Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: ASXL1

Red List (low evidence)

Comment on list classification: As reviewed by Boaz Palterer, there is a single case reported in literature with biallelic variants in ASXL1 and features of primary immunodeficiency. This gene should be rated Red for Primary immunodeficiency or monogenic inflammatory bowel disease until more evidence emerges.
ASXL1 is associated with AD Bohring-Opitz syndrome, OMIM:605039 and Myelodysplastic syndrome, somatic, OMIM: 614286 (OMIM accessed 3rd Nov 2025).

Created: 3 Nov 2025, 5:08 p.m. | Last Modified: 3 Nov 2025, 5:12 p.m.

Panel Version: 8.72

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
combined immunodeficiency MONDO:0015131

Publications

• 40742536

Red List (low evidence)

Fu et al. present a single case report with biallelic germline missense variants in ASXL1. The patient had a history of hematologic abnormalities and viral-associated complications, including chronic macrocytosis, persistent vaccine-strain rubella granulomas, and EBV-associated Hodgkin lymphoma. Immunophenotyping revealed loss of B cells, hypogammaglobulinemia, and impairments in cytotoxic T and NK cell populations. T cells exhibited skewing toward an exhausted memory phenotype, global DNA methylation loss, and increased epigenetic aging. These aberrations were ameliorated by wild-type ASXL1 transduction, confirming the patient variants’ pathogenicity.
Sources: Literature

Created: 31 Jul 2025, 7:28 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
chronic viral infections; viral-associated malignancies; combined immune deficiency

Publications

• 40742536