Hand2

HAND2, otherwise known as heart and neural crest derivatives-expressed 2, is a kind of gene used for encoding the protein heart and neural crest derivatives-expressed protein 2. This protein is a crucial aspect of the human body, as it has many different functions that add to survivability.

The HAND2 protein is important for the development of vital organs in the body. Most of HAND2’s major roles have to do with the heart. Along with the HAND1 protein, it forms the right ventricle and aortic arch in the heart and helps prevent heart disease. Additionally, this protein was found to have a large part in the proper development of limbs and the creation of a proper environment for pregnancy in mammals such as mice and humans, establishing the anterior and posterior parts of an organism. It also plays a part in developing the nervous system in humans, specifically enteric neurons and noradrenergic neurons. HAND2 works as a transcription factor, meaning it controls the rate of transcription of RNA from DNA, essentially controlling the production of proteins as well.

Some tests have already been run on organisms with HAND2, such as mice and zebrafish, by manipulating the amount of HAND2 in their bodies. Without HAND2, the mice showed signs of limb deficiency, and had shorter, symmetrical limb segments instead of their regular limbs. HAND2 is especially important for zebrafish, as it is very important in influencing heart movement and the environment surrounding cardiogenic regions. 

In mammals, an abundance of HAND2 was shown to exist in the body throughout pregnancy; it gradually decreases as the pregnancy nears its end. Studies show that the amount of HAND2 impacts birth weight and the length of the pregnancy. Other studies have begun to use HAND2 as a detector of colorectal cancer, and  it has been shown to outperform other traditional detectors. 

The benefits of HAND2 are still being researched and studied to this day. Its role in the development of vital organs and proteins has allowed scientists to acknowledge its potential as a reprogramming factor by turning regular cells into heart cells, or as a cancer detector, among other things.

References:

Amir Mahdi Nili, et al. “Non-Invasive Colorectal Cancer Biomarkers: HAND2 and GPM6A Methylation in Circulating Tumour DNA.” Cancer Cell International, vol. 25, no. 1, 18 July 2025, pmc.ncbi.nlm.nih.gov/articles/PMC12273382/, https://doi.org/10.1186/s12935-025-03898-5. Accessed 29 Sept. 2025.

Dai, Yan-Shan, and Peter Cserjesi. “The Basic Helix-Loop-Helix Factor, HAND2, Functions as a Transcriptional Activator by Binding to E-Boxes as a Heterodimer.” Journal of Biological Chemistry, vol. 277, no. 15, Apr. 2002, pp. 12604–12612, https://doi.org/10.1074/jbc.m200283200. Accessed 2 May 2022.

Galli, Antonella, et al. “Distinct Roles of Hand2 in Initiating Polarity and Posterior Shh Expression during the Onset of Mouse Limb Bud Development.” PLoS Genetics, vol. 6, no. 4, 8 Apr. 2010, p. e1000901, https://doi.org/10.1371/journal.pgen.1000901. Accessed 10 Nov. 2021.

Garavito-Aguilar, Zayra V., et al. “Hand2 Ensures an Appropriate Environment for Cardiac Fusion by Limiting Fibronectin Function.” Development, vol. 137, no. 19, 1 Oct. 2010, pp. 3215–3220, https://doi.org/10.1242/dev.052225. Accessed 24 May 2022.

“Hand2 Heart and Neural Crest Derivatives Expressed 2 [Mus Musculus (House Mouse)] - Gene - NCBI.” Nih.gov, 2025, www.ncbi.nlm.nih.gov/gene/15111.

Haridhasapavalan, Krishna Kumar, et al. “Generation of a Recombinant Version of a Biologically Active Cell-Permeant Human HAND2 Transcription Factor from E. Coli.” Scientific Reports, vol. 12, no. 1, 27 Sept. 2022, p. 16129, www.nature.com/articles/s41598-022-19745-w, https://doi.org/10.1038/s41598-022-19745-w.

Wikipedia Contributors. “HAND2.” Wikipedia, Wikimedia Foundation, 17 July 2025.