Numerous papers linking CASR variants with pancreatitis. Often in combination with other mutations (trans-heterozygosity) or as susceptibility allele. Also supported by one paper with functional data for Arginine rich domain in C-terminal.
PMID: 16497624 Patients with both p.(N34S) SPINK1 gene mutation and CASR mutation developed pancreatitis, whereas in the healthy parents and children only an isolated CASR or N34S SPINK1 gene mutation could be detected. Therefore proposes as co-factor in a multifactorial genetic setting of SPINK1-related pancreatitis that alters the susceptibility for pancreatitis in these patients.
PMID: 26166472 Overrepresentation of Rare CASR Coding Variants in a Sample of Young French Patients With Idiopathic Chronic Pancreatitis
PMID: 29173301 Targeted Gene Next-Generation Sequencing in Chinese Children with Chronic Pancreatitis and Acute Recurrent Pancreatitis. Found CASR mutations in 5 patients (out of CP 55; ARP 14)
PMID: 23207607 CASR believed to regulate CFTR opening to clear trypsin or excessive calcium from the duct.
PMID: 20798521 Calcium sensing receptor (CaSR) mutations implicated in familial hypocalciuric hypercalcemia, pancreatitis and idiopathic epilepsy syndrome map to an extended arginine-rich region in the proximal carboxyl terminus. R886P, R896H or R898Q, altered CaSR targeting to the plasma membrane. Targeting was enhanced by all three mutations, and Ca2+-stimulated ERK1/2 phosphorylation was increased for R896H and R898Q. Mutation(s) identified in chronic pancreatitis and idiopathic epilepsy syndrome therefore increase plasma membrane targeting of CaSR, likely
contributing to the altered Ca2+ signaling characteristic of these diseases.
PMID: 30134826 Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis.
Created: 17 Jan 2019, 5:49 p.m.
Mode of inheritance
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: CASR; Suggested intial gene rating: Amber; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Created: 7 Jan 2019, 4:15 p.m.
Variants in this gene seem to be a possible risk factor, unclear currently whether variants in this gene in isolation are causative of pancreatitis.
Created: 6 Dec 2018, 1 p.m.
Comment on publications: PMID: 26166472 - Overrepresentation of Rare CASR Coding Variants in a Sample of Young French Patients With Idiopathic Chronic Pancreatitis. PMID: 18680227 - case-control study in 57 patients and 21 controls found the R990G polymorphism was significantly associated with chronic pancreatitis (OR, 2.01; 95% CI, 1.12-3.59; P = 0.015).
Created: 6 Dec 2018, 12:59 p.m.
Comment on publications: PMID: 29173301 - 5 children with the R986S variant (rs1801725) in this gene with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) were identified in next-generation sequencing of 10 genes, but unclear from the article whether these were considered diagnostic. This variant is found at a frequency of T=0.12923 in GnomAD, and is deemed benign (2 stars) in ClinVar for Hypoparathyroidism. PMID: 17853337 - CASR gene was examined in patients with pancreatitis in primary hyperparathyroidism and no assoication with variants in this gene was found.
Created: 6 Dec 2018, 12:45 p.m.
Nothing obviously related to pancreatitis in OMIM.
Created: 6 Dec 2018, 12:16 p.m.
Phenotypes for gene: CASR were changed from to Pancreatitis
Publications for gene: CASR were set to 29173301; 17853337; 26166472; 18680227; 20798521; 18938753
Source NHS GMS was added to CASR.
Ellen McDonagh: Nothing obviously related to p
Publications for gene: CASR were set to 29173301; 17853337
Publications for gene: CASR were set to
CASR was added to Pancreatitis panel. Sources: EUROPAC
CASR was created by Ellen McDonagh