HPRI
MCID: HYP110
MIFTS: 37

Hyperproinsulinemia (HPRI)

Categories: Genetic diseases, Immune diseases

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 glucose intolerance. An important gene associated with Hyperproinsulinemia is INS (Insulin), and among its related pathways/superpathways are Type II diabetes mellitus and Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers. The drugs Vildagliptin and Hormone Antagonists have been mentioned in the context of this disorder. Affiliated tissues include kidney, pancreas and ovary, 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 41)
# Related Disease Score Top Affiliating Genes
1 insulinoma 30.4 INS SCT
2 glucose intolerance 29.7 IGFBP1 INS SHBG
3 gestational diabetes 29.6 INS SHBG
4 diabetes mellitus 29.5 CPE IGFBP1 INS INS-IGF2 SHBG
5 diabetes mellitus, insulin-dependent, 2 10.2 INS INS-IGF2
6 type 1 diabetes mellitus 2 10.2 INS INS-IGF2
7 segawa syndrome, autosomal recessive 10.2 INS INS-IGF2
8 maturity-onset diabetes of the young, type 10 10.2 INS INS-IGF2
9 hyperglycemia 10.2
10 pancreas disease 10.1 INS SCT
11 maturity-onset diabetes of the young, type 6 10.1 CPE INS
12 diabetes mellitus, permanent neonatal 10.1 INS INS-IGF2
13 insulinomatosis and diabetes mellitus 10.1 INS SCT
14 dumping syndrome 10.1 INS SCT
15 gastrinoma 10.1 INS SCT
16 maturity-onset diabetes of the young, type 7 10.1 INS SCT
17 type 1 diabetes mellitus 7 10.1 IGFBP1 INS
18 duodenal ulcer 10.1 INS SCT
19 thalassemia 10.0
20 hypoglycemia 10.0
21 fetal erythroblastosis 10.0 INS SHBG
22 sex differentiation disease 10.0 INS SHBG
23 anovulation 10.0 INS SHBG
24 acromegaly 10.0 IGFBP1 INS
25 acanthosis nigricans 10.0 INS SHBG
26 hypoadrenalism 9.9 PCSK1 SHBG
27 multiple endocrine neoplasia, type i 9.9 INS SCT
28 overnutrition 9.9 INS SHBG
29 gonadal disease 9.9 INS SHBG
30 acquired metabolic disease 9.9 INS SHBG
31 prader-willi syndrome 9.9 IGFBP1 INS PCSK1
32 hyperthyroidism 9.9 INS SHBG
33 turner syndrome 9.8 IGFBP1 SHBG
34 diabetes mellitus, insulin-dependent 9.8 CPE IGFBP1 INS INS-IGF2
35 endocrine pancreas disease 9.8 IGFBP1 INS SHBG
36 hyperandrogenism 9.8 IGFBP1 INS SHBG
37 insulin-like growth factor i 9.8 IGFBP1 INS SHBG
38 hyperinsulinism 9.8 IGFBP1 INS SHBG
39 polycystic ovary syndrome 9.8 IGFBP1 INS SHBG
40 ovarian disease 9.8 IGFBP1 INS SHBG
41 body mass index quantitative trait locus 11 9.5 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 Hormone Antagonists Phase 4
3 Sitagliptin Phosphate Phase 4
4 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4
5
protease inhibitors Phase 4
6 insulin Phase 4
7 Incretins Phase 4
8 Hormones Phase 4
9 HIV Protease Inhibitors Phase 4
10 Insulin, Globin Zinc Phase 4
11 Dipeptidyl-Peptidase IV Inhibitors Phase 4
12 Hypoglycemic Agents 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
Kidney, Pancreas, Ovary

Publications for Hyperproinsulinemia

Articles related to Hyperproinsulinemia:

(show all 49)
# Title Authors Year
1
Hyperproinsulinemia in obesity and in type 2 diabetes and its relation to cardiovascular disease. ( 30058886 )
2017
2
HPRI data tracks. Urology workforce trends. ( 22315881 )
2012
3
The ACS HPRI: shaping surgical workforce policy through evidence-based analyses. ( 22312822 )
2011
4
HPRI data tracks. Developing an index of surgical underservice. ( 22315900 )
2011
5
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
6
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
7
Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes. ( 16271990 )
2005
8
The impact of insulin resistance on proinsulin secretion in pregnancy: hyperproinsulinemia is not a feature of gestational diabetes. ( 16249544 )
2005
9
Transient hyperproinsulinemia during treatment with clozapine and amisulpride. ( 15291669 )
2004
10
Sagittal abdominal diameter is a strong anthropometric marker of insulin resistance and hyperproinsulinemia in obese men. ( 15277437 )
2004
11
Disruption of a receptor-mediated mechanism for intracellular sorting of proinsulin in familial hyperproinsulinemia. ( 12829804 )
2003
12
[Insulinoma with hyperproinsulinemia: a two cases report]. ( 12193882 )
2002
13
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
14
PASSflow Syntheses Using Functionalized Monolithic Polymer/Glass Composites in Flow-Through Microreactors Part of these studies were supported by the Fonds der Chemischen Industrie and the European Community (EC project number HPRI-CT-1999-00085) for which we are grateful. PASSflow=Polymer Assisted Solution-Phase Synthesis technique in flow-through mode. ( 12404472 )
2001
15
Association between hyperproinsulinemia and anti-GAD65 antibodies in a patient with new onset type I diabetes. ( 10834528 )
2000
16
Hyperproinsulinemia is not a characteristic feature in the offspring of patients with different phenotypes of type II diabetes. ( 10913945 )
2000
17
Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance. ( 10372712 )
1999
18
Insulinoma with hyperproinsulinemia during hypoglycemia and loss of expression of vacuolar-type H(+)-ATPase (V-ATPase) in the tumor tissue. ( 10211416 )
1999
19
Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic beta-cell demand in men. ( 9951550 )
1998
20
Glucose intolerance in patients with thalassemia major: insulin resistance and hyperproinsulinemia. ( 10091170 )
1998
21
Acarbose controls postprandial hyperproinsulinemia in non-insulin dependent diabetes mellitus. ( 9237780 )
1997
22
A novel point mutation in the insulin gene giving rise to hyperproinsulinemia. ( 9141561 )
1997
23
Relative hyperproinsulinemia of NIDDM persists despite the reduction of hyperglycemia with insulin or sulfonylurea therapy. ( 9313749 )
1997
24
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
25
Hyperproinsulinemia is associated with increased beta cell demand after hemipancreatectomy in humans. ( 8567967 )
1996
26
Hyperinsulinemia, hyperproinsulinemia and insulin resistance in the metabolic syndrome. ( 8641379 )
1996
27
Hyperproinsulinemia in the diabetic Psammomys obesus is a result of increased secretory demand on the beta-cell. ( 7664638 )
1995
28
Increased secretory demand rather than a defect in the proinsulin conversion mechanism causes hyperproinsulinemia in a glucose-infusion rat model of non-insulin-dependent diabetes mellitus. ( 7883951 )
1995
29
What beta-cell defect could lead to hyperproinsulinemia in NIDDM? Some clues from recent advances made in understanding the proinsulin-processing mechanism. ( 8138054 )
1994
30
Hyperproinsulinemia in Japan. ( 7859596 )
1994
31
Hyperproinsulinemia of type II diabetes is not present before the development of hyperglycemia. ( 7821172 )
1994
32
Hyperproinsulinemia and insulin deficiency in the diabetic Psammomys obesus. ( 8033810 )
1994
33
Familial hyperproinsulinemia associated with NIDDM. A case study. ( 8269791 )
1993
34
Evidence that fasting hyperproinsulinemia after combined pancreas-kidney transplantation diminishes over time. ( 8279032 )
1993
35
Point mutation in a family with hyperproinsulinemia detected by single stranded conformational polymorphism. ( 8445019 )
1993
36
A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto). ( 1601997 )
1992
37
Hyperproinsulinemia in type II diabetes. ( 1516496 )
1992
38
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
39
A new case of familial hyperproinsulinemia. ( 2684621 )
1989
40
Hyperproinsulinemia and amyloid in NIDDM. Clues to etiology of islet beta-cell dysfunction? ( 2695369 )
1989
41
A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia. ( 3470784 )
1987
42
Proinsulin radioimmunoassay in the evaluation of insulinomas and familial hyperproinsulinemia. ( 3023795 )
1986
43
Hyperproinsulinemia in a family with a proposed defect in conversion is linked to the insulin gene. ( 2991050 )
1985
44
Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia. ( 4019786 )
1985
45
Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin. ( 6382002 )
1984
46
Familial hyperproinsulinemia. Two cohorts secreting indistinguishable type II intermediates of proinsulin conversion. ( 6368587 )
1984
47
Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material. ( 288074 )
1979
48
Familial hyperproinsulinemia. An autosomal dominant defect. ( 815812 )
1976
49
Hyperproinsulinemia in hypoglycemic subjects. ( 5065149 )
1972

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 space GO:0005615 9.43 CPE IGFBP1 INS PCSK1 PCSK2 SCT
2 transport vesicle GO:0030133 9.33 INS PCSK1 PCSK2
3 extracellular region GO:0005576 9.17 CPE IGFBP1 INS INS-IGF2 PCSK2 SCT

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

# Name GO ID Score Top Affiliating Genes
1 regulation of signaling receptor activity GO:0010469 9.5 INS INS-IGF2 SCT
2 positive regulation of cell growth GO:0030307 9.37 IGFBP1 INS
3 insulin receptor signaling pathway GO:0008286 9.26 IGFBP1 INS
4 peptide hormone processing GO:0016486 9.16 PCSK1 PCSK2
5 protein processing GO:0016485 9.13 CPE PCSK1 PCSK2
6 insulin processing GO:0030070 8.62 CPE PCSK2

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

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 8.8 INS INS-IGF2 SCT

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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