INS
Chr 11ADARinsulin
Also known as: IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10, PNDM4
Insulin is a peptide hormone that decreases blood glucose concentration and increases cellular uptake of glucose, amino acids, and fatty acids. Mutations cause multiple forms of diabetes including permanent neonatal diabetes, maturity-onset diabetes of the young type 10, insulin-dependent diabetes, and hyperproinsulinemia, with both autosomal dominant and autosomal recessive inheritance patterns. The gene has intermediate constraint against loss-of-function variants and is covered in GeneReviews for additional clinical guidance.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
225 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 5 | 32 | 0 | 37 |
Likely Pathogenic | 1 | 19 | 4 | 0 | 24 |
VUS | 2 | 38 | 35 | 0 | 75 |
Likely Benign | 0 | 0 | 22 | 16 | 38 |
Benign | 0 | 0 | 16 | 0 | 16 |
Conflicting | — | 29 | |||
| Total | 3 | 62 | 109 | 16 | 219 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
INS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Effect of Tirzepatide on Brown Adipose Tissue in Obesity
ACTIVE NOT RECRUITINGTraining for Men Undergoing Androgen Deprivation Therapy.
RECRUITINGComplex Effects of Dietary Manipulation on Metabolic Function, Inflammation and Health
ACTIVE NOT RECRUITINGCorrelation Between Gut Microbiota and Pancreatic Β-Cell Function in Diabetic Patients
ENROLLING BY INVITATIONProbiotic Impact on Cognitive Performance, and Metabolic Outcomes in Overweight Young Adults With Impaired Glucose Regulation
RECRUITINGMASLD in Type 2 Diabetes in Primary Care - a Follow-up Study
ENROLLING BY INVITATIONIdentifying Periods of High Training Load Considering the Menstrual Cycle Phases in Elite and Non-elite Female Athletes
RECRUITINGPhysical and Behavioral Traits of Overweight and Obese Adults
RECRUITINGCardiometabolic Risk of Obese Subjects: Cross-sectional Study
RECRUITINGA Biological Atlas of Severe Obesity (Biological Tissue Collection)
RECRUITINGAvocado Consumption and Cellular Aging in Breast Cancer Survivors
RECRUITINGRole of High-Throughput Whole Genome Sequencing for the Diagnosis and Care of Atypical Diabetes
RECRUITINGExternal Resources
Links to major genomics databases and tools