Polycystic liver disease

Gene: PKHD1

Green List (high evidence)

Comment on mode of inheritance: Susceptibility genes should be excluded from PanelApp GMS panels. This gene has MOI set to BIALLELIC on other GMS Green panels. Based on the review by Florentina Sava, this gene will be recommended for expert review regarding the mode of inheritance (changing to BIALLELIC only versus leaving MOI as BOTH).

Created: 13 Feb 2026, 12:48 p.m. | Last Modified: 13 Feb 2026, 12:48 p.m.

Panel Version: 1.32

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polycystic kidney disease 4, with or without hepatic disease, OMIM:263200

Green List (high evidence)

Following discussions with relevant clinicians and an extensive review of the literature on the PKHD1 gene in relation to monoallelic inheritance in polycystic liver disease, we conclude that heterozygous (likely) pathogenic PKHD1 variants confer genetic susceptibility to ductal plate malformation, rather than causing a fully penetrant autosomal dominant disorder.
Individuals carrying a heterozygous (likely) pathogenic PKHD1 variant typically show a late-onset, often subclinical phenotype that is frequently identified incidentally. The clinical spectrum is broad and includes features such as congenital hepatic fibrosis and liver cysts.
We therefore propose that diagnostic reports for individuals with a monoallelic pathogenic PKHD1 variant referred for the R173 PLD NGS panel should state: “Consistent with genetic susceptibility to ductal plate malformation.”

Created: 21 Jan 2026, 3:31 p.m. | Last Modified: 21 Jan 2026, 3:31 p.m.

Panel Version: 1.31

Mode of inheritance
Other

Phenotypes
Ductal plate malformation; Polycystic liver disease; Congenital hepatic fibrosis; Caroli's disease; Biliary dysplasia

Publications

• PMID: 28375157
• PMID: 21945273
• PMID: 30600684
• PMID: 33554127
• Internal Sheffield data
• KDIGO guidelines
• ClinGen PKHD1 gene

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Not aware of exceptions to loss of function

Created: 25 Nov 2018, 9:02 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Polycystic kidney; liver cysts; congenital hepatic fibrosis; Caroli's disease; biliary dysplasia

Publications

• PMID: 11919560 PMID: 30211211

Mode of pathogenicity
Other

Green List (high evidence)

Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.

Created: 12 Mar 2019, 11:27 a.m.

Initial gene list and info collated by Miranda Durkie Sheffield Diagnostic Genetics Service December 2018 on behalf of the GMS Gastrohepatology specialist test group. Gene Symbol submitted: PKHD1; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 8 Jan 2019, 9:38 a.m.

Comment when marking as ready: PKHD1 is on the Eligibility statement and received a green review from Bill Griffiths (Cambridge University Hospitals).

Created: 26 Nov 2018, 12:02 p.m.

Comment on mode of inheritance: Changed from Biallelic to Both monoallelic and biallelic as a paper (PMID:30211211) provided by Bill Griffiths (Cambridge University Hospitals) reported 2 probands who have Ductal plate malformation with different heterozygous variants (1 a small deletion and another a missense variant) in the PKHD1 gene, suggesting an dominant mode of inheritance. Previous publications have reported recessive variants.

Created: 26 Nov 2018, 12:01 p.m.

Green gene on the Rare multisystem ciliopathy disorders (Version 1.78). It is a confirmed causative gene for Polycystic kidney disease 4 with or without hepatic disease on Gene2Phenotype. There are 4 probands with LOF mutations and have liver cysts and there are murine models that support this.

Created: 12 Nov 2018, 1:55 p.m.

Publications

• 28862642
• 11337358
• 11135065