Pancreatic Agenesis malady

NIH Rare Diseases: Pancreatic agenesis is a rare condition that occurs when the pancreas fails to develop before birth. The severity depends on how much functional pancreatic tissue is present. Children with this condition usually have permanent neonatal diabetes mellitus due to a lack of insulin. Pancreatic agenesis can also be associated with abnormalities in other parts of the body. Mutations in the GATA6, PDX1, and PTF1A genes have been found to cause pancreatic agenesis.³⁰

MalaCards: Pancreatic Agenesis, also known as pancreatic agenesis, congenital, is related to pancreatitis and neonatal diabetes mellitus. An important gene associated with Pancreatic Agenesis is PDX1 (pancreatic and duodenal homeobox 1), and among its related pathways are Inwardly rectifying K+ channels and Potassium transporters- outward current. The compounds glucose and cibenzoline have been mentioned in the context of this disorder. Affiliated tissues include pancreas, and related mouse phenotypes are liver/biliary system and endocrine/exocrine gland.

OMIM: 260370

pancreatic agenesis 7 30 33 pancreatic agenesis, congenital 30

congenital pancreatic agenesis 30

Diseases related to pancreatic agenesis by text searches and GeneDecks gene sharing:

(show all 49)

id	Related Disease	Score	Top Affiliating Genes
1	pancreatitis	27.6	GATA6, ABCC8, PDX1, INS, KCNJ11, GCK
2	neonatal diabetes mellitus	27.2	ABCC8, PDX1, INS, KCNJ11, GCK
3	diabetes mellitus	27.0	ABCC8, PDX1, INS, KCNJ11, GCK
4	hyperinsulinism, focal	12.9	ABCC8, KCNJ11
5	diabetes, permanent neonatal	12.9	ABCC8, KCNJ11
6	recessive developmental delay, small stature, microcephaly and brain calcifications	12.7	KCNJ11, ABCC8
7	diabetes mellitus, noninsulin-dependent	12.7	GCK, ABCC8
8	glucagonoma	12.6	INS, PDX1
9	gastrinoma	12.5	PDX1, INS
10	hyperinsulinemic hypoglycemia	12.5	INS, ABCC8
11	ketoacidosis due to scot deficiency	12.5	INS, ABCC8
12	3-hydroxyacyl-coa dehydrogenase deficiency	12.4	GCK, INS
13	leucine-sensitive hypoglycemia of infancy	12.3	GCK, KCNJ11, ABCC8
14	persistent hyperinsulinemic hypoglycemia of infancy	12.3	GCK, KCNJ11, ABCC8
15	hyperammonemia with hypoornithinemia	12.3	ABCC8, KCNJ11, GCK
16	transient neonatal diabetes mellitus	12.1	ABCC8, INS, KCNJ11
17	hyperuricemia	12.1	INS, GCK
18	acute insulin response	12.1	KCNJ11, INS, ABCC8
19	diabetes, type 2	12.1	KCNJ11, INS, ABCC8
20	beckwith-wiedemann syndrome	12.1	KCNJ11, INS, ABCC8
21	myostatin-related muscle hypertrophy	12.0	GATA6, INS
22	type 1 diabetes mellitus	12.0	PDX1, INS, GCK
23	polycystic ovary syndrome	12.0	GATA6, INS, KCNJ11
24	permanent neonatal diabetes mellitus	12.0	ABCC8, INS, GCK
25	duodenitis	11.9	GCK, INS, PDX1
26	arterial calcification	11.9	KCNJ11, INS
27	bilirubin metabolic disorder	11.8	ABCC8, INS, GCK
28	essential hypertension	11.8	GCK, KCNJ11, INS
29	pituitary adenoma	11.8	ABCC8, INS, GCK
30	twinning	11.7	ABCC8, INS, GCK
31	maturity-onset diabetes of the young	11.6	PDX1, INS, KCNJ11, GCK
32	gestational diabetes	11.5	ABCC8, INS, KCNJ11, GCK
33	glucose intolerance	11.5	GCK, KCNJ11, INS, ABCC8
34	hyperinsulinism	11.5	ABCC8, INS, KCNJ11, GCK
35	primary hyperoxaluria	11.4	ABCC8, PDX1, INS, GCK
36	ischemia	11.4	GCK, KCNJ11, INS, ABCC8
37	fibrosis	11.4	GATA6, ABCC8, INS, KCNJ11
38	adenoma	11.2	GCK, INS, ABCC8, GATA6
39	pancreatic cancer	11.2	GCK, INS, PDX1, GATA6
40	hypoglycemia of infancy	11.1	ABCC8, PDX1, INS, KCNJ11, GCK
41	cerebritis	11.1	GCK, INS, PDX1, ABCC8
42	hypoglycemia	11.1	ABCC8, PDX1, INS, KCNJ11, GCK
43	insulinoma	11.1	ABCC8, PDX1, INS, KCNJ11, GCK
44	hyperglycemia	11.1	ABCC8, PDX1, INS, KCNJ11, GCK
45	type 2 diabetes mellitus	11.1	ABCC8, PDX1, INS, KCNJ11, GCK
46	insulin resistance	11.0	GCK, KCNJ11, INS, PDX1, ABCC8
47	obesity	11.0	ABCC8, PDX1, INS, KCNJ11, GCK
48	cholesterol	11.0	GCK, INS, ABCC8, GATA6
49	pancreatic agenesis and congenital heart defects	7.0

Clinical features from OMIM: 260370

Approved drugs:

Drug clinical trials:

MalaCards organs/tissues related to pancreatic agenesis:

²²

MGI Mouse Phenotypes related to pancreatic agenesis:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	liver/biliary system phenotype	MP:0005370	7.8	GCK, INS, PDX1, GATA6
2	endocrine/exocrine gland phenotype	MP:0005379	7.6	INS, KCNJ11, GCK, PDX1, ABCC8
3	growth/size phenotype	MP:0005378	7.6	GATA6, PDX1, INS, KCNJ11, GCK
4	homeostasis/metabolism phenotype	MP:0005376	7.0	ABCC8, PDX1, INS, KCNJ11, GCK, GATA6

Articles related to pancreatic agenesis:

id	Title	Authors	Year	Affiliating Genes
1	GATA6 haploinsufficiency causes pancreatic agenesis in humans. (22158542)	Allen H.L.... Ellard S.	2012	GATA6
2	Neonatal diabetes mellitus with pancreatic agenesis i n an infant with homozygous IPF-1 Pro63fsX60 mutation. (19496967)	Thomas I.H.... Fajans S.S.	2009	GCK, ABCC8, KCNJ11
3	Neonatal diabetes mellitus because of pancreatic agenesis with dysmorphic features and recurrent bacterial infections. (18547237)	Taha D.... Polak M.	2008	ABCC8, KCNJ11
4	Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. (8988180)	Stoffers D.A.... Habener J.F.	1997	PDX1

Genes related to pancreatic agenesis according to GeneCards:

id	Symbol	Description	Score	GeneCards Section Context
1	PDX1	pancreatic and duodenal homeobox 1	11.1	Summaries, Publications
2	KCNJ11	potassium inwardly-rectifying channel, subfamily J, member 11	11.0	Publications
3	ABCC8	ATP-binding cassette, sub-family C (CFTR/MRP), member 8	11.0	Publications
4	GCK	glucokinase (hexokinase 4)	11.0	Publications
5	INS	insulin	11.0	Publications
6	GATA6	GATA binding protein 6	9.8	Publications

Pathways related to pancreatic agenesis according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Inwardly rectifying K+ channels38	9.6	KCNJ11, ABCC8
2	Potassium transporters- outward current10	9.5	KCNJ11, ABCC8
3	Antiarrhythmic Pathway, Pharmacodynamics34	9.5	KCNJ11, ABCC8
4	Development_Leptin signaling via PI3K-dependent pathway41	9.4	KCNJ11, ABCC8
5	Selected targets of HNF110	9.4	PDX1, INS
6	Development Leptin signaling via PI3K-dependent pathway10	9.2	ABCC8, KCNJ11
7	MODY (Maturity-Onset Diabetes of Young)36	9.1	GCK, INS
8	Maturity onset diabetes of the young20	8.8	INS, PDX1, GCK
9	Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics34	7.9	PDX1, GCK, KCNJ11, INS, ABCC8
10	Type II diabetes mellitus20	7.8	PDX1, INS, KCNJ11, GCK, ABCC8

Compounds related to pancreatic agenesis according to GeneDecks:

(show all 37)

id	Compound	Score	Top Affiliating Genes
1	glucose32	9.9	PDX1, KCNJ11
2	cibenzoline32	9.9	ABCC8, KCNJ11
3	mgadp32	9.8	ABCC8, KCNJ11
4	Glyburide9 9	10.7	KCNJ11, ABCC8
5	proglucagon32	9.7	PDX1, GCK
6	meglitinide32	9.5	ABCC8, INS
7	mitiglinide32 9 9	11.5	INS, ABCC8
8	glipizide32 9 9	11.4	INS, ABCC8
9	chlorpropamide32 9 9	11.4	INS, ABCC8
10	chromium picolinate32	9.4	GCK, INS
11	nicotinamide32 9 9	11.3	INS, PDX1
12	dehydroepiandrosterone sulfate32	9.2	GATA6, INS
13	aicar32 42 9 18 9	13.2	INS, GCK
14	pip232	9.2	ABCC8, KCNJ11
15	repaglinide32 42 9 9	12.1	INS, KCNJ11, ABCC8
16	glimepiride32 34 9 9	12.1	ABCC8, INS, KCNJ11
17	gliclazide32 34 9 9	12.0	ABCC8, INS, KCNJ11
18	nateglinide32 42 9 9	12.0	ABCC8, KCNJ11, INS
19	glibenclamide32 34	10.0	KCNJ11, INS, ABCC8
20	potassium32 9 18 9	12.0	ABCC8, KCNJ11, GCK
21	preproinsulin32	9.0	PDX1, INS, GCK
22	i-app32	9.0	INS, PDX1, GCK
23	incretin32	9.0	PDX1, INS, GCK
24	streptozotocin32	9.0	INS, GCK, PDX1
25	2-deoxyglucose32	8.9	GCK, INS
26	leucine32	8.9	GCK, ABCC8, KCNJ11
27	glycogen32 18	9.7	GCK, INS, ABCC8
28	c-peptide32	8.6	GCK, PDX1, INS, KCNJ11
29	fatty acid32	8.5	INS, GCK, ABCC8
30	diazoxide32 42 9 9	11.5	GCK, KCNJ11, INS, ABCC8
31	tolbutamide32 34 9 9	11.5	GCK, KCNJ11, INS, ABCC8
32	metformin32 34 9 9	11.5	INS, GCK, KCNJ11, ABCC8
33	arginine32	8.3	INS, KCNJ11, GCK, ABCC8
34	glutamate32	8.3	INS, KCNJ11, GCK, ABCC8
35	cholesterol32 9 18 9	11.3	GCK, GATA6, ABCC8, INS
36	sulfonylurea32	8.1	GCK, KCNJ11, INS, PDX1, ABCC8
37	katp32	8.1	ABCC8, PDX1, INS, KCNJ11, GCK

Cellular components related to pancreatic agenesis according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	voltage-gated potassium channel complex	GO:008076	9.2	KCNJ11, ABCC8
2	secretory granule	GO:030141	9.0	GCK, INS

Biological processes related to pancreatic agenesis according to GeneDecks:

(show all 14)

id	Name	GO ID	Score	Top Affiliating Genes
1	type B pancreatic cell differentiation	GO:003309	10.2	GATA6
2	detection of glucose	GO:051594	9.7	GCK, PDX1
3	potassium ion transmembrane transport	GO:071805	9.7	KCNJ11, ABCC8
4	liver development	GO:001889	9.5	GATA6, PDX1
5	negative regulation of gluconeogenesis	GO:045721	9.2	GCK, INS
6	positive regulation of glycolysis	GO:045821	9.1	INS, GCK
7	positive regulation of glycogen biosynthetic process	GO:045725	9.0	INS, GCK
8	glucose transport	GO:015758	8.9	GCK, INS
9	glucose metabolic process	GO:006006	8.9	PDX1, INS, KCNJ11
10	endocrine pancreas development	GO:031018	8.9	GCK, PDX1, INS
11	glucose homeostasis	GO:042593	8.8	PDX1, INS, GCK
12	energy reserve metabolic process	GO:006112	8.8	KCNJ11, INS, ABCC8
13	regulation of insulin secretion	GO:050796	8.3	KCNJ11, GCK, INS, ABCC8
14	small molecule metabolic process	GO:044281	7.8	ABCC8, INS, KCNJ11, GCK

Molecular functions related to pancreatic agenesis according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	ion channel binding	GO:044325	9.5	KCNJ11, ABCC8