HPRI
MCID: HYP110
MIFTS: 37

Hyperproinsulinemia (HPRI)

Categories: Cardiovascular diseases, Genetic diseases, Immune diseases

Aliases & Classifications for Hyperproinsulinemia

MalaCards integrated aliases for Hyperproinsulinemia:

Name: Hyperproinsulinemia 57 73 29 6 39 17 71
Hpri 73

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant


HPO:

31
hyperproinsulinemia:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM® 57 616214
MeSH 44 D003920
MedGen 41 C0342283
UMLS 71 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) (Updated 05-Mar-2021)

MalaCards based summary : Hyperproinsulinemia, also known as hpri, is related to hyperinsulinism and glucose intolerance. 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. Affiliated tissues include kidney, pancreas and pituitary, and related phenotypes are hyperinsulinemia and hyperglycemia

UniProtKB/Swiss-Prot : 73 Hyperproinsulinemia: An autosomal dominant condition characterized by elevated levels of serum proinsulin-like material.

Wikipedia : 74 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 top 50) (show all 70)
# Related Disease Score Top Affiliating Genes
1 hyperinsulinism 30.0 SHBG INS IGFBP1
2 glucose intolerance 29.8 SHBG INS IGFBP1
3 gestational diabetes 29.7 SHBG INS IGFBP1
4 insulinoma 29.5 SCT PCSK2 INS CPE
5 body mass index quantitative trait locus 11 28.4 SHBG PCSK2 PCSK1 INS IGFBP1 CPE
6 diabetes mellitus, permanent neonatal, 4 10.2 INS-IGF2 INS
7 maturity-onset diabetes of the young, type 10 10.2 INS-IGF2 INS
8 type 1 diabetes mellitus 2 10.2 INS-IGF2 INS
9 monogenic diabetes 10.2 INS-IGF2 INS
10 hyperglycemia 10.2
11 marasmus 10.1 SHBG INS
12 kwashiorkor 10.1 SHBG INS
13 skin tag 10.1 SHBG INS
14 graves disease 1 10.1 SHBG INS
15 steroid inherited metabolic disorder 10.1 SHBG INS
16 androgenic alopecia 10.1 SHBG INS
17 hypoglycemia 10.1
18 pigmentation disease 10.1 SHBG INS
19 protein-deficiency anemia 10.1 INS IGFBP1
20 sebaceous gland disease 10.1 SHBG INS
21 sexual disorder 10.1 SHBG INS
22 acanthosis nigricans 10.0 SHBG INS
23 ovarian hyperstimulation syndrome 10.0 SHBG INS
24 disorder of sexual development 10.0 SHBG INS
25 impotence 10.0 SHBG INS
26 androgen insensitivity syndrome 10.0 SHBG INS
27 hyperprolactinemia 10.0 SHBG INS
28 wolfram syndrome 10.0 PCSK2 INS
29 persistent fetal circulation syndrome 10.0 INS IGFBP1
30 amenorrhea 10.0 SHBG INS
31 maturity-onset diabetes of the young 9.9 PCSK1 INS-IGF2 INS
32 dumping syndrome 9.9 SCT INS
33 hair disease 9.9 SHBG INS
34 uterine benign neoplasm 9.9 SHBG IGFBP1
35 gastrinoma 9.9 SCT INS
36 duodenal ulcer 9.9 SCT INS
37 body mass index quantitative trait locus 9 9.9
38 body mass index quantitative trait locus 8 9.9
39 body mass index quantitative trait locus 4 9.9
40 body mass index quantitative trait locus 10 9.9
41 body mass index quantitative trait locus 7 9.9
42 body mass index quantitative trait locus 12 9.9
43 body mass index quantitative trait locus 14 9.9
44 body mass index quantitative trait locus 18 9.9
45 body mass index quantitative trait locus 19 9.9
46 fasting hypoglycemia 9.9
47 thalassemia 9.9
48 hypogonadism 9.9 SHBG PCSK1 INS
49 thyroid gland disease 9.8 SHBG INS
50 type 1 diabetes mellitus 9.8 INS IGFBP1 CPE

Graphical network of the top 20 diseases related to Hyperproinsulinemia:



Diseases related to Hyperproinsulinemia

Symptoms & Phenotypes for Hyperproinsulinemia

Human phenotypes related to Hyperproinsulinemia:

31
# Description HPO Frequency HPO Source Accession
1 hyperinsulinemia 31 occasional (7.5%) HP:0000842
2 hyperglycemia 31 occasional (7.5%) HP:0003074

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
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 (Updated 05-Mar-2021)

Drugs & Therapeutics for Hyperproinsulinemia

Search Clinical Trials , 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:

40
Kidney, Pancreas, Pituitary

Publications for Hyperproinsulinemia

Articles related to Hyperproinsulinemia:

(show top 50) (show all 132)
# Title Authors PMID Year
1
A novel point mutation in the insulin gene giving rise to hyperproinsulinemia. 61 57 6
9141561 1997
2
A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia. 57 6 61
3470784 1987
3
Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin. 6 57 61
6382002 1984
4
Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding [SerB24]insulin. 57 6
6312455 1983
5
Three mutant insulins in man. 6 57
6339950 1983
6
Loss of a restriction endonuclease cleavage site in the gene of a structurally abnormal human insulin. 6 57
6261753 1981
7
Diabetes due to secretion of an abnormal insulin. 57 6
7350438 1980
8
A structurally abnormal insulin causing human diabetes. 57 6
381941 1979
9
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. 6 61
8636380 1996
10
A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto). 6 61
1601997 1992
11
A mutant human proinsulin is secreted from islets of Langerhans in increased amounts via an unregulated pathway. 61 6
3057496 1988
12
A superactive insulin: [B10-aspartic acid]insulin(human). 6 61
3306677 1987
13
Hyperproinsulinemia in a family with a proposed defect in conversion is linked to the insulin gene. 6 61
2991050 1985
14
Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia. 6 61
4019786 1985
15
Familial hyperproinsulinemia. Two cohorts secreting indistinguishable type II intermediates of proinsulin conversion. 6 61
6368587 1984
16
Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material. 57 61
288074 1979
17
Familial hyperproinsulinemia. An autosomal dominant defect. 61 57
815812 1976
18
Familial hyperproinsulinaemia due to a mutation substituting histidine for arginine at position 65 in proinsulin: identification of the mutation by restriction enzyme mapping. 6
9667398 1998
19
Paradoxical structure and function in a mutant human insulin associated with diabetes mellitus. 6
8421693 1993
20
Structurally abnormal insulin in a diabetic patient. Characterization of the mutant insulin A3 (Val----Leu) isolated from the pancreas. 6
3537011 1986
21
Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus. 57
3512591 1986
22
Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin. 6
3511099 1986
23
Familial hyperinsulinemia due to a structurally abnormal insulin. Definition of an emerging new clinical syndrome. 57
6371526 1984
24
Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution. 57
6424111 1983
25
A human proinsulin variant at arginine 65. 6
7242673 1981
26
The insulinopathies. 57
7350441 1980
27
Beta Cell Function is Disrupted in Patients with Systemic Lupus Erythematosus. 61
33369681 2020
28
Plasma levels of acylated ghrelin in patients with insulinoma and expression of ghrelin and its receptor in insulinomas. 61
32124259 2020
29
eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice. 61
31300553 2019
30
[Diagnostics value and regulatory functions of roinsulin.] 61
31408590 2019
31
Increased β-Cell Workload Modulates Proinsulin-to-Insulin Ratio in Humans. 61
30131390 2018
32
Hyperproinsulinemia in obesity and in type 2 diabetes and its relation to cardiovascular disease. 61
30058886 2017
33
Dissecting carboxypeptidase E: properties, functions and pathophysiological roles in disease. 61
28348001 2017
34
How does radiotherapy impact swallowing function in nasopharynx and oropharynx cancer? Short-term results of a prospective study. 61
27070541 2016
35
Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes. 61
27035557 2016
36
Both fasting and glucose-stimulated proinsulin levels predict hyperglycemia and incident type 2 diabetes: a population-based study of 9,396 Finnish men. 61
25853252 2015
37
GLP-1 analog liraglutide enhances proinsulin processing in pancreatic β-cells via a PKA-dependent pathway. 61
25051441 2014
38
Role of dietary fats in modulating cardiometabolic risk during moderate weight gain: a randomized double-blind overfeeding trial (LIPOGAIN study). 61
25319187 2014
39
Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic β cells. 61
24843127 2014
40
Estimated proinsulin processing activity of prohormone convertase (PC) 1/3 rather than PC2 is decreased in pancreatic β-cells of type 2 diabetic patients. 61
24705588 2014
41
HPRI data tracks. Urology workforce trends. 61
22315881 2012
42
Admission proinsulin is associated with mortality in patients with admission hyperglycemia during acute coronary syndrome: results from a pilot observational study. 61
21784763 2011
43
Differential regulation and localization of carboxypeptidase D and carboxypeptidase E in human and mouse β-cells. 61
21628999 2011
44
Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in β-cells. 61
21723250 2011
45
HPRI data tracks. Developing an index of surgical underservice. 61
22315900 2011
46
The ACS HPRI: shaping surgical workforce policy through evidence-based analyses. 61
22312822 2011
47
Independent relationships of obesity and insulin resistance with serum proinsulin level in prepubertal children with normal glucose tolerance. 61
21214701 2011
48
Insulin gene mutations and diabetes. 61
24843467 2011
49
Bileopancreatic diversion with duodenal switch lowers both early and late phases of glucose, insulin and proinsulin responses after meal. 61
20198453 2010
50
Mutant proinsulin proteins associated with neonatal diabetes are retained in the endoplasmic reticulum and not efficiently secreted. 61
20034470 2010

Variations for Hyperproinsulinemia

ClinVar genetic disease variations for Hyperproinsulinemia:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 INS-IGF2 NM_000207.3(INS):c.147C>G (p.Phe49Leu) SNV Pathogenic 13377 rs148685531 11:2182055-2182055 11:2160825-2160825
2 INS-IGF2 NM_000207.3(INS):c.143T>C (p.Phe48Ser) SNV Pathogenic 13378 rs80356668 11:2182059-2182059 11:2160829-2160829
3 INS-IGF2 NM_000207.3(INS):c.100C>G (p.His34Asp) SNV Pathogenic 13379 rs121918101 11:2182102-2182102 11:2160872-2160872
4 INS-IGF2 NM_000207.3(INS):c.266G>A (p.Arg89His) SNV Pathogenic 13380 rs28933985 11:2181149-2181149 11:2159919-2159919
5 INS-IGF2 NM_000207.3(INS):c.274G>T (p.Val92Leu) SNV Pathogenic 13381 rs121918102 11:2181141-2181141 11:2159911-2159911
6 INS-IGF2 NM_000207.3(INS):c.266G>T (p.Arg89Leu) SNV Pathogenic 13382 rs28933985 11:2181149-2181149 11:2159919-2159919
7 INS-IGF2 NM_000207.3(INS):c.266G>C (p.Arg89Pro) SNV Pathogenic 13383 rs28933985 11:2181149-2181149 11:2159919-2159919

UniProtKB/Swiss-Prot genetic disease variations for Hyperproinsulinemia:

73
# 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

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 9.63 SCT PCSK2 PCSK1 INS IGFBP1 CPE
2 extracellular region GO:0005576 9.5 SHBG SCT PCSK2 INS-IGF2 INS IGFBP1
3 transport vesicle GO:0030133 8.92 PCSK2 PCSK1 INS CPE

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

# Name GO ID Score Top Affiliating Genes
1 insulin receptor signaling pathway GO:0008286 9.32 INS IGFBP1
2 positive regulation of cell growth GO:0030307 9.26 INS IGFBP1
3 regulation of synaptic plasticity GO:0048167 9.16 SCT INS
4 peptide hormone processing GO:0016486 8.96 PCSK2 PCSK1
5 protein processing GO:0016485 8.8 PCSK2 PCSK1 CPE

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 SCT INS-IGF2 INS

Sources for Hyperproinsulinemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....