Insulinoma-associated 1 (INSM1) gene is intronless and encodes a protein containing both a zinc finger DNA-binding domain and a putative prohormone domain. This gene is a sensitive marker for neuroendocrine differentiation of human lung tumors. [provided by RefSeq, Jul 2008] See more...

Aliases for INSM1 Gene

Aliases for INSM1 Gene

  • INSM Transcriptional Repressor 1 2 3 5
  • IA1 2 3 4
  • Insulinoma-Associated Protein 1 3 4
  • Zinc Finger Protein IA-1 3 4
  • Insulinoma-Associated 1 2 3
  • IA-1 2 3
  • Insulinoma Associated 1 2
  • INSM1 5

External Ids for INSM1 Gene

Previous GeneCards Identifiers for INSM1 Gene

  • GC20P020336
  • GC20P020343
  • GC20P020296
  • GC20P020348

Summaries for INSM1 Gene

Entrez Gene Summary for INSM1 Gene

  • Insulinoma-associated 1 (INSM1) gene is intronless and encodes a protein containing both a zinc finger DNA-binding domain and a putative prohormone domain. This gene is a sensitive marker for neuroendocrine differentiation of human lung tumors. [provided by RefSeq, Jul 2008]

GeneCards Summary for INSM1 Gene

INSM1 (INSM Transcriptional Repressor 1) is a Protein Coding gene. Diseases associated with INSM1 include Insulinoma and Neuroendocrine Tumor. Among its related pathways are Developmental Biology and Regulation of beta-cell development. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and proximal promoter DNA-binding transcription repressor activity, RNA polymerase II-specific. An important paralog of this gene is INSM2.

UniProtKB/Swiss-Prot Summary for INSM1 Gene

  • Sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and/or fetal development. Binds to the consensus sequence 5'-[TG][TC][TC][TT][GA]GGG[CG]A-3' in target promoters. Acts as a transcriptional repressor of NEUROD1 and INS expression via its interaction with cyclin CCND1 in a cell cycle-independent manner. Negatively regulates skeletal muscle-specific gene expression in endocrine cells of the pituitary by inhibiting the Notch signaling pathway. Represses target gene transcription by recruiting chromatin-modifying factors, such as HDAC1, HDAC2, HDAC3, KDM1A and RCOR1 histone deacetylases. Binds to its own promoter, suggesting autoregulation as a self-control feedback mechanism. Competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (PubMed:23721412). Promotes the generation and expansion of neuronal basal progenitor cells in the developing neocortex. Involved in the differentiation of endocrine cells of the developing anterior pituitary gland, of the pancreas and intestine, and of sympatho-adrenal cells in the peripheral nervous system. Promotes cell cycle signaling arrest and inhibition of cellular proliferation.

Gene Wiki entry for INSM1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for INSM1 Gene

Genomics for INSM1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for INSM1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH20J020366 Promoter/Enhancer 1.2 Ensembl ENCODE 250.7 +1.4 1420 5.8 ZNF10 ZSCAN16 POLR2A ZIC2 ZBTB10 FEZF1 ZNF341 KLF7 KLF9 ZNF610 INSM1 lnc-RALGAPA2-4 ENSG00000225417 CFAP61 RALGAPA2 HSALNG0129047
GH20J020367 Enhancer 0.3 Ensembl 250.7 -1.8 -1803 0.2 CBX2 EZH2 INSM1 HSALNG0129045 lnc-RALGAPA2-4 CRNKL1
GH20J020407 Enhancer 1.2 FANTOM5 Ensembl dbSUPER 12.7 +43.4 43397 7.4 NCOR1 IKZF1 ZNF600 ATF2 ZNF10 NFIC ZIC2 HES1 BHLHE40 FEZF1 lnc-CRNKL1-6 INSM1 RPS15AP1 CRNKL1 RPL24P2 HSALNG0129052 piR-39200 RALGAPA2
GH20J020451 Enhancer 1.3 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 12.3 +84.3 84265 0.9 JUND POLR2A SIN3A YY1 EBF1 MAX CTCF BATF NFATC1 NR2F1 lnc-INSM1-8 INSM1 CFAP61 NAA20 ENSG00000225417 lnc-INSM1-4 RALGAPA2
GH20J020392 Enhancer 0.8 Ensembl ENCODE dbSUPER 11.7 +25.7 25697 2.8 ZNF316 NFE2 MAFG EGR1 BHLHE40 NFE2L2 EMSY INSM1 lnc-RALGAPA2-5-002 HSALNG0129052 RALGAPA2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around INSM1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for INSM1

Top Transcription factor binding sites by QIAGEN in the INSM1 gene promoter:
  • aMEF-2
  • MEF-2A
  • RSRFC4
  • Sp1

Genomic Locations for INSM1 Gene

Latest Assembly
chr20:20,368,104-20,370,949
(GRCh38/hg38)
Size:
2,846 bases
Orientation:
Plus strand

Previous Assembly
chr20:20,348,748-20,351,593
(GRCh37/hg19 by Entrez Gene)
Size:
2,846 bases
Orientation:
Plus strand

chr20:20,348,765-20,351,590
(GRCh37/hg19 by Ensembl)
Size:
2,826 bases
Orientation:
Plus strand

Genomic View for INSM1 Gene

Genes around INSM1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
INSM1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for INSM1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for INSM1 Gene

Proteins for INSM1 Gene

  • Protein details for INSM1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q01101-INSM1_HUMAN
    Recommended name:
    Insulinoma-associated protein 1
    Protein Accession:
    Q01101

    Protein attributes for INSM1 Gene

    Size:
    510 amino acids
    Molecular mass:
    52923 Da
    Quaternary structure:
    • Interacts (via the SNAG domain) with HDAC1 (PubMed:16569215). Interacts (via the SNAG domain) with HDAC2 (By similarity). Interacts (via the SNAG domain) with KDM1A (PubMed:23721412). Interacts (via the SNAG domain) with RCOR1. Interacts with SORBS1 (By similarity). Interacts (via the N-terminal region) with CCND1 (via cyclin N-terminal domain); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and increases its transcriptional repressor activity (PubMed:16569215, PubMed:18417529, PubMed:19124461). Interacts with HDAC3; the interaction increases its transcriptional repressor activity (PubMed:16569215, PubMed:18417529).

    Three dimensional structures from OCA and Proteopedia for INSM1 Gene

neXtProt entry for INSM1 Gene

Post-translational modifications for INSM1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for INSM1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for INSM1
  • Boster Bio Antibodies for INSM1

No data available for DME Specific Peptides for INSM1 Gene

Domains & Families for INSM1 Gene

Gene Families for INSM1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for INSM1 Gene

InterPro:
Blocks:
  • C2H2-type zinc finger signature

Suggested Antigen Peptide Sequences for INSM1 Gene

GenScript: Design optimal peptide antigens:
  • Zinc finger protein IA-1 (INSM1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q01101

UniProtKB/Swiss-Prot:

INSM1_HUMAN :
  • The C-terminal region is necessary for NEUROD1 promoter DNA-binding and transcriptional repressor activity.
  • Belongs to the INSM1 family.
Domain:
  • The C-terminal region is necessary for NEUROD1 promoter DNA-binding and transcriptional repressor activity.
Family:
  • Belongs to the INSM1 family.
genes like me logo Genes that share domains with INSM1: view

Function for INSM1 Gene

Molecular function for INSM1 Gene

UniProtKB/Swiss-Prot Function:
Sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and/or fetal development. Binds to the consensus sequence 5'-[TG][TC][TC][TT][GA]GGG[CG]A-3' in target promoters. Acts as a transcriptional repressor of NEUROD1 and INS expression via its interaction with cyclin CCND1 in a cell cycle-independent manner. Negatively regulates skeletal muscle-specific gene expression in endocrine cells of the pituitary by inhibiting the Notch signaling pathway. Represses target gene transcription by recruiting chromatin-modifying factors, such as HDAC1, HDAC2, HDAC3, KDM1A and RCOR1 histone deacetylases. Binds to its own promoter, suggesting autoregulation as a self-control feedback mechanism. Competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (PubMed:23721412). Promotes the generation and expansion of neuronal basal progenitor cells in the developing neocortex. Involved in the differentiation of endocrine cells of the developing anterior pituitary gland, of the pancreas and intestine, and of sympatho-adrenal cells in the peripheral nervous system. Promotes cell cycle signaling arrest and inhibition of cellular proliferation.
UniProtKB/Swiss-Prot Induction:
Up-regulated by transcription factors, such as MASH1, NEUROD1, NEUROG3, NGN3 and TCF3.
GENATLAS Biochemistry:
insulinoma and other neuroendocrine tumor cell lines,intron less gene

Phenotypes From GWAS Catalog for INSM1 Gene

Gene Ontology (GO) - Molecular Function for INSM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 11842116
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IDA 16569215
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IDA 11842116
GO:0030332 cyclin binding IPI 16569215
genes like me logo Genes that share ontologies with INSM1: view
genes like me logo Genes that share phenotypes with INSM1: view

Animal Models for INSM1 Gene

MGI Knock Outs for INSM1:

miRNA for INSM1 Gene

miRTarBase miRNAs that target INSM1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for INSM1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for INSM1 Gene

Localization for INSM1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for INSM1 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for INSM1 gene
Compartment Confidence
nucleus 5
extracellular 2
cytoskeleton 2
mitochondrion 2
cytosol 2
plasma membrane 1
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for INSM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,ISS --
GO:0005654 nucleoplasm TAS --
GO:0017053 transcriptional repressor complex IBA,IDA 16569215
genes like me logo Genes that share ontologies with INSM1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for INSM1 Gene

Pathways & Interactions for INSM1 Gene

genes like me logo Genes that share pathways with INSM1: view

SIGNOR curated interactions for INSM1 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for INSM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 11842116
GO:0001933 negative regulation of protein phosphorylation IDA 19124461
GO:0003309 type B pancreatic cell differentiation IEA,ISS --
GO:0003310 pancreatic A cell differentiation IEA,ISS --
GO:0003323 type B pancreatic cell development IEA --
genes like me logo Genes that share ontologies with INSM1: view

Drugs & Compounds for INSM1 Gene

(1) Drugs for INSM1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with INSM1: view

Transcripts for INSM1 Gene

mRNA/cDNA for INSM1 Gene

1 REFSEQ mRNAs :
2 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for INSM1

Alternative Splicing Database (ASD) splice patterns (SP) for INSM1 Gene

No ASD Table

Relevant External Links for INSM1 Gene

GeneLoc Exon Structure for
INSM1

Expression for INSM1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for INSM1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for INSM1 Gene

This gene is overexpressed in Pituitary (x16.2), Brain - Cerebellar Hemisphere (x7.3), and Brain - Cerebellum (x6.9).

Protein differential expression in normal tissues from HIPED for INSM1 Gene

This gene is overexpressed in Heart (64.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for INSM1 Gene



Protein tissue co-expression partners for INSM1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for INSM1

SOURCE GeneReport for Unigene cluster for INSM1 Gene:

Hs.89584

mRNA Expression by UniProt/SwissProt for INSM1 Gene:

Q01101-INSM1_HUMAN
Tissue specificity: Expressed in pancreatic duct cells. Expressed in several tumor cell lines of neuroendocrine origin including pheochromocytoma, medullary thyroid carcinoma, insulinoma, medulloblastoma, retinoblastoma, pheochromacytoma, medullary thyroid carcinoma and small cell lung carcinoma.

Evidence on tissue expression from TISSUES for INSM1 Gene

  • Pancreas(3.2)
  • Lung(2.5)
  • Nervous system(2.3)
  • Lymph node(2.1)
genes like me logo Genes that share expression patterns with INSM1: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for INSM1 Gene

Orthologs for INSM1 Gene

This gene was present in the common ancestor of animals.

Orthologs for INSM1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia INSM1 29 30
  • 99.54 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia INSM1 29 30
  • 91.57 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Insm1 29 16 30
  • 87.06 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia LOC100912563 29
  • 84.15 (n)
Dog
(Canis familiaris)
Mammalia INSM1 30
  • 76 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia INSM1 30
  • 63 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia INSM1 30
  • 56 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia INSM1 30
  • 55 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia insm1 29
  • 75.03 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.14733 29
Zebrafish
(Danio rerio)
Actinopterygii insm1a 29 30
  • 66.67 (n)
ManyToMany
insm1b 30
  • 53 (a)
ManyToMany
wufc13a09 29
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4749 29
Fruit Fly
(Drosophila melanogaster)
Insecta nerfin-1 30
  • 21 (a)
ManyToMany
nerfin-2 30 31
  • 16 (a)
ManyToMany
Worm
(Caenorhabditis elegans)
Secernentea egl-46 30
  • 29 (a)
OneToMany
Species where no ortholog for INSM1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for INSM1 Gene

ENSEMBL:
Gene Tree for INSM1 (if available)
TreeFam:
Gene Tree for INSM1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for INSM1: view image
Alliance of Genome Resources:
Additional Orthologs for INSM1

Paralogs for INSM1 Gene

Paralogs for INSM1 Gene

genes like me logo Genes that share paralogs with INSM1: view

Variants for INSM1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for INSM1 Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
rs866758930 Benign: not provided 20,368,447(+) G/A
NM_002196.3(INSM1):c.180G>A (p.Glu60=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for INSM1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for INSM1 Gene

Variant ID Type Subtype PubMed ID
esv2666074 CNV deletion 23128226
nsv1133501 CNV deletion 24896259

Variation tolerance for INSM1 Gene

Gene Damage Index Score: 0.73; 15.41% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for INSM1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
INSM1
Leiden Open Variation Database (LOVD)
INSM1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for INSM1 Gene

Disorders for INSM1 Gene

MalaCards: The human disease database

(26) MalaCards diseases for INSM1 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
insulinoma
  • insulin-producing tumor of islet cells
neuroendocrine tumor
  • neuroendocrine neoplasm
early invasive cervical adenocarcinoma
microinvasive cervical squamous cell carcinoma
  • early invasive cervical squamous cell carcinoma
papillary squamous carcinoma
  • papillary epidermoid carcinoma
- elite association - COSMIC cancer census association via MalaCards
Search INSM1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for INSM1

genes like me logo Genes that share disorders with INSM1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for INSM1 Gene

Publications for INSM1 Gene

  1. INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of cyclin D1 and histone deacetylases. (PMID: 16569215) Liu WD … Lan MS (The Biochemical journal 2006) 2 3 4 22
  2. Genomic organization, 5'-upstream sequence, and chromosomal localization of an insulinoma-associated intronless gene, IA-1. (PMID: 8188699) Lan MS … Notkins AL (The Journal of biological chemistry 1994) 2 3 4 22
  3. IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas. (PMID: 16511571) Mellitzer G … Heimberg H (The EMBO journal 2006) 3 4 22
  4. NeuroD1/E47 regulates the E-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system. (PMID: 12890672) Breslin MB … Lan MS (The Journal of biological chemistry 2003) 3 4 22
  5. Neuroendocrine differentiation factor, IA-1, is a transcriptional repressor and contains a specific DNA-binding domain: identification of consensus IA-1 binding sequence. (PMID: 11842116) Breslin MB … Lan MS (Nucleic acids research 2002) 3 4 22

Products for INSM1 Gene

Sources for INSM1 Gene