MODY8 CEL

Maturity-onset diabetes of the young type 8 (MODY8) is characterized by onset of diabetes before age 25 years, with slowly progressive pancreatic exocrine dysfunction, fatty replacement of pancreatic parenchyma (lipomatosis), and development of pancreatic cysts¹. Other types of this disease have been associated with various genes and variant types. Comorbidity has been proposed between MODY and fecal elastase deficiency (FED).

Prevalence

Found in individuals of Danish and Norwegian ancestry^2,3.

Age of Onset Details

11-17³

Locus

hg19

chr9:135946564-135947124

hg38

chr9:133071177-133071737

t2t

chr9:145285333-145285861

Details

The locus contains 17 imperfect 33 bp motifs, with a stretch of 7 perfect GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG motifs. Several pathogenic mutations have been proposed. A single basepair deletion causing a frameshift mutation^2,3. Another is a 1bp deletion of (C)8 to (C)7 within the VNTR, causing a motif change (this is the pathogenic motif represented here). Also, a contraction that deletes one of the VNTR repeats may be pathogenic, with reduced penetrance, although evidence for this is sparse³. Another study identified a c.2041_2042delinsCGG p.(Val681Argfs*6) mutation in the 12th motif (one of the imperfect motifs)⁴. Several non-tandem repeat pathogenic MODY variants have also been reported in this gene. Given limited data and multiple proposed pathogenic variants, the normal and pathogenic ranges are currently difficult to define.

Mechanism

Loss of function at the protein level may be part of the molecular mechanism. Research suggests that the mutations disrupt the C-terminal protein, leading to reduced stability of the mutant lipase in vitro².

Year

2005

Location in Gene

Exon 11

Gene Strand

Alleles

Ref. Motif

GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG

Pathogenic (ref.)

GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG

Pathogenic (gene)

ACGGGTGACTCCGGGGCCCCCCCGTGCCGCCC

References

Direct supporting references for info on this page.

omim:609812

Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction.

Helge,Raeder, Stefan,Johansson, Pål I,Holm, Ingfrid S,Haldorsen, Eric,Mas, Véronique,Sbarra, Ingrid,Nermoen, Stig A,Eide, Louise,Grevle, Lise,Bjørkhaug, Jørn V,Sagen, Lage,Aksnes, Oddmund,Søvik, Dominique,Lombardo, Anders,Molven, Pål Rasmus,Njølstad

Nature genetics · 2005-12-20

pmid:16369531

Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes.

Janniche,Torsvik, Stefan,Johansson, Anders,Johansen, Jakob,Ek, Jayne,Minton, Helge,Raeder, Sian,Ellard, Andrew,Hattersley, Oluf,Pedersen, Torben,Hansen, Anders,Molven, Pål R,Njølstad

Human genetics · 2009-09-17

pmid:19760265

Unraveling the genetic basis of MODY: insights from next-generation sequencing.

Metin,Eser, Gulam,Hekimoglu, Fatma,Dursun

Journal of applied genetics · 2024-10-03

pmid:39361122

Additional Literature

Additional literature related to this locus.

Dexamethasone prophylaxis for excessive lymphocyte expansion after cilta-cel in multiple myeloma.

Peter A,Forsberg, Jacqueline A,Turner, Marita,Meyer, Diana,Abbott, Sara,Nicholson, Henning,Schade, Jeffrey V,Matous, Tara,Gregory

Blood advances · 2026-03-27

pmid:41894686

Routine Monitoring of CAR-T-Cells Expansion and Persistence in Patients With Aggressive Large B-Cell Lymphoma by Flow Cytometry: A Single-Center Experience.

Alexandra,Zduniak, Jérémie,Martinet, Emilie,Lévêque, Stéphanie,Becker, David,Tonnelet, Elodie Dos,Santos, Claire,Leroy, Mustafa,Alani, Jean,Rouvet, Marine,Brousseau, Camille,Giverne, Alexis,Cuffel, Serge,Jacquot, Arnaud,Roucheux, Alice,Veuiller, Nicolas,Lecornu, Misa Eugene,Norbert, Olivier,Boyer, Hervé,Tilly, Fabrice,Jardin, Jean-Baptiste,Latouche, Vincent,Camus

Hematological oncology · 2025-11-01

pmid:41057236

Early-onset diabetes with low utilization of lipid as an energy source carrying a rare missense mutation in the CEL gene.

Ayana,Fujii, Hiroko,Nakabayashi, Yuko,Nagao, Masaru,Akiyama, Akihiko,Taguchi, Kaito,Yorimoto, Risako,Hamada, Issei,Saeki, Naoki,Yamamoto, Taro,Takami, Kenji,Watanabe, Yoichi,Mizukami, Yasuharu,Ohta

Endocrinology, diabetes & metabolism case reports · 2025-08-18

pmid:40840513

Characterizing Cellular Expansion of Idecabtagene Vicleucel and Association with Clinical Efficacy and Safety in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma.

Fan,Wu, Xirong,Zheng, Joseph,Burnett, Madhan,Masilamani, Wanying,Zhang, Xiaobo,Zhong, Andrea,Caia, Mark,Cook, Julia,Piasecki, Anna,Kondic, Manisha,Lamba, Jian,Zhou

Journal of clinical pharmacology · 2025-07-10

pmid:40641008

Brexucabtagene autoleucel in-vivo expansion and BTKi refractoriness have a negative influence on progression-free survival in mantle cell lymphoma: Results from CART-SIE study.

Federico,Stella, Annalisa,Chiappella, Martina,Magni, Francesca,Bonifazi, Chiara,De Philippis, Maurizio,Musso, Ilaria,Cutini, Silva,Ljevar, Anna Maria,Barbui, Mirko,Farina, Massimo,Martino, Massimo,Massaia, Giovanni,Grillo, Piera,Angelillo, Barbara,Botto, Francesca,Patriarca, Mauro,Krampera, Luca,Arcaini, Maria Chiara,Tisi, Pierluigi,Zinzani, Federica,Sorà, Stefania,Bramanti, Martina,Pennisi, Cristiana,Carniti, Paolo,Corradini

British journal of haematology · 2024-12-22

pmid:39710966

Common single-base insertions in the VNTR of the carboxyl ester lipase (CEL) gene are benign and also likely to arise somatically in the exocrine pancreas.

Ranveig S,Brekke, Anny,Gravdal, Khadija,El Jellas, Grace E,Curry, Jianguo,Lin, Steven J,Wilhelm, Solrun J,Steine, Eric,Mas, Stefan,Johansson, Mark E,Lowe, Bente B,Johansson, Xunjun,Xiao, Karianne,Fjeld, Anders,Molven

Human molecular genetics · 2024-05-18

pmid:38483348

Unlocking Predictive Power: Quantitative Assessment of CAR-T Expansion with Digital Droplet Polymerase Chain Reaction (ddPCR).

Eugenio,Galli, Marcello,Viscovo, Federica,Fosso, Ilaria,Pansini, Giacomo,Di Cesare, Camilla,Iacovelli, Elena,Maiolo, Federica,Sorà, Stefan,Hohaus, Simona,Sica, Silvia,Bellesi, Patrizia,Chiusolo

International journal of molecular sciences · 2024-02-26

pmid:38473919

Early Chimeric Antigen Receptor T Cell Expansion Is Associated with Prolonged Progression-Free Survival for Patients with Relapsed/Refractory Multiple Myeloma Treated with Ide-Cel: A Retrospective Monocentric Study.

Leo,Caillot, Emmanuel,Sleiman, Ingrid,Lafon, Marie-Lorraine,Chretien, Pauline,Gueneau, Alexandre,Payssot, Romain,Pedri, Daniela,Lakomy, François,Bailly, Julien,Guy, Jean-Pierre,Quenot, Herve,Avet-Loiseau, Denis,Caillot

Transplantation and cellular therapy · 2024-03-07

pmid:38458477

The genetic risk factor CEL-HYB1 causes proteotoxicity and chronic pancreatitis in mice.

Karianne,Fjeld, Anny,Gravdal, Ranveig S,Brekke, Jahedul,Alam, Steven J,Wilhelm, Khadija,El Jellas, Helene N,Pettersen, Jianguo,Lin, Marie H,Solheim, Solrun J,Steine, Bente B,Johansson, Pål R,Njølstad, Caroline S,Verbeke, Xunjun,Xiao, Mark E,Lowe, Anders,Molven

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2022-11-09

pmid:36379850