Gene: INS

Alternate names for this Gene: IDDM|IDDM1|IDDM2|ILPR|IRDN|MODY10|PNDM4

Gene Summary: This gene encodes insulin, a peptide hormone that plays a vital role in the regulation of carbohydrate and lipid metabolism. After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. A multitude of mutant alleles with phenotypic effects have been identified, including insulin-dependent diabetes mellitus, permanent neonatal diabetes diabetes mellitus, maturity-onset diabetes of the young type 10 and hyperproinsulinemia. There is a read-through gene, INS-IGF2, which overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region.

Gene is located in Chromosome: 11

Location in Chromosome : 11p15.5

Description of this Gene: insulin

Type of Gene: protein-coding

Gene: INS-IGF2

Alternate names for this Gene: INSIGF

Gene Summary: This locus includes two alternatively spliced read-through transcript variants which align to the INS gene in the 5' region and to the IGF2 gene in the 3' region. One transcript is predicted to encode a protein which shares the N-terminus with the INS protein but has a distinct and longer C-terminus, whereas the other transcript is a candidate for nonsense-mediated decay (NMD). The transcripts are imprinted and are paternally expressed in the limb and eye.

Gene is located in Chromosome: 11

Location in Chromosome : 11p15.5

Description of this Gene: INS-IGF2 readthrough

Type of Gene: protein-coding

rs689 in INS;INS-IGF2 gene and Autoantibody measurement PMID 21829393 2011 Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.

rs121908272 in INS;INS-IGF2 gene and DIABETES MELLITUS, PERMANENT NEONATAL PMID 18162506 2008 Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood.

PMID 17855560 2007 Insulin gene mutations as a cause of permanent neonatal diabetes.

PMID 20133622 2010 Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis.

PMID 21592955 2011 Disruption of a novel Kruppel-like transcription factor p300-regulated pathway for insulin biosynthesis revealed by studies of the c.-331 INS mutation found in neonatal diabetes mellitus.

rs689 in INS;INS-IGF2 gene and Diabetes Mellitus, Insulin-Dependent PMID 21829393 2011 Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.

PMID 25751624 2015 Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.

PMID 31152121 2019 Identification of Novel T1D Risk Loci and Their Association With Age and Islet Function at Diagnosis in Autoantibody-Positive T1D Individuals: Based on a Two-Stage Genome-Wide Association Study.

rs689 in INS;INS-IGF2 gene and Diabetes Mellitus, Non-Insulin-Dependent PMID 30254083 2018 First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes.

rs121918101 in INS;INS-IGF2 gene and Hyperproinsulinemia PMID 1601997 1992 A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto).

PMID 3470784 1987 A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia.

PMID 4019786 1985 Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia.

PMID 2196279 1990 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.

PMID 2196279 1990 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.

rs689 in INS;INS-IGF2 gene and Latent Autoimmune Diabetes in Adults PMID 30254083 2018 First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes.

rs121908259 in INS;INS-IGF2 gene and Maturity-onset diabetes of the young, type 10 PMID 25423173 2014 Structural and functional study of the GlnB22-insulin mutant responsible for maturity-onset diabetes of the young.

PMID 20226046 2010 Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY).

PMID 18192540 2008 Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes.

PMID 18162506 2008 Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood.