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Gene Review

HAND1  -  heart and neural crest derivatives...

Homo sapiens

Synonyms: BHLHA27, Class A basic helix-loop-helix protein 27, EHAND, Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1, Heart-and neural crest derivatives-expressed protein 1, ...
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Disease relevance of HAND1

  • CIMP-N, CIMP-I, and CIMP-H status was determined by the number (0, 1-3, and 4-5, respectively) of methylated marker genes (LOX, HRASLS, FLNc, HAND1, and TM), that were newly identified as highly methylated in gastric cancer cell lines [1].
  • Human HAND genes are expressed in the adult heart and HAND1 expression is downregulated in cardiomyopathies [2].
  • HAND1 and HAND2 are expressed in the adult-rodent heart and are modulated during cardiac hypertrophy [2].
  • BACKGROUND: Hand hygiene prevents cross infection in hospitals, but compliance with recommended instructions is commonly poor [3].
  • Participants also completed standardized measures including demographic information; the Short Form 36; Western Ontario and McMaster Universities Osteoarthritis Index; and Disabilities of the Arm, Shoulder and Hand questionnaire [4].

Psychiatry related information on HAND1

  • RESULTS: Hand motor skill was significantly familial (maximum heritability=41%), as were reading-related measures [5].
  • In the present study, we analyzed how high-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor hand area (M1-Hand) shapes anticipatory motor activity in frontal areas as indexed by the contingent negative variation (CNV) [6].
  • The five psychomotor tests were: Intentional Hand Steadiness Test (IHST); Finger Tapping: The One-Hole Test: NES Simple Reaction Time (SRT); and Hand Tremor [7].
  • All children took a standardized intelligence test (Wechsler Intelligence Scale for Children-III) and completed a modified version of the Edinburgh Hand Preference Questionnaire [8].
  • In addition, medical review showed an improvement on the Hand Apraxia Scale for a higher proportion of girls on L-carnitine [9].

High impact information on HAND1


Chemical compound and disease context of HAND1


Biological context of HAND1

  • The action of HAND1 does not require heterodimerization with class I basic helix-loop-helix factors or DNA binding through E-box elements [18].
  • The highly conserved cardiogenic bHLH factor Hand is specifically expressed in circular visceral muscle progenitor cells and in all cell types of the dorsal vessel during Drosophila embryogenesis [19].
  • Targeted mutations of dHAND and eHAND in mice have revealed novel pathways of organogenesis in mesodermal and neural crest derivatives. dHAND mutants exhibit hypoplasia of the right ventricle, branchial arches, and aortic arch arteries [20].
  • RESULTS: In H. pylori-negative individuals, significant increasing trends were present in the order of HV, S cases, and M cases for FLNc and HAND1 methylation levels (P < 0.01, Spearman's rank-order test) [21].
  • The basic helix-loop-helix (bHLH) transcription factor, Hand1, plays an important role in the development of the murine extra-embryonic trophoblast cell lineage [22].

Anatomical context of HAND1

  • This may account for the distinct functions of HAND1 in giant cells and their precursors [23].
  • Transcripts encoding HAND1 are expressed by cells in the epithelial lining of the small intestine and colon [24].
  • The basic helix-loop-helix transcription factors, HAND2 and HAND1, are expressed in the gastrointestinal tract, but neither the growth factors that induce their expression nor the cell types that express them in the gut are known [24].
  • In the esophagus and gizzard, where HAND1 is not normally expressed, treatment with BMP4 induced the expression of transcripts encoding HAND1 in nonneural crest-derived cells [24].
  • In conclusion, human Hand1 may play an important role in the differentiation of the amniotic membrane and the pre-implanting trophoblast [22].

Associations of HAND1 with chemical compounds


Physical interactions of HAND1

  • MEF2 binding to DNA is not enhanced in the presence of HAND1 [18].

Regulatory relationships of HAND1

  • We show that transcripts encoding HAND2 are expressed in all segments of the developing gut while those encoding HAND1 are confined to the small intestine and colon [24].

Other interactions of HAND1

  • The bHLH factors HAND1 and HAND2 are required for heart, vascular, neuronal, limb, and extraembryonic development [11].
  • Instead, HAND1 is recruited to the promoter via physical interaction with MEF2 proteins [18].
  • GDNF had no detectable effect on the expression of transcripts encoding HAND1 [24].
  • Mutational analyses of GAL-Hand1 suggested that two protein regions located within its N-terminal portion mainly confer the repressing activity [22].
  • These include an upstream suites of transcription factors such as Mash-2, Hand-1 and Gem1, and a downstream set of effectors such as adhesion molecules, proteinases, and the trophoblast major histocompatibility antigen HLA-G [29].

Analytical, diagnostic and therapeutic context of HAND1


  1. CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus. Chang, M.S., Uozaki, H., Chong, J.M., Ushiku, T., Sakuma, K., Ishikawa, S., Hino, R., Barua, R.R., Iwasaki, Y., Arai, K., Fujii, H., Nagai, H., Fukayama, M. Clin. Cancer Res. (2006) [Pubmed]
  2. HAND1 and HAND2 are expressed in the adult-rodent heart and are modulated during cardiac hypertrophy. Thattaliyath, B.D., Livi, C.B., Steinhelper, M.E., Toney, G.M., Firulli, A.B. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  3. Effectiveness of a hospital-wide programme to improve compliance with hand hygiene. Infection Control Programme. Pittet, D., Hugonnet, S., Harbarth, S., Mourouga, P., Sauvan, V., Touveneau, S., Perneger, T.V. Lancet (2000) [Pubmed]
  4. "What do you expect? You're just getting older": A comparison of perceived osteoarthritis-related and aging-related health experiences in middle- and older-age adults. Gignac, M.A., Davis, A.M., Hawker, G., Wright, J.G., Mahomed, N., Fortin, P.R., Badley, E.M. Arthritis Rheum. (2006) [Pubmed]
  5. Familial and genetic effects on motor coordination, laterality, and reading-related cognition. Francks, C., Fisher, S.E., Marlow, A.J., MacPhie, I.L., Taylor, K.E., Richardson, A.J., Stein, J.F., Monaco, A.P. The American journal of psychiatry. (2003) [Pubmed]
  6. 5 Hz repetitive TMS increases anticipatory motor activity in the human cortex. Holler, I., Siebner, H.R., Cunnington, R., Gerschlager, W. Neurosci. Lett. (2006) [Pubmed]
  7. Behavioral effects of low-level exposure to Hg0 among dental professionals: a cross-study evaluation of psychomotor effects. Bittner, A.C., Echeverria, D., Woods, J.S., Aposhian, H.V., Naleway, C., Martin, M.D., Mahurin, R.K., Heyer, N.J., Cianciola, M. Neurotoxicology and teratology. (1998) [Pubmed]
  8. Effects of mothers' autoimmune disease during pregnancy on learning disabilities and hand preference in their children. Ross, G., Sammaritano, L., Nass, R., Lockshin, M. Archives of pediatrics & adolescent medicine. (2003) [Pubmed]
  9. Rett syndrome: randomized controlled trial of L-carnitine. Ellaway, C., Williams, K., Leonard, H., Higgins, G., Wilcken, B., Christodoulou, J. J. Child Neurol. (1999) [Pubmed]
  10. Right and left go dHAND and eHAND. Overbeek, P.A. Nat. Genet. (1997) [Pubmed]
  11. PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation. Firulli, B.A., Howard, M.J., McDaid, J.R., McIlreavey, L., Dionne, K.M., Centonze, V.E., Cserjesi, P., Virshup, D.M., Firulli, A.B. Mol. Cell (2003) [Pubmed]
  12. Limb mammary syndrome: a new genetic disorder with mammary hypoplasia, ectrodactyly, and other Hand/Foot anomalies maps to human chromosome 3q27. van Bokhoven, H., Jung, M., Smits, A.P., van Beersum, S., Rüschendorf, F., van Steensel, M., Veenstra, M., Tuerlings, J.H., Mariman, E.C., Brunner, H.G., Wienker, T.F., Reis, A., Ropers, H.H., Hamel, B.C. Am. J. Hum. Genet. (1999) [Pubmed]
  13. Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand. Henriksen, G.L., Ketchum, N.S., Michalek, J.E., Swaby, J.A. Epidemiology (Cambridge, Mass.) (1997) [Pubmed]
  14. Effects of sertraline on kinematic aspects of hand movements in patients with obsessive-compulsive disorder. Mergl, R., Mavrogiorgou, P., Juckel, G., Zaudig, M., Hegerl, U. Psychopharmacology (Berl.) (2004) [Pubmed]
  15. Hand antisepsis: evaluation of a sprayer system for alcohol distribution. Barrau, K., Rovery, C., Drancourt, M., Brouqui, P. Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America. (2003) [Pubmed]
  16. Wearing test with 2 different types of latex gloves with and without the use of a skin protection cream. Allmers, H. Contact Derm. (2001) [Pubmed]
  17. Serum dioxin and psychological functioning in U.S. Air Force veterans of the Vietnam War. Michalek, J.E., Barrett, D.H., Morris, R.D., Jackson, W.G. Military medicine. (2003) [Pubmed]
  18. MEF2-dependent recruitment of the HAND1 transcription factor results in synergistic activation of target promoters. Morin, S., Pozzulo, G., Robitaille, L., Cross, J., Nemer, M. J. Biol. Chem. (2005) [Pubmed]
  19. The highly conserved cardiogenic bHLH factor Hand is specifically expressed in circular visceral muscle progenitor cells and in all cell types of the dorsal vessel during Drosophila embryogenesis. Kölsch, V., Paululat, A. Dev. Genes Evol. (2002) [Pubmed]
  20. HAND proteins: molecular mediators of cardiac development and congenital heart disease. Srivastava, D. Trends Cardiovasc. Med. (1999) [Pubmed]
  21. Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers. Nakajima, T., Maekita, T., Oda, I., Gotoda, T., Yamamoto, S., Umemura, S., Ichinose, M., Sugimura, T., Ushijima, T., Saito, D. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  22. Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains. Knöfler, M., Meinhardt, G., Bauer, S., Loregger, T., Vasicek, R., Bloor, D.J., Kimber, S.J., Husslein, P. Biochem. J. (2002) [Pubmed]
  23. The HAND1 basic helix-loop-helix transcription factor regulates trophoblast differentiation via multiple mechanisms. Scott, I.C., Anson-Cartwright, L., Riley, P., Reda, D., Cross, J.C. Mol. Cell. Biol. (2000) [Pubmed]
  24. Transcripts encoding HAND genes are differentially expressed and regulated by BMP4 and GDNF in developing avian gut. Wu, X., Howard, M.J. Gene Expr. (2002) [Pubmed]
  25. Cardiomyogenic differentiation in cardiac myxoma expressing lineage-specific transcription factors. Kodama, H., Hirotani, T., Suzuki, Y., Ogawa, S., Yamazaki, K. Am. J. Pathol. (2002) [Pubmed]
  26. Lysophosphatidic acid stimulates the G-protein-coupled receptor EDG-1 as a low affinity agonist. Lee, M.J., Thangada, S., Liu, C.H., Thompson, B.D., Hla, T. J. Biol. Chem. (1998) [Pubmed]
  27. Serum dioxin, insulin, fasting glucose, and sex hormone-binding globulin in veterans of Operation Ranch Hand. Michalek, J.E., Akhtar, F.Z., Kiel, J.L. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  28. 17beta-Estradiol protects isolated human pancreatic islets against proinflammatory cytokine-induced cell death: molecular mechanisms and islet functionality. Contreras, J.L., Smyth, C.A., Bilbao, G., Young, C.J., Thompson, J.A., Eckhoff, D.E. Transplantation (2002) [Pubmed]
  29. To proliferate or to divide - to be or not to be. Genbacev, O. Early pregnancy (Online) (2001) [Pubmed]
  30. Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted expression in cytotrophoblastic cells and heart. Knöfler, M., Meinhardt, G., Vasicek, R., Husslein, P., Egarter, C. Gene (1998) [Pubmed]
  31. Human eHAND, but not dHAND, is down-regulated in cardiomyopathies. Natarajan, A., Yamagishi, H., Ahmad, F., Li, D., Roberts, R., Matsuoka, R., Hill, S., Srivastava, D. J. Mol. Cell. Cardiol. (2001) [Pubmed]
  32. Successful hand transplantation. One-year follow-up. Louisville Hand Transplant Team. Jones, J.W., Gruber, S.A., Barker, J.H., Breidenbach, W.C. N. Engl. J. Med. (2000) [Pubmed]
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