HAND2 Gene - Heart and Neural Crest Derivatives Expressed 2
Key transcription factor in cardiac development, limb formation, and neurogenesis
Gene Information Card
| Symbol | HAND2 |
|---|---|
| Full Name | Heart and neural crest derivatives expressed 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q34.1 |
| NCBI Gene ID | 9464 ncbi.nlm.nih.gov/gene/9464 |
| Ensembl ID | ENSG00000164197 |
| UniProt ID | P61296 |
| OMIM ID | 602407 |
| HGNC ID | 4808 |
| Aliases | bHLHa26, dHand, Hed, Thing2 |
Description
HAND2 (Heart and neural crest derivatives expressed 2) is a basic helix-loop-helix (bHLH) transcription factor essential for cardiac morphogenesis, limb development, and autonomic nervous system differentiation. It regulates gene expression by binding E-box sequences and interacting with other bHLH factors such as HAND1 and GATA4. HAND2 is critical for right ventricle development, pharyngeal arch patterning, and sympathetic neuron specification.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital heart disease (CHD) | Loss-of-function variants impair cardiac neural crest migration and right ventricle formation | ClinVar, OMIM |
| Hypoplastic left heart syndrome | Reduced HAND2 expression disrupts left-right cardiac asymmetry | NCBI Gene, OMIM |
| Neuroblastoma | HAND2 overexpression promotes tumor cell proliferation and sympathetic lineage maintenance | COSMIC, PubMed |
| Endometrial cancer | Somatic mutations and copy number alterations in HAND2 contribute to tumorigenesis | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 45.2 | High |
| Adipose tissue | 12.8 | Medium |
| Brain | 8.5 | Medium |
| Lung | 6.1 | Low |
| Liver | 1.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 0.2 | Not expressed |
| HeLa (cervical) | 0.5 | Not expressed |
| SH-SY5Y (neuroblastoma) | 35.1 | High expression |
| H9 (embryonic stem) | 22.4 | Medium expression |
| HUVEC (endothelial) | 1.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, loss of function |
| c.364C>T (p.Arg122*) | Nonsense | Rare | Premature truncation, loss of function |
| c.488G>A (p.Arg163Gln) | Missense | <0.01% | Impaired DNA binding |
| c.589_590insA | Frameshift | Rare | Frameshift, loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss variants that abolish protein function are associated with congenital heart disease.
Gain of Function (GOF)
Amplification and overexpression in neuroblastoma suggest oncogenic gain-of-function activity.
Dominant Negative (DN)
Missense mutations in the bHLH domain may interfere with dimerization and act in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cardiac progenitor differentiation (Reactome: R-HSA-5576891)
• Neural crest differentiation (Reactome: R-HSA-375276)
• HAND2-GATA4 transcriptional network (PMID: 21900206)
Protein Summary
HAND2 is a 217-amino acid bHLH transcription factor (UniProt P61296) that forms heterodimers with E12/E47 and other bHLH proteins. It localizes to the nucleus and activates transcription of genes involved in cardiac and neural crest development. The protein contains a conserved bHLH domain (residues 109-160) required for DNA binding and dimerization. Post-translational modifications include phosphorylation, which modulates its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HAND2 Knockout HEK293 Cell Line | EDJ-KQ6595 | Human | 9464 | Details Get a Quote |
| HAND2 Knockout HeLa Cell Line | EDJ-KQ55172 | Human | 9464 | Details Get a Quote |
| HAND2 Knockout A-549 Cell Line | EDJ-KQ63652 | Human | 9464 | Details Get a Quote |
| HAND2 Knockout HCT 116 Cell Line | EDJ-KQ72112 | Human | 9464 | Details Get a Quote |
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