Polycystic liver disease

Gene: SEC61B

I don't know

Two loss-of-function heterozygous SEC61B variants have been reported in two individuals with polycystic liver disease, one of these cases also had a renal cyst (PMID: 28862642). SEC61B variants have not been associated with a phenotype in OMIM or Gen2Phen and ClinGen Gene-Disease Validity assessment is "Limited", based on the evidence published in PMID: 28862642.

Created: 2 Apr 2025, 11:11 a.m. | Last Modified: 2 Apr 2025, 11:11 a.m.

Panel Version: 1.31

Green List (high evidence)

SEC61B is now routinely described as a causative gene in isolated polycystic liver disease reviews.

Besse et al. (2017) identified 2 heterozygous variants in the SEC61B gene (609214.0001 and 609214.0002) in 2 unrelated adult patients ascertained from a cohort of 102 patients with polycystic liver disease (see, e.g., PCLD1, 174050) who did not have mutations in the PRKCSH (177060) or SEC63 (608648) genes and who underwent whole-exome sequencing. The variants were predicted to result in a loss of function. Statistical analysis of the frequency of these variants among patients compared to controls suggested that it is a candidate gene for the disorder. Functional studies of the variants and studies of patient cells were not performed, but inactivation of both Sec61b alleles in a mouse epithelial cell line resulted in almost undetectable levels of the Pkd1 (601313) protein and evidence of activation of the unfolded protein response. Reexpression of Sec61b restored Pkd1 levels. The findings indicated that loss of SEC61B results in defective maturation of PKD1 in the endoplasmic reticulum, suggesting that impaired PKD1 function and signaling mechanistically underlies the development of cysts

Created: 29 Mar 2025, 7:10 a.m. | Last Modified: 29 Mar 2025, 7:10 a.m.

Panel Version: 1.31

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Polycystic liver disease

Publications

• PMID: 28375157

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 not enough evidence to rate this gene green. Therefore, this gene has been given an amber rating.

Created: 12 Mar 2019, 11:28 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: SEC61B; 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: There is currently not enough evidence to promote SEC61B to a green gene; therefore, have applied the 'Watchlist' tag.

Created: 26 Nov 2018, 2:48 p.m.

There are 2 unrelated probands with LOF mutations, which were confirmed with functional studies (cell studies). Therefore promoted from red to amber

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

Publications

• 28862642