INS

Protein identityUniProt · HPA

UniProt accession

P01308

Gene

INS

Ensembl

ENSG00000254647

Chromosome

11

Canonical length

110 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted secreted proteins, RAS pathway related proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

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. [provided by RefSeq, May 2020]

Canonical amino-acid sequenceUniProt

110 residues, UniProt reviewed canonical sequence.

>P01308|INS
     1  MALWMRLLPL LALLALWGPD PAAAFVNQHL CGSHLVEALY LVCGERGFFY TPKTRREAED
    61  LQVGQVELGG GPGAGSLQPL ALEGSLQKRG IVEQCCTSIC SLYQLENYCN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against INS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Unknown

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.67

Highest tissue expression

12,197 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about INS.

Disease | GeneticClinVar

36 pathogenic / likely-pathogenic of 187 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Diabetes mellitus, permanent neonatal 4
• Hyperproinsulinemia
• Maturity-onset diabetes of the young type 10
• Neonatal diabetes mellitus
• Permanent neonatal diabetes mellitus

Disease | ImmuneIEDB

Conditions an epitope on INS was assayed in.

• type 1 diabetes mellitus B and T cell
• prediabetes syndrome T cell
• type 2 diabetes mellitus T cell
• autoimmune thyroiditis B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against INS are reported. Each links to that disease's full target list.

• Diabetes Mellitus, Type 1 932
• Insulin Resistance 150
• Diabetes Mellitus, Type 2 120
• Lupus Erythematosus, Systemic 41
• Graves Disease 26
• Obesity 18
• Celiac Disease 16
• Thyroiditis, Autoimmune 15
• Arthritis, Rheumatoid 8
• Hashimoto Disease 8
• Hypothyroidism 7
• COVID-19 6
• Glomerulonephritis 5
• Hepatitis C, Chronic 4
• Addison Disease 3
• Adenocarcinoma 3
• Calcinosis 3
• Diabetic Nephropathies 3
• Hyperthyroidism 3
• Lupus Nephritis 3

Showing 20 of 53 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for INS from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.17

gnomAD pLI

0.3

gnomAD missense Z

0.9

DepMap mean gene effect

-0.22

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

InteractionsUniProt · HPA

Protein binding partners of INS in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• IAPP