Details of Disease

Disease Name

Maturity-onset diabetes of the young

Mason type diabetes; maturity-onset diabetes of the young; MODY; Mason-type diabetes; maturity onset diabetes of the young; maturity-onset diabetes of the young (disease)

Definition

MODY (maturity-onset diabetes of the young) is a rare, familial, clinically and genetically heterogeneous form of diabetes characterized by young age of onset (generally 10-45 years of age) with maintenance of endogenous insulin production, lack of pancreatic beta-cell autoimmunity, absence of obesity and insulin resistance and extra-pancreatic manifestations in some subtypes.

Disease Hierarchy

DISEB8Q0: Monogenic diabetes

DIS30PPZ: Disorder of glycolysis

DISG75M5: Maturity-onset diabetes of the young

Disease Identifiers

MONDO ID

MONDO_0018911

MESH ID

C562772

UMLS CUI

C0342276

OMIM ID

606391

MedGen ID

87433

HPO ID

HP:0004904

Orphanet ID

552

SNOMED CT ID

609561005

General Information of Disease (ID: DISG75M5)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 23 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABCC8	TTP835K	Limited	Genetic Variation	[1]
ADA	TTLP57V	Limited	Genetic Variation	[2]
BLK	TTNDSC3	Limited	Genetic Variation	[3]
CEL	TTTRNQW	Limited	Genetic Variation	[4]
BLK	TTNDSC3	Supportive	Autosomal dominant	[5]
GCK	TTDLNGZ	Supportive	Autosomal dominant	[6]
HNF1A	TT01M3K	Supportive	Autosomal dominant	[6]
HNF4A	TT2F3CD	Supportive	Autosomal dominant	[6]
INS	TTZOPHG	Supportive	Autosomal dominant	[7]
PDX1	TT8SGZK	Supportive	Autosomal dominant	[6]
GAD1	TTKGEP3	Strong	Biomarker	[8]
GPD1	TTKTEAH	Strong	Genetic Variation	[9]
KCNC4	TTODZF1	Strong	Biomarker	[10]
KCNJ1	TTJ13ST	Strong	Biomarker	[9]
KCNJ11	TT329V4	Strong	Genetic Variation	[11]
MAP4K2	TTQFRP0	Strong	Genetic Variation	[12]
MTNR1B	TT32JK8	Strong	Genetic Variation	[13]
PASK	TTC0V1J	Strong	Genetic Variation	[14]
PLCG1	TT6T4JI	Strong	Genetic Variation	[15]
PRKG1	TT7IZSA	Strong	Biomarker	[16]
SLC19A2	TT2A1DZ	Strong	Genetic Variation	[11]
SLC30A8	TTXIGT7	Strong	Biomarker	[17]
TGM2	TT2F4OL	Strong	Genetic Variation	[18]
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⏷ Show the Full List of 23 DTT(s)

This Disease Is Related to 4 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCC8	DTI58LU	Supportive	Autosomal dominant	[19]
KCNJ11	DTGZICY	Supportive	Autosomal dominant	[20]
SLC2A2	DTUJPOL	Strong	Genetic Variation	[21]
SLC30A10	DTYBI73	Strong	Biomarker	[17]
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This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
FXYD2	DEULQ45	Strong	Altered Expression	[22]
HK1	DEDMAGE	Strong	Genetic Variation	[23]
PCK1	DEPLH5Z	Strong	Biomarker	[24]
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This Disease Is Related to 32 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ABCC8	OTCWQ54I	Supportive	Autosomal dominant	[19]
APPL1	OT8VR95S	Supportive	Autosomal dominant	[25]
BLK	OT1EB8MT	Supportive	Autosomal dominant	[5]
GCK	OTR3Q0NN	Supportive	Autosomal dominant	[6]
HNF1A	OT9DOUKL	Supportive	Autosomal dominant	[6]
HNF4A	OTY1TOAB	Supportive	Autosomal dominant	[6]
INS	OTZ85PDU	Supportive	Autosomal dominant	[7]
KCNJ11	OTPUUELV	Supportive	Autosomal dominant	[20]
KLF11	OTKVQDJD	Supportive	Autosomal dominant	[6]
NEUROD1	OTZQ7QJ2	Supportive	Autosomal dominant	[6]
PDX1	OTX1DKRA	Supportive	Autosomal dominant	[6]
APOM	OTI3FQQC	Strong	Biomarker	[26]
CYB5R4	OTF552H6	Strong	Biomarker	[27]
FUBP1	OT77SC9N	Strong	Biomarker	[28]
GCKR	OTSIWXGG	Strong	Genetic Variation	[29]
HNF1B	OTSYIC3T	Strong	Genetic Variation	[30]
ISL1	OTVNVKAX	Strong	Genetic Variation	[31]
MAFA	OTBCA105	Strong	Biomarker	[32]
MED25	OTDBY87B	Strong	Biomarker	[33]
NEUROD4	OTGYOIOJ	Strong	Genetic Variation	[34]
NKX6-1	OT5QC0BF	Strong	Biomarker	[35]
NR2F2	OTJFS67N	Strong	Genetic Variation	[36]
ONECUT1	OTK1QUQT	Strong	Genetic Variation	[37]
PCBD1	OTDSRUD5	Strong	Genetic Variation	[22]
PDHX	OTG7O271	Strong	Biomarker	[38]
PPP1R3B	OTVCRXEZ	Strong	Genetic Variation	[39]
PTPRN	OTAP7NOL	Strong	Biomarker	[40]
RAB14	OTF1J0TB	Strong	Biomarker	[28]
RFX6	OT8H77DL	Strong	Genetic Variation	[41]
SACM1L	OT6ORKTD	Strong	Biomarker	[42]
SERPINA7	OTUYVTSU	Strong	Biomarker	[43]
TCF7	OT1ID822	Strong	Genetic Variation	[12]
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⏷ Show the Full List of 32 DOT(s)

References

1	Phenotypic variability in two siblings with monogenic diabetes due to the same ABCC8 gene mutation.Pediatr Diabetes. 2019 Jun;20(4):482-485. doi: 10.1111/pedi.12826. Epub 2019 Apr 2.
2	A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK pedigree with maturity-onset diabetes of the young.Diabetologia. 1997 Jul;40(7):859-62. doi: 10.1007/s001250050760.
3	Reassessment of the putative role of BLK-p.A71T loss-of-function mutation in MODY and type 2 diabetes.Diabetologia. 2013 Mar;56(3):492-6. doi: 10.1007/s00125-012-2794-8. Epub 2012 Dec 6.
4	A recombined allele of the lipase gene CEL and its pseudogene CELP confers susceptibility to chronic pancreatitis.Nat Genet. 2015 May;47(5):518-522. doi: 10.1038/ng.3249. Epub 2015 Mar 16.
5	Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14460-5. doi: 10.1073/pnas.0906474106. Epub 2009 Aug 10.
6	Review on monogenic diabetes. Curr Opin Endocrinol Diabetes Obes. 2011 Aug;18(4):252-8. doi: 10.1097/MED.0b013e3283488275.
7	The lessons of early-onset monogenic diabetes for the understanding of diabetes pathogenesis. Best Pract Res Clin Endocrinol Metab. 2012 Apr;26(2):171-87. doi: 10.1016/j.beem.2011.12.001.
8	Traditional clinical criteria outperform high-sensitivity C-reactive protein for the screening of hepatic nuclear factor 1 alpha maturity-onset diabetes of the young among young Asians with diabetes.Ther Adv Endocrinol Metab. 2018 May 22;9(9):271-282. doi: 10.1177/2042018818776167. eCollection 2018 Sep.
9	Mitochondrial FAD-glycerophosphate dehydrogenase and G-protein-coupled inwardly rectifying K+ channel: No evidence for linkage in maturity-onset diabetes of the young or NIDDM.Diabetes. 1996 May;45(5):639-41. doi: 10.2337/diab.45.5.639.
10	No evidence for mutations in a putative beta-cell ATP-sensitive K+ channel subunit in MODY, NIDDM, or GDM.Diabetes. 1995 May;44(5):597-600. doi: 10.2337/diab.44.5.597.
11	Wholeexome sequencing in Russian children with nontype 1 diabetes mellitus reveals a wide spectrum of genetic variants in MODYrelated and unrelated genes.Mol Med Rep. 2019 Dec;20(6):4905-4914. doi: 10.3892/mmr.2019.10751. Epub 2019 Oct 16.
12	Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1.Pediatr Diabetes. 2008 Aug;9(4 Pt 2):367-72. doi: 10.1111/j.1399-5448.2008.00379.x. Epub 2008 Mar 5.
13	MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans.Diabetes. 2010 Jun;59(6):1539-48. doi: 10.2337/db09-1757. Epub 2010 Mar 3.
14	Human mutation within Per-Arnt-Sim (PAS) domain-containing protein kinase (PASK) causes basal insulin hypersecretion.J Biol Chem. 2011 Dec 23;286(51):44005-44014. doi: 10.1074/jbc.M111.254995. Epub 2011 Nov 7.
15	A genetic map of chromosome 20q12-q13.1: multiple highly polymorphic microsatellite and RFLP markers linked to the maturity-onset diabetes of the young (MODY) locus.Am J Hum Genet. 1993 Jan;52(1):110-23.
16	Phenotype Heterogeneity in Glucokinase-Maturity-Onset Diabetes of the Young (GCK-MODY) Patients.J Clin Res Pediatr Endocrinol. 2017 Sep 1;9(3):246-252. doi: 10.4274/jcrpe.4461. Epub 2017 Jun 30.
17	Autoantibodies against ZnT8 are rare in Central-European LADA patients and absent in MODY patients, including those positive for other autoantibodies.J Diabetes Complications. 2019 Jan;33(1):46-52. doi: 10.1016/j.jdiacomp.2018.10.004. Epub 2018 Oct 13.
18	Missense mutations in the TGM2 gene encoding transglutaminase 2 are found in patients with early-onset type 2 diabetes. Mutation in brief no. 982. Online.Hum Mutat. 2007 Nov;28(11):1150. doi: 10.1002/humu.9511.
19	Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia. 2012 Jan;55(1):123-7. doi: 10.1007/s00125-011-2319-x. Epub 2011 Oct 12.
20	Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One. 2012;7(6):e37423. doi: 10.1371/journal.pone.0037423. Epub 2012 Jun 11.
21	Linkage analysis of maturity-onset diabetes of the young with microsatellite polymorphisms. No linkage to ADA or GLUT2 genes in two families.Diabetes. 1992 Aug;41(8):962-7. doi: 10.2337/diab.41.8.962.
22	Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol. 2014 Mar;25(3):574-86.
23	beta-cell genes and diabetes: quantitative and qualitative differences in the pathophysiology of hepatic nuclear factor-1alpha and glucokinase mutations.Diabetes. 2001 Feb;50 Suppl 1:S101-7. doi: 10.2337/diabetes.50.2007.s101.
24	cDNA sequence and localization of polymorphic human cytosolic phosphoenolpyruvate carboxykinase gene (PCK1) to chromosome 20, band q13.31: PCK1 is not tightly linked to maturity-onset diabetes of the young.Hum Mol Genet. 1993 Jan;2(1):1-4. doi: 10.1093/hmg/2.1.1.
25	Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus. Am J Hum Genet. 2015 Jul 2;97(1):177-85. doi: 10.1016/j.ajhg.2015.05.011. Epub 2015 Jun 11.
26	Apolipoprotein M can discriminate HNF1A-MODY from Type 1 diabetes.Diabet Med. 2013 Feb;30(2):246-50. doi: 10.1111/dme.12066.
27	Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus.Diabetes. 2004 Nov;53(11):2992-7. doi: 10.2337/diabetes.53.11.2992.
28	Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome 9q22.3 and evaluation in non-insulin-dependent diabetes mellitus.Genomics. 1995 Sep 1;29(1):187-94. doi: 10.1006/geno.1995.1230.
29	Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.Am J Hum Genet. 2008 May;82(5):1185-92. doi: 10.1016/j.ajhg.2008.03.015. Epub 2008 Apr 24.
30	Clinical manifestations of a sporadic maturity-onset diabetes of the young (MODY) 5 with a whole deletion of HNF1B based on 17q12 microdeletion.Endocr J. 2019 Dec 25;66(12):1113-1116. doi: 10.1507/endocrj.EJ19-0020. Epub 2019 Aug 8.
31	The LIM-homeodomain protein ISL1 activates insulin gene promoter directly through synergy with BETA2.J Mol Biol. 2009 Sep 25;392(3):566-77. doi: 10.1016/j.jmb.2009.07.036. Epub 2009 Jul 17.
32	MafA is a key regulator of glucose-stimulated insulin secretion.Mol Cell Biol. 2005 Jun;25(12):4969-76. doi: 10.1128/MCB.25.12.4969-4976.2005.
33	MED25 is a mediator component of HNF4-driven transcription leading to insulin secretion in pancreatic beta-cells.PLoS One. 2012;7(8):e44007. doi: 10.1371/journal.pone.0044007. Epub 2012 Aug 30.
34	beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the gene encoding the basic helix-loop-helix transcription factor neurogenic differentiation 4 (NEUROD4) in Japanese patients with MODY.Diabetes. 2000 Nov;49(11):1955-7. doi: 10.2337/diabetes.49.11.1955.
35	Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India.BMC Med Genet. 2018 Feb 13;19(1):22. doi: 10.1186/s12881-018-0528-6.
36	Functional study of the E276Q mutant hepatocyte nuclear factor-4alpha found in type 1 maturity-onset diabetes of the young: impaired synergy with chicken ovalbumin upstream promoter transcription factor II on the hepatocyte nuclear factor-1 promoter.Diabetes. 1999 May;48(5):1162-7. doi: 10.2337/diabetes.48.5.1162.
37	Mutation screening of the hepatocyte nuclear factor (HNF)-6 gene in Japanese subjects with diabetes mellitus.Diabetes Res Clin Pract. 2001 Jun;52(3):171-4. doi: 10.1016/s0168-8227(01)00222-4.
38	Increased DNA methylation and decreased expression of PDX-1 in pancreatic islets from patients with type 2 diabetes.Mol Endocrinol. 2012 Jul;26(7):1203-12. doi: 10.1210/me.2012-1004. Epub 2012 May 8.
39	Increased frequency of rare missense PPP1R3B variants among Danish patients with type 2 diabetes.PLoS One. 2019 Jan 10;14(1):e0210114. doi: 10.1371/journal.pone.0210114. eCollection 2019.
40	The role of late-onset autoimmune diabetes in white familial NIDDM pedigrees.Diabetes Care. 1997 Aug;20(8):1248-51. doi: 10.2337/diacare.20.8.1248.
41	A heterozygous protein-truncating RFX6 variant in a family with childhood-onset, pregnancy-associated and adult-onset diabetes.Diabet Med. 2020 Oct;37(10):1772-1776. doi: 10.1111/dme.13970. Epub 2019 Jun 5.
42	Molecular and clinical characterization of an insertional polymorphism of the insulin-receptor gene.Diabetes. 1989 Jun;38(6):737-43. doi: 10.2337/diab.38.6.737.
43	Quantitative Evaluation of Serum Proteins Uncovers a Protein Signature Related to Maturity-Onset Diabetes of the Young (MODY).J Proteome Res. 2018 Jan 5;17(1):670-679. doi: 10.1021/acs.jproteome.7b00727. Epub 2017 Dec 14.