WP5269 - Genetic causes of porto-sinusoidal vascular disease - Homo sapiens

Porto sinusoidal vascular disease (PSVD), or formerly known as idiopathic portal vein hypertension (INCPH), is a condition with often unclear origin. There are currently three genes directly linked to this condition: C4orf54, a protein with unknown function, DGUOK, a desoxyguanosine kinase involved in purine metabolism, and KCNN3, a potassium channel regulated i.a. via estradiol.
Additionally, some genetic syndromes show increased portal vein hypertension as one of their symptoms/phenotypes. These syndromes are X-linked agammaglobulinemia, Adams-Oliver syndrome, chronic granulomatous disease and Shwachmann syndrome.
X-linked agammaglobulinemia (XLA) is caused by mutations in BTK. BTK is involved in signal transduction from virus single stranded RNA recognition by toll like receptors (TLR8 and TLR9) to NFKB1 mediated gene expression as response.
Adams-Oliver Syndrome can be caused by mutations in RBPJ, ARHGAP31, DOCK6, DLL4, EOGT and NOTCH1. Most of these genes are involved in the Notch pathway but there is also a link via RAC1 to the phagocyte NADPH oxidase complex (ComplexPortal).
Mutations in some proteins of this complex (CYBA, NCF1, NCF2 or NCF4), or their chaperones (CYBC1) can cause chronic granulomatous disease. Shwachmann syndrome is caused by mutations in SBDS or EFL1 which are both part of the pre-60S ribosomal subunit and are responsible for cleaving off the EIF6 protein for maturation to 60S ribosomal subunit.