Monogenic diabetes

Gene: CEL

Green List (high evidence)

CEL (carboxyl ester lipase)
EnsemblGeneIds (GRCh38): ENSG00000170835
EnsemblGeneIds (GRCh37): ENSG00000170835
OMIM: 114840, Gene2Phenotype
CEL is in 5 panels

4 reviews

Jayne Houghton (Royal Devon and Exeter Foundation Trust)

Green List (high evidence)

Specific dominant negative/gain of function mutations occurring within the first 1-5 repeats of the CEL VNTR are known to cause MODY with pancreatic exocrine dysfunction (MIM609812) (PMID: 24062244, PMID: 21784842, PMID: 19760265, PMID:18544793, PMID:17989309, PMID: 16369531).Heterozygous missense variants and variants resulting in a PTC that will trigger nonsense mediated decay are not expected to cause monogenic diabetes. These VNTR-located mutations cause a shift in the reading frame and generate a highly extended protein at the C-terminus that has been shown to aggregate in pancreatic islets resulting in ER stress and apoptosis (PMID:27650499). CEL mutant proteins were observed as an aggregate at the cell surface and inside large cytoplasmic vacuoles. Many of the vacuoles were identified as components of the endosomal system, and after its secretion, the mutant CEL protein was re-internalized, transported to the lysosomes, and degraded. Internalization of CEL-MUT also led to reduced viability of pancreatic acinar and beta cells (PMID: 25160620).
Created: 15 Feb 2019, 10:28 a.m.

Publications

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoted from red to green as advised via email communication with Jane Houghton (South West GLH).
Created: 28 Jan 2019, 9:37 a.m.
Initial gene list and info collated by Sian Ellard, University of Exeter Medical School, August 2018 on behalf of the GMS Endocrinology specialist test group. Gene Symbol submitted: CEL; 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; Phenotypes: Diabetes and pancreatic exocrine dysfunction.
Created: 11 Jan 2019, 10:04 a.m.

Ellen McDonagh (Genomics England Curator)

Comment when marking as ready: Gene kept on the red list due to expert review and complication with reporting of specific variants within this gene.
Created: 7 Jun 2016, 9:59 a.m.

Sian Ellard (University of Exeter Medical School)

Red List (low evidence)

This is a very rare cause of diabetes and exocrine pancreatic dysfunction (2 families). The CEL gene is difficult to sequence and interpret due to the VNTR repeat sequences. The Exeter lab would only report frameshift mutations in the VNTR-containing exon 11 as pathogenic mutations.
Created: 23 Aug 2015, 4:32 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Maturity-onset diabetes of the young, type VIII, 609812
  • Diabetes and pancreatic exocrine dysfunction
OMIM
114840
Clinvar variants
Variants in CEL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

15 Jul 2019, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: CEL were changed from Maturity-onset diabetes of the young, type VIII, 609812 to Maturity-onset diabetes of the young, type VIII, 609812; Diabetes and pancreatic exocrine dysfunction

1 May 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: CEL were set to 16369531

30 Jan 2019, Gel status: 3

Panel promoted to version 1.0

Ivone Leong (Genomics England Curator)

Ivone Leong: Initial gene list and info col

28 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: cel has been classified as Green List (High Evidence).

11 Jan 2019, Gel status: 1

Added New Source

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to CEL.

18 Dec 2018, Gel status: 1

Set Phenotypes, Set publications

Ellen McDonagh (Genomics England Curator)

Added phenotypes Maturity-onset diabetes of the young, type VIII, 609812 for gene: CEL Publications for gene CEL were changed from PMID: 16369531 to 16369531

18 Dec 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: CEL was added gene: CEL was added to Monogenic diabetes. Sources: Expert Review Red Mode of inheritance for gene: CEL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CEL were set to PMID: 16369531 Phenotypes for gene: CEL were set to Maturity-onset diabetes of the young, type VIII, 609812