MCID: DBT047
MIFTS: 37

Diabetes Mellitus, Noninsulin-Dependent, Association with malady

Genetic diseases (common) category

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MalaCards based summary: Diabetes Mellitus, Noninsulin-Dependent, Association with is related to familial hyperinsulinism and hyperinsulinemic hypoglycemia. An important gene associated with Diabetes Mellitus, Noninsulin-Dependent, Association with is WFS1 (Wolfram syndrome 1 (wolframin)), and among its related pathways are Prolactin signaling pathway and Integration of energy metabolism. The compounds [3h]2-deoxyglucose and 3-o-methylglucose have been mentioned in the context of this disorder. Related mouse phenotypes are renal/urinary system and cellular.

Description from OMIM:46 125853

Aliases & Classifications for Diabetes Mellitus, Noninsulin-Dependent, Association with

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Diabetes Mellitus, Noninsulin-Dependent, Association with, Aliases & Descriptions:

Name: Diabetes Mellitus, Noninsulin-Dependent, Association with 46


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases (common)


Related Diseases for Diabetes Mellitus, Noninsulin-Dependent, Association with

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Diseases related to Diabetes Mellitus, Noninsulin-Dependent, Association with via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 35)
idRelated DiseaseScoreTop Affiliating Genes
1familial hyperinsulinism10.4ABCC8
2hyperinsulinemic hypoglycemia10.4ABCC8
3neonatal diabetes mellitus10.4HNF1B, SLC2A2, ABCC8
4hyperinsulinism10.3ABCC8, INSR, IRS1
5diabetes mellitus, noninsulin-dependent10.3HMGA1, SLC30A8
6maturity-onset diabetes of the young10.3NEUROD1, PAX4, HNF4A, HNF1B
7polycystic ovary syndrome10.3INSR, CAPN10, IRS1
8hypertriglyceridemia10.3INSR, IRS1, SLC2A4
9cystic kidney10.2ENPP1, HNF1B
10ovarian cancer10.1HNF1B, AKT2, HNF4A, SLC2A4, INSR
11kidney cancer10.1SLC2A4, INSR, HNF4A, HNF1B
12hypercholesterolemia10.1INSR, HMGA1, CAPN10
13metabolic syndrome x10.1INSR, SLC2A2, HNF4A, ABCC8, CAPN10
14hypoglycemia10.1INSR, SLC2A4, SLC2A2, HNF4A, GCGR, ABCC8
15sepsis10.1IL6, INSR, IRS1, SLC2A4
16pancreatic cancer10.1AKT2, HNF4A, HMGA1, SLC2A4, IRS1
17type 1 diabetes mellitus10.1NEUROD1, WFS1, HNF4A, ENPP1, PAX4, INSR
18ischemia10.1INSR, ABCC8, MAPK8IP1, SLC2A4
19coronary artery anomaly10.0IRS1, IL6, HMGA1
20liver cirrhosis10.0SLC2A4, IRS1, INSR
21tongue squamous cell carcinoma10.0INSR, SLC2A4, IRS1, AKT2, HNF4A
22insulinoma10.0PAX4, SLC2A2, INSR, ABCC8, GPD2, WFS1
23glucose intolerance10.0SLC2A4, ENPP1, INSR, PAX4, CAPN10
24atherosclerosis9.9HNF4A, CAPN10, IL6, IRS1, ENPP1
25adenocarcinoma9.9AKT2, NEUROD1, INSR, HNF1B, HNF4A, SLC2A4
26type 2 diabetes mellitus9.9SLC2A4, PPP1R3A, IRS1, AKT2, MAPK8IP1, INSR
27primary hyperoxaluria9.9HNF1B, CAPN10, ENPP1, INSR, IL6, HNF4A
28liver cancer9.9SLC2A2, IRS1, HNF1B, HNF4A, HMGA1, IL6
29gestational diabetes9.9IRS1, INSR, ABCC8, CAPN10, HNF4A, ENPP1
30prostate cancer9.8HNF4A, HMGA1, HNF1B, MAPK8IP1, IL6, AKT2
31breast cancer9.8HNF4A, SLC2A2, ENPP1, HMGA1, AKT2, IRS1
32hyperglycemia9.6IRS1, HNF1B, HNF4A, GCGR, ENPP1, SLC2A4
33obesity9.5IRS1, IL6, INSR, SLC2A2, ENPP1, GCGR
34insulin resistance9.1AKT2, ABCC8, INSR, PAX4, IL6, CAPN10
35diabetes mellitus9.0WFS1, CAPN10, HNF1B, HNF4A, GCGR, ENPP1

Graphical network of the top 20 diseases related to Diabetes Mellitus, Noninsulin-Dependent, Association with:



Diseases related to diabetes mellitus, noninsulin-dependent, association with

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Clinical features from OMIM:

125853

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Variations for Diabetes Mellitus, Noninsulin-Dependent, Association with

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UniProtKB/Swiss-Prot genetic disease variations for Diabetes Mellitus, Noninsulin-Dependent, Association with:

63 (show all 11)
id Symbol AA change Variation ID SNP ID
1AKT2p.Arg274HisVAR_067310
2HNF1Bp.Ser465ArgVAR_017665
3HNF4Ap.Val402IleVAR_004670rs137853337
4INSRp.Arg1191GlnVAR_004098
5INSRp.Thr858AlaVAR_015917rs182552223
6INSRp.Arg1158GlnVAR_015927
7IRS1p.Ser1043TyrVAR_005302
8IRS1p.Cys1095TyrVAR_005303
9MAPK8IP1p.Ser59AsnVAR_012243
10PPP1R3Ap.Ala931GluVAR_019699rs35449651
11SLC2A4p.Val383IleVAR_007170rs121434581

Clinvar genetic disease variations for Diabetes Mellitus, Noninsulin-Dependent, Association with:

7 (show all 32)
id Gene Name Type Significance SNP ID Assembly Location
1HNF1BNM_000458.2(HNF1B): c.1395C> G (p.Ser465Arg)single nucleotide variantPathogenicrs121918673GRCh37Chr 17, 36061127: 36061127
2ENPP1ENPP1, IVS20AS, 1-BP DEL, T, -11deletionrisk factor
3ENPP1NM_006208.2(ENPP1): c.517A> C (p.Lys173Gln)single nucleotide variantrisk factorrs1044498GRCh37Chr 6, 132172368: 132172368
4PAX4NM_006193.2(PAX4): c.361C> T (p.Arg121Trp)single nucleotide variantPathogenicrs114202595GRCh37Chr 7, 127254587: 127254587
5AKT2NM_001626.5(AKT2): c.821G> A (p.Arg274His)single nucleotide variantPathogenicrs121434593GRCh37Chr 19, 40743886: 40743886
6SLC30A8NM_173851.2(SLC30A8): c.412C> T (p.Arg138Ter)single nucleotide variantprotectivers200185429GRCh37Chr 8, 118165323: 118165323
7SLC30A8NM_173851.2(SLC30A8): c.101_107delAAGATCA (p.Lys34Serfs)deletionprotectiveGRCh37Chr 8, 118159222: 118159228
8LIPCLIPC, -250G-Asingle nucleotide variantrisk factor
9INSRNM_000208.2(INSR): c.3572G> A (p.Arg1191Gln)single nucleotide variantPathogenicrs121913150GRCh37Chr 19, 7120718: 7120718
10INSRNM_000208.2(INSR): c.3034G> A (p.Val1012Met)single nucleotide variantLikely pathogenic, Pathogenicrs1799816GRCh37Chr 19, 7125518: 7125518
11IL6IL6, -174G-Csingle nucleotide variantrisk factor
12GPD2NM_001083112.2(GPD2): c.1904T> C (p.Phe635Ser)single nucleotide variantPathogenicrs121918407GRCh37Chr 2, 157435621: 157435621
13SLC2A2NM_000340.1(SLC2A2): c.589G> A (p.Val197Ile)single nucleotide variantPathogenicrs121909741GRCh37Chr 3, 170724960: 170724960
14GCGRNM_000160.4(GCGR): c.118G> A (p.Gly40Ser)single nucleotide variantPathogenicrs1801483GRCh37Chr 17, 79767715: 79767715
15IGF2BP2NM_006548.4(IGF2BP2): c.239+29254C> Asingle nucleotide variantrisk factorrs4402960GRCh37Chr 3, 185511687: 185511687
16IRS1IRS1, 3-BP DEL, GLY723deletionPathogenic
17IRS1NM_005544.2(IRS1): c.1823C> G (p.Thr608Arg)single nucleotide variantPathogenicrs104893642GRCh37Chr 2, 227661632: 227661632
18HMGA1HMGA1, 1-BP INS, IVS5, -13insertionrisk factor
19RETNRETN, +62G-Asingle nucleotide variantrisk factor
20CAPN10NM_023083.3(CAPN10): c.471-176G> Asingle nucleotide variantrisk factorrs3792267GRCh37Chr 2, 241531174: 241531174
21CAPN10CAPN10, IVS6, INS/DEL, 39-BPindelrisk factor
22CAPN10CAPN10, IVS13, g.16378G-Tsingle nucleotide variantrisk factor
23CAPN10CAPN10, IVS3, g.4841T-Csingle nucleotide variantrisk factor
24MAPK8IP1NM_005456.3(MAPK8IP1): c.176G> A (p.Ser59Asn)single nucleotide variantPathogenicrs119489103GRCh37Chr 11, 45919710: 45919710
25TCF7L2NM_030756.4(TCF7L2): c.382-41435C> Tsingle nucleotide variantrisk factorrs7903146GRCh37Chr 10, 114758349: 114758349
26TCF7L2NM_030756.4(TCF7L2): c.483+9017G> Tsingle nucleotide variantrisk factorrs12255372GRCh37Chr 10, 114808902: 114808902
27TCF7L2NM_030756.4(TCF7L2): c.483+7162G> Csingle nucleotide variantrisk factorrs11196205GRCh37Chr 10, 114807047: 114807047
28NEUROD1NM_002500.4(NEUROD1): c.332G> T (p.Arg111Leu)single nucleotide variantPathogenicrs104893649GRCh37Chr 2, 182543256: 182543256
29KCNJ11NM_000525.3(KCNJ11): c.67A> G (p.Lys23Glu)single nucleotide variantdrug response, risk factorrs5219GRCh37Chr 11, 17409572: 17409572
30ABCC8NM_001287174.1(ABCC8): c.4138C> T (p.Arg1380Cys)single nucleotide variantPathogenicrs137852673GRCh37Chr 11, 17417462: 17417462
31ABCC8NM_001287174.1(ABCC8): c.1744C> G (p.Leu582Val)single nucleotide variantPathogenicrs137852674GRCh37Chr 11, 17452434: 17452434
32HNF4ANM_000457.4(HNF4A): c.1204G> A (p.Val402Ile)single nucleotide variantPathogenicrs137853337GRCh37Chr 20, 43057049: 43057049

Expression for genes affiliated with Diabetes Mellitus, Noninsulin-Dependent, Association with

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Expression patterns in normal tissues for genes affiliated with Diabetes Mellitus, Noninsulin-Dependent, Association with

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Pathways for genes affiliated with Diabetes Mellitus, Noninsulin-Dependent, Association with

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Pathways related to Diabetes Mellitus, Noninsulin-Dependent, Association with according to GeneCards/GeneDecks:

(show all 37)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
Prolactin Signaling Pathway37
Development Prolactin receptor signaling59
Leptin signaling pathway37
9.9SLC2A2, AKT2, IRS1
2
Show member pathways
9.9SLC2A2, GCGR, ABCC8
39.9ABCC8, HNF4A, SLC2A2
49.9SLC2A2, SLC2A4, HNF4A
5
Show member pathways
9.8INSR, IRS1, AKT2
6
Show member pathways
DNA damage response (only ATM dependent)37
Wnt Signaling Pathway and Pluripotency37
9.8AKT2, IRS1, INSR
7
Show member pathways
Insulin Pathway37
9.8AKT2, IRS1, INSR
89.8SLC2A4, AKT2, IRS1
9
Show member pathways
9.8AKT2, INSR, PPP1R3A
10
Show member pathways
9.7SLC2A2, HNF4A, NEUROD1, INSR
11
Show member pathways
9.7SLC2A2, SLC2A4, HMGA1
12
Show member pathways
9.7INSR, AKT2, CAPN10
13
Show member pathways
Translation Non genomic rapid action of Androgen Receptor59
9.7IL6, AKT2, IRS1
149.6INSR, AKT2, IL6
159.6INSR, AKT2, HNF4A, SLC2A4
16
Show member pathways
9.6INSR, IRS1, AKT2, SLC2A4
179.5ABCC8, IRS1, AKT2, SLC2A4
189.5SLC2A4, AKT2, INSR, PPP1R3A
19
Show member pathways
9.5PPP1R3A, INSR, IRS1, SLC2A4
20
Show member pathways
9.4IL6, AKT2, IRS1, INSR
219.4INSR, IRS1, AKT2, IL6
22
Show member pathways
9.4PPP1R3A, INSR, IRS1, IL6
23
Show member pathways
9.3PAX4, NEUROD1, AKT2, HNF1B, HNF4A, SLC2A2
24
Show member pathways
Transcription Receptor mediated HIF regulation59
Development CNTF receptor signaling59
Class IB PI3K non-lipid kinase events37
ErbB2/ErbB3 signaling events37
Development Growth hormone signaling via PI3K AKT and MAPK cascades59
Translation Regulation activity of EIF259
Regulation of lipid metabolism Insulin signaling generic cascades59
Transcription PPAR Pathway59
Cell adhesion PLAU signaling59
Translation Regulation activity of EIF4F59
9.3PPP1R3A, INSR, IRS1, AKT2, SLC2A4
25
Show member pathways
9.3SLC2A2, SLC2A4, HNF4A, IL6, AKT2
269.2IRS1, IL6, HMGA1, SLC2A4
27
Show member pathways
9.2PPP1R3A, INSR, AKT2, IL6, GCGR
28
Show member pathways
9.2INSR, IRS1, AKT2, IL6, SLC2A4
29
Show member pathways
PLK2 and PLK4 events37
Polo-like kinase signaling events in the cell cycle37
9.2INSR, IRS1, AKT2, IL6, SLC2A4
30
Show member pathways
IL-9 Signaling Pathway37
Development Thrombopoietin regulated cell processes59
IL-7 Signaling Pathway37
Immune response IL 9 signaling pathway59
9.2SLC2A4, IL6, AKT2, IRS1, INSR
31
Show member pathways
9.1INSR, IRS1, AKT2, IL6, MAPK8IP1, HNF4A
32
Show member pathways
9.1PAX4, NEUROD1, AKT2, HNF1B, HNF4A, SLC2A4
339.0PPP1R3A, INSR, IRS1, AKT2, ENPP1, SLC2A4
34
Show member pathways
9.0INSR, IRS1, AKT2, IL6, MAPK8IP1, SLC2A4
35
Show member pathways
8.8SLC2A2, ABCC8, INSR, NEUROD1, IRS1, HNF1B
368.7INSR, NEUROD1, IRS1, AKT2, WFS1, HNF4A
37
Show member pathways
8.4PPP1R3A, INSR, IRS1, AKT2, IL6, MAPK8IP1

Compounds for genes affiliated with Diabetes Mellitus, Noninsulin-Dependent, Association with

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Compounds related to Diabetes Mellitus, Noninsulin-Dependent, Association with according to GeneCards/GeneDecks:

(show top 50)    (show all 71)
idCompoundScoreTop Affiliating Genes
1[3h]2-deoxyglucose2910.3SLC2A4, SLC2A2
23-o-methylglucose4410.2SLC2A4, SLC2A2, INSR
3vanadium4410.2IRS1, INSR, SLC2A4
4c-peptide4410.1IRS1, HNF4A, INSR, SLC2A2
5fructose44 1211.1SLC2A2, SLC2A4, GCGR
6gliclazide44 50 1212.1SLC2A4, INSR, ABCC8
7glimepiride44 50 1212.1INSR, ABCC8, SLC2A4
8phosphoenolpyruvate44 1211.1SLC2A4, HNF4A, IRS1, SLC2A2
9phenylarsine oxide4410.0SLC2A4, IRS1, INSR
10streptozotocin4410.0IRS1, INSR, SLC2A2, SLC2A4
11sulfonylurea4410.0SLC2A2, IRS1, ABCC8, SLC2A4
12grp-14410.0INSR, SLC2A4
13glucosamine44 25 1212.0SLC2A4, IRS1, INSR
14palmitate449.9HNF4A, INSR, IRS1, SLC2A4
15repaglinide50 44 1211.9NEUROD1, SLC30A8, ABCC8, PAX4
16ibmx44 60 2911.9SLC2A2, SLC2A4, IRS1, INSR
17glibenclamide44 29 50 6012.9INSR, SLC2A4, ABCC8
18pyruvate449.9GPD2, SLC2A2, SLC2A4, HNF4A
19glycerol44 25 1211.9SLC2A4, IRS1, HNF4A, INSR
202-deoxyglucose44 1210.8SLC2A4, PPP1R3A, INSR, IRS1, SLC2A2
21vanadyl sulfate449.7IRS1, INSR
22pioglitazone29 44 50 1212.7SLC2A4, IL6, IRS1, INSR
23anisomycin44 1210.7IRS1, SLC2A4, IL6, INSR
24sterol449.7SLC2A2, HNF4A, IRS1, SLC2A4, HMGA1
25rosiglitazone29 44 50 25 1213.7SLC2A4, INSR, IL6, IRS1
26troglitazone44 29 60 1212.7INSR, IL6, SLC2A4, IRS1
27metformin44 50 1211.6INSR, IRS1, ENPP1, ABCC8, SLC2A4
28phosphotyrosine449.6SLC2A4, INSR, IRS1, MAPK8IP1
29sb 20358044 6010.5SLC2A4, AKT2, INSR, IRS1, IL6
30pd 98,059449.5IL6, SLC2A4, HNF4A, INSR, IRS1
31epinephrine44 25 1211.5PPP1R3A, INSR, IL6, GCGR
32phosphatidylinositol449.4HNF4A, ENPP1, SLC2A4, INSR, IRS1, AKT2
33atp44 2910.3MAPK8IP1, HNF4A, GCGR, ENPP1, SLC2A2, ABCC8
34rapamycin449.3INSR, HMGA1, IRS1, AKT2, ENPP1, SLC2A4
35testosterone44 60 25 1212.3INSR, ABCC8, IL6, SLC2A4, HNF4A, IRS1
36h2o2449.3IRS1, GPD2, SLC2A2, SLC2A4, INSR
37ly294002449.2IRS1, INSR, SLC2A4, HMGA1, IL6, AKT2
38fatty acid449.2GCGR, IRS1, HNF4A, HMGA1, ENPP1, SLC2A4
39dexamethasone44 50 29 1212.2INSR, IRS1, IL6, ENPP1, HNF4A, SLC2A4
40cholesterol44 29 25 1212.1HNF1B, HNF4A, HMGA1, ABCC8, CAPN10, IL6
41estrogen449.1IL6, HNF4A, IRS1, INSR, AKT2, HMGA1
42retinoic acid44 2510.0HNF4A, HMGA1, HNF1B, IL6, IRS1, SLC2A4
43arginine449.0HMGA1, HNF1B, SLC2A2, HNF4A, CAPN10, IRS1
44threonine449.0AKT2, MAPK8IP1, SLC2A4, HNF4A, ENPP1, HMGA1
45serine448.7HNF4A, INSR, ABCC8, IRS1, AKT2, MAPK8IP1
46tyrosine448.5INSR, HNF4A, SLC2A4, ENPP1, HMGA1, IL6
47calcium44 50 25 1211.4HNF4A, MAPK8IP1, GCGR, HMGA1, CAPN10, GPD2
48glycogen44 259.3SLC2A2, SLC2A4, ENPP1, PPP1R3A, ABCC8, INSR
49lipid447.9PPP1R3A, AKT2, ABCC8, INSR, IRS1, CAPN10
50glucose446.5PAX4, NEUROD1, IRS1, AKT2, IL6, MAPK8IP1

GO Terms for genes affiliated with Diabetes Mellitus, Noninsulin-Dependent, Association with

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Cellular components related to Diabetes Mellitus, Noninsulin-Dependent, Association with according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1insulin receptor complexGO:0058999.7IRS1, INSR
2plasma membraneGO:0058868.0INSR, IRS1, AKT2, CAPN10, GCGR, ENPP1

Biological processes related to Diabetes Mellitus, Noninsulin-Dependent, Association with according to GeneCards/GeneDecks:

(show all 23)
idNameGO IDScoreTop Affiliating Genes
1negative regulation of type B pancreatic cell apoptotic processGO:200067510.4NEUROD1, WFS1
2regulation of cell cycle arrestGO:07115610.3AKT2, NEUROD1
3positive regulation of glucose import in response to insulin stimulusGO:200127510.3AKT2, IRS1
4positive regulation of glucose metabolic processGO:01090710.3IRS1, AKT2
5positive regulation of fatty acid beta-oxidationGO:03200010.3IRS1, AKT2
6positive regulation of glycogen biosynthetic processGO:04572510.2INSR, AKT2, IRS1
7insulin secretionGO:03007310.1SLC30A8, HNF1B, NEUROD1
8energy reserve metabolic processGO:00611210.1SLC2A2, ABCC8, GCGR
9positive regulation of cell differentiationGO:04559710.0NEUROD1, PAX4
10positive regulation of type B pancreatic cell apoptotic processGO:200067610.0CAPN10, IL6
11signal transduction involved in regulation of gene expressionGO:02301910.0NEUROD1, HNF4A
12regulation of insulin secretionGO:05079610.0HNF4A, SLC2A2, NEUROD1, ABCC8
13response to glucoseGO:0097499.9SLC30A8, HNF4A, HNF1B, NEUROD1
14bone remodelingGO:0468499.9ENPP1, IL6
15insulin receptor signaling pathwayGO:0082869.9AKT2, IRS1, INSR
16positive regulation of glucose importGO:0463269.8IRS1, AKT2, CAPN10, INSR
17carbohydrate metabolic processGO:0059759.7INSR, SLC2A2, SLC2A4, ABCC8
18negative regulation of insulin receptor signaling pathwayGO:0466279.7IRS1, ENPP1
19endocrine pancreas developmentGO:0310189.5NEUROD1, SLC2A2, HNF4A, HNF1B, IL6, PAX4
20positive regulation of transcription, DNA-templatedGO:0458939.4HNF1B, HMGA1, HNF4A, IL6, NEUROD1
21cellular response to insulin stimulusGO:0328699.2CAPN10, AKT2, IRS1, SLC2A4, ENPP1, INSR
22small molecule metabolic processGO:0442819.1SLC2A2, SLC2A4, ENPP1, GCGR, GPD2, ABCC8
23glucose homeostasisGO:0425939.1IRS1, NEUROD1, INSR, GCGR, HNF4A, SLC2A4

Molecular functions related to Diabetes Mellitus, Noninsulin-Dependent, Association with according to GeneCards/GeneDecks:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1D-glucose transmembrane transporter activityGO:05505610.2SLC2A2, SLC2A4
2insulin-like growth factor receptor bindingGO:00515910.1INSR, IRS1
3phosphatidylinositol 3-kinase bindingGO:04354810.0IRS1, INSR
4insulin receptor bindingGO:00515810.0ENPP1, IRS1
5sequence-specific DNA bindingGO:0435659.4HNF4A, HNF1B, NEUROD1, PAX4
6sequence-specific DNA binding transcription factor activityGO:0037009.2PAX4, NEUROD1, HNF1B, HNF4A, HMGA1
7protein bindingGO:0055157.9INSR, NEUROD1, IRS1, AKT2, IL6, MAPK8IP1

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4CDC
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23GTR
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29IUPHAR
30KEGG
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