Genetic causes of porto-sinusoidal vascular disease (WP5269)

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.


Friederike Ehrhart , Egon Willighagen , Eric Weitz , and Lars Willighagen


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Homo sapiens


Rare Diseases


Disease Ontology

portal hypertension chronic granulomatous disease X-linked agammaglobulinemia Adams-Oliver syndrome

Pathway Ontology

disease pathway


Label Type Compact URI Comment
L-threonine residue Metabolite chebi:30013
viral RNA Metabolite chebi:33697
O-phospho-L-tyrosyl-[protein] Metabolite chebi:82620
2'-deoxyguanosine Metabolite chebi:17172
UDP Metabolite chebi:17659
L-tyrosyl-[protein] Metabolite chebi:46858
O-(N-acetyl-β-D-glucosaminyl)-L-threonine residue Metabolite chebi:90840
3-O-(N-acetyl-β-D-glucosaminyl)-L-seryl-[protein] Metabolite chebi:90838
K+ Metabolite chebi:29103
Estradiol Metabolite hmdb:HMDB00151
2'-deoxyguanosine0 5'-monophosphate(2−) Metabolite chebi:57673
L-serine residue Metabolite chebi:29999
2'-deoxyadenosine 5'-monophosphate(2−) Metabolite chebi:58245
UDP-N-acetyl-α-D-glucosamine Metabolite chebi:57705
2'-deoxyadenosine Metabolite chebi:17256
K+ Metabolite chebi:29103
Ca2+ Metabolite chebi:29108
CYBB GeneProduct ensembl:ENSG00000165168
NOTCH4 GeneProduct ensembl:ENSG00000204301
DLL4 GeneProduct ensembl:ENSG00000128917
NOTCH1 GeneProduct ensembl:ENSG00000148400
BTK GeneProduct ensembl:ENSG00000010671
SHCBP1 GeneProduct ensembl:ENSG00000171241
RBPJ GeneProduct ensembl:ENSG00000168214 CBF1
MAPK1 GeneProduct ensembl:ENSG00000100030 ERK2
CHCHD2 GeneProduct ensembl:ENSG00000106153
DOCK6 GeneProduct ensembl:ENSG00000130158
ER1 GeneProduct ensembl:ENSG00000091831
EBNA2 GeneProduct uniprot:Q5322596
CXXC5 GeneProduct ensembl:ENSG00000171604
EIF6 GeneProduct ensembl:ENSG00000242372
NFKB1 GeneProduct ensembl:ENSG00000109320
CDC42 GeneProduct ensembl:ENSG00000070831
COX4I2 GeneProduct ensembl:ENSG00000131055
NOX3 GeneProduct ensembl:ENSG00000074771
ARHGAP31 GeneProduct ensembl:ENSG00000031081 CdGAP
TLR9 GeneProduct ensembl:ENSG00000239732
SP1 GeneProduct ensembl:ENSG00000185591
EOGT GeneProduct ensembl:ENSG00000163378
KCNN3 GeneProduct ensembl:ENSG00000143603
BEND6 GeneProduct ensembl:ENSG00000151917
C4orf54 GeneProduct ensembl:ENSG00000248713 FOPV
GTF2I GeneProduct ensembl:ENSG00000263001 BAP-135
TLR8 GeneProduct ensembl:ENSG00000101916
SBDS GeneProduct ensembl:ENSG00000126524
DGUOK GeneProduct ensembl:ENSG00000114956
MAPK3 GeneProduct ensembl:ENSG00000102882 ERK1
IBTK GeneProduct ensembl:ENSG00000005700
CYBC1 GeneProduct ensembl:ENSG00000178927
NCF1 GeneProduct ensembl:ENSG00000158517
NCF2 GeneProduct ensembl:ENSG00000116701
NCF4 GeneProduct ensembl:ENSG00000100365
EFL1 GeneProduct ensembl:ENSG00000140598
BTK GeneProduct ensembl:ENSG00000010671
GTF2I GeneProduct ensembl:ENSG00000263001 BAP-135
CYBA GeneProduct ensembl:ENSG00000051523
RAC1 GeneProduct ensembl:ENSG00000136238
COX4I2 Protein ensembl:ENSG00000131055


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