pro499Leu) presenting with hypogammaglobulinemia, recurrent infections, and impaired B cell activity.
From literature review 17 patients with KARS-related diseases were identified. Recurrent/severe infections (9/17) and B cell abnormalities (either B cell lymphopenia [3/9], hypogammaglobulinemia [either IgG, IgA or IgM; 6/15] or impaired vaccine responses [4/7]) were frequently reported.
Sources: Literature

Created: 17 Jun 2026, 3:47 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
progressive leukoencephalopathy; peripheral neuropathy; deafness; antibody deficiency; hypogammaglobulinemia

Publications

• 37770806