SHOX2: Short Stature Homeobox 2 Gene
Key regulator of embryonic development and implicated in skeletal and cardiac disorders
Gene Information Card
| Symbol | SHOX2 |
|---|---|
| Full Name | Short Stature Homeobox 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q25.32 |
| NCBI Gene ID | 6474 ncbi.nlm.nih.gov/gene/6474 |
| Ensembl ID | ENSG00000169174 |
| UniProt ID | O60902 |
| OMIM ID | 602504 |
| HGNC ID | 10854 |
| Aliases | SHOT, OG12, OG12X |
Description
SHOX2 (Short Stature Homeobox 2) is a homeobox-containing transcription factor that plays a critical role in embryonic development, particularly in limb and cardiac morphogenesis. It is a member of the paired-related homeobox gene family and is essential for proper formation of the sinoatrial node and regulation of heart rate. Mutations in SHOX2 are associated with skeletal dysplasias and atrial fibrillation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atrial Fibrillation (AF) | Loss-of-function mutations impair sinoatrial node development, leading to arrhythmia | ClinVar, OMIM |
| Short Stature (idiopathic) | Haploinsufficiency of SHOX2 disrupts limb growth plate development | OMIM, NCBI |
| Skeletal Dysplasia (Léri-Weill type) | Deletions or mutations affecting SHOX2 contribute to disproportionate short stature | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal Muscle | 8.3 | Low |
| Lung | 6.1 | Low |
| Brain | 4.2 | Low |
| Kidney | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPS-derived) | 15.2 | High expression in developing cardiac cells |
| Fibroblasts (skin) | 2.1 | Low baseline expression |
| Osteoblasts | 5.4 | Moderate expression during differentiation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.479G>A (p.Arg160Gln) | Missense | Rare | Loss of DNA-binding activity; associated with AF |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; linked to short stature |
| Deletion of entire SHOX2 gene | Copy number loss | 0.01% | Haploinsufficiency; skeletal dysplasia |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations that reduce or abolish transcriptional activity; associated with atrial fibrillation and short stature.
Gain of Function (GOF)
Not reported in literature or curated databases.
Dominant Negative (DN)
Not documented for SHOX2; most pathogenic mutations act via haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Developmental Biology (REACT:14797)
• Transcriptional regulation by homeobox proteins (REACT:111045)
Protein Summary
SHOX2 is a 331-amino acid homeodomain-containing transcription factor that binds DNA as a monomer or heterodimer. It regulates genes involved in cell proliferation and differentiation during limb and heart development. The protein localizes to the nucleus and is expressed in mesodermal derivatives. Structural integrity of the homeodomain is essential for function; mutations in this region disrupt target gene activation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SHOX2 Knockout HEK293 Cell Line | EDJ-KQ50629 | Human | 6474 | Details Get a Quote |
| SHOX2 Knockout HeLa Cell Line | EDJ-KQ54465 | Human | 6474 | Details Get a Quote |
| SHOX2 Knockout A-549 Cell Line | EDJ-KQ62953 | Human | 6474 | Details Get a Quote |
| SHOX2 Knockout HCT 116 Cell Line | EDJ-KQ71425 | Human | 6474 | Details Get a Quote |
