Provide a comprehensive cross-database identifier and functional mapping reference for human INS. This should serve as a definitive lookup resource for researchers. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 1: GENE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Provide ALL gene-level database identifiers: - 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 ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 2: TRANSCRIPT IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL transcript-level identifiers: - Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.) How many total transcripts? - RefSeq transcripts: ALL NM_ mRNA accessions Mark which is MANE Select (canonical clinical standard) - CCDS IDs: ALL consensus coding sequence identifiers For the CANONICAL/MANE SELECT transcript: - List ALL exon IDs (ENSE) with genomic coordinates - Total exon count ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 3: PROTEIN IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL protein-level identifiers: - 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 - Include: domain name, type (domain/family/superfamily), and ID ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 4: STRUCTURE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Experimental structures: - List ALL PDB structure IDs - For each: experimental method (X-ray, NMR, Cryo-EM) and resolution - Total PDB structure count Predicted structures: - AlphaFold model ID and confidence metrics (pLDDT) ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 5: CROSS-SPECIES ORTHOLOGS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List orthologous genes in key model organisms (where available): - 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 ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Clinical variant annotations: - Total variant count in clinical databases - Breakdown by classification: Pathogenic, Likely Pathogenic, Uncertain Significance (VUS), Likely Benign, Benign - List TOP 50 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: Total count List TOP 50 predicted splice-altering variants with delta scores - Missense pathogenicity predictions: Total count List TOP 50 predicted pathogenic missense variants with scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Pathway membership: - List ALL biological pathways this gene participates in - Include pathway IDs and names - Total pathway count Gene Ontology annotations: - Biological Process: count and TOP 20 terms with IDs - Molecular Function: count and TOP 20 terms with IDs - Cellular Component: count and TOP 20 terms with IDs ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Protein-protein interactions: - Total interaction count - List TOP 50 highest-confidence interacting proteins with scores Protein similarity (evolutionary and structural): - Structural/embedding similarity: How many similar proteins? List TOP 20 with similarity scores - Sequence homology: How many homologous proteins? List TOP 20 with identity/similarity scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene encodes a transcription factor: Downstream targets (genes regulated BY this TF): - Total target gene count - List TOP 50 target genes with regulation type (activates/represses) DNA binding profiles: - List ALL known binding motif IDs - Motif family classification Upstream regulators (TFs that regulate THIS gene): - List known transcriptional regulators with evidence type ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 10: DRUG & PHARMACOLOGY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene/protein is a drug target: Targeting molecules: - How many drug/compound molecules target this protein? - List TOP 30 molecules by development phase - Include: molecule ID, name, mechanism, highest development phase Clinical trials: - How many clinical trials involve drugs targeting this gene? - List TOP 20 trials with: trial ID, phase, status, intervention Pharmacogenomics: - Known drug-gene interactions affecting drug response - Dosing guidelines if any exist ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 11: EXPRESSION PROFILES ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Tissue expression: - Which tissues express this gene most highly? - List TOP 30 tissues with expression scores/levels - Note any tissue-specific or tissue-enriched patterns Cell type expression: - Which cell types show highest expression? - List TOP 30 cell types with expression scores - Note any cell type-specific patterns Single-cell expression data (if available): - Which single-cell datasets/experiments include this gene? - Notable cell population patterns ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 12: DISEASE ASSOCIATIONS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Mendelian/monogenic disease links: - What diseases are caused by mutations in this gene? - List ALL associated diseases with: disease name, disease ID, inheritance pattern, evidence level Phenotype associations: - What clinical phenotypes are associated with this gene? - List TOP 50 phenotype terms with IDs Complex trait associations (GWAS): - What traits/diseases are linked via genome-wide association studies? - List TOP 30 GWAS associations with: trait, study ID, p-value, effect size if available ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ FORMATTING REQUIREMENTS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ - Present each section with clear headers - Use tables for listing multiple items - Always include COUNTS for every category - For lists with 50 items: show total count + TOP 50 - For lists with

Question

Provide a comprehensive cross-database identifier and functional mapping
reference for human INS. This should serve as a definitive
lookup resource for researchers.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 1: GENE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Provide ALL gene-level database identifiers:
- 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

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 2: TRANSCRIPT IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL transcript-level identifiers:
- Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.)
  How many total transcripts?
- RefSeq transcripts: ALL NM_ mRNA accessions
  Mark which is MANE Select (canonical clinical standard)
- CCDS IDs: ALL consensus coding sequence identifiers

For the CANONICAL/MANE SELECT transcript:
- List ALL exon IDs (ENSE) with genomic coordinates
- Total exon count

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 3: PROTEIN IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL protein-level identifiers:
- 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
- Include: domain name, type (domain/family/superfamily), and ID

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 4: STRUCTURE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Experimental structures:
- List ALL PDB structure IDs
- For each: experimental method (X-ray, NMR, Cryo-EM) and resolution
- Total PDB structure count

Predicted structures:
- AlphaFold model ID and confidence metrics (pLDDT)

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 5: CROSS-SPECIES ORTHOLOGS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List orthologous genes in key model organisms (where available):
- 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
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Clinical variant annotations:
- Total variant count in clinical databases
- Breakdown by classification: Pathogenic, Likely Pathogenic,
  Uncertain Significance (VUS), Likely Benign, Benign
- List TOP 50 pathogenic/likely pathogenic variants with:
  variant ID, HGVS notation, associated condition

AI-based variant effect predictions:
- Splice effect predictions: Total count
  List TOP 50 predicted splice-altering variants with delta scores
- Missense pathogenicity predictions: Total count
  List TOP 50 predicted pathogenic missense variants with scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Pathway membership:
- List ALL biological pathways this gene participates in
- Include pathway IDs and names
- Total pathway count

Gene Ontology annotations:
- Biological Process: count and TOP 20 terms with IDs
- Molecular Function: count and TOP 20 terms with IDs
- Cellular Component: count and TOP 20 terms with IDs

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Protein-protein interactions:
- Total interaction count
- List TOP 50 highest-confidence interacting proteins with scores

Protein similarity (evolutionary and structural):
- Structural/embedding similarity: How many similar proteins?
  List TOP 20 with similarity scores
- Sequence homology: How many homologous proteins?
  List TOP 20 with identity/similarity scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene encodes a transcription factor:

Downstream targets (genes regulated BY this TF):
- Total target gene count
- List TOP 50 target genes with regulation type (activates/represses)

DNA binding profiles:
- List ALL known binding motif IDs
- Motif family classification

Upstream regulators (TFs that regulate THIS gene):
- List known transcriptional regulators with evidence type

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 10: DRUG & PHARMACOLOGY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene/protein is a drug target:

Targeting molecules:
- How many drug/compound molecules target this protein?
- List TOP 30 molecules by development phase
- Include: molecule ID, name, mechanism, highest development phase

Clinical trials:
- How many clinical trials involve drugs targeting this gene?
- List TOP 20 trials with: trial ID, phase, status, intervention

Pharmacogenomics:
- Known drug-gene interactions affecting drug response
- Dosing guidelines if any exist

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 11: EXPRESSION PROFILES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Tissue expression:
- Which tissues express this gene most highly?
- List TOP 30 tissues with expression scores/levels
- Note any tissue-specific or tissue-enriched patterns

Cell type expression:
- Which cell types show highest expression?
- List TOP 30 cell types with expression scores
- Note any cell type-specific patterns

Single-cell expression data (if available):
- Which single-cell datasets/experiments include this gene?
- Notable cell population patterns

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 12: DISEASE ASSOCIATIONS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Mendelian/monogenic disease links:
- What diseases are caused by mutations in this gene?
- List ALL associated diseases with: disease name, disease ID,
  inheritance pattern, evidence level

Phenotype associations:
- What clinical phenotypes are associated with this gene?
- List TOP 50 phenotype terms with IDs

Complex trait associations (GWAS):
- What traits/diseases are linked via genome-wide association studies?
- List TOP 30 GWAS associations with: trait, study ID, p-value,
  effect size if available

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
FORMATTING REQUIREMENTS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
- Present each section with clear headers
- Use tables for listing multiple items
- Always include COUNTS for every category
- For lists with >50 items: show total count + TOP 50
- For lists with <50 items: show ALL items
- Always include database identifiers (IDs), not just names
- Mark canonical/primary/reviewed entries where applicable
- If a section has no data available, state "No data available"
  rather than omitting the section

Accepted Answer

Section 1: Gene Identifiers
DatabaseIdentifierDetails HGNCHGNC:6081Approved symbol: INS HGNC NameinsulinStatus: Approved Ensembl GeneENSG00000254647Homo sapiens NCBI Entrez3630 OMIM176730Gene/locus CCDSCCDS7729 Genomic Location (GRCh38/hg38) AttributeValue Chromosome11 Cytogenetic Band11p15.5 Start Position2,159,779 End Position2,161,221 StrandMinus (-) Gene Length1,443 bp Gene Metadata Locus Type: Gene with protein product (protein-coding) Previous Symbols: IDDM2, IDDM1 Previous Names: …

Transcript ID	Biotype	Start	End	Strand
ENST00000250971	protein_coding	2,159,779	2,161,221	-
ENST00000381330	protein_coding	2,159,779	2,161,209	-
ENST00000397262	protein_coding	2,159,779	2,161,204	-
ENST00000421783	non_stop_decay	2,159,783	2,161,158	-
ENST00000512523	protein_coding	2,159,852	2,160,971	-

RefSeq mRNA	Status	MANE Select
NM_000207	REVIEWED	Yes (Canonical)
NM_001185097	REVIEWED	No
NM_001185098	REVIEWED	No
NM_001291897	REVIEWED	No

RefSeq Protein	Status	MANE Select
NP_000198	REVIEWED	Yes (Canonical)
NP_001172026	REVIEWED	No
NP_001172027	REVIEWED	No
NP_001278826	REVIEWED	No

Exon ID	Start	End	Strand
ENSE00001488186	2,161,142	2,161,221	-
ENSE00003494357	2,160,785	2,160,988	-
ENSE00003901829	2,159,779	2,159,997	-

UniProt ID	Status	Name	Length	Mass
P01308	Reviewed (Swiss-Prot)	Insulin	110 aa	11,981 Da
A6XGL2	Unreviewed	Insulin	-	-
C9JNR5	Unreviewed	Insulin	-	-
I3WAC9	Unreviewed	INS-IGF2 read-through	-	-

INS Gene Complete Identifier and Functional Mapping Reference

Structured Data Sources

Database	Identifier	Details
HGNC	HGNC:6081	Approved symbol: INS
HGNC Name	insulin	Status: Approved
Ensembl Gene	ENSG00000254647	Homo sapiens
NCBI Entrez	3630
OMIM	176730	Gene/locus
CCDS	CCDS7729

Attribute	Value
Chromosome	11
Cytogenetic Band	11p15.5
Start Position	2,159,779
End Position	2,161,221
Strand	Minus (-)
Gene Length	1,443 bp

InterPro ID	Name	Type
IPR004825	Insulin	Family
IPR016179	Insulin-like	Domain
IPR022352	Ins/IGF/rlx	Family
IPR022353	Insulin_CS	Conserved_site
IPR036438	Insulin-like_sf	Homologous_superfamily

PDB ID	Method	Resolution (Å)	Title
3W7Y	X-ray	0.92	2Zn human insulin at 100K
1MSO	X-ray	1.0	T6 Human Insulin
3W7Z	X-ray	1.15	2Zn human insulin at 293K
3TT8	X-ray	1.12	Cu Human Insulin Derivative
1G7A	X-ray	1.2	T3R3 human insulin at 100K
4AJX	X-ray	1.2	Acylated insulin hexamer
1G7B	X-ray	1.3	T3R3 human insulin at 100K
3BXQ	X-ray	1.3	Mutant insulin TR transition
3FQ9	X-ray	1.35	Insulin analog receptor selectivity
3EXX	X-ray	1.35	T6 human insulin with nickel
2OMH	X-ray	1.36	Insulin with ARG-12 peptide
3W80	X-ray	1.4	Dodecamer human insulin
1BEN	X-ray	1.4	Insulin with 4-hydroxybenzamide
4CY7	X-ray	1.4	NMe-AlaB8-insulin
1ZEH	X-ray	1.5	Human insulin
2WRX	X-ray	1.5	NMeAlaB26-insulin at pH 3.0
2WS6	X-ray	1.5	NMeTyrB26-insulin hexamer
4CXL	X-ray	1.5	D-ProB8-insulin
2OMG	X-ray	1.52	Insulin with protamine and urea
4EXX	X-ray	1.55	Human Insulin
2WRU	X-ray	1.57	NMeAlaB26-DTI-NH2
3E7Y	X-ray	1.6	Human insulin
1TRZ	X-ray	1.6	T3R3 human insulin hexamer
1UZ9	X-ray	1.6	N-lithocholyl insulin
2WS1	X-ray	1.6	NMeTyrB26-insulin monomer
1ZEG	X-ray	1.6	B28 Asp insulin with phenol
3ZU1	X-ray	1.6	Insulin degludec
3I3Z	X-ray	1.6	Human insulin
1GUJ	X-ray	1.62	Insulin at pH 2
3UTQ	X-ray	1.67	HLA-A*0201-ALWGPDPAAA

Attribute	Value
AlphaFold ID	AF-P01308-F1
Global pLDDT	53.19
Sequence Length	839 (includes INS-IGF2 read-through)
Fraction Very High Confidence	0.00
Fraction Confident	0.13
Fraction Low	0.37
Fraction Very Low	0.50
Version	4

Species	Gene ID	Symbol	Biotype
Mouse (Mus musculus)	ENSMUSG00000000215	Ins2	protein_coding
Mouse (Mus musculus)	ENSMUSG00000035804	Ins1	protein_coding
Rat (Rattus norvegicus)	ENSRNOG00000012052	Ins1	protein_coding
Rat (Rattus norvegicus)	ENSRNOG00000020405	Ins2	protein_coding
Zebrafish (Danio rerio)	ENSDARG00000035350	ins	protein_coding
Zebrafish (Danio rerio)	ENSDARG00000034610	insb	protein_coding
Fruit fly (D. melanogaster)	No direct ortholog	-	-
Worm (C. elegans)	No direct ortholog	-	-
Yeast (S. cerevisiae)	No data available	-	-

Classification	Count
Pathogenic	12
Likely Pathogenic	22
Pathogenic/Likely Pathogenic	8
Uncertain Significance (VUS)	52
Likely Benign	28
Benign	25
Benign/Likely Benign	15
Conflicting Classifications	25
Not Provided	3

ClinVar ID	HGVS Notation	Classification	Condition
1455986	c.1A>G (p.Met1Val)	Pathogenic/LP	Neonatal diabetes
431443	c.-152C>G	Pathogenic	PNDM
431442	c.-152C>A	Pathogenic/LP	Diabetes
13378	c.143T>C (p.Phe48Ser)	Pathogenic	Hyperinsulinemia
13382	c.266G>T (p.Arg89Leu)	Pathogenic	Diabetes
13383	c.266G>C (p.Arg89Pro)	Pathogenic	Diabetes
13392	c.163C>T (p.Arg55Cys)	Pathogenic/LP	PNDM
21122	c.94G>A (p.Gly32Ser)	Pathogenic/LP	PNDM
253331	c.125T>C (p.Val42Ala)	Pathogenic/LP	MODY10
211186	c.188-31G>A	Pathogenic/LP	PNDM
1162205	c.115C>T (p.Leu39Phe)	Likely Pathogenic	Diabetes
1336487	c.289A>C (p.Thr97Pro)	Likely Pathogenic	Diabetes
1338622	c.95G>T (p.Gly32Val)	Likely Pathogenic	Diabetes
1338640	c.103C>G (p.Leu35Val)	Likely Pathogenic	Diabetes
13389	c.143T>G (p.Phe48Cys)	Likely Pathogenic	Hyperproinsulinemia
1526009	c.293G>T (p.Ser98Ile)	Likely Pathogenic	Diabetes
1526010	c.322T>G (p.Tyr108Asp)	Likely Pathogenic	Diabetes
1526012	c.101A>C (p.His34Pro)	Likely Pathogenic	Diabetes
1526013	c.103C>A (p.Leu35Met)	Likely Pathogenic	Diabetes
1801850	c.155C>G (p.Pro52Arg)	Likely Pathogenic	Diabetes
2630345	c.136C>T (p.Arg46Ter)	Likely Pathogenic	PNDM
2631502	c.284G>A (p.Cys95Tyr)	Likely Pathogenic	Diabetes
3393374	c.283T>C (p.Cys95Arg)	Likely Pathogenic	Diabetes
3773933	c.129C>G (p.Cys43Trp)	Likely Pathogenic	Diabetes
36401	c.71C>T (p.Ala24Val)	Likely Pathogenic	MODY10
65581	c.*59A>G	Likely Pathogenic	Diabetes
916729	c.174del (p.Glu59fs)	Likely Pathogenic	PNDM
1457228	g.(?2181023)(2193087_?)del	Pathogenic	PNDM
1459937	g.(?2181023)(2182533_?)del	Pathogenic	PNDM
931331	INS-IGF2: c.155C>T (p.Pro52Leu)	Pathogenic	Diabetes

Variant	Effect	Delta Score
11:2159796:ATT:A	donor_gain	0.92
11:2159798:T:TA	donor_gain	0.92
11:2159870:CAG:C	acceptor_gain	0.60
11:2159837:G:GA	donor_gain	0.57
11:2159896:TA:T	acceptor_gain	0.55
11:2159873:C:CC	acceptor_gain	0.53
11:2159877:T:A	acceptor_gain	0.51
11:2159897:AC:A	acceptor_gain	0.51
11:2159872:G:C	acceptor_gain	0.48
11:2159938:C:G	acceptor_gain	0.46
11:2159919:CGCTT:C	acceptor_gain	0.45
11:2159986:C:CT	donor_gain	0.45
11:2159871:A:T	acceptor_gain	0.42
11:2159869:CCAG:C	acceptor_gain	0.41
11:2159874:TG:T	acceptor_gain	0.41
11:2159875:GG:G	acceptor_gain	0.41
11:2159876:G:C	acceptor_gain	0.40
11:2159985:TC:T	donor_gain	0.40
11:2159895:G:T	acceptor_gain	0.39
11:2159889:ATGCT:A	acceptor_gain	0.38

Variant	Protein Change	Pathogenicity Score	Classification
11:2159858:G:C	C109W	0.999	likely_pathogenic
11:2159859:C:A	C109F	0.999	likely_pathogenic
11:2159859:C:T	C109Y	0.999	likely_pathogenic
11:2159862:T:C	Y108C	0.999	likely_pathogenic
11:2159885:G:C	C100W	0.998	likely_pathogenic
11:2159886:C:G	C100S	0.998	likely_pathogenic
11:2159886:C:T	C100Y	0.998	likely_pathogenic
11:2159898:C:G	C96S	0.997	likely_pathogenic
11:2159898:C:T	C96Y	0.998	likely_pathogenic
11:2159897:A:C	C96W	0.997	likely_pathogenic
11:2159859:C:G	C109S	0.998	likely_pathogenic
11:2159860:A:G	C109R	0.996	likely_pathogenic
11:2159871:A:G	L105P	0.997	likely_pathogenic
11:2159886:C:A	C100F	0.997	likely_pathogenic
11:2159887:A:G	C100R	0.998	likely_pathogenic
11:2159898:C:A	C96F	0.996	likely_pathogenic
11:2159899:A:G	C96R	0.995	likely_pathogenic
11:2159863:A:G	Y108H	0.994	likely_pathogenic
11:2159863:A:C	Y108D	0.992	likely_pathogenic
11:2159871:A:T	L105Q	0.991	likely_pathogenic
11:2159887:A:C	C100G	0.991	likely_pathogenic
11:2159863:A:T	Y108N	0.988	likely_pathogenic
11:2159862:T:G	Y108S	0.985	likely_pathogenic
11:2159860:A:C	C109G	0.983	likely_pathogenic
11:2159871:A:C	L105R	0.983	likely_pathogenic
11:2159899:A:C	C96G	0.982	likely_pathogenic
11:2159883:G:A	S101F	0.979	likely_pathogenic
11:2159868:T:A	E106V	0.972	likely_pathogenic
11:2159855:G:C	N110K	0.970	likely_pathogenic
11:2159855:G:T	N110K	0.970	likely_pathogenic

Pathway ID	Pathway Name	Disease?
R-HSA-74752	Signaling by Insulin receptor	No
R-HSA-74751	Insulin receptor signalling cascade	No
R-HSA-74713	IRS activation	No
R-HSA-74749	Signal attenuation	No
R-HSA-77387	Insulin receptor recycling	No
R-HSA-264876	Insulin processing	No
R-HSA-422356	Regulation of insulin secretion	No
R-HSA-210745	Regulation of gene expression in beta cells	No
R-HSA-422085	Synthesis, secretion, and deacylation of Ghrelin	No
R-HSA-6807878	COPI-mediated anterograde transport	No
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	No
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	No
R-HSA-9768919	NPAS4 regulates expression of target genes	No
R-HSA-977225	Amyloid fiber formation	No

GO ID	Term
GO:0005179	hormone activity
GO:0005158	insulin receptor binding
GO:0005159	insulin-like growth factor receptor binding
GO:0048018	receptor ligand activity
GO:0042802	identical protein binding
GO:0002020	protease binding

GO ID	Term
GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005788	endoplasmic reticulum lumen
GO:0005796	Golgi lumen
GO:0000139	Golgi membrane
GO:0030133	transport vesicle
GO:0031904	endosome lumen
GO:0033116	ER-Golgi intermediate compartment membrane
GO:0034774	secretory granule lumen

GO ID	Term
GO:0008286	insulin receptor signaling pathway
GO:0042593	glucose homeostasis
GO:0006006	glucose metabolic process
GO:0046326	positive regulation of D-glucose import across plasma membrane
GO:0045725	positive regulation of glycogen biosynthetic process
GO:0045818	negative regulation of glycogen catabolic process
GO:0045821	positive regulation of glycolytic process
GO:0045721	negative regulation of gluconeogenesis
GO:0055089	fatty acid homeostasis
GO:0046889	positive regulation of lipid biosynthetic process
GO:0050995	negative regulation of lipid catabolic process
GO:0045922	negative regulation of fatty acid metabolic process
GO:0008284	positive regulation of cell population proliferation
GO:0030307	positive regulation of cell growth
GO:0030335	positive regulation of cell migration
GO:0045597	positive regulation of cell differentiation
GO:0010976	positive regulation of neuron projection development
GO:0051897	positive regulation of PI3K/AKT signaling
GO:0043410	positive regulation of MAPK cascade
GO:0046628	positive regulation of insulin receptor signaling pathway

Partner UniProt	Gene	Score	Description
P01308	INS	999	Self (homo-oligomerization)
P06213	INSR	999	Insulin receptor
P08069	IGF1R	999	IGF-1 receptor
P35568	IRS1	999	Insulin receptor substrate 1
P02768	ALB	999	Serum albumin
P01343	GH1	999	Growth hormone
P01275	GCG	997	Glucagon
P17936	IGFBP3	995	IGF binding protein 3
P08833	IGFBP1	994	IGF binding protein 1
P11717	IGF2R	990	IGF-2 receptor
Q12988	IGHMBP2	990	Helicase
Q16270	IGFBP7	990	IGF binding protein 7
P04629	NTRK1	989	Neurotrophic receptor
P41159	LEP	986	Leptin
Q9Y4H2	IRS2	986	Insulin receptor substrate 2
P02144	MB	985	Myoglobin
P01344	IGF2	982	IGF-2
P18065	IGFBP2	982	IGF binding protein 2
P14672	SLC2A4	978	GLUT4 transporter
P10997	IAPP	970	Islet amyloid polypeptide
P14735	IDE	967	Insulin-degrading enzyme
Q15848	ADIPOQ	961	Adiponectin
P01133	EGF	953	Epidermal growth factor
P31749	AKT1	953	AKT kinase
P01166	SST	949	Somatostatin
P01189	POMC	947	Proopiomelanocortin
P35557	GCK	945	Glucokinase
P37231	PPARG	944	PPAR-gamma
P01236	PRL	941	Prolactin
P11168	SLC2A2	941	GLUT2 transporter

Partner Gene	Interaction Type	Confidence
INSR	Direct interaction	0.93
INS (self)	Direct interaction	0.97
IDE	Direct interaction, protein cleavage	0.62
IGF1R	Direct binding	0.89
HLA-DRB1	Physical association	0.40
HLA-A	Physical association	0.40
BACE2	Protein cleavage	0.44
DCN	Direct interaction	0.44
MAPK6	Physical association	0.37
LAMA5	Association	0.35
GCG	Colocalization	0.27

UniProt	Top Similarity	Avg Similarity	Description
P01308	1.0000	0.9679	Human INS (self)
Q6YK33	1.0000	0.9679	Insulin
P30407	0.9998	0.9658	Chicken insulin
P30406	0.9998	0.9647	Chicken insulin
Q8HXV2	0.9996	0.9680	Insulin
P30410	0.9994	0.9693	Turkey insulin
P01323	0.9991	0.9797	Rat insulin 2
P01326	0.9991	0.9792	Rat insulin 1
P01322	0.9989	0.9787	Mouse insulin 2
Q91XI3	0.9989	0.9699	Mouse insulin
Q69045	0.9988	0.9753	Bovine insulin
P01325	0.9980	0.9787	Mouse insulin 1
P01313	0.9980	0.9795	Pig insulin
Q62587	0.9979	0.9793	Guinea pig insulin
P01315	0.9975	0.9677	Dog insulin
P01321	0.9973	0.9721	Rabbit insulin
P67972	0.9970	0.9773	Horse insulin
P06306	0.9969	0.9726	Salmon insulin
P81025	0.9969	0.9743	Catfish insulin

UniProt	Identity (%)	Bitscore	Description
P01308	100.0	226.0	Human INS (self)
P18254	100.0	268.0	Primate insulin
P51462	100.0	258.0	Gorilla insulin
P01323	95.8	216.0	Rat Ins2
P01326	95.8	216.0	Rat Ins1
P01317	95.2	209.0	Rabbit insulin
P01318	95.2	209.0	Rabbit insulin
P01322	93.6	215.0	Mouse Ins2
P01313	92.6	207.0	Pig insulin
P01315	91.3	189.0	Dog insulin
P01311	91.3	184.0	Bovine insulin
P01321	91.3	201.0	Rabbit insulin
P01325	91.8	202.0	Mouse Ins1

TF Gene	Regulation	Confidence	Role
PDX1	Activation	High	Master beta-cell TF
MAFA	Activation	High	Beta-cell maturation
MAFB	Activation	High	Beta-cell development
NEUROD1	Activation	High	Beta-cell differentiation
NEUROG3	Activation	High	Endocrine specification
ISL1	Activation	High	Islet cell TF
HNF1A	Activation	High	MODY3 gene
HNF1B	Activation	High	MODY5 gene
NKX6-1	Activation	High	Beta-cell identity
GLIS3	Activation	High	Neonatal diabetes
KLF11	Activation	High	MODY7 gene
CDX2	Activation	High	Homeodomain TF
ESR1	Activation	High	Estrogen receptor
NR1H4	Activation	High	FXR nuclear receptor
ATF2	Activation	High	cAMP-responsive TF

TF Gene	Regulation	Confidence	Role
PAX4	Repression	High	Alpha/beta balance
PAX6	Repression	High	Pancreatic development
JUN	Repression	High	AP-1 component
ATF6	Repression	High	ER stress response
NR0B2	Repression	High	SHP nuclear receptor
PPARG	Repression	High	Adipogenesis master TF
AP1	Repression	High	Stress response
KLF7	Repression	-	KLF family

Target Gene	Effect	Evidence
COMT	Activation	CollecTRI
INSR	Activation	CollecTRI
LPL	Activation	CollecTRI
PPARG	Activation	CollecTRI
HNRNPK	Repression	CollecTRI

Attribute	Value
ChEMBL ID	CHEMBL1201631
Name	INSULIN HUMAN
Type	Protein
Highest Development Phase	Phase 4 (Approved)

ATC Code	Description
A10AB01	Insulin (human) fast-acting
A10AC01	Insulin (human) intermediate-acting
A10AD01	Insulin (human) combinations
A10AE01	Insulin (human) long-acting
A10AF01	Insulin (human) inhalation

Phase	Count	Status Examples
Phase 4	400+	Post-marketing studies
Phase 3	150+	Late-stage efficacy
Phase 2	40+	Dose-finding
Phase 1	10+	Safety studies

Trial ID	Title	Phase	Status
NCT00118963	Repaglinide vs Metformin in Non-Obese T2DM	Phase 4	COMPLETED
NCT00276393	Long Acting Insulin in Type 1 Diabetes	Phase 4	COMPLETED
NCT00384085	Insulin Glargine All to Target Trial	Phase 4	COMPLETED
NCT00535925	Nephropathy In Type 2 Diabetes	Phase 4	COMPLETED
NCT01087567	INSPIRE: Basal Bolus Insulin as Primary Treatment	Phase 4	COMPLETED
NCT01109927	Early Insulin in Latent Autoimmune Diabetes	Phase 4	COMPLETED
NCT01524705	FLAT-SUGAR: GLP-1 and Insulin Study	Phase 4	COMPLETED
NCT02758522	NPH and Regular Insulin Comparison	Phase 4	COMPLETED
NCT03013985	Glargine U300 Hospital Trial	Phase 4	COMPLETED
NCT00365170	Insulin Aspart vs Human Insulin in Pregnancy	Phase 4	COMPLETED

Indication	Development Phase
Diabetes mellitus	Phase 4 (Approved)
Type 1 diabetes	Phase 4
Type 2 diabetes	Phase 4
Gestational diabetes	Phase 4
Diabetic ketoacidosis	Phase 4
Hyperglycemia	Phase 3
Heart failure	Phase 3
Myocardial infarction	Phase 3
Atherosclerosis	Phase 3
Obesity	Phase 1

Attribute	Value
PharmGKB ID	PA201
VIP Gene	Yes (Very Important Pharmacogene)
CPIC Guideline	No
Clinical Annotations	Multiple drug-gene associations

Interaction	Effect	Mechanism	Direct?	Score
INS → INSR	Up-regulates activity	Binding	Yes	0.93
INS → IGF1R	Up-regulates	Binding	Yes	0.89
INS → AKT1	Up-regulates	-	No	0.75
INS → AKT	Up-regulates	-	No	0.75
INS → IRS1	Down-regulates activity	-	No	0.68
INS → SLC2A4	Up-regulates activity	-	No	0.49
INS → PPARG	Up-regulates expression	Transcriptional	No	0.49
INS → FOXO1	Down-regulates activity	-	No	0.48
INS → LPL	Up-regulates	Transcriptional	No	0.46
INS → GSK3B	Down-regulates	-	No	0.46
IDE → INS	Down-regulates (destabilization)	Cleavage	Yes	0.72
PDX1 → INS	Up-regulates expression	Transcriptional	Yes	0.64

Rank	Tissue/Cell Type	Expression	Score	Quality
1	Type B pancreatic cell (β-cell)	Present	100.00	Gold
2	Islet of Langerhans	Present	99.96	Gold
3	Body of pancreas	Present	99.78	Gold
4	Pancreas	Present	99.05	Gold
5	Epithelial cell of pancreas	Present	80.80	Gold
6	Right lobe of liver	Present	64.33	Gold
7	Right adrenal gland	Present	63.29	Gold
8	Left adrenal gland	Present	62.29	Gold
9	Left adrenal gland cortex	Present	61.07	Gold
10	Right adrenal gland cortex	Present	60.43	Gold
11	Adrenal cortex	Present	59.95	Gold
12	Ectocervix	Present	59.63	Gold
13	Descending thoracic aorta	Present	59.02	Gold
14	Adrenal gland	Present	58.33	Gold
15	Left uterine tube	Present	57.44	Gold
16	Right coronary artery	Present	55.87	Gold
17	Lower esophagus mucosa	Present	55.80	Gold
18	Endocervix	Present	54.73	Gold
19	Fundus of stomach	Present	54.26	Gold
20	Substantia nigra	Present	53.69	Gold
21	Spleen	Present	53.16	Gold
22	Uterine cervix	Present	52.58	Gold
23	Urinary bladder	Present	52.35	Gold
24	Midbrain	Present	52.34	Gold
25	Thoracic aorta	Present	52.31	Gold
26	Body of uterus	Present	51.94	Gold
27	Body of stomach	Present	51.82	Gold
28	Ascending aorta	Present	51.79	Gold
29	Esophagus mucosa	Present	51.76	Gold
30	Gall bladder	Present	51.71	Gold

Experiment ID	Description	Species	Cells
E-HCAD-31	Pancreatic islet cells (healthy + T2D)	Homo sapiens	38,217
E-MTAB-5061	Pancreas from healthy + T2D patients	Homo sapiens	3,386
E-GEOD-81547	Single cell human pancreas transcriptome	Homo sapiens	2,544
E-GEOD-81608	Islet cells from diabetic organ donors	Homo sapiens	1,600
E-MTAB-10137	Dermal blood vascular endothelium	Homo sapiens	1,523
E-ENAD-27	Islet cell signatures in T2D	Homo sapiens	1,145
E-GEOD-83139	Pancreatic endocrine cells across ages	Homo sapiens	635

Disease	OMIM/MONDO	Classification	Inheritance	Evidence
Permanent neonatal diabetes mellitus 4	OMIM:618858	Strong	AD & AR	Strong
Maturity-onset diabetes of the young type 10 (MODY10)	OMIM:613370	Strong	AD	Strong
Transient neonatal diabetes mellitus	MONDO:0020525	Strong	AD & AR	Strong
Hyperproinsulinemia	OMIM:616214	Strong/Limited	AD	Strong
Type 1 diabetes mellitus 2	OMIM:125852	Strong	AD	Strong
Permanent neonatal diabetes mellitus	MONDO:0100164	Strong	AD	Strong
MODY (general)	ORPHANET:552	Supportive	AD	Supportive
Isolated permanent neonatal diabetes	ORPHANET:99885	Supportive	AD	Supportive

Orphanet ID	Disease	Type	Gene Count
552	MODY	Disease	13 genes
99885	Isolated permanent neonatal diabetes mellitus	Disease	6 genes

HPO ID	Phenotype
HP:0000819	Diabetes mellitus
HP:0000857	Neonatal insulin-dependent diabetes mellitus
HP:0004904	Maturity-onset diabetes of the young
HP:0100651	Type I diabetes mellitus
HP:0008255	Transient neonatal diabetes mellitus
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000842	Hyperinsulinemia
HP:0000831	Insulin-resistant diabetes mellitus
HP:0003074	Hyperglycemia
HP:0001998	Neonatal hypoglycemia
HP:0001952	Glucose intolerance
HP:0001953	Diabetic ketoacidosis
HP:0003076	Glycosuria
HP:0002919	Ketonuria
HP:0040217	Elevated hemoglobin A1c
HP:0040216	Hypoinsulinemia
HP:0030795	Reduced C-peptide level
HP:0006274	Reduced pancreatic beta cells
HP:0000112	Nephropathy
HP:0000488	Retinopathy
HP:0003477	Peripheral axonal neuropathy
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001520	Large for gestational age
HP:0001513	Obesity
HP:0000956	Acanthosis nigricans
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001508	Failure to thrive
HP:0001263	Global developmental delay

Study ID	Trait	P-value	Mapped Genes
GCST010681	Type 1 diabetes	1×10⁻¹⁶⁰	INS-IGF2, INS
GCST001191	Type 1 diabetes	5×10⁻¹⁹⁶	INS-IGF2, INS
GCST005536	Type 1 diabetes	1×10⁻¹⁰⁰	INS-IGF2, INS
GCST000392	Type 1 diabetes	4×10⁻⁴⁸	MIR4686-ASCL2
GCST000488	Prostate cancer	3×10⁻³³	MIR4686-ASCL2
GCST90000529	Type 1 diabetes	2×10⁻³¹	MIR4686-ASCL2
GCST007847	Type 2 diabetes	3×10⁻¹³	MIR4686-ASCL2
GCST007246	Latent autoimmune diabetes vs T2D	1×10⁻¹⁸	INS-IGF2, INS
GCST010118	Type 2 diabetes	1×10⁻¹⁶	MIR4686-ASCL2
GCST009916	Type 1 diabetes	1×10⁻¹³	INS-TH
GCST003097	Pediatric autoimmune diseases	8×10⁻¹¹	INS-IGF2, IGF2
GCST005146	Birth weight	7×10⁻¹⁰	H19-IGF2
GCST000054	Type 1 diabetes	4×10⁻⁹	INS-IGF2, IGF2