Pancreatitis
Gene: CELA3B

CELA3B (chymotrypsin like elastase family member 3B)
EnsemblGeneIds (GRCh38): ENSG00000219073
EnsemblGeneIds (GRCh37): ENSG00000219073
CELA3B is in 1 panel

2 reviews

Ivone Leong (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 4:39 p.m. | Last Modified: 3 Mar 2022, 4:39 p.m.

Panel Version: 2.12

Comment on list classification: New gene added by Miranda Durkie. This gene is not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 31369399. Other affected members of this large family could not be tested and therefore the genetic status of the affected individuals are unknown. The family also has a variant in FOXN1, as the gene is not expressed in the pancreas the authors hypothesised that the FOXN1 variant was not causative.

PMID: 33565216. Four patients with p.Arg90Leu (c.269G>T) were from cases with familial chronic pancreatitis and young cases with idiopathic chronic pancreatitis (2 each). The familial chronic pancreatitis cases each have an affected first‐degree relative who have not been analysed yet.

This gene has been added as an Amber gene and will be reviewed by the GMS specialist group to see if there is enough evidence to promote to Green status.
Created: 12 Apr 2021, 10:13 a.m. | Last Modified: 12 Apr 2021, 10:13 a.m.

Panel Version: 2.10

Created: 12 Apr 2021, 10:13 a.m.
Last Modified: 12 Apr 2021, 10:13 a.m.
Panel version: 2.12

Miranda Durkie (Genetics)

Green List (high evidence)

PMID: 31369399 - 1 large family with 17 affected family members across 4 generations. Exome sequencing identified c.268C>T p.(Arg90Cys) in CELA3B gene in affected mother and affected daughter (not present in unaffected son). Does not segregate with disease in a further 6 unaffected family members. Functional studies showed both this variant and p.(Arg90Leu) variants cause translational upregulation of CELA3B, which, upon secretion and activation by
trypsin, leads to uncontrolled proteolysis and recurrent pancreatitis.
PMID: 33565216 - Sequenced CELA3B in 644 genetically unexplained French chronic pancreatitis (CP) patients (all unrelated) and 566 controls. No loss of function variants found, however found p.Arg90Leu (c.269G>T) in four patients but no controls.
Therefore 5 families identified with p.(Arg90Cys) or p.(Arg90Leu) and supporting functional assay for these variants only.
Sources: Literature
Created: 25 Feb 2021, 11:57 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Chronic Pancreatitis; Diabetes; Pancreatic cancer

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Created: 25 Feb 2021, 11:57 a.m.

Panel version: 2.7

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green

Phenotypes

Chronic Pancreatitis, MONDO:0005003
diabetes mellitus (disease), MONDO:0005015
Pancreatic cancer

Tags

gene-checked

Clinvar variants

Variants in CELA3B

Penetrance

Incomplete

Publications

Mode of Pathogenicity

Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Panels with this gene

Pancreatitis

History Filter Activity

7 May 2022, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag gene-checked tag was added to gene: CELA3B.

3 Mar 2022, Gel status: 3