This gene encodes a member of the LIM/homeodomain family of transcription factors. The encoded protein binds to the enhancer region of the insulin gene, among others, and may play an important role in regulating insulin gene expression. The encoded protein is central to the development of pancreatic cell lineages and may also be required for motor neuron generation. Mutations i... See more...

Aliases for ISL1 Gene

Aliases for ISL1 Gene

  • ISL LIM Homeobox 1 2 3 5
  • Insulin Gene Enhancer Protein ISL-1 3 4
  • Islet-1 3 4
  • ISLET1 2 3
  • Isl-1 2 3
  • ISL1 Transcription Factor, LIM/Homeodomain, (Islet-1) 2
  • ISL1 5

External Ids for ISL1 Gene

Previous GeneCards Identifiers for ISL1 Gene

  • GC05P050856
  • GC05P052121
  • GC05P050649
  • GC05P050695
  • GC05P050714
  • GC05P047642

Summaries for ISL1 Gene

Entrez Gene Summary for ISL1 Gene

  • This gene encodes a member of the LIM/homeodomain family of transcription factors. The encoded protein binds to the enhancer region of the insulin gene, among others, and may play an important role in regulating insulin gene expression. The encoded protein is central to the development of pancreatic cell lineages and may also be required for motor neuron generation. Mutations in this gene have been associated with maturity-onset diabetes of the young. [provided by RefSeq, Jul 2008]

GeneCards Summary for ISL1 Gene

ISL1 (ISL LIM Homeobox 1) is a Protein Coding gene. Diseases associated with ISL1 include Bladder Exstrophy And Epispadias Complex and Bladder Exstrophy. Among its related pathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Signaling pathways regulating pluripotency of stem cells. Gene Ontology (GO) annotations related to this gene include sequence-specific DNA binding and RNA polymerase II activating transcription factor binding. An important paralog of this gene is ISL2.

UniProtKB/Swiss-Prot Summary for ISL1 Gene

  • DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina. Involved in the specification of motor neurons in cooperation with LHX3 and LDB1. Binds to insulin gene enhancer sequences. Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (By similarity).

Gene Wiki entry for ISL1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ISL1 Gene

Genomics for ISL1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ISL1 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
GH05J051378 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 250.7 +1.0 971 12.4 ZNF654 ZNF600 JUND POLR2A ZIC2 ZBTB10 ETS1 FEZF1 ZNF341 CTCF ISL1 ISL1-DT EMB HSALNG0041684
GH05J050965 Promoter/Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 23.8 -415.6 -415605 4.7 IRF2 YY1 TAF1 IKZF1 ZNF398 EGR1 SP1 GATA2 KLF1 EGR2 ENSG00000250360 ISL1 ENSG00000248918 PARP8 EMB LINC02106
GH05J050962 Promoter/Enhancer 1.3 ENCODE CraniofacialAtlas dbSUPER 10.1 -419.7 -419700 1.6 MYC ZNF654 ZBTB10 CTCF REST ZNF592 DEK TRIM22 BHLHE40 FEZF1 ENSG00000248918 ISL1 PARP8 EMB piR-38351-367
GH05J051411 Enhancer 0.4 VISTA 11.7 +29.1 29104 1.6 GATA2 CHD2 POLR2A ISL1 HMGB1P47 HSALNG0041688-001 HSALNG0041688-002
GH05J051409 Enhancer 0.2 dbSUPER 12 +26.9 26936 1.9 HMGB1P47 lnc-EMB-9 ISL1 HSALNG0041688-001 HSALNG0041688-002
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ISL1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ISL1

Top Transcription factor binding sites by QIAGEN in the ISL1 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • POU2F1
  • POU2F1a
  • STAT1
  • STAT3

Genomic Locations for ISL1 Gene

Latest Assembly
chr5:51,383,448-51,394,730
(GRCh38/hg38)
Size:
11,283 bases
Orientation:
Plus strand

Previous Assembly
chr5:50,679,282-50,690,564
(GRCh37/hg19 by Entrez Gene)
Size:
11,283 bases
Orientation:
Plus strand

chr5:50,678,921-50,690,564
(GRCh37/hg19 by Ensembl)
Size:
11,644 bases
Orientation:
Plus strand

Genomic View for ISL1 Gene

Genes around ISL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ISL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ISL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ISL1 Gene

Proteins for ISL1 Gene

  • Protein details for ISL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P61371-ISL1_HUMAN
    Recommended name:
    Insulin gene enhancer protein ISL-1
    Protein Accession:
    P61371
    Secondary Accessions:
    • P20663
    • P47894

    Protein attributes for ISL1 Gene

    Size:
    349 amino acids
    Molecular mass:
    39036 Da
    Quaternary structure:
    • At neuronal promoters, displaces LDB1 from LHX3 LIM domain to form a ternary complex in which ISL1 contacts both LHX3 and LDB1. Interacts (via C-terminus) with POU4F2 (via C-terminus). Interacts with POU3F2. Interacts with POU4F3. Interacts (via N-terminal domain) with MLIP; the interaction represses ISL1 transactivator activity (By similarity).

neXtProt entry for ISL1 Gene

Post-translational modifications for ISL1 Gene

Other Protein References for ISL1 Gene

Antibodies for research

No data available for DME Specific Peptides for ISL1 Gene

Domains & Families for ISL1 Gene

Gene Families for ISL1 Gene

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

Protein Domains for ISL1 Gene

Suggested Antigen Peptide Sequences for ISL1 Gene

GenScript: Design optimal peptide antigens:
  • Insulin gene enhancer protein ISL-1 (ISL1_HUMAN)
genes like me logo Genes that share domains with ISL1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ISL1 Gene

Function for ISL1 Gene

Molecular function for ISL1 Gene

UniProtKB/Swiss-Prot Function:
DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina. Involved in the specification of motor neurons in cooperation with LHX3 and LDB1. Binds to insulin gene enhancer sequences. Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (By similarity).
GENATLAS Biochemistry:
islet-1 nuclear protein,binding to the enhancer region of the insulin gene,LIM-homeo doamin family

Phenotypes From GWAS Catalog for ISL1 Gene

Gene Ontology (GO) - Molecular Function for ISL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IEA --
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IEA,ISA --
GO:0000987 proximal promoter sequence-specific DNA binding NAS 7789634
GO:0001102 RNA polymerase II activating transcription factor binding IPI 19619559
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IEA --
genes like me logo Genes that share ontologies with ISL1: view
genes like me logo Genes that share phenotypes with ISL1: view

Human Phenotype Ontology for ISL1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ISL1 Gene

MGI Knock Outs for ISL1:

miRNA for ISL1 Gene

Targeted motifs for ISL1 Gene
HOMER Transcription Factor Regulatory Elements motif ISL1
  • Consensus sequence: CTAATKGV Submotif: canonical Cell Type: Neuron GEO ID: GSE31456

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ISL1

No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targets for ISL1 Gene

Localization for ISL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ISL1 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 ISL1 gene
Compartment Confidence
nucleus 5
cytoskeleton 3
mitochondrion 3
cytosol 3
plasma membrane 2
extracellular 2
endoplasmic reticulum 2
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (2)
  • Nuclear speckles (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ISL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IEA,NAS 7907017
GO:0005737 cytoplasm NAS 7907017
genes like me logo Genes that share ontologies with ISL1: view

Pathways & Interactions for ISL1 Gene

genes like me logo Genes that share pathways with ISL1: view

SIGNOR curated interactions for ISL1 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for ISL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA,ISS --
GO:0001755 neural crest cell migration IEA --
GO:0003007 heart morphogenesis IEA --
GO:0003139 secondary heart field specification IMP 20520780
GO:0003148 outflow tract septum morphogenesis IEA,ISS --
genes like me logo Genes that share ontologies with ISL1: view

Drugs & Compounds for ISL1 Gene

(2) Additional Compounds for ISL1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ISL1: view

Transcripts for ISL1 Gene

mRNA/cDNA for ISL1 Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
3 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 ISL1

Alternative Splicing Database (ASD) splice patterns (SP) for ISL1 Gene

No ASD Table

Relevant External Links for ISL1 Gene

GeneLoc Exon Structure for
ISL1

Expression for ISL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ISL1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ISL1 Gene

This gene is overexpressed in Vagina (x9.9), Prostate (x6.4), Stomach (x5.9), Esophagus - Gastroesophageal Junction (x5.4), and Cervix - Ectocervix (x4.6).

Protein differential expression in normal tissues from HIPED for ISL1 Gene

This gene is overexpressed in Retina (61.3) and Skin (7.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ISL1 Gene



Protein tissue co-expression partners for ISL1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ISL1

SOURCE GeneReport for Unigene cluster for ISL1 Gene:

Hs.505

mRNA Expression by UniProt/SwissProt for ISL1 Gene:

P61371-ISL1_HUMAN
Tissue specificity: Expressed in subsets of neurons of the adrenal medulla and dorsal root ganglion, inner nuclear and ganglion cell layers in the retina, the pineal and some regions of the brain.

Evidence on tissue expression from TISSUES for ISL1 Gene

  • Pancreas(4.5)
  • Blood(4.4)
  • Nervous system(2.9)
  • Eye(2.6)
  • Muscle(2.5)
  • Heart(2.5)
  • Liver(2.4)
  • Skin(2.3)
  • Kidney(2.1)
  • Stomach(2)
  • Adrenal gland(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ISL1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • immune
  • reproductive
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Abdomen:
  • abdominal wall
  • intestine
  • kidney
Pelvis:
  • anus
  • pelvis
  • penis
  • rectum
  • ureter
  • urethra
  • urinary bladder
  • vulva
General:
  • blood
  • white blood cell
genes like me logo Genes that share expression patterns with ISL1: view

Primer products for research

Orthologs for ISL1 Gene

This gene was present in the common ancestor of animals.

Orthologs for ISL1 Gene

Organism Taxonomy Gene Similarity Type Details
Oppossum
(Monodelphis domestica)
Mammalia ISL1 30
  • 100 (a)
OneToOne
Chimpanzee
(Pan troglodytes)
Mammalia ISL1 29 30
  • 99.71 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia ISL1 30
  • 98 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia ISL1 30
  • 96 (a)
OneToOne
LOC612954 29
  • 95.22 (n)
Cow
(Bos Taurus)
Mammalia ISL1 29 30
  • 93.98 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Isl1 29
  • 93.22 (n)
Mouse
(Mus musculus)
Mammalia Isl1 29 16 30
  • 93.03 (n)
OneToOne
Chicken
(Gallus gallus)
Aves ISL1 29 30
  • 89.49 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ISL1 30
  • 92 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia Str.10452 29
Zebrafish
(Danio rerio)
Actinopterygii isl1 29 30
  • 80.99 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta tup 29 30 31
  • 62.23 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010209 29
  • 61.44 (n)
Worm
(Caenorhabditis elegans)
Secernentea lim-7 29 30
  • 51.05 (n)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 54 (a)
OneToMany
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.14227 29
Species where no ortholog for ISL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • 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)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • 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 ISL1 Gene

ENSEMBL:
Gene Tree for ISL1 (if available)
TreeFam:
Gene Tree for ISL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ISL1: view image
Alliance of Genome Resources:
Additional Orthologs for ISL1

Paralogs for ISL1 Gene

Paralogs for ISL1 Gene

(14) SIMAP similar genes for ISL1 Gene using alignment to 2 proteins:

  • ISL1_HUMAN
  • D6RBJ1_HUMAN
genes like me logo Genes that share paralogs with ISL1: view

Variants for ISL1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ISL1 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
rs121913540 Benign: not provided 51,389,680(+) G/A
NM_002202.3(ISL1):c.513G>A (p.Arg171=)
SYNONYMOUS
rs121913541 Benign: not provided 51,389,734(+) C/T
NM_002202.3(ISL1):c.567C>T (p.Asn189=)
SYNONYMOUS
rs1561208602 Uncertain Significance: Heart, malformation of 51,391,273(+) G/A
NM_002202.3(ISL1):c.766-1G>A
SPLICE_ACCEPTOR
rs202190389 Likely Benign: not provided 51,391,264(+) C/T
NM_002202.3(ISL1):c.766-10C>T
INTRON
rs2303750 Uncertain Significance: Exstrophy-epispadias complex 51,389,642(+) G/A
NM_002202.3(ISL1):c.479-4G>A
INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ISL1 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 ISL1 Gene

Variant ID Type Subtype PubMed ID
nsv830288 CNV gain 17160897

Variation tolerance for ISL1 Gene

Residual Variation Intolerance Score: 30.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.63; 56.63% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ISL1 Gene

Human Gene Mutation Database (HGMD)
ISL1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ISL1
Leiden Open Variation Database (LOVD)
ISL1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ISL1 Gene

Disorders for ISL1 Gene

MalaCards: The human disease database

(31) MalaCards diseases for ISL1 Gene - From: ORP, COP, and GCD

Disorder Aliases PubMed IDs
bladder exstrophy and epispadias complex
  • beec
bladder exstrophy
  • exstrophy of the bladder
double outlet right ventricle
  • dextrotransposition of aorta
salivary gland carcinoma
  • salivary gland cancer
bladder exstrophy-epispadias-cloacal exstrophy complex
  • exstrophy-epispadias complex
- elite association - COSMIC cancer census association via MalaCards
Search ISL1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ISL1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with ISL1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ISL1 Gene

Publications for ISL1 Gene

  1. Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected]. (PMID: 7912209) Tanizawa Y … Permutt MA (Diabetes 1994) 2 3 4 22
  2. Association study for genes at chromosome 5p13-q11 in attention deficit hyperactivity disorder. (PMID: 18081024) Laurin N … Barr CL (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2008) 3 22 40
  3. The LIM domain homeobox gene isl-1: conservation of human, hamster, and rat complementary deoxyribonucleic acid sequences and expression in cell types of nonneuroendocrine lineage. (PMID: 7907017) Wang M … Drucker DJ (Endocrinology 1994) 3 4 22
  4. Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy. (PMID: 25763902) Draaken M … Reutter H (PLoS genetics 2015) 3 72
  5. Common variation in ISL1 confers genetic susceptibility for human congenital heart disease. (PMID: 20520780) Stevens KN … Gruber PJ (PloS one 2010) 3 40

Products for ISL1 Gene

Sources for ISL1 Gene