Cholestasis

Gene: PSKH1

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 10 Dec 2025, 2:45 p.m. | Last Modified: 10 Dec 2025, 2:45 p.m.

Panel Version: 3.14

Comment on list classification: There is sufficient evidence (four unrelated cases and functional studies) available for the promotion of this gene to green rating in the next GMS update.

Created: 18 Sep 2024, 10:57 a.m. | Last Modified: 18 Sep 2024, 10:57 a.m.

Panel Version: 3.6

PMID:39132680 reported the identification of homozygous PSKH1 variants in four consanguineous families from a cohort of 279 families with intrahepatic cholestasis. Two of the four families (families 1 and 2) had the same homozygous founder variant (p.Arg121Trp), while different homozygous variants were reported in the other two families (family 3 - p.Ile126Val & family 4 - p.Arg183Cys).

The clinical presentations of the cases are as follows:
Family 1 - One patient died at 10 months of age with cholestasis/ liver impairment and kidney impairment.
Family 2 - Three cousins with cholestasis (two with liver failure needing transplant) and kidney features (two with kidney failure, 1 with renal echogenicity).
Family 3 - Two siblings with hepatic fibrosis (one with unilateral renal agenesis).
Family 4 - Two siblings with unexplained liver cirrhosis (one needing transplant) but normal kidney function.

Patient fibroblasts displayed abnormal cilia that are long and show abnormal transport. A homozygous Pskh1 mutant mouse faithfully recapitulated the human phenotype and displayed abnormally long cilia.

This gene has not yet been associated with any relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature

Created: 18 Sep 2024, 10:55 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
hepatorenal syndrome, MONDO:0001382

Publications

• 39132680