This gene represents a homolog of the Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of neurogenesis. The encoded protein is ubiquitinated by RING-IBR-RING-type E3 ubiquitin ligases, including the parkin RBR E3 ubiquitin protein ligase. This gene maps within the so-called Down syndrome chromosomal region, and is thus thought... See more...

Aliases for SIM2 Gene

Aliases for SIM2 Gene

  • SIM BHLH Transcription Factor 2 2 3 5
  • BHLHe15 2 3 4
  • Single-Minded Family BHLH Transcription Factor 2 2 3
  • Class E Basic Helix-Loop-Helix Protein 15 3 4
  • Transcription Factor SIM2 2 3
  • Single-Minded Homolog 2 3 4
  • Single-Minded (Drosophila) Homolog 2 2
  • Single-Minded Homolog 2 (Drosophila) 2
  • MGC119447 2
  • HMC13F06 3
  • HMC29C01 3
  • BHLHE15 4
  • SIM2 5
  • SIM 3

External Ids for SIM2 Gene

Previous HGNC Symbols for SIM2 Gene

  • SIM

Previous GeneCards Identifiers for SIM2 Gene

  • GC21P034649
  • GC21P036991
  • GC21P036992
  • GC21P036993
  • GC21P038071
  • GC21P023547

Summaries for SIM2 Gene

Entrez Gene Summary for SIM2 Gene

  • This gene represents a homolog of the Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of neurogenesis. The encoded protein is ubiquitinated by RING-IBR-RING-type E3 ubiquitin ligases, including the parkin RBR E3 ubiquitin protein ligase. This gene maps within the so-called Down syndrome chromosomal region, and is thus thought to contribute to some specific Down syndrome phenotypes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

GeneCards Summary for SIM2 Gene

SIM2 (SIM BHLH Transcription Factor 2) is a Protein Coding gene. Diseases associated with SIM2 include Down Syndrome and Cyclotropia. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and obsolete signal transducer activity. An important paralog of this gene is SIM1.

UniProtKB/Swiss-Prot Summary for SIM2 Gene

  • Transcription factor that may be a master gene of CNS development in cooperation with Arnt. It may have pleiotropic effects in the tissues expressed during development.

Gene Wiki entry for SIM2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SIM2 Gene

Genomics for SIM2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SIM2 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
GH21J036697 Promoter/Enhancer 2 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 270 +2.0 1977 7 ZSCAN16 ZIC2 ZNF521 ZNF639 MAX ZNF341 ZNF148 GABPB1 CTBP1 SIN3A SIM2 ENSG00000224269 LOC107985492 SETD4 ENSG00000242553 RIMKLBP1 TTC3 DSCR9 MORC3 LOC105369308
GH21J036707 Promoter/Enhancer 1.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 253.2 +8.2 8186 5 CTCF ZIC2 CBX8 MAX ZNF189 ZNF148 POLR2A EZH2 RAD21 USF1 SIM2 RIPPLY3 ENSG00000224269 HSALNG0132958 LOC107985492 HLCS
GH21J036698 Enhancer 0.5 ENCODE dbSUPER 250.7 -1.9 -1879 0.2 CBX8 EZH2 LOC105369308 SIM2 ENSG00000224269 ENSG00000231324 CLDN14
GH21J036730 Enhancer 1 ENCODE dbSUPER 12.2 +31.8 31820 0.2 CEBPA KDM6A FOXA2 SMAD4 SAP130 ETV4 RARA TEAD3 DMAP1 THRB ENSG00000224269 SIM2 RF00017-3701 HSALNG0132958 HLCS
GH21J036772 Enhancer 1 Ensembl ENCODE CraniofacialAtlas 11.2 +74.5 74465 1.6 SMAD4 RXRA RARA TEAD3 ZNF316 JUND HNF4A RAD21 TFAP4 MAX ENSG00000224269 SIM2 RF00017-3702 HSALNG0132959 RF00017-3701 HLCS
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SIM2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SIM2

Top Transcription factor binding sites by QIAGEN in the SIM2 gene promoter:
  • E47
  • HNF-4alpha1
  • IRF-1
  • NF-kappaB
  • NF-kappaB1
  • Nkx2-5
  • Tal-1beta

Genomic Locations for SIM2 Gene

Latest Assembly
chr21:36,699,115-36,750,219
(GRCh38/hg38)
Size:
51,105 bases
Orientation:
Plus strand

Previous Assembly
chr21:38,071,415-38,122,218
(GRCh37/hg19 by Entrez Gene)
Size:
50,804 bases
Orientation:
Plus strand

chr21:38,071,433-38,122,218
(GRCh37/hg19 by Ensembl)
Size:
50,786 bases
Orientation:
Plus strand

Genomic View for SIM2 Gene

Genes around SIM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIM2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIM2 Gene

Proteins for SIM2 Gene

  • Protein details for SIM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14190-SIM2_HUMAN
    Recommended name:
    Single-minded homolog 2
    Protein Accession:
    Q14190
    Secondary Accessions:
    • O60766
    • Q15470
    • Q15471
    • Q15472
    • Q15473
    • Q16532
    • Q2TBD8

    Protein attributes for SIM2 Gene

    Size:
    667 amino acids
    Molecular mass:
    73219 Da
    Quaternary structure:
    • Efficient DNA binding requires dimerization with another bHLH protein. Heterodimer of SIM2 and ARNT.

    Alternative splice isoforms for SIM2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SIM2 Gene

Post-translational modifications for SIM2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SIM2 Gene

Antibodies for research

  • Abcam antibodies for SIM2
  • Boster Bio Antibodies for SIM2
  • Santa Cruz Biotechnology (SCBT) Antibodies for SIM2

No data available for DME Specific Peptides for SIM2 Gene

Domains & Families for SIM2 Gene

Gene Families for SIM2 Gene

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

Protein Domains for SIM2 Gene

InterPro:
Blocks:
  • PAS domain
  • Nuclear translocator signature
  • Basic helix-loop-helix dimerization domain bHLH
  • PAC motif
  • PAS fold-3
  • PAS fold
  • Single-minded, C-terminal
ProtoNet:

Suggested Antigen Peptide Sequences for SIM2 Gene

GenScript: Design optimal peptide antigens:
  • Class E basic helix-loop-helix protein 15 (SIM2_HUMAN)
genes like me logo Genes that share domains with SIM2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for SIM2 Gene

Function for SIM2 Gene

Molecular function for SIM2 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor that may be a master gene of CNS development in cooperation with Arnt. It may have pleiotropic effects in the tissues expressed during development.
GENATLAS Biochemistry:
Drosophila master regulator of fruit fly neurogenesis,single-minded 2 homolog,expressed in brain,kidney,skeletal muscle,prostate,located in the Down syndrome critical region with four alternatively spliced isoforms,involved in the development of midline cells in the central nervous system

Phenotypes From GWAS Catalog for SIM2 Gene

Gene Ontology (GO) - Molecular Function for SIM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISA --
GO:0003677 DNA binding IEA,TAS 8661114
GO:0003700 DNA-binding transcription factor activity IEA,TAS 8661114
GO:0005515 protein binding IEA --
genes like me logo Genes that share ontologies with SIM2: view
genes like me logo Genes that share phenotypes with SIM2: view

Animal Models for SIM2 Gene

MGI Knock Outs for SIM2:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SIM2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SIM2 Gene

Localization for SIM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIM2 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 SIM2 gene
Compartment Confidence
nucleus 5
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SIM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0016604 nuclear body IDA --
genes like me logo Genes that share ontologies with SIM2: view

Pathways & Interactions for SIM2 Gene

PathCards logo

SuperPathways for SIM2 Gene

No Data Available

SIGNOR curated interactions for SIM2 Gene

Activates:

Gene Ontology (GO) - Biological Process for SIM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007275 multicellular organism development IEA --
GO:0007399 nervous system development IEA --
genes like me logo Genes that share ontologies with SIM2: view

No data available for Pathways by source for SIM2 Gene

Drugs & Compounds for SIM2 Gene

No Compound Related Data Available

Transcripts for SIM2 Gene

mRNA/cDNA for SIM2 Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
5 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 SIM2

Alternative Splicing Database (ASD) splice patterns (SP) for SIM2 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12
SP1: - - -
SP2: -
SP3: -
SP4:

Relevant External Links for SIM2 Gene

GeneLoc Exon Structure for
SIM2

Expression for SIM2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SIM2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SIM2 Gene

This gene is overexpressed in Esophagus - Mucosa (x14.0) and Kidney - Cortex (x9.6).

Protein differential expression in normal tissues from HIPED for SIM2 Gene

This gene is overexpressed in Platelet (68.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SIM2 Gene



Protein tissue co-expression partners for SIM2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SIM2

SOURCE GeneReport for Unigene cluster for SIM2 Gene:

Hs.146186

Evidence on tissue expression from TISSUES for SIM2 Gene

  • Nervous system(4.5)
  • Muscle(4.3)
genes like me logo Genes that share expression patterns with SIM2: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for SIM2 Gene

Orthologs for SIM2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SIM2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SIM2 30 31
  • 99.45 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SIM2 30 31
  • 91.67 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SIM2 30 31
  • 89.19 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Sim2 30 17 31
  • 88.31 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Sim2 30
  • 87.6 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia SIM2 31
  • 76 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SIM2 31
  • 65 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SIM2 30 31
  • 73.91 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SIM2 31
  • 66 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia sim2 30
  • 70.89 (n)
African clawed frog
(Xenopus laevis)
Amphibia sim2-A 30
Zebrafish
(Danio rerio)
Actinopterygii sim2 30
  • 73.35 (n)
SIM2 31
  • 32 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta sim 31 32
  • 41 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea hlh-34 31
  • 28 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 62 (a)
OneToMany
Species where no ortholog for SIM2 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)
  • 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 Vase (Ciona intestinalis)
  • 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 SIM2 Gene

ENSEMBL:
Gene Tree for SIM2 (if available)
TreeFam:
Gene Tree for SIM2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SIM2: view image

Paralogs for SIM2 Gene

Paralogs for SIM2 Gene

(4) SIMAP similar genes for SIM2 Gene using alignment to 3 proteins:

  • SIM2_HUMAN
  • H7BZX8_HUMAN
  • V9GY04_HUMAN
genes like me logo Genes that share paralogs with SIM2: view

Variants for SIM2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SIM2 Gene

SNP ID Clinical significance and condition Chr 21 pos Variation AA Info Type
rs112429649 Benign: not provided 36,726,223(+) G/A
NM_005069.6(SIM2):c.648G>A (p.Ser216=)
SYNONYMOUS
rs147054081 Benign: not provided 36,719,859(+) T/C
NM_005069.6(SIM2):c.387T>C (p.His129=)
SYNONYMOUS
rs61750768 Benign: not provided 36,744,946(+) G/A
NM_005069.6(SIM2):c.1386G>A (p.Pro462=)
SYNONYMOUS
rs983944490 Likely Benign: not provided 36,747,792(+) G/C
NM_005069.6(SIM2):c.1704G>C (p.Gly568=)
SYNONYMOUS
rs995636470 Likely Benign: not provided 36,747,876(+) C/T
NM_005069.6(SIM2):c.1788C>T (p.Pro596=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SIM2 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 SIM2 Gene

Variant ID Type Subtype PubMed ID
nsv1073128 CNV deletion 25765185
nsv1133526 CNV deletion 24896259
nsv519597 CNV loss 19592680
nsv828876 CNV loss 20364138
nsv953361 CNV deletion 24416366

Variation tolerance for SIM2 Gene

Residual Variation Intolerance Score: 16% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.65; 86.36% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SIM2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SIM2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIM2 Gene

Disorders for SIM2 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SIM2 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
down syndrome
  • trisomy 21
cyclotropia
hypertropia
holoprosencephaly
  • holoprosencephaly sequence
scoliosis
- elite association - COSMIC cancer census association via MalaCards
Search SIM2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for SIM2

Genetic Association Database
(GAD)
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 SIM2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SIM2 Gene

Publications for SIM2 Gene

  1. A novel nuclear localization signal in the human single-minded proteins SIM1 and SIM2. (PMID: 14697214) Yamaki A … Shimizu Y (Biochemical and biophysical research communications 2004) 3 4 23
  2. Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region. (PMID: 9199934) Chrast R … Antonarakis SE (Genome research 1997) 3 4 23
  3. The mammalian single-minded (SIM) gene: mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome. (PMID: 8661114) Yamaki A … Shimizu N (Genomics 1996) 3 4 23
  4. Down syndrome-critical region contains a gene homologous to Drosophila sim expressed during rat and human central nervous system development. (PMID: 7568099) Dahmane N … Delabar JM (Proceedings of the National Academy of Sciences of the United States of America 1995) 3 4 23
  5. Single minded 2-s (SIM2-s) gene is expressed in human GBM cells and involved in GBM invasion. (PMID: 20448453) He Q … Zhang J (Cancer biology & therapy 2010) 3 23

Products for SIM2 Gene

Sources for SIM2 Gene