MODY4
MCID: MTR021
MIFTS: 41

Maturity-Onset Diabetes of the Young, Type 4 (MODY4)

Categories: Endocrine diseases, Genetic diseases, Liver diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Maturity-Onset Diabetes of the Young, Type 4

MalaCards integrated aliases for Maturity-Onset Diabetes of the Young, Type 4:

Name: Maturity-Onset Diabetes of the Young, Type 4 57 53 29 6
Mody4 57 12 53 74
Mody Type 4 12 53 74
Maturity-Onset Diabetes of the Young Type 4 12 15
Mody, Type Iv 57 13
Diabetes of the Young, Maturity-Onset, Type 4 40
Maturity-Onset Diabetes of the Young, Type Iv 72
Type 4 Maturity-Onset Diabetes of the Young 53
Mody Insulin Promoter Factor-1 Related 53
Maturity-Onset Diabetes of the Young 4 74
Diabetes Mellitus Mody Type 4 53
Mody, Type 4 57
Mody-4 74

Characteristics:

HPO:

32
maturity-onset diabetes of the young, type 4:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0111103
OMIM 57 606392
MeSH 44 D003924
MedGen 42 C1833382
UMLS 72 C1833382

Summaries for Maturity-Onset Diabetes of the Young, Type 4

UniProtKB/Swiss-Prot : 74 Maturity-onset diabetes of the young 4: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.

MalaCards based summary : Maturity-Onset Diabetes of the Young, Type 4, also known as mody4, is related to insulinoma and diabetes mellitus, permanent neonatal. An important gene associated with Maturity-Onset Diabetes of the Young, Type 4 is PDX1 (Pancreatic And Duodenal Homeobox 1), and among its related pathways/superpathways are Developmental Biology and Glucose / Energy Metabolism. Affiliated tissues include pancreas and pancreatic islet, and related phenotypes are type ii diabetes mellitus and maturity-onset diabetes of the young

Disease Ontology : 12 A maturity-onset diabetes of the young that has material basis in mutation in the PDX1 gene on chromosome 13q12.2.

More information from OMIM: 606392

Related Diseases for Maturity-Onset Diabetes of the Young, Type 4

Diseases in the Maturity-Onset Diabetes of the Young family:

Maturity-Onset Diabetes of the Young, Type 1 Maturity-Onset Diabetes of the Young, Type 2
Maturity-Onset Diabetes of the Young, Type 3 Maturity-Onset Diabetes of the Young, Type 4
Maturity-Onset Diabetes of the Young, Type 6 Maturity-Onset Diabetes of the Young, Type 7
Maturity-Onset Diabetes of the Young, Type 9 Maturity-Onset Diabetes of the Young, Type 10
Maturity-Onset Diabetes of the Young, Type 11 Maturity-Onset Diabetes of the Young, Type 13
Maturity-Onset Diabetes of the Young, Type 14

Diseases related to Maturity-Onset Diabetes of the Young, Type 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 27)
# Related Disease Score Top Affiliating Genes
1 insulinoma 30.2 PDX1 GCK
2 diabetes mellitus, permanent neonatal 30.2 PDX1 GCK
3 pancreatic agenesis 29.2 PDX1 HMX1 GCK
4 diabetes mellitus, noninsulin-dependent 28.4 PDX1 HNF4A HNF1B HNF1A GCK
5 maturity-onset diabetes of the young, type 3 28.2 PDX1 HNF4A HNF1B HNF1A GCK
6 maturity-onset diabetes of the young 28.2 PDX1 HNF4A HNF1B HNF1A GCK
7 diabetes mellitus 28.1 PDX1 HNF4A HNF1B HNF1A GCK
8 maturity-onset diabetes of the young, type 7 27.1 PDX1 HNF4A HNF1B HNF1A HMX1 GCK
9 pancreas, dorsal, agenesis of 10.1
10 pancreatic agenesis 1 10.1
11 intestinal atresia 10.1 PDX1 GCK
12 hyperinsulinemic hypoglycemia 9.9 HNF4A GCK
13 maturity-onset diabetes of the young, type 14 9.9 HNF1A GCK
14 chromophobe renal cell carcinoma 9.9 HNF1B HNF1A
15 aminoaciduria 9.9 HNF4A HNF1A
16 polycystic kidney disease 4 with or without polycystic liver disease 9.8 HNF1B HNF1A
17 autosomal genetic disease 9.7 HNF1A GCK
18 neonatal diabetes mellitus 9.7 PDX1 HNF1B GCK
19 gestational diabetes 9.7 HNF4A GCK
20 hyperglycemia 9.5 PDX1 HNF1A GCK
21 hyperinsulinism 9.5 HNF4A GCK
22 maturity-onset diabetes of the young, type 13 9.5 HNF4A HNF1A GCK
23 monogenic diabetes 9.1 PDX1 HNF4A HNF1A GCK
24 maturity-onset diabetes of the young, type 2 8.7 PDX1 HNF4A HNF1B HNF1A GCK
25 renal cysts and diabetes syndrome 8.7 PDX1 HNF4A HNF1B HNF1A GCK
26 maturity-onset diabetes of the young, type 6 8.7 PDX1 HNF4A HNF1B HNF1A GCK
27 maturity-onset diabetes of the young, type 1 8.7 PDX1 HNF4A HNF1B HNF1A GCK

Graphical network of the top 20 diseases related to Maturity-Onset Diabetes of the Young, Type 4:



Diseases related to Maturity-Onset Diabetes of the Young, Type 4

Symptoms & Phenotypes for Maturity-Onset Diabetes of the Young, Type 4

Human phenotypes related to Maturity-Onset Diabetes of the Young, Type 4:

32
# Description HPO Frequency HPO Source Accession
1 type ii diabetes mellitus 32 HP:0005978
2 maturity-onset diabetes of the young 32 HP:0004904

Clinical features from OMIM:

606392

GenomeRNAi Phenotypes related to Maturity-Onset Diabetes of the Young, Type 4 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased free cholesterol GR00340-A-2 8.62 HNF1A HNF4A

MGI Mouse Phenotypes related to Maturity-Onset Diabetes of the Young, Type 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.73 GCK HMX1 HNF1A HNF1B HNF4A PDX1
2 liver/biliary system MP:0005370 9.55 GCK HNF1A HNF1B HNF4A PDX1
3 mortality/aging MP:0010768 9.43 GCK HMX1 HNF1A HNF1B HNF4A PDX1
4 renal/urinary system MP:0005367 8.92 GCK HNF1A HNF1B PDX1

Drugs & Therapeutics for Maturity-Onset Diabetes of the Young, Type 4

Search Clinical Trials , NIH Clinical Center for Maturity-Onset Diabetes of the Young, Type 4

Genetic Tests for Maturity-Onset Diabetes of the Young, Type 4

Genetic tests related to Maturity-Onset Diabetes of the Young, Type 4:

# Genetic test Affiliating Genes
1 Maturity-Onset Diabetes of the Young, Type 4 29 PDX1

Anatomical Context for Maturity-Onset Diabetes of the Young, Type 4

MalaCards organs/tissues related to Maturity-Onset Diabetes of the Young, Type 4:

41
Pancreas, Pancreatic Islet

Publications for Maturity-Onset Diabetes of the Young, Type 4

Articles related to Maturity-Onset Diabetes of the Young, Type 4:

(show top 50) (show all 53)
# Title Authors PMID Year
1
Obesity and hyperinsulinemia in a family with pancreatic agenesis and MODY caused by the IPF1 mutation Pro63fsX60. 38 8 71
20621032 2010
2
Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. 38 8 71
9326926 1997
3
Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation. 8 71
19496967 2009
4
Insulin promoter factor-1 gene mutation linked to early-onset type 2 diabetes mellitus directs expression of a dominant negative isoprotein. 8 71
9649577 1998
5
Permanent neonatal diabetes mellitus and pancreatic exocrine insufficiency resulting from congenital pancreatic agenesis. 8 71
8506821 1993
6
Maturity-Onset Diabetes of the Young Overview 71
29792621 2018
7
Analysis of protein-coding genetic variation in 60,706 humans. 71
27535533 2016
8
Insulin promoter factor-1 mutations and diabetes in Trinidad: identification of a novel diabetes-associated mutation (E224K) in an Indo-Trinidadian family. 71
14764823 2004
9
Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. 8
11575290 2001
10
Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. 71
8988180 1997
11
First Case Report of Maturity-Onset Diabetes of the Young Type 4 Pedigree in a Chinese Family. 38
31333579 2019
12
Genome-wide analysis of PDX1 target genes in human pancreatic progenitors. 38
29396371 2018
13
PDX1 -MODY and dorsal pancreatic agenesis: New phenotype of a rare disease. 38
28436541 2018
14
Generation of a human induced pluripotent stem cell (iPSC) line from a patient carrying a P33T mutation in the PDX1 gene. 38
27879211 2016
15
Generation of a human induced pluripotent stem cell (iPSC) line from a patient with family history of diabetes carrying a C18R mutation in the PDX1 gene. 38
27879214 2016
16
Genetically Targeted Dipeptidyl Peptidase-4 Inhibitor Use in a Patient with a Novel Mutation of MODY type 4. 38
26543388 2015
17
Sox17 regulates insulin secretion in the normal and pathologic mouse β cell. 38
25144761 2014
18
Sox9-haploinsufficiency causes glucose intolerance in mice. 38
21829703 2011
19
Identification of 9-cis-retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion. 38
21115832 2010
20
Loss of Nix in Pdx1-deficient mice prevents apoptotic and necrotic β cell death and diabetes. 38
20978346 2010
21
An infant with combination gene mutations for Monogenic Diabetes of Youth (MODY) 2 and 4, presenting with Diabetes Mellitus Requiring Insulin (DMRI) at 8 months of age. 38
19515026 2009
22
MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. 38
19843526 2009
23
Pdx1 (MODY4) regulates pancreatic beta cell susceptibility to ER stress. 38
19855005 2009
24
PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. 38
19656489 2009
25
The diabetes gene Pdx1 regulates the transcriptional network of pancreatic endocrine progenitor cells in mice. 38
19487809 2009
26
Permanent Neonatal Diabetes Mellitus 38
20301620 2008
27
Meta-analysis of the IPF1 D76N polymorphism in a worldwide type 2 diabetes population. 38
17592437 2007
28
Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. 38
17327436 2007
29
IPF-1/MODY4 gene missense mutation in an Italian family with type 2 and gestational diabetes. 38
16092045 2005
30
The coactivator Bridge-1 increases transcriptional activation by pancreas duodenum homeobox-1 (PDX-1). 38
15885879 2005
31
Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity. 38
15121856 2004
32
Experimental models of transcription factor-associated maturity-onset diabetes of the young. 38
12475772 2002
33
Pancreatic Duodenal Homeobox (PDX-1) in health and disease. 38
12503852 2002
34
Large Family With Maturity-Onset Diabetes of the Young and a Novel V121I Mutation in HNF4A. 38
12203996 2002
35
Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. 38
12145169 2002
36
[Insulin-dependent neonatal and infant diabetes: genetics and physiopathology]. 38
12085668 2002
37
Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood. 38
11834421 2002
38
Screening for MODY mutations, GAD antibodies, and type 1 diabetes--associated HLA genotypes in women with gestational diabetes mellitus. 38
11772903 2002
39
Pancreatic duodenal homeobox-1, PDX-1, a major regulator of beta cell identity and function. 38
11692168 2001
40
A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young. 38
11590126 2001
41
[Diabetes mellitus]. 38
11307309 2001
42
Functional consequences of mutations in the MODY4 gene (IPF1) and coexistence with MODY3 mutations. 38
11270685 2001
43
Hepatocyte nuclear factor 1 alpha (HNF-1 alpha) mutations in maturity-onset diabetes of the young. 38
11058894 2000
44
Molecular and genetic bases for maturity onset diabetes of youth. 38
10943822 2000
45
Molecular and biochemical analysis of the MODY syndromes. 38
15016234 2000
46
[Molecular background and clinical characteristics of autosomal dominant type 2 diabetes mellitus]. 38
11293229 2000
47
Monogenic diabetes mellitus in youth. The MODY syndromes. 38
10609119 1999
48
Identification of a nuclear localization signal, RRMKWKK, in the homeodomain transcription factor PDX-1. 38
10567702 1999
49
Hepatocyte nuclear factor-6: associations between genetic variability and type II diabetes and between genetic variability and estimates of insulin secretion. 38
10491763 1999
50
Maturity-onset diabetes of the young (MODY): a new challenge for pediatric diabetologists. 38
10417964 1999

Variations for Maturity-Onset Diabetes of the Young, Type 4

ClinVar genetic disease variations for Maturity-Onset Diabetes of the Young, Type 4:

6 (show all 15)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PDX1 NM_000209.4(PDX1): c.188del (p.Pro63fs) deletion Pathogenic rs193929377 13:28494463-28494463 13:27920326-27920326
2 PDX1 NM_000209.4(PDX1): c.533A> G (p.Glu178Gly) single nucleotide variant Pathogenic rs387906777 13:28498519-28498519 13:27924382-27924382
3 PDX1 PDX1, 1-BP DEL, 188C deletion Pathogenic
4 PDX1 NM_000209.4(PDX1): c.502A> C (p.Asn168His) single nucleotide variant Likely pathogenic rs1555241857 13:28498488-28498488 13:27924351-27924351
5 PDX1 NM_000209.4(PDX1): c.442C> G (p.Arg148Gly) single nucleotide variant Likely pathogenic rs193922355 13:28498428-28498428 13:27924291-27924291
6 PDX1 NM_000209.4(PDX1): c.571A> C (p.Lys191Gln) single nucleotide variant Likely pathogenic rs193922356 13:28498557-28498557 13:27924420-27924420
7 PDX1 NM_000209.4(PDX1): c.773A> G (p.Glu258Gly) single nucleotide variant Likely pathogenic rs193922360 13:28498759-28498759 13:27924622-27924622
8 PDX1 NM_000209.4(PDX1): c.714_716GCC[6] (p.Pro244dup) short repeat Conflicting interpretations of pathogenicity rs193922357 13:28498712-28498714 13:27924575-27924577
9 PDX1 NM_000209.4(PDX1): c.543C> T (p.Val181=) single nucleotide variant Conflicting interpretations of pathogenicity rs75498935 13:28498529-28498529 13:27924392-27924392
10 PDX1 NM_000209.4(PDX1): c.226G> A (p.Asp76Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs137852783 13:28494501-28494501 13:27920364-27920364
11 PDX1 NM_000209.4(PDX1): c.670G> A (p.Glu224Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs137852787 13:28498656-28498656 13:27924519-27924519
12 PDX1 NM_000209.4(PDX1): c.-18C> T single nucleotide variant Conflicting interpretations of pathogenicity rs193922351 13:28494258-28494258 13:27920121-27920121
13 PDX1 NM_000209.4(PDX1): c.-50_-44CTCCCGG[5] short repeat Uncertain significance rs193922352 13:28494247-28494253 13:27920110-27920116
14 PDX1 NM_000209.4(PDX1): c.318G> T (p.Pro106=) single nucleotide variant Likely benign rs193922354 13:28494593-28494593 13:27920456-27920456
15 PDX1 NM_000209.4(PDX1): c.162G> A (p.Leu54=) single nucleotide variant Benign/Likely benign rs28509441 13:28494437-28494437 13:27920300-27920300

Expression for Maturity-Onset Diabetes of the Young, Type 4

Search GEO for disease gene expression data for Maturity-Onset Diabetes of the Young, Type 4.

Pathways for Maturity-Onset Diabetes of the Young, Type 4

Pathways related to Maturity-Onset Diabetes of the Young, Type 4 according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.98 PDX1 HNF4A HNF1B HNF1A GCK
2 12.12 PDX1 HNF4A HNF1A
3
Show member pathways
12.05 HNF4A HNF1B HNF1A
4 11.98 HNF4A HNF1B HNF1A
5
Show member pathways
11.65 PDX1 HNF4A HNF1B HNF1A GCK
6 11.63 PDX1 HNF1B
7
Show member pathways
11.58 HNF4A HNF1B HNF1A
8
Show member pathways
11.35 PDX1 HNF4A HNF1B HNF1A GCK
9 11.31 HNF4A GCK
10 11.2 PDX1 HNF4A HNF1A GCK
11
Show member pathways
11 PDX1 HNF4A HNF1B HNF1A GCK
12 10.22 HNF4A HNF1A

GO Terms for Maturity-Onset Diabetes of the Young, Type 4

Cellular components related to Maturity-Onset Diabetes of the Young, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.1 PDX1 HNF4A HNF1B HNF1A HMX1 GCK

Biological processes related to Maturity-Onset Diabetes of the Young, Type 4 according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.88 PDX1 HNF4A HNF1A HMX1
2 regulation of transcription by RNA polymerase II GO:0006357 9.86 PDX1 HNF4A HNF1B HNF1A
3 positive regulation of transcription by RNA polymerase II GO:0045944 9.84 PDX1 HNF4A HNF1B HNF1A
4 positive regulation of transcription, DNA-templated GO:0045893 9.8 PDX1 HNF4A HNF1B HNF1A
5 liver development GO:0001889 9.61 PDX1 HNF1B HNF1A
6 transcription by RNA polymerase II GO:0006366 9.58 PDX1 HNF1A
7 response to glucose GO:0009749 9.58 HNF4A HNF1B HNF1A
8 glucose metabolic process GO:0006006 9.57 PDX1 GCK
9 SMAD protein signal transduction GO:0060395 9.55 HNF4A HNF1A
10 regulation of Wnt signaling pathway GO:0030111 9.52 HNF1B HNF1A
11 endocrine pancreas development GO:0031018 9.51 PDX1 HNF1A
12 hepatocyte differentiation GO:0070365 9.48 HNF4A HNF1B
13 positive regulation of transcription initiation from RNA polymerase II promoter GO:0060261 9.46 HNF1B HNF1A
14 regulation of insulin secretion GO:0050796 9.37 HNF4A GCK
15 insulin secretion GO:0030073 9.33 PDX1 HNF1B HNF1A
16 detection of glucose GO:0051594 9.32 PDX1 GCK
17 regulation of pronephros size GO:0035565 9.26 HNF1B HNF1A
18 pancreas development GO:0031016 9.13 PDX1 HNF1B HNF1A
19 glucose homeostasis GO:0042593 8.92 PDX1 HNF4A HNF1A GCK

Molecular functions related to Maturity-Onset Diabetes of the Young, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.72 PDX1 HNF4A HNF1B HNF1A HMX1
2 DNA-binding transcription factor activity GO:0003700 9.56 PDX1 HNF4A HNF1B HNF1A
3 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.54 PDX1 HNF4A HNF1A
4 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.35 PDX1 HNF4A HNF1B HNF1A HMX1
5 transcription regulatory region DNA binding GO:0044212 9.33 HNF4A HNF1B HNF1A
6 sequence-specific DNA binding GO:0043565 9.02 PDX1 HNF4A HNF1B HNF1A HMX1

Sources for Maturity-Onset Diabetes of the Young, Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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