This gene is a member of the homeobox family of genes that encode proteins containing a 60-amino acid residue motif that represents a DNA binding domain. Homeobox genes have been characterized extensively as transcriptional regulators involved in pattern formation in both invertebrate and vertebrate species. Several human genetic disorders are caused by aberrations in human hom... See more...

Aliases for SHOX2 Gene

Aliases for SHOX2 Gene

  • Short Stature Homeobox 2 2 3 5
  • OG12X 2 3 4
  • SHOT 2 3 4
  • Paired-Related Homeobox Protein SHOT 3 4
  • Short Stature Homeobox Protein 2 3 4
  • Homeobox Protein Og12X 3 4
  • OG12 2 3
  • SHOX Homologous Gene On Chromosome 3 3
  • SHOX2 5

External Ids for SHOX2 Gene

Previous GeneCards Identifiers for SHOX2 Gene

  • GC03M154850
  • GC03M158760
  • GC03M159095
  • GC03M159135
  • GC03M159297
  • GC03M157813
  • GC03M155210

Summaries for SHOX2 Gene

Entrez Gene Summary for SHOX2 Gene

  • This gene is a member of the homeobox family of genes that encode proteins containing a 60-amino acid residue motif that represents a DNA binding domain. Homeobox genes have been characterized extensively as transcriptional regulators involved in pattern formation in both invertebrate and vertebrate species. Several human genetic disorders are caused by aberrations in human homeobox genes. This locus represents a pseudoautosomal homeobox gene that is thought to be responsible for idiopathic short stature, and it is implicated in the short stature phenotype of Turner syndrome patients. This gene is considered to be a candidate gene for Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

GeneCards Summary for SHOX2 Gene

SHOX2 (Short Stature Homeobox 2) is a Protein Coding gene. Diseases associated with SHOX2 include Turner Syndrome and Cornelia De Lange Syndrome. Gene Ontology (GO) annotations related to this gene include sequence-specific DNA binding. An important paralog of this gene is SHOX.

UniProtKB/Swiss-Prot Summary for SHOX2 Gene

  • May be a growth regulator and have a role in specifying neural systems involved in processing somatosensory information, as well as in face and body structure formation.

Gene Wiki entry for SHOX2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SHOX2 Gene

Genomics for SHOX2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SHOX2 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
GH03J158101 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 261.1 -0.5 -526 10.9 BCLAF1 SP1 ZNF207 MYC IKZF1 ZNF600 ZNF580 KLF9 POLR2A CEBPA SHOX2 RSRC1 CCNL1 LXN MLF1 ENSG00000240207 ENSG00000272247 GFM1 RF00994-696
GH03J158057 Enhancer 1 VISTA UCNEbase 7.8 +47.3 47338 2.3 FOXK2 ATF2 MEIS2 CUX1 PKNOX1 CTBP1 SOX6 POLR2A SHOX2 ENSG00000242536 MLF1 piR-60885-084 MK280073-477 RSRC1 VEPH1
GH03J158094 Enhancer 0.5 Ensembl 10.8 +11.3 11298 2 EBF1 BHLHE40 CBX8 ZBTB33 NR2F1 RAD21 EZH2 POLR2A SHOX2 ENSG00000242536 RSRC1 VEPH1
GH03J158160 Enhancer 0.9 Ensembl ENCODE 5 -53.7 -53681 3.4 NCOR1 ATF2 TAL1 ZNF316 ZNF843 MYNN PRDM6 JUND FOXM1 HDAC2 HSALNG0030145 lnc-SHOX2-3 ENSG00000240207 RSRC1 SHOX2 MLF1 lnc-SHOX2-7 ENSG00000241723
GH03J158419 Enhancer 0.9 Ensembl ENCODE 4.6 -314.5 -314481 2.2 BCLAF1 BCL11A TRIM22 IRF4 SMARCA5 SPI1 BATF STAT5A IKZF1 BMI1 RSRC1 MLF1 ENSG00000271778 SHOX2 L13713-163 RF00994-697
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SHOX2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SHOX2

Top Transcription factor binding sites by QIAGEN in the SHOX2 gene promoter:
  • aMEF-2
  • AREB6
  • COMP1
  • CP2
  • CUTL1
  • POU3F2

Genomic Locations for SHOX2 Gene

Latest Assembly
chr3:158,095,905-158,106,420
(GRCh38/hg38)
Size:
10,516 bases
Orientation:
Minus strand

Previous Assembly
chr3:157,813,694-157,824,209
(GRCh37/hg19 by Entrez Gene)
Size:
10,516 bases
Orientation:
Minus strand

chr3:157,814,948-157,824,292
(GRCh37/hg19 by Ensembl)
Size:
9,345 bases
Orientation:
Minus strand

Genomic View for SHOX2 Gene

Genes around SHOX2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SHOX2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SHOX2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SHOX2 Gene

Proteins for SHOX2 Gene

  • Protein details for SHOX2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O60902-SHOX2_HUMAN
    Recommended name:
    Short stature homeobox protein 2
    Protein Accession:
    O60902
    Secondary Accessions:
    • O60465
    • O60467
    • O60903

    Protein attributes for SHOX2 Gene

    Size:
    331 amino acids
    Molecular mass:
    34953 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAC39662.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAA05341.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAA05342.1; Type=Erroneous initiation; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 1]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Alternative splice isoforms for SHOX2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SHOX2 Gene

Post-translational modifications for SHOX2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for SHOX2 Gene

Domains & Families for SHOX2 Gene

Gene Families for SHOX2 Gene

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

Protein Domains for SHOX2 Gene

InterPro:
Blocks:
  • Lambda and other repressor helix-turn-helix signature
  • Paired-like homeodomain protein, OAR

Suggested Antigen Peptide Sequences for SHOX2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ38019 fis, clone CTONG2012758, highly similar to Short stature homeobox protein 2 (A6NLG4_HUMAN)
  • Paired-related homeobox protein SHOT (SHOX2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O60902

UniProtKB/Swiss-Prot:

SHOX2_HUMAN :
  • Belongs to the paired homeobox family. Bicoid subfamily.
Family:
  • Belongs to the paired homeobox family. Bicoid subfamily.
genes like me logo Genes that share domains with SHOX2: view

Function for SHOX2 Gene

Molecular function for SHOX2 Gene

UniProtKB/Swiss-Prot Function:
May be a growth regulator and have a role in specifying neural systems involved in processing somatosensory information, as well as in face and body structure formation.
GENATLAS Biochemistry:
murine homeo box Og12X homolog,strongly expressed in developing craniofacial,brain,heart and in the mesenchym of developing limbs,highly homologous to SHOX

Phenotypes From GWAS Catalog for SHOX2 Gene

Gene Ontology (GO) - Molecular Function for SHOX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IEA,ISA --
GO:0003677 DNA binding IEA --
GO:0005515 protein binding IPI --
GO:1990837 sequence-specific double-stranded DNA binding IBA 21873635
genes like me logo Genes that share ontologies with SHOX2: view
genes like me logo Genes that share phenotypes with SHOX2: view

Animal Models for SHOX2 Gene

MGI Knock Outs for SHOX2:

miRNA for SHOX2 Gene

miRTarBase miRNAs that target SHOX2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SHOX2

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SHOX2 Gene

Localization for SHOX2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SHOX2 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 SHOX2 gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
cytosol 2
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for SHOX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IEA,IBA 21873635
genes like me logo Genes that share ontologies with SHOX2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SHOX2 Gene

Pathways & Interactions for SHOX2 Gene

PathCards logo

SuperPathways for SHOX2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for SHOX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II ISS --
GO:0001501 skeletal system development TAS 9482898
GO:0001649 osteoblast differentiation IEA --
GO:0002053 positive regulation of mesenchymal cell proliferation IEA --
GO:0002062 chondrocyte differentiation IEA --
genes like me logo Genes that share ontologies with SHOX2: view

No data available for Pathways by source and SIGNOR curated interactions for SHOX2 Gene

Drugs & Compounds for SHOX2 Gene

No Compound Related Data Available

Transcripts for SHOX2 Gene

mRNA/cDNA for SHOX2 Gene

3 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
6 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 SHOX2

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for SHOX2 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b · 7c
SP1: - - -
SP2: - - - -
SP3: - - - - -
SP4: -
SP5:

Relevant External Links for SHOX2 Gene

GeneLoc Exon Structure for
SHOX2

Expression for SHOX2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SHOX2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SHOX2 Gene

This gene is overexpressed in Artery - Tibial (x7.2), Nerve - Tibial (x6.2), and Adipose - Subcutaneous (x5.1).

Protein differential expression in normal tissues from HIPED for SHOX2 Gene

This gene is overexpressed in Pancreas (25.0), Platelet (17.9), and Urine (13.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SHOX2 Gene



Protein tissue co-expression partners for SHOX2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SHOX2

SOURCE GeneReport for Unigene cluster for SHOX2 Gene:

Hs.55967

mRNA Expression by UniProt/SwissProt for SHOX2 Gene:

O60902-SHOX2_HUMAN
Tissue specificity: Expressed in heart, skeletal muscle, liver, lung, bone marrow fibroblast, pancreas and placenta.

Evidence on tissue expression from TISSUES for SHOX2 Gene

  • Muscle(4.4)
genes like me logo Genes that share expression patterns with SHOX2: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for SHOX2 Gene

Orthologs for SHOX2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SHOX2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SHOX2 29 30
  • 99.81 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SHOX2 30
  • 99 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SHOX2 30
  • 97 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia SHOX2 29 30
  • 94.16 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Shox2 29
  • 92.13 (n)
Mouse
(Mus musculus)
Mammalia Shox2 29 16 30
  • 92.02 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SHOX2 29 30
  • 90.8 (n)
OneToOne
Chicken
(Gallus gallus)
Aves SHOX2 29 30
  • 82.34 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SHOX2 30
  • 89 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia shox2 29
  • 78.86 (n)
Zebrafish
(Danio rerio)
Actinopterygii shox2 29 30
  • 78.37 (n)
OneToOne
zgc65884 29
Fruit Fly
(Drosophila melanogaster)
Insecta CG34367 30
  • 33 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea alr-1 30
  • 19 (a)
ManyToMany
Species where no ortholog for SHOX2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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 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 SHOX2 Gene

ENSEMBL:
Gene Tree for SHOX2 (if available)
TreeFam:
Gene Tree for SHOX2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SHOX2: view image
Alliance of Genome Resources:
Additional Orthologs for SHOX2

Paralogs for SHOX2 Gene

(14) SIMAP similar genes for SHOX2 Gene using alignment to 2 proteins:

  • SHOX2_HUMAN
  • A6NLG4_HUMAN
genes like me logo Genes that share paralogs with SHOX2: view

Variants for SHOX2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SHOX2 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
872139 Uncertain Significance: not provided 158,105,721(-) C/T
NM_001163678.2(SHOX2):c.304G>A (p.Ala102Thr)
MISSENSE
rs201444043 Benign: not provided 158,099,932(-) G/A
NM_001163678.2(SHOX2):c.630C>T (p.Ala210=)
SYNONYMOUS
rs375389609 Uncertain Significance: not provided 158,105,730(-) T/A
NM_003030.4(SHOX2):c.295A>T (p.Met99Leu)
MISSENSE
rs747236738 Uncertain Significance: not provided 158,105,803(-) G/A
NM_003030.4(SHOX2):c.222C>T (p.Gly74=)
SYNONYMOUS
rs753047735 Uncertain Significance: not provided 158,105,089(-) C/T
NM_003030.4(SHOX2):c.387G>A (p.Leu129=)
SYNONYMOUS_VARIANT,INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SHOX2 Gene

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

Variation tolerance for SHOX2 Gene

Residual Variation Intolerance Score: 13.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.60; 12.93% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SHOX2 Gene

Human Gene Mutation Database (HGMD)
SHOX2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SHOX2
Leiden Open Variation Database (LOVD)
SHOX2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for SHOX2 Gene

Disorders for SHOX2 Gene

MalaCards: The human disease database

(11) MalaCards diseases for SHOX2 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
turner syndrome
  • bonnevie-ullrich syndrome
cornelia de lange syndrome
  • brachmann de lange syndrome
familial atrial fibrillation
  • atfb
leri-weill dyschondrosteosis
  • lwd
cleft palate, isolated
  • cpi
- elite association - COSMIC cancer census association via MalaCards
Search SHOX2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for SHOX2

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 SHOX2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SHOX2 Gene

Publications for SHOX2 Gene

  1. SHOT, a SHOX-related homeobox gene, is implicated in craniofacial, brain, heart, and limb development. (PMID: 9482898) Blaschke RJ … Rappold GA (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 22
  2. A new human homeobox gene OGI2X is a member of the most conserved homeobox gene family and is expressed during heart development in mouse. (PMID: 9466998) Semina EV … Murray JC (Human molecular genetics 1998) 2 3 4 22
  3. High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men. (PMID: 19453261) Yerges LM … MrOS Research Group (Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2009) 3 40
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  5. An unappreciated role for RNA surveillance. (PMID: 14759258) Hillman RT … Brenner SE (Genome biology 2004) 3 4

Products for SHOX2 Gene

Sources for SHOX2 Gene