INS Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human INS — a definitive lookup resource covering: ### Section …

Provide a comprehensive cross-database identifier and functional mapping reference for human INS — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene INS, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene INS, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene INS protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene INS protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene INS, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene INS, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene INS, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene INS protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene INS, summarize transcription factor regulatory data. If INS is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate INS — names with evidence type (ChIP-seq / predicted / experimentally validated) If INS is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene INS protein as a drug target, summarize pharmacology data. If INS is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If INS is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene INS, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene INS, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in INS: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

INS

Executive summary

INS (HGNC:6081) encodes human insulin, the 110-amino acid pancreatic peptide hormone that is the master regulator of glucose homeostasis and one of the most clinically consequential proteins in medicine. Expressed almost exclusively in pancreatic beta cells and islets of Langerhans (expression score 100.00), insulin acts through the insulin receptor (INSR) to drive glucose uptake, glycogen synthesis, and lipid metabolism across 14 Reactome pathways. The gene harbors ~170 ClinVar variants, with pathogenic and likely pathogenic mutations causing a spectrum of monogenic diabetes syndromes including permanent neonatal diabetes mellitus, maturity-onset diabetes of the young type 10 (MODY10), and hyperproinsulinemia; GWAS links the locus to type 1 diabetes at p-values as low as 1e-196. Structurally, insulin is among the best-characterized human proteins, with 380 PDB entries spanning X-ray, NMR, and cryo-EM. Therapeutically, the gene product itself is the drug: five approved insulin-based biologics (including insulin glargine and insulin aspart) have collectively accumulated over 1,700 clinical trials.

Gene identifiers

IdentifierValue
HGNC IDHGNC:6081
Approved symbolINS
Ensembl gene IDENSG00000254647
NCBI Entrez Gene ID3630
OMIM gene ID176730
Chromosome11
Start position (GRCh38)2,159,779
End position (GRCh38)2,161,221
Strand− (minus)

Transcript identifiers

Ensembl Transcripts

Transcript IDBiotype
ENST00000250971protein_coding
ENST00000381330protein_coding
ENST00000397262protein_coding
ENST00000421783non_stop_decay
ENST00000512523protein_coding

Total: 5 transcripts

RefSeq mRNA Accessions

AccessionMANE Select
NM_000207✓ Yes
NM_001185097No
NM_001185098No
NM_001291897No

Total: 4 mRNA accessions

CCDS IDs

  • CCDS7729

MANE SELECT / Canonical Transcript (ENST00000381330)

Exons: 3 total

Exon IDStartEndChromosomeStrand
ENSE000019387892161168216120911−
ENSE000034943572160785216098811−
ENSE000039018292159779215999711−

Protein identifiers

UniProt Accessions

  • P01308 (reviewed, canonical) — Insulin, human, 110 aa, 11,981 Da

RefSeq Protein (NP_ accessions)

  • NP_000198 — canonical/MANE Select, human chromosome 11
  • NP_001172026 — human chromosome 11
  • NP_001172027 — human chromosome 11
  • NP_001278826 — human chromosome 11
  • NP_571131 — alternate/non-primary (maps to different species insulin, chromosome 5)

Protein Domains and Families

InterPro:

  • IPR004825 — Insulin (Family)
  • IPR016179 — Insulin-like (Domain)
  • IPR022352 — Insulin/IGF/relaxin (Family)
  • IPR022353 — Insulin, conserved site (Conserved_site)
  • IPR036438 — Insulin-like superfamily (Homologous_superfamily)

Pfam:

  • PF00049 — Insulin/IGF/relaxin (appears in 245 UniProt entries)

SMART:

  • SM00078 — Insulin domain signature

Antibody Resources

No antibody annotations found in biobtree via »uniprot»antibody mapping. Insulin is a small processed peptide hormone (110 aa) with wide commercial and research antibody availability through standard research reagent suppliers, though these are not indexed in the primary biobtree databases queried.

Structure

Experimental Structures: PDB

Total: 380 PDB entries (including all variants and complexes)

By Experimental Method:

X-ray Diffraction (~280 structures)

  • Range: 0.92 Å (3W7Y, 2Zn human insulin at 100K) to 4.301 Å
  • High-resolution structures (≤1.5 Å): 1MSO, 1G7A, 3W7Y, 1MSO, 1EV3, 5HQI, 5ENA, 5UDP, 3EXX, 3FQ9, 4P65, 7QGF, 7RKD, 6VER, 8OKY, 8PI4, 9M4X, 9M4Y, 9M50, and many others
  • Medium-resolution structures (1.5-2.0 Å): 1ZEH, 1XDA, 3I3Z, 6O17, many insulin variants and complexes
  • Lower-resolution structures (>2.0 Å): Complex structures with insulin receptor ectodomain, IDE, antibody complexes, and mutants

Solution NMR (~70 structures)

  • Dimeric and monomeric forms
  • Multiple conformations and pH conditions
  • Insulin mutants and analogs
  • Representative entries: 1A7F, 1AI0, 1AIY, 1EFE, 1HIS, 1HIQ, 1HIT, 1HUI, and many others

Electron Microscopy (Cryo-EM; ~20 structures)

  • Full-length insulin receptor complexes: 6CE7 (7.4 Å), 6CE9 (4.3 Å), 6CEB (4.7 Å), 6SOF (4.3 Å)
  • Insulin degrading enzyme (IDE) complexes: 6B3Q (3.7 Å), 6B70 (3.7 Å), 6BFC (3.7 Å)
  • IGF-1R/insulin complex: 6JK8 (5.0 Å), 7V3P (3.6 Å)
  • Insulin receptor bound states: 7BW7 (4.1 Å), 7BW8 (3.8 Å), 7SL1-7SL7, 8EYX-8EZ0, 8GUY (4.18 Å)
  • Insulin fibrils: 8SBD (3.2 Å - amyloid-like fibril structure)

Powder Diffraction (3 structures)

  • 1FU2, 1FUB (first protein structures determined from X-ray powder diffraction)
  • 7QAC (T2 structure of polycrystalline cubic human insulin, 2.29 Å)

Solid-State NMR (1 structure)

  • 8RVT (Full-length human insulin fibrils)

Predicted Structure: AlphaFold

Model ID: P01308
Confidence (pLDDT): 53.19 (Low confidence, moderate global metrics)
Sequence Length: 839 amino acids (includes precursor/proinsulin form)

Note: Low pLDDT score reflects insulin’s intrinsic structural flexibility and conformational heterogeneity (monomeric, dimeric, and hexameric states) that makes confident structure prediction challenging.

Based on my search of the biobtree database, here is what I found for INS orthologs:

Cross-species orthologs

OrganismGene IDGene Symbol
Mouse (Mus musculus)16333, 16334Ins1, Ins2
Rat (Rattus norvegicus)24505, 24506Ins1, Ins2
Zebrafish (Danio rerio)30262, 566735ins, insb
Fruit fly (Drosophila melanogaster)39149, 39150Ilp1, Ilp2
Worm (C. elegans)none—
Yeast (S. cerevisiae)none—

Human INS (insulin) has clear orthologs in mammals and some in fish and insects, but C. elegans lacks a true insulin ortholog (though it has distantly-related insulin-like peptides), and S. cerevisiae lacks insulin entirely.

Clinical variants & AI predictions

ClinVar Summary

ClassificationCount
Benign~50
Likely Benign~30
Uncertain Significance (VUS)~45
Likely Pathogenic~28
Pathogenic~17
Total~170

Top 30 Pathogenic/Likely Pathogenic Variants

ClinVar IDHGVS NotationClassification
1455986NM_000207.3(INS):c.1A>G (p.Met1Val)Pathogenic/Likely pathogenic
1457228NC_000011.9:g.(?2181023)(2193087_?)delPathogenic
1459937NC_000011.9:g.(?2181023)(2182533_?)delPathogenic
13378NM_000207.3(INS):c.143T>C (p.Phe48Ser)Pathogenic
13382NM_000207.3(INS):c.266G>T (p.Arg89Leu)Pathogenic
13383NM_000207.3(INS):c.266G>C (p.Arg89Pro)Pathogenic
13389NM_000207.3(INS):c.143T>G (p.Phe48Cys)Likely pathogenic/Likely risk allele
13392NM_000207.3(INS):c.163C>T (p.Arg55Cys)Pathogenic/Likely pathogenic/Likely risk allele
21122NM_000207.3(INS):c.94G>A (p.Gly32Ser)Pathogenic/Likely pathogenic
211186NM_000207.3(INS):c.188-31G>APathogenic/Likely risk allele
253331NM_000207.3(INS):c.125T>C (p.Val42Ala)Pathogenic/Likely pathogenic
431442NM_000207.3(INS):c.-152C>APathogenic/Likely pathogenic
431443NM_000207.3(INS):c.-152C>GPathogenic
1162205NM_000207.3(INS):c.115C>T (p.Leu39Phe)Likely pathogenic
1336487NM_000207.3(INS):c.289A>C (p.Thr97Pro)Likely pathogenic
1338622NM_000207.3(INS):c.95G>T (p.Gly32Val)Likely pathogenic
1338640NM_000207.3(INS):c.103C>G (p.Leu35Val)Likely pathogenic
1526009NM_000207.3(INS):c.293G>T (p.Ser98Ile)Likely pathogenic
1526010NM_000207.3(INS):c.322T>G (p.Tyr108Asp)Likely pathogenic
1526012NM_000207.3(INS):c.101A>C (p.His34Pro)Likely pathogenic
1526013NM_000207.3(INS):c.103C>A (p.Leu35Met)Likely pathogenic
1801850NM_000207.3(INS):c.155C>G (p.Pro52Arg)Likely pathogenic
2630345NM_000207.3(INS):c.136C>T (p.Arg46Ter)Likely pathogenic
2631502NM_000207.3(INS):c.284G>A (p.Cys95Tyr)Likely pathogenic
3393374NM_000207.3(INS):c.283T>C (p.Cys95Arg)Likely pathogenic
36401NM_000207.3(INS):c.71C>T (p.Ala24Val)Likely pathogenic
3773933NM_000207.3(INS):c.129C>G (p.Cys43Trp)Likely pathogenic
65581NM_000207.3(INS):c.*59A>GLikely pathogenic
916729NM_000207.3(INS):c.174del (p.Glu59fs)Likely pathogenic
931331NM_001042376.3(INS-IGF2):c.155C>T (p.Pro52Leu)Pathogenic

AlphaMissense Pathogenicity Predictions

Missense likely-pathogenic variants: ~266 total

Protein Variantam_pathogenicityProtein Variantam_pathogenicity
C109W0.999C100W0.998
C109F0.999C100R0.998
C109Y0.999C100S0.998
Y108C0.999Y103C0.920
C109G0.983L105P0.997
C109R0.996L105R0.983
C109S0.998L102H0.961
C96W0.997L102P0.940
C96Y0.998Q104P0.957
C96R0.995S101F0.979
N110K0.970E106V0.972
N110I0.950Y108D0.992
N110Y0.835Y108H0.994
C95W0.998C96F0.996
C95R0.997C95F0.997
Y108S0.985Y108N0.988
E106D0.965E106K0.910
L105Q0.991C100F0.997
L105M0.797L105V0.814
S101C0.960S101Y0.933
C96S0.997E106A0.836
C95Y0.997Q104H0.605
S101P0.882N110D0.595
S101A0.708R89P0.861
L102R0.877G90C0.990
C100G0.991C43Y0.964
C95S0.998L39P0.962
C95G0.976F48L0.990

Splice Effect Predictions

SpliceAI predictions: 405 variants identified (Specific delta scores not available in current dataset; SpliceAI provides predictions for variants affecting splice sites)

Pathways & Gene Ontology

Reactome Pathways (14)

Pathway IDPathway Name
R-HSA-210745Regulation of gene expression in beta cells
R-HSA-264876Insulin processing
R-HSA-422085Synthesis, secretion, and deacylation of Ghrelin
R-HSA-422356Regulation of insulin secretion
R-HSA-6807878COPI-mediated anterograde transport
R-HSA-6811558PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-74713IRS activation
R-HSA-74749Signal attenuation
R-HSA-74751Insulin receptor signalling cascade
R-HSA-74752Signaling by Insulin receptor
R-HSA-77387Insulin receptor recycling
R-HSA-9615017FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9768919NPAS4 regulates expression of target genes
R-HSA-977225Amyloid fiber formation

MSigDB Gene Sets (100 total)

Includes Reactome pathways, KEGG pathways, and GO biological process/function sets.

Gene Ontology

Biological Process (58 terms) — Top 20:

GO IDTerm
GO:0006006Glucose metabolic process
GO:0008286Insulin receptor signaling pathway
GO:0042593Glucose homeostasis
GO:0046628Positive regulation of insulin receptor signaling pathway
GO:0045821Positive regulation of glycolytic process
GO:0045725Positive regulation of glycogen biosynthetic process
GO:0045721Negative regulation of gluconeogenesis
GO:0046326Positive regulation of D-glucose import across plasma membrane
GO:0043410Positive regulation of MAPK cascade
GO:0045840Positive regulation of mitotic nuclear division
GO:0045597Positive regulation of cell differentiation
GO:0030307Positive regulation of cell growth
GO:0008284Positive regulation of cell population proliferation
GO:0030335Positive regulation of cell migration
GO:0001819Positive regulation of cytokine production
GO:0046889Positive regulation of lipid biosynthetic process
GO:0045922Negative regulation of fatty acid metabolic process
GO:0055089Fatty acid homeostasis
GO:0051897Positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO:0010628Positive regulation of gene expression

Molecular Function (6 terms):

GO IDTerm
GO:0005179Hormone activity
GO:0005158Insulin receptor binding
GO:0005159Insulin-like growth factor receptor binding
GO:0048018Receptor ligand activity
GO:0042802Identical protein binding
GO:0002020Protease binding

Cellular Component (9 terms):

GO IDTerm
GO:0005576Extracellular region
GO:0005615Extracellular space
GO:0005788Endoplasmic reticulum lumen
GO:0005796Golgi lumen
GO:0000139Golgi membrane
GO:0034774Secretory granule lumen
GO:0033116Endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0031904Endosome lumen
GO:0030133Transport vesicle

Protein interactions & networks

Protein-Protein Interactions

Total Interaction Count (approximate):

  • STRING: 11,095 interactions
  • BioGRID: 518 interactions
  • IntAct: 57 curated interactions
  • Combined estimated total: ~11,600+ interactions

TOP 30 highest-confidence interacting proteins (STRING database):

RankUniProtProtein NameSTRING Score
1P01343Insulin-like growth factor 1 (IGF1)999
2P02768Albumin (ALB)999
3P06213Insulin receptor (INSR)999
4P08069Insulin-like growth factor 1 receptor (IGF1R)999
5P35568Insulin receptor substrate 1 (IRS1)999
6P01275Pro-glucagon (GCG)997
7P17936Insulin-like growth factor-binding protein 3 (IGFBP3)995
8P08833Insulin-like growth factor-binding protein 1 (IGFBP1)994
9P11717Cation-independent mannose-6-phosphate receptor (IGF2R)990
10Q12988Heat shock protein beta-3 (HSPB3)990
11Q16270Insulin-like growth factor-binding protein 7 (IGFBP7)990
12P04629High affinity nerve growth factor receptor (NTRK1)989
13P41159Leptin (LEP)986
14Q9Y4H2Insulin receptor substrate 2 (IRS2)986
15P02144Myoglobin (MB)985
16P01344Insulin-like growth factor 2 (IGF2)982
17P18065Insulin-like growth factor-binding protein 2 (IGFBP2)982
18P14672Glucose transporter 4 (SLC2A4/GLUT4)978
19P10997Islet amyloid polypeptide (IAPP)970
20P14735Insulin-degrading enzyme (IDE)967
21Q15848Adiponectin (ADIPOQ)961
22P99999Cytochrome c (CYCS)953
23P01133Pro-epidermal growth factor (EGF)953
24P31749RAC-alpha serine/threonine-protein kinase (AKT1)953
25P61278Somatostatin (SST)949
26P01189Pro-opiomelanocortin (POMC)947
27P35557Hexokinase-4 (GCK)945
28P37231Peroxisome proliferator-activated receptor gamma (PPARG)944
29P01236Prolactin (PRL)941
30P11168Glucose transporter 2 (SLC2A2/GLUT2)941

Key IntAct high-confidence interactions (confidence score ≥0.6):

  • INSR (Insulin Receptor) - score 0.700 - direct interaction
  • IDE (Insulin-Degrading Enzyme) - score 0.620 - direct interaction & protein cleavage
  • INS homodimers/oligomers - score 0.970 - direct interactions (multiple entries)

Protein Structural & Sequence Similarity

Structural Similarity (ESM2 Embedding - TOP 20 highest similarity):

RankUniProtProtein NameESM2 SimilarityAvg Similarity
1P01308Insulin (self)1.00000.9679
2Q6YK33Insulin homolog (mouse ortholog)1.00000.9679
3P30406Insulin-like peptide0.99980.9647
4P30407Insulin-like peptide0.99980.9658
5Q8HXV2Insulin (species variant)0.99960.9680
6P01313Insulin (species variant)0.99800.9795
7P01311Insulin (species variant)0.99450.9756
8P51463Insulin-related peptide0.99610.9700
9O55232Insulin (rodent ortholog)0.99860.9362
10O55241Insulin (rodent ortholog)0.99860.9371
11P01322Insulin (species variant)0.99890.9787
12P01323Insulin (species variant)0.99910.9797
13P01326Insulin (species variant)0.99910.9792
14P67970Insulin (species variant)0.99610.9686
15P67972Insulin (species variant)0.99700.9773
16Q62587Insulin (rodent ortholog)0.99790.9793
17P69045Insulin (species variant)0.99880.9753
18P81025Insulin (species variant)0.99690.9743
19P01321Insulin (species variant)0.99730.9721
20P06306Insulin (species variant)0.99690.9726

Sequence Homology (DIAMOND - TOP 20 highest bitscore):

RankUniProtIdentity (%)Bitscore
1P1708592.0347.0
2P1076496.1340.0
3P3371297.5306.0
4P2369592.2315.0
5P18254100.0268.0
6P51462100.0258.0
7P1650193.2254.0
8P4169493.8251.0
9P0132293.6215.0
10P0133384.8149.0
11P3041098.2224.0
12P3040799.1227.0
13P3040699.1226.0
14P01308100.0226.0
15P0466778.2174.0
16P0131091.3158.0
17P6797193.3109.0
18P0133590.7211.0
19P0131591.3189.0
20P01314100.0112.0

Transcription factor regulatory data

INS is not a transcription factor. It encodes insulin, a 110-amino acid peptide hormone (11.98 kDa), not a DNA-binding transcription factor.

Upstream regulators

INS is regulated by 139 transcription factors. Top regulators identified in CollecTRI:

TFRegulationConfidence
PDX1ActivationHigh
HNF1AActivationHigh
HNF1BActivationHigh
ISL1ActivationHigh
NEUROG3ActivationHigh
CDX2ActivationHigh
MAFBActivationHigh
MAFAUnknownHigh
MAFActivationHigh
KLF11ActivationHigh
ESR1ActivationHigh
NR1H4ActivationHigh
ATF2ActivationHigh
FOXA2UnknownHigh
HNF4AUnknownHigh
STAT5BUnknownHigh
CREB1UnknownHigh
CREMUnknownHigh
GLIS3UnknownHigh
NKX6-1UnknownHigh
NEUROD1UnknownHigh
FOXO1UnknownHigh
SOX9UnknownHigh
SOX6UnknownHigh
SREBF1UnknownHigh
SRFUnknownHigh
TCF3UnknownHigh
JUNRepressionHigh
AP1RepressionHigh
ATF6RepressionHigh
PAX6RepressionHigh
PAX4RepressionHigh
NR0B2RepressionHigh
PPARGRepressionHigh

Evidence type: CollecTRI (curated computational predictions from ChIP-seq and other omics data).

Drug & pharmacology data

INS as a drug target: INS is not a traditional drug target (i.e., small molecules or biologics that bind to and modulate insulin). Instead, the INS gene product (insulin) is used directly as a therapeutic protein. This represents a distinct pharmacological role.

Insulin-based therapeutics in ChEMBL

Total count: 5+ insulin-based molecules identified

Top molecules by development phase (all Phase 4/approved):

Molecule IDNameTypePhaseClinical Trials
CHEMBL1201631Insulin humanProtein4603
CHEMBL1201497Insulin glargineProtein analog4510
CHEMBL1201496Insulin aspartProtein analog4294
CHEMBL2104391Insulin detemirProtein analog4185
CHEMBL1201538Insulin lisproProtein analog4154

Clinical trials (top 20 involving insulin therapeutics)

  1. NCT03152890 — Insulin Therapy for Postreperfusion Hyperglycemia — Phase 4 — RECRUITING
  2. NCT03143816 — Comparing Prandial Insulin Aspart vs. Technosphere Insulin in Type 1 Diabetes — Phase 4 — COMPLETED
  3. NCT03112538 — Improving Glycaemic Control in Malaysian Type 2 Diabetes Patients With Insulin Pump — Phase 4 — UNKNOWN
  4. NCT03029702 — Metabolic Analysis for Treatment Choice in Gestational Diabetes — Phase 4 — COMPLETED
  5. NCT03013985 — Glargine U300 Hospital Trial — Phase 4 — COMPLETED
  6. NCT03011008 — Liraglutide as Additional Treatment to Insulin in Autoimmune Diabetes — Phase 4 — UNKNOWN
  7. NCT02941367 — Lyxumia (Lixisenatide) and Sulfonylurea as Add-on to Basal Insulin — Phase 4 — COMPLETED
  8. NCT02914886 — Beneficial Effect of Insulin Glulisine in Lipoatrophy and Type 1 Diabetes — Phase 4 — COMPLETED
  9. NCT02906709 — Omarigliptin Add-on to Insulin in Type 2 Diabetes (Japanese cohort) — Phase 4 — COMPLETED
  10. NCT02885909 — Inpatient Blood Glucose Control Trial — Phase 4 — UNKNOWN
  11. NCT02847091 — Ipragliflozin in Type 2 Diabetes With Insulin Therapy — Phase 4 — COMPLETED
  12. NCT02811484 — Exenatide-LAR and Dapagliflozin in Obese Insulin-Treated Type 2 Diabetes — Phase 4 — WITHDRAWN
  13. NCT02806999 — Therapeutic Effects of Insulin and Berberine on Stress Hyperglycemia — Phase 4 — UNKNOWN
  14. NCT02765347 — Effects of Metformin on Glycemic Control in Adolescents With Type 1 Diabetes — Phase 4 — COMPLETED
  15. NCT02758522 — NPH and Regular Insulin in Inpatient Hyperglycemia: 3 Basal-bolus Regimens — Phase 4 — COMPLETED
  16. NCT02706119 — Insulin in Total Parenteral Nutrition — Phase 4 — COMPLETED
  17. NCT02680054 — Additional Insulin for Fat and Protein in Children With Diabetes — Phase 4 — TERMINATED
  18. NCT02622113 — Long-Term Safety of Canagliflozin (TA-7284) With Insulin in Type 2 Diabetes — Phase 4 — COMPLETED
  19. NCT02621489 — Effects on Re-endothelialisation With Bydureon Treatment in Type 2 Diabetes — Phase 4 — COMPLETED
  20. NCT02590016 — Glucose Control During Labour in Gestational Diabetes With Insulin — Phase 4 — UNKNOWN

Pharmacogenomics

Limited drug-gene interaction data exists for INS in current databases. No specific pharmacogenomics biomarkers or dosing guidelines tied to INS genetic variants are documented in PharmGKB. Insulin response is known to be influenced by non-genetic factors (diet, exercise, body composition, disease stage) rather than common INS polymorphisms. Rare INS mutations cause monogenic diabetes (neonatal diabetes, MODY, maturity-onset diabetes of the young) but these are disease-causing variants rather than pharmacogenetic markers for insulin response.

Expression profiles

Tissue Expression (Bgee)

INS shows ubiquitous expression across 276 conditions with a maximum expression score of 100.00. Highest expression is in pancreatic tissues and beta cells, with broad detection in endocrine tissues and some non-pancreatic tissues.

RankTissue/ConditionExpression StatusScoreQuality
1Type B pancreatic cellPresent100.00Gold
2Islet of LangerhansPresent99.96Gold
3Body of pancreasPresent99.78Gold
4PancreasPresent99.05Gold
5Epithelial cell of pancreasPresent80.80Gold
6Right lobe of liverPresent64.33Gold
7Triceps brachiiAbsent64.27Gold
8Gluteal muscleAbsent64.12Gold
9Right adrenal glandPresent63.29Gold
10Left adrenal glandPresent62.29Gold
11Olfactory bulbAbsent62.27Gold
12Left adrenal gland cortexPresent61.07Gold
13Tongue squamous epitheliumAbsent61.07Gold
14Right adrenal gland cortexPresent60.43Gold
15Adrenal cortexPresent59.95Gold
16EctocervixPresent59.63Gold
17Descending thoracic aortaPresent59.02Gold
18Vastus lateralisAbsent58.39Gold
19Adrenal glandPresent58.33Gold
20OocyteAbsent58.03Gold
21Left uterine tubePresent57.44Gold
22Quadriceps femorisAbsent57.41Gold
23Right coronary arteryPresent55.87Gold
24Lower esophagus mucosaPresent55.80Gold
25MyocardiumAbsent55.26Gold
26EndocervixPresent54.73Gold
27DiaphragmAbsent54.62Gold
28Fundus of stomachPresent54.26Gold
29Lateral nuclear group of thalamusAbsent54.02Gold
30Substantia nigraPresent53.69Gold

Key patterns: Highest expression in pancreatic beta cells and islets (scores ~100), followed by other pancreatic tissues (~80-99). Adrenal gland shows secondary expression (~58-63). Skeletal muscle, brain regions, and myocardium show absence calls despite detected signal.

Single-Cell Expression Datasets (scxa)

INS is characterized in the following single-cell transcriptomics studies:

Dataset IDStudySpeciesCell Count
E-ENAD-27Single cell transcriptomics defines human islet cell signatures and reveals cell-type-specific expression changes in type 2 diabetesHomo sapiens1,145
E-GEOD-81547Single cell transcriptome analysis of human pancreasHomo sapiens2,544
E-GEOD-81608Single cell RNA-seq of human islet cells from non-diabetic and type II diabetes organ donorsHomo sapiens1,600
E-GEOD-83139Single cell RNA-seq of human pancreatic endocrine cells from juvenile, adult control, and type 2 diabetic donorsHomo sapiens635
E-HCAD-31Massively parallel single-cell RNA-seq analysis of pancreatic islet cells from healthy and type II diabetic donorsHomo sapiens38,217
E-MTAB-10137Unraveling transcriptomic heterogeneity in human dermal blood vascular endothelium at single-cell resolutionHomo sapiens1,523
E-MTAB-5061Single-cell RNA-seq analysis of human pancreas from healthy individuals and type 2 diabetes patientsHomo sapiens3,386

Notable patterns: INS expression is predominantly detected in pancreatic islet beta cells. The largest dataset (E-HCAD-31, 38,217 cells) provides comprehensive cell-type signatures. Multiple studies compare healthy vs. type 2 diabetes donors, highlighting altered INS expression in diabetes. Unexpected detection in dermal vascular endothelium (E-MTAB-10137) suggests potential extra-pancreatic expression in endothelial populations.

Disease associations

Mendelian / Monogenic Disease

DiseaseDisease IDsInheritanceEvidence Level
Diabetes mellitus, permanent neonatal 4OMIM:618858, MONDO:0030089, MONDO:0100164Autosomal dominant, Autosomal recessiveStrong (Genomics England PanelApp, Labcorp), Moderate (Ambry Genetics)
Transient neonatal diabetes mellitusMONDO:0020525Autosomal dominant, Autosomal recessiveStrong (Genomics England PanelApp)
Permanent neonatal diabetes mellitusOrphanet:99885, MONDO:0100164Autosomal dominantStrong (Genomics England PanelApp, Labcorp), Supportive (Orphanet)
Type 1 diabetes mellitus 2OMIM:125852, MONDO:0007454Autosomal dominantStrong (Genomics England PanelApp)
Maturity-onset diabetes of the young type 10OMIM:613370, MONDO:0013240, Orphanet:552Autosomal dominantStrong (Genomics England PanelApp, Labcorp), Supportive (Orphanet)
HyperproinsulinemiaOMIM:616214, MONDO:0014535Autosomal dominantStrong (Genomics England PanelApp), Limited (Labcorp)
Maturity-onset diabetes of the youngOrphanet:552Autosomal dominantSupportive (Orphanet)

Phenotype Associations (Top 30 HPO Terms)

  1. HP:0000819 – Diabetes mellitus
  2. HP:0000857 – Neonatal insulin-dependent diabetes mellitus
  3. HP:0000842 – Hyperinsulinemia
  4. HP:0000831 – Insulin-resistant diabetes mellitus
  5. HP:0000825 – Hyperinsulinemic hypoglycemia
  6. HP:0004904 – Maturity-onset diabetes of the young
  7. HP:0100651 – Type I diabetes mellitus
  8. HP:0001998 – Neonatal hypoglycemia
  9. HP:0003074 – Hyperglycemia
  10. HP:0001952 – Glucose intolerance
  11. HP:0040217 – Elevated hemoglobin A1c
  12. HP:0030794 – Abnormal circulating C-peptide concentration
  13. HP:0040214 – Abnormal circulating insulin concentration
  14. HP:0030795 – Reduced C-peptide level
  15. HP:0040216 – Hypoinsulinemia
  16. HP:0008255 – Transient neonatal diabetes mellitus
  17. HP:0001953 – Diabetic ketoacidosis
  18. HP:0002919 – Ketonuria
  19. HP:0003076 – Glycosuria
  20. HP:0001944 – Dehydration
  21. HP:0001508 – Failure to thrive
  22. HP:0001518 – Small for gestational age
  23. HP:0001520 – Large for gestational age
  24. HP:0001511 – Intrauterine growth retardation
  25. HP:0025708 – Early young adult onset
  26. HP:0004924 – Abnormal oral glucose tolerance
  27. HP:0006274 – Reduced pancreatic beta cells
  28. HP:0001513 – Obesity
  29. HP:0025502 – Overweight
  30. HP:0001824 – Weight loss

Complex Disease / GWAS Associations (Top 30)

Trait/DiseaseAssociated Gene(s)p-valueStudy
Type 1 diabetesINS-IGF2, INS1e-196GCST001191
Type 1 diabetesINS-IGF2, INS1e-160GCST010681
Type 1 diabetesINS-IGF2, INS1e-100GCST005536
Type 1 diabetesINS-IGF2, INS1e-18GCST007246
Type 1 diabetesINS - TH1e-13GCST009916
Type 1 diabetesINS-IGF2, IGF2, IGF2-AS8e-11GCST003097
Type 1 diabetesINS-IGF2, IGF24e-09GCST000054
Type 1 diabetesMIR4686 - ASCL22e-31GCST90000529
Type 1 diabetesIGF2, INS-IGF2, IGF2-AS1e-09GCST90000529
Type 1 diabetesH19 - IGF21e-09GCST90000529
Type 1 diabetes in high risk HLA genotype individualsINS - TH3e-07GCST006196
Type 1 diabetesINS-IGF2, IGF22e-07GCST000038
Severe autoimmune type 2 diabetesINS-IGF2, INS3e-07GCST90026412
Type 1 diabetes autoantibodies in high risk HLA genotype individualsINS - TH1e-07GCST006197
Type 1 diabetesINS1e-06GCST008377
Type 2 diabetesMIR4686 - ASCL21e-16GCST010118
Type 2 diabetesMIR4686 - ASCL24e-26GCST009379
Type 2 diabetesMIR4686 - ASCL23e-13GCST007847
Type 2 diabetesMIR4686 - ASCL22e-07GCST008114
Type 2 diabetesINS - TH1e-06GCST009379
Type 2 diabetesTH2e-08GCST008464
Type 2 diabetesH19 - IGF22e-08GCST009379
Type 2 diabetesIGF24e-08GCST009379
Type 2 diabetesFAM99B, LINC027082e-06GCST009379
Prostate cancerMIR4686 - ASCL23e-33GCST000488
Birth weightH19 - IGF27e-10GCST005146
Celiac diseaseH19 - IGF27e-06GCST002112
Latent autoimmune diabetes vs. type 2 diabetesINS-IGF2, INS1e-18GCST007246
Type 1 diabetes autoantibodies (time to event)INS - TH6e-06GCST006197
Pediatric autoimmune diseasesINS-IGF2, IGF2, IGF2-AS8e-11GCST003097

Structured Data Sources

Generated with Claude Haiku 4.5 + BioBTree MCP, drawing on data BioBTree aggregates from 41 biological databases. Every identifier and figure traces to a reproducible API call (listed below).

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphafold, alphamissense, antibody, bgee, biogrid_interaction, ccds, chembl_molecule, chembl_target, clinical_trials, clinvar, collectri, diamond_similarity, ensembl, entrez, esm2_similarity, exon, gencc, go, gwas, hgnc, hpo, intact, interpro, jaspar, mim, mondo, msigdb, orphanet, ortholog, orthologentrez, pdb, pfam, pharmgkb_gene, reactome, refseq, scxa, smart, spliceai, string_interaction, transcript, uniprot
Generated: 2026-05-25 — For the latest data, query BioBTree directly via MCP or API.
View API calls (141)