Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: TNFSF9

Red List (low evidence)

Comment on list classification: As reviewed by Boaz Palterer, there is one individual reported in literature with a homozygous mutation in TNSF9, linked to EBV susceptibility. Based on the available evidence, this gene should be rated Red for Primary immunodeficiency or monogenic inflammatory bowel disease.
TNFSF9 is not yet associated with a phenotype in OMIM (accessed 31st Oct 2025).

Created: 31 Oct 2025, 2:25 p.m. | Last Modified: 31 Oct 2025, 2:25 p.m.

Panel Version: 8.71

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
EBV lymphoproliferation

Publications

• 35657354

Red List (low evidence)

Fournier et al. described one patient with DiGeorge syndrome with a unique susceptibility to EBV with broad EBV infection and smooth muscle tumors. He was found to have a homozygous missense mutation (p.V140G) in TNFSF9 coding for CD137L/4-1BBL, the ligand of the T cell co-stimulatory molecule CD137/4-1BB, whose deficiency predisposes to EBV infection.

They show that CD137LV140G mutant was weakly expressed on patient cells or when ectopically expressed in HEK and P815 cells. Importantly, patient EBV-infected B cells failed to trigger the expansion of EBV-specific T cells, resulting in decreased T cell effector responses. T cell expansion was recovered when CD137L expression was restored on B cells.
Sources: Literature

Created: 10 Nov 2024, 11:28 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
EBV lymphoproliferation; smooth muscle tumors

Publications

• 35657354