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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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INS
insulin
Chromosome 11 Β· 11p15.5
NCBI Gene: 3630Ensembl: ENSG00000254647.7HGNC: HGNC:6081UniProt: I3WAC9
1,033PubMed Papers
24Diseases
0Drugs
31Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of protein localization to nucleusprotease bindinginsulin receptor bindinginsulin-like growth factor receptor bindingdiabetes mellitus, permanent neonatal 4MODYhyperproinsulinemiatype 1 diabetes mellitus
✦AI Summary

The INS gene encodes insulin, a critical peptide hormone that primarily functions to regulate glucose homeostasis by decreasing blood glucose concentration and increasing cellular permeability to monosaccharides, amino acids, and fatty acids. Insulin promotes anabolic processes including glycolysis, the pentose phosphate cycle, and glycogen synthesis in the liver. Recent research reveals that insulin gene expression and secretion are tightly regulated at multiple levels. A protective genetic variant (rs3842752 G>A) in the INS 3' untranslated region creates an IRE1Ξ± digestion motif that leads to accelerated insulin mRNA decay during endoplasmic reticulum stress, providing protection against type 1 diabetes 1. Insulin expression can be suppressed by regulatory peptides such as GIP_HUMAN [22-51], which downregulates insulin mRNA expression and secretion through NF-ΞΊB-dependent mechanisms 2. The FTO gene plays an essential role in maintaining insulin secretion and Ξ²-cell function, with FTO expression being reduced in diabetic pancreatic islets and its silencing impairing insulin release 3. Dysregulation of insulin expression and secretion is associated with multiple forms of diabetes, including permanent neonatal diabetes, maturity-onset diabetes of the young, and both type 1 and type 2 diabetes mellitus.

Sources cited
1
A protective genetic variant in INS creates an IRE1Ξ± digestion motif leading to accelerated insulin mRNA decay and protection against type 1 diabetes
PMID: 40112799
2
GIP_HUMAN [22-51] peptide suppresses insulin mRNA expression and secretion through NF-ΞΊB-dependent mechanisms
PMID: 37895259
3
FTO gene is essential for insulin secretion and Ξ²-cell function, with reduced expression in diabetic pancreatic islets
PMID: 38232799
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜24
diabetes mellitus, permanent neonatal 4Open Targets
0.78Strong
MODYOpen Targets
0.75Strong
hyperproinsulinemiaOpen Targets
0.74Strong
type 1 diabetes mellitusOpen Targets
0.69Moderate
maturity-onset diabetes of the young type 10Open Targets
0.69Moderate
permanent neonatal diabetes mellitusOpen Targets
0.68Moderate
diabetes mellitusOpen Targets
0.59Moderate
monogenic diabetesOpen Targets
0.56Moderate
type 2 diabetes mellitusOpen Targets
0.52Moderate
transient neonatal diabetes, dominant/recessiveOpen Targets
0.51Moderate
maturity-onset diabetes of the youngOpen Targets
0.49Moderate
diabetic retinopathyOpen Targets
0.48Moderate
AL amyloidosisOpen Targets
0.46Moderate
diabetic ketoacidosisOpen Targets
0.45Moderate
autoimmune diseaseOpen Targets
0.44Moderate
retinopathyOpen Targets
0.43Moderate
neonatal diabetes mellitusOpen Targets
0.43Moderate
type 1 diabetes nephropathyOpen Targets
0.40Weak
Neonatal insulin-dependent diabetes mellitusOpen Targets
0.40Weak
transient neonatal diabetes mellitusOpen Targets
0.39Weak
Diabetes mellitus, permanent neonatal, 4UniProt
HyperproinsulinemiaUniProt
Maturity-onset diabetes of the young 10UniProt
Type 1 diabetes mellitus 2UniProt
Pathogenic Variants31
NM_000207.3(INS):c.-152C>GPathogenic
Permanent neonatal diabetes mellitus|not specified|Diabetes mellitus, permanent neonatal 4;Hyperproinsulinemia;Type 1 diabetes mellitus 2;Maturity-onset diabetes of the young type 10|Diabetes mellitus, permanent neonatal 4|not provided|Diabetes mellitus|Amyotrophic lateral sclerosis, susceptibility to, 24
β˜…β˜…β˜†β˜†2025
NM_000207.3(INS):c.-152C>APathogenic
Permanent neonatal diabetes mellitus|not provided|INS-related disorder|Diabetes mellitus, permanent neonatal 4;Hyperproinsulinemia;Type 1 diabetes mellitus 2;Maturity-onset diabetes of the young type 10
β˜…β˜…β˜†β˜†2025
NM_000207.3(INS):c.163C>T (p.Arg55Cys)Pathogenic
Type 1 diabetes mellitus 2|not provided|Diabetes mellitus type 1|Monogenic diabetes|INS-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 55
NM_000207.3(INS):c.127T>G (p.Cys43Gly)Pathogenic
Permanent neonatal diabetes mellitus|Neonatal diabetes mellitus|Diabetes mellitus, permanent neonatal 4|Type 2 diabetes mellitus|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 43
NM_000207.3(INS):c.125T>C (p.Val42Ala)Pathogenic
Maturity-onset diabetes of the young type 10|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 42
NM_000207.3(INS):c.266G>A (p.Arg89His)Pathogenic
Hyperproinsulinemia|not provided|INS-related disorder|Diabetes mellitus, permanent neonatal 4;Type 1 diabetes mellitus 2;Hyperproinsulinemia;Maturity-onset diabetes of the young type 10
β˜…β˜…β˜†β˜†2024β†’ Residue 89
NM_000207.3(INS):c.188-31G>APathogenic
Permanent neonatal diabetes mellitus|not provided|Diabetes mellitus, permanent neonatal 4|Neonatal insulin-dependent diabetes mellitus
β˜…β˜…β˜†β˜†2024
NM_000207.3(INS):c.71C>A (p.Ala24Asp)Pathogenic
Permanent neonatal diabetes mellitus|Diabetes mellitus, permanent neonatal 4|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 24
NM_000207.3(INS):c.265C>T (p.Arg89Cys)Pathogenic
Permanent neonatal diabetes mellitus|Diabetes mellitus, permanent neonatal 4|Neonatal diabetes mellitus|not provided|INS-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 89
NM_000207.3(INS):c.1A>G (p.Met1Val)Pathogenic
not provided|Hyperproinsulinemia;Type 1 diabetes mellitus 2;Maturity-onset diabetes of the young type 10;Diabetes mellitus, permanent neonatal 4
β˜…β˜…β˜†β˜†2022β†’ Residue 1
NM_000207.3(INS):c.71C>T (p.Ala24Val)Likely pathogenic
Neonatal diabetes mellitus|not provided
β˜…β˜…β˜†β˜†2019β†’ Residue 24
NM_000207.3(INS):c.143T>G (p.Phe48Cys)Likely pathogenic
Permanent neonatal diabetes mellitus|Diabetes mellitus, permanent neonatal 4|Neonatal diabetes mellitus
β˜…β˜…β˜†β˜†β†’ Residue 48
NM_000207.3(INS):c.129C>G (p.Cys43Trp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 43
NM_000207.3(INS):c.*59A>GLikely pathogenic
Permanent neonatal diabetes mellitus|Maturity-onset diabetes of the young type 10;Type 1 diabetes mellitus 2;Hyperproinsulinemia;Diabetes mellitus, permanent neonatal 4
β˜…β˜†β˜†β˜†2024
NM_000207.3(INS):c.284G>A (p.Cys95Tyr)Likely pathogenic
INS-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 95
NM_000207.3(INS):c.136C>T (p.Arg46Ter)Likely pathogenic
INS-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 46
NM_000207.3(INS):c.103C>G (p.Leu35Val)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 35
NM_000207.3(INS):c.95G>T (p.Gly32Val)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 32
NM_000207.3(INS):c.289A>C (p.Thr97Pro)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 97
NM_000207.3(INS):c.155C>G (p.Pro52Arg)Likely pathogenic
Neonatal insulin-dependent diabetes mellitus
β˜…β˜†β˜†β˜†β†’ Residue 52
View on ClinVar β†—
Related Genes
CTRB1Protein interaction100%PDGFBProtein interaction100%NPPAProtein interaction100%CTRB2Protein interaction100%INS-IGF2Protein interaction100%NTRK1Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Ovary
29%
Brain
0%
Heart
0%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
INSCTRB1PDGFBNPPACTRB2INS-IGF2NTRK1
PROTEIN STRUCTURE
Preparing viewer…
PDB3W7Y Β· 0.92 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.20LoF Tolerant
pLIβ“˜
0.02Tolerant
Observed/Expected LoF0.64 [0.36–1.20]
RankingsWhere INS stands among ~20K protein-coding genes
  • #149of 20,598
    Most Researched1,033 Β· top 1%
  • #1,770of 5,498
    Most Pathogenic Variants31
  • #12,545of 17,882
    Most Constrained (LOEUF)1.20
Genes detectedINS
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Increased post-mitotic senescence in aged human neurons is a pathological feature of Alzheimer's disease.
PMID: 36459967
Cell Stem Cell Β· 2022
1.00
2
Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects.
PMID: 26456686
Cell Stem Cell Β· 2015
0.90
3
RORB and RORC associate with human islet dysfunction and inhibit insulin secretion in INS-1 cells.
PMID: 30762474
Islets Β· 2019
0.84
4
Local co-expression of GLP1R and INS in human cortical interneurons.
PMID: 41970992
Front Endocrinol (Lausanne) Β· 2026
0.82
5
Genetic protection from type 1 diabetes resulting from accelerated insulin mRNA decay.
PMID: 40112799
Cell Β· 2025
0.80