Aliases & Classifications for Hyperproinsulinemia

MalaCards integrated aliases for Hyperproinsulinemia:

Name: Hyperproinsulinemia 57 75 29 6 40 73
Hpri 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
hyperproinsulinemia:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 616214
MedGen 42 C0342283
MeSH 44 D003920
UMLS 73 C0342283

Summaries for Hyperproinsulinemia

OMIM : 57 Insulin (INS; 176730) is produced posttranslationally from its precursor molecule, proinsulin, by site-directed proteolysis in beta-cell granules. Conversion involves cleavage at pairs of basic residues that link both the insulin A and B chains to C-peptide. Human proinsulin conversion has a preferred sequential route, such that cleavage at the B-chain/C-peptide junction occurs first, producing des-31,32 split proinsulin as the major conversion intermediate. Under normal circumstances, proinsulin conversion is largely completed before secretion, and low plasma levels of intact proinsulin and conversion intermediates are found. Structural abnormalities in the proinsulin molecule can impair conversion, leading to the accumulation of proinsulin-like material in the circulation. Such defects show an autosomal dominant mode of inheritance and are the main cause of familial hyperproinsulinemia (summary by Warren-Perry et al., 1997). (616214)

MalaCards based summary : Hyperproinsulinemia, also known as hpri, is related to insulinoma and gestational diabetes. An important gene associated with Hyperproinsulinemia is INS (Insulin), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Peptide hormone metabolism. The drugs Vildagliptin and Dipeptidyl-Peptidase IV Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include heart, and related phenotypes are hyperinsulinemia and hyperglycemia

UniProtKB/Swiss-Prot : 75 Hyperproinsulinemia: An autosomal dominant condition characterized by elevated levels of serum proinsulin-like material.

Wikipedia : 76 Hyperproinsulinemia is a disease where insulin is not sufficiently processed before secretion and... more...

Related Diseases for Hyperproinsulinemia

Diseases related to Hyperproinsulinemia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 44)
# Related Disease Score Top Affiliating Genes
1 insulinoma 29.6 INS SCT
2 gestational diabetes 28.9 INS SHBG
3 glucose intolerance 28.8 IGFBP1 INS SHBG
4 diabetes mellitus 27.4 CPE IGFBP1 INS INS-IGF2 SHBG
5 maturity-onset diabetes of the young, type 10 10.6 INS INS-IGF2
6 diabetes mellitus, insulin-dependent, 2 10.5 INS INS-IGF2
7 type 1 diabetes mellitus 2 10.5 INS INS-IGF2
8 segawa syndrome, autosomal recessive 10.5 INS INS-IGF2
9 diabetes mellitus, permanent neonatal 10.3 INS INS-IGF2
10 type 1 diabetes mellitus 7 10.3 IGFBP1 INS
11 hyperinsulinemic hypoglycemia, familial, 2 10.2 INS SCT
12 dumping syndrome 10.2 INS SCT
13 gastrinoma 10.2 INS SCT
14 diabetes mellitus, noninsulin-dependent 10.2
15 pancreas disease 10.1 INS SCT
16 duodenal ulcer 10.1 INS SCT
17 acromegaly 10.0 IGFBP1 INS
18 fetal erythroblastosis 9.9 INS SHBG
19 sex differentiation disease 9.9 INS SHBG
20 gonadal disease 9.9 INS SHBG
21 acanthosis nigricans 9.9 INS SHBG
22 female reproductive system disease 9.9 INS SHBG
23 reproductive system disease 9.8 INS SHBG
24 hypoadrenalism 9.8 PCSK1 SHBG
25 aging 9.8
26 thalassemia 9.8
27 hyperglycemia 9.8
28 pancreatitis 9.8
29 hypoglycemia 9.8
30 type i 9.8
31 prader-willi syndrome 9.8 IGFBP1 INS PCSK1
32 overnutrition 9.8 INS SHBG
33 acquired metabolic disease 9.7 INS SHBG
34 hyperthyroidism 9.6 INS SHBG
35 turner syndrome 9.6 IGFBP1 SHBG
36 diabetes mellitus, insulin-dependent 9.5 CPE IGFBP1 INS INS-IGF2
37 multiple endocrine neoplasia, type i 9.4 INS SCT
38 anovulation 9.4 IGFBP1 INS SHBG
39 hyperandrogenism 9.4 IGFBP1 INS SHBG
40 ovarian disease 9.4 IGFBP1 INS SHBG
41 insulin-like growth factor i 9.4 IGFBP1 INS SHBG
42 hyperinsulinism 9.4 IGFBP1 INS SHBG
43 polycystic ovary syndrome 9.4 IGFBP1 INS SHBG
44 body mass index quantitative trait locus 11 8.4 CPE IGFBP1 INS PCSK1 SHBG

Graphical network of the top 20 diseases related to Hyperproinsulinemia:



Diseases related to Hyperproinsulinemia

Symptoms & Phenotypes for Hyperproinsulinemia

Symptoms via clinical synopsis from OMIM:

57
Endocrine Features:
hyperproinsulinemia (asymptomatic in some patients)
hyperinsulinemia (in some patients)
hyperglycemia (in some patients)
normal response to exogenously administered insulin


Clinical features from OMIM:

616214

Human phenotypes related to Hyperproinsulinemia:

32
# Description HPO Frequency HPO Source Accession
1 hyperinsulinemia 32 occasional (7.5%) HP:0000842
2 hyperglycemia 32 occasional (7.5%) HP:0003074

Drugs & Therapeutics for Hyperproinsulinemia

Drugs for Hyperproinsulinemia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Vildagliptin Approved, Investigational Phase 4 274901-16-5 6918537
2 Dipeptidyl-Peptidase IV Inhibitors Phase 4
3 HIV Protease Inhibitors Phase 4
4 Hormone Antagonists Phase 4
5 Hormones Phase 4
6 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4
7 Hypoglycemic Agents Phase 4
8 Incretins Phase 4
9 insulin Phase 4
10 Insulin, Globin Zinc Phase 4
11
protease inhibitors Phase 4
12 Sitagliptin Phosphate Phase 4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Vildagliptin vs Sitagliptin add-on to Insulin - Impact on Glycemic Profile and Correlation of Hypoglycemic Episodes and Heart Function Completed NCT01686932 Phase 4 Vildagliptin;Sitagliptin

Search NIH Clinical Center for Hyperproinsulinemia

Genetic Tests for Hyperproinsulinemia

Genetic tests related to Hyperproinsulinemia:

# Genetic test Affiliating Genes
1 Hyperproinsulinemia 29 INS

Anatomical Context for Hyperproinsulinemia

MalaCards organs/tissues related to Hyperproinsulinemia:

41
Heart

Publications for Hyperproinsulinemia

Articles related to Hyperproinsulinemia:

(show all 31)
# Title Authors Year
1
Disproportionate hyperproinsulinemia, beta-cell restricted prohormone convertase 2 deficiency, and cell cycle inhibitors expression by human islets transplanted into athymic nude mice: insights into nonimmune-mediated mechanisms of delayed islet graft failure. ( 19364070 )
2008
2
Disproportionate Hyperproinsulinemia, I^-Cell Restricted Prohormone Convertase 2 Deficiency, and Cell Cycle Inhibitors Expression by Human Islets Transplanted into Athymic Nude Mice: Insights into Nonimmune-Mediated Mechanisms of Delayed Islet Graft Failure. ( 28876095 )
2008
3
Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes. ( 16271990 )
2005
4
The impact of insulin resistance on proinsulin secretion in pregnancy: hyperproinsulinemia is not a feature of gestational diabetes. ( 16249544 )
2005
5
Transient hyperproinsulinemia during treatment with clozapine and amisulpride. ( 15291669 )
2004
6
Sagittal abdominal diameter is a strong anthropometric marker of insulin resistance and hyperproinsulinemia in obese men. ( 15277437 )
2004
7
Disruption of a receptor-mediated mechanism for intracellular sorting of proinsulin in familial hyperproinsulinemia. ( 12829804 )
2003
8
[Insulinoma with hyperproinsulinemia: a two cases report]. ( 12193882 )
2002
9
Hyperproinsulinemia and proinsulin-to-insulin ratios in Swedish middle-aged men: association with glycemia and insulin resistance but not with family history of diabetes. ( 11978587 )
2002
10
Association between hyperproinsulinemia and anti-GAD65 antibodies in a patient with new onset type I diabetes. ( 10834528 )
2000
11
Hyperproinsulinemia is not a characteristic feature in the offspring of patients with different phenotypes of type II diabetes. ( 10913945 )
2000
12
Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance. ( 10372712 )
1999
13
Insulinoma with hyperproinsulinemia during hypoglycemia and loss of expression of vacuolar-type H(+)-ATPase (V-ATPase) in the tumor tissue. ( 10211416 )
1999
14
Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic beta-cell demand in men. ( 9951550 )
1998
15
Glucose intolerance in patients with thalassemia major: insulin resistance and hyperproinsulinemia. ( 10091170 )
1998
16
Acarbose controls postprandial hyperproinsulinemia in non-insulin dependent diabetes mellitus. ( 9237780 )
1997
17
A novel point mutation in the insulin gene giving rise to hyperproinsulinemia. ( 9141561 )
1997
18
Relative hyperproinsulinemia of NIDDM persists despite the reduction of hyperglycemia with insulin or sulfonylurea therapy. ( 9313749 )
1997
19
Hyperproinsulinemia in a three-generation Caucasian family due to mutant proinsulin (Arg65-His) not associated with imparied glucose tolerance: the contribution of mutant proinsulin to insulin bioactivity. ( 8636380 )
1996
20
Hyperproinsulinemia is associated with increased beta cell demand after hemipancreatectomy in humans. ( 8567967 )
1996
21
Hyperinsulinemia, hyperproinsulinemia and insulin resistance in the metabolic syndrome. ( 8641379 )
1996
22
Hyperproinsulinemia in the diabetic Psammomys obesus is a result of increased secretory demand on the beta-cell. ( 7664638 )
1995
23
What beta-cell defect could lead to hyperproinsulinemia in NIDDM? Some clues from recent advances made in understanding the proinsulin-processing mechanism. ( 8138054 )
1994
24
Hyperproinsulinemia in Japan. ( 7859596 )
1994
25
A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto). ( 1601997 )
1992
26
Two unrelated patients with familial hyperproinsulinemia due to a mutation substituting histidine for arginine at position 65 in the proinsulin molecule: identification of the mutation by direct sequencing of genomic deoxyribonucleic acid amplified by polymerase chain reaction. ( 2196279 )
1990
27
A new case of familial hyperproinsulinemia. ( 2684621 )
1989
28
A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia. ( 3470784 )
1987
29
Hyperproinsulinemia in a family with a proposed defect in conversion is linked to the insulin gene. ( 2991050 )
1985
30
Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia. ( 4019786 )
1985
31
Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin. ( 6382002 )
1984

Variations for Hyperproinsulinemia

UniProtKB/Swiss-Prot genetic disease variations for Hyperproinsulinemia:

75
# Symbol AA change Variation ID SNP ID
1 INS p.His34Asp VAR_003971 rs121918101
2 INS p.Arg89His VAR_003974 rs28933985
3 INS p.Arg89Leu VAR_003975 rs28933985

ClinVar genetic disease variations for Hyperproinsulinemia:

6
(show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 INS NM_001185097.1(INS): c.147C> G (p.Phe49Leu) single nucleotide variant Pathogenic rs148685531 GRCh37 Chromosome 11, 2182055: 2182055
2 INS NM_001185097.1(INS): c.147C> G (p.Phe49Leu) single nucleotide variant Pathogenic rs148685531 GRCh38 Chromosome 11, 2160825: 2160825
3 INS NM_000207.2(INS): c.143T> C (p.Phe48Ser) single nucleotide variant Pathogenic rs80356668 GRCh37 Chromosome 11, 2182059: 2182059
4 INS NM_000207.2(INS): c.143T> C (p.Phe48Ser) single nucleotide variant Pathogenic rs80356668 GRCh38 Chromosome 11, 2160829: 2160829
5 INS NM_000207.2(INS): c.100C> G (p.His34Asp) single nucleotide variant Pathogenic rs121918101 GRCh37 Chromosome 11, 2182102: 2182102
6 INS NM_000207.2(INS): c.100C> G (p.His34Asp) single nucleotide variant Pathogenic rs121918101 GRCh38 Chromosome 11, 2160872: 2160872
7 INS NM_000207.2(INS): c.266G> A (p.Arg89His) single nucleotide variant Pathogenic rs28933985 GRCh37 Chromosome 11, 2181149: 2181149
8 INS NM_000207.2(INS): c.266G> A (p.Arg89His) single nucleotide variant Pathogenic rs28933985 GRCh38 Chromosome 11, 2159919: 2159919
9 INS NM_000207.2(INS): c.274G> T (p.Val92Leu) single nucleotide variant Pathogenic rs121918102 GRCh37 Chromosome 11, 2181141: 2181141
10 INS NM_000207.2(INS): c.274G> T (p.Val92Leu) single nucleotide variant Pathogenic rs121918102 GRCh38 Chromosome 11, 2159911: 2159911
11 INS NM_000207.2(INS): c.266G> T (p.Arg89Leu) single nucleotide variant Pathogenic rs28933985 GRCh37 Chromosome 11, 2181149: 2181149
12 INS NM_000207.2(INS): c.266G> T (p.Arg89Leu) single nucleotide variant Pathogenic rs28933985 GRCh38 Chromosome 11, 2159919: 2159919
13 INS NM_000207.2(INS): c.266G> C (p.Arg89Pro) single nucleotide variant Pathogenic rs28933985 GRCh37 Chromosome 11, 2181149: 2181149
14 INS NM_000207.2(INS): c.266G> C (p.Arg89Pro) single nucleotide variant Pathogenic rs28933985 GRCh38 Chromosome 11, 2159919: 2159919

Expression for Hyperproinsulinemia

Search GEO for disease gene expression data for Hyperproinsulinemia.

Pathways for Hyperproinsulinemia

GO Terms for Hyperproinsulinemia

Cellular components related to Hyperproinsulinemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.5 CPE IGFBP1 INS INS-IGF2 PCSK2 SCT
2 secretory granule lumen GO:0034774 9.43 INS PCSK1 PCSK2
3 transport vesicle GO:0030133 9.33 INS PCSK1 PCSK2
4 extracellular space GO:0005615 9.17 CPE IGFBP1 INS INS-IGF2 PCSK1 PCSK2

Biological processes related to Hyperproinsulinemia according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 regulation of signaling receptor activity GO:0010469 9.67 INS INS-IGF2 SCT
2 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.51 INS INS-IGF2
3 insulin receptor signaling pathway GO:0008286 9.48 IGFBP1 INS
4 positive regulation of cell growth GO:0030307 9.46 IGFBP1 INS
5 response to glucose GO:0009749 9.43 INS INS-IGF2
6 response to insulin GO:0032868 9.4 INS INS-IGF2
7 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.37 INS INS-IGF2
8 response to nutrient levels GO:0031667 9.32 INS INS-IGF2
9 peptide hormone processing GO:0016486 9.26 PCSK1 PCSK2
10 positive regulation of insulin receptor signaling pathway GO:0046628 9.16 INS INS-IGF2
11 insulin processing GO:0030070 8.96 CPE PCSK2
12 protein processing GO:0016485 8.8 CPE PCSK1 PCSK2

Molecular functions related to Hyperproinsulinemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 insulin receptor binding GO:0005158 9.26 INS INS-IGF2
2 insulin-like growth factor receptor binding GO:0005159 9.16 INS INS-IGF2
3 hormone activity GO:0005179 9.13 INS INS-IGF2 SCT
4 receptor activator activity GO:0030546 8.62 INS INS-IGF2

Sources for Hyperproinsulinemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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