Gene Symbol: RASSF2
Description: Ras association domain family member 2
Alias: CENP-34, RASFADIN, ras association domain-containing protein 2, Ras association (RalGDS/AF-6) domain family 2, Ras association (RalGDS/AF-6) domain family member 2, centromere protein 34
Species: human
Products:     RASSF2

Top Publications

  1. Vos M, Ellis C, Elam C, Ulku A, Taylor B, Clark G. RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor. J Biol Chem. 2003;278:28045-51 pubmed
    ..We now identify a novel third member of this family, designated RASSF2. RASSF2 binds directly to K-Ras in a GTP-dependent manner via the Ras effector domain...
  2. Hesson L, Wilson R, Morton D, Adams C, Walker M, Maher E, et al. CpG island promoter hypermethylation of a novel Ras-effector gene RASSF2A is an early event in colon carcinogenesis and correlates inversely with K-ras mutations. Oncogene. 2005;24:3987-94 pubmed
    ..and characterisation of a novel member of the ras association domain family 1 (RASSF1)/NORE1 family, namely, RASSF2, located at chromosomal region 20p13...
  3. Akino K, Toyota M, Suzuki H, Mita H, Sasaki Y, Ohe Toyota M, et al. The Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancer. Gastroenterology. 2005;129:156-69 pubmed
    ..Colony formation assays and flow cytometry were used to assess the tumor suppressor activities of RASSF1 and RASSF2. Immunofluorescence microscopy was used to determine the effect of altered RASSF2 expression on cell morphology...
  4. Tian L, Cao J, Jiao H, Zhang J, Ren X, Liu X, et al. circRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/ IGF-1R axis. Clin Sci (Lond). 2019;: pubmed publisher
    ..We focused on hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2...
  5. Dong Y, Yang L, Luo W, Zhu T, Yan W, Kong J, et al. Mannose receptor C type 2 mediates 1,25(OH)2D3/vitamin D receptor-regulated collagen metabolism through collagen type 5, alpha 2 chain and matrix metalloproteinase 13 in murine MC3T3-E1 cells. Mol Cell Endocrinol. 2019;483:74-86 pubmed publisher
    ..Three up-regulated proteins (MRC2, WWTR1 and RASSF2) related to bone metabolism were confirmed in this study...
  6. Freitas Ã, Gribble S, Simioni M, Vieira T, Silva Grecco R, Balarin M, et al. Maternally inherited partial monosomy 9p (pter → p24.1) and partial trisomy 20p (pter → p12.1) characterized by microarray comparative genomic hybridization. Am J Med Genet A. 2011;155A:2754-61 pubmed publisher
    ..the phenotype of our patient with those already reported in the literature, and discuss the role of DMRT, DOCK8, FOXD4, VLDLR, RSPO4, AVP, RASSF2, PROKR2, BMP2, MKKS, and JAG1, all genes mapping to the deleted and duplicated regions.
  7. Dutta U, Rao S, Pidugu V, V S V, Bhattacherjee A, Bhowmik A, et al. Breakpoint mapping of a novel de novo translocation t(X;20)(q11.1;p13) by positional cloning and long read sequencing. Genomics. 2018;: pubmed publisher
    ..1 and on 20p13 between RASSF2 and SLC23A2 genes...
  8. Mezzanotte J, Hill V, Schmidt M, Shinawi T, Tommasi S, Krex D, et al. RASSF6 exhibits promoter hypermethylation in metastatic melanoma and inhibits invasion in melanoma cells. Epigenetics. 2014;9:1496-503 pubmed publisher
    ..RASSF1A and RASSF2 have been shown to undergo promoter methylation at high frequency in primary lung and breast tumors and in brain ..
  9. Knierim E, Hirata H, Wolf N, Morales Gonzalez S, Schottmann G, Tanaka Y, et al. Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures. Am J Hum Genet. 2016;98:473-489 pubmed publisher
    ..neuronal migration, and pathfinding (SERPINF1, DAB1, SEMA3D, SEMA3A), as well as with bone development (TNFRSF11B, RASSF2, STC1)...

More Information


  1. Blanco Luquin I, Guarch R, Ojer A, Pérez Janices N, Martín Sánchez E, Maria Ruiz S, et al. Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix. Pathol Int. 2015;65:476-85 pubmed publisher
    ..Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in ..
  2. Martin Sanchez E, Pernaut Leza E, Mendaza S, Cordoba A, Vicente García F, Monreal Santesteban I, et al. Gene promoter hypermethylation is found in sentinel lymph nodes of breast cancer patients, in samples identified as positive by one-step nucleic acid amplification of cytokeratin 19 mRNA. Virchows Arch. 2016;469:51-9 pubmed publisher
    ..analysed the promoter methylation status of five genes, involved in adhesion (EPB41L3, TSLC-1), apoptosis (RASSF1, RASSF2) or angiogenesis (TSP-1), in intraoperative sentinel lymph node (SLN) biopsy samples from patients with breast ..
  3. Zhang L, Huang Y, Zhuo W, Zhu Y, Zhu B, Chen Z. Identification and characterization of biomarkers and their functions for Lapatinib-resistant breast cancer. Med Oncol. 2017;34:89 pubmed publisher
    ..A total of 300 DEGs, such as HSPA5, MAP1LC3A and RASSF2, were screened out...
  4. Kanwal S, Jamil F, Ali A, Sehgal S. Comparative Modeling, Molecular Docking, and Revealing of Potential Binding Pockets of RASSF2; a Candidate Cancer Gene. Interdiscip Sci. 2017;9:214-223 pubmed publisher
    b>RASSF2, potential tumor suppressor gene, acts as a KRAS-specific effectors protein and may promote apoptosis and cell cycle arrest. It stabilizes STK3/MST2 by protecting it from proteasomal degradation...
  5. Barnoud T, Wilkey D, Merchant M, Clark J, Donninger H. Proteomics Analysis Reveals Novel RASSF2 Interaction Partners. Cancers (Basel). 2016;8: pubmed publisher
    b>RASSF2 is a tumor suppressor that shares homology with other Ras-association domain (RASSF) family members. It is a powerful pro-apoptotic K-Ras effector that is frequently inactivated in many human tumors...
  6. Cirenajwis H, Lauss M, Ekedahl H, Törngren T, Kvist A, Saal L, et al. NF1-mutated melanoma tumors harbor distinct clinical and biological characteristics. Mol Oncol. 2017;11:438-451 pubmed publisher
    ..mutated genes revealed the RASopathy genes PTPN11 and RASA2, as well as another RAS domain-containing gene RASSF2 enriched in the NF1 subtype after adjustment for mutational burden...
  7. Cooper W, Dickinson R, Dallol A, Grigorieva E, Pavlova T, Hesson L, et al. Epigenetic regulation of the ras effector/tumour suppressor RASSF2 in breast and lung cancer. Oncogene. 2008;27:1805-11 pubmed
    b>RASSF2 is a recently identified member of a class of novel tumour suppressor genes, all containing a ras-association domain. RASSF2 resides at 20p13, a region frequently lost in human cancers...
  8. Song H, Oh S, Oh H, Lim D. Role of the tumor suppressor RASSF2 in regulation of MST1 kinase activity. Biochem Biophys Res Commun. 2010;391:969-73 pubmed publisher
    The tumor suppressor, RASSF2 (Ras association domain family 2), is frequently downregulated in a number of cancers...
  9. Liu C, Pan Y, Wang X, Lu J, Huang B, Li X. Activation of RASSF2A by p300 induces late apoptosis through histone hyperacetylation. Cell Biol Int. 2010;34:1133-9 pubmed publisher
    ..Overall, data arising from this study indicate that Sp1-mediated RASSF2A gene transcription is activated by p300 through histone acetylation, and this activation plays an important role in inducing late apoptosis. ..
  10. Guo W, Dong Z, Guo Y, Shen S, Guo X, Kuang G, et al. Decreased expression and frequent promoter hypermethylation of RASSF2 and RASSF6 correlate with malignant progression and poor prognosis of gastric cardia adenocarcinoma. Mol Carcinog. 2016;55:1655-1666 pubmed publisher
    ..The present study investigated the role and methylation status of RASSF2, RASSF3, RASSF4, and RASSF6 in the pathogenesis and prognosis of GCA...
  11. Zhao L, Cui Q, Lu Z, Chen J. Aberrant methylation of RASSF2A in human pancreatic ductal adenocarcinoma and its relation to clinicopathologic features. Pancreas. 2012;41:206-11 pubmed publisher
    ..The RASSF2 expression in 8 pancreatic carcinoma cell lines and 1 normal pancreatic tissue was detected...
  12. Fujita H, Fukuhara S, Sakurai A, Yamagishi A, Kamioka Y, Nakaoka Y, et al. Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes. J Biol Chem. 2005;280:5022-31 pubmed
    ..Collectively, the locally activated Rap1 and its association with RAPL controls the directional migration of vascular endothelial cells. ..
  13. Kaira K, Sunaga N, Tomizawa Y, Yanagitani N, Ishizuka T, Saito R, et al. Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers. Int J Oncol. 2007;31:169-73 pubmed
    b>RASSF2, a member of the RAS association domain family 1 (RASSF1), is a candidate tumor suppressor gene (TSG) that is silenced by promoter hypermethylation in several human cancers...
  14. Schagdarsurengin U, Richter A, Hornung J, Lange C, Steinmann K, Dammann R. Frequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequences. Mol Cancer. 2010;9:264 pubmed publisher
    ..In our study, we analyzed the role of RASSF2, RASSF3, RASSF4, RASSF5A, RASSF5C and RASSF6 and the effectors MST1, MST2 and WW45 in thyroid carcinogenesis...
  15. Guo W, Dong Z, Cui J, Guo Y, Shen S, Guo X, et al. Aberrant hypermethylation of RASSF2 in tumors and peripheral blood DNA as a biomarker for malignant progression and poor prognosis of esophageal squamous cell carcinoma. Clin Exp Metastasis. 2016;33:73-85 pubmed
    As a tumor suppressor gene, RAS-association domain family 2 (RASSF2) is inactivated by promoter hypermethylation in different tumor cell lines and primary tumors...
  16. Zhang X, Ma Y, Wu Y, Lin L, Ma X, Zhang Y. Aberrant promoter methylation and silencing of RASSF2A gene in cervical cancer. J Obstet Gynaecol Res. 2014;40:1375-81 pubmed publisher
    ..2%, respectively; P < 0.05). Promoter hypermethylation of RASSF2A is observed in CC, while not in normal cervical tissues. RASSF2A is inactivated in CC by promoter hypermethylation and may play a role in cervical carcinogenesis. ..
  17. Huang K, Huang S, Chen I, Liao C, Wang H, Hsieh L. Methylation of RASSF1A, RASSF2A, and HIN-1 is associated with poor outcome after radiotherapy, but not surgery, in oral squamous cell carcinoma. Clin Cancer Res. 2009;15:4174-80 pubmed publisher
    ..Our study indicates that epigenetic silencing of tumor suppressor genes involved in the Ras/PI3K/AKT pathway plays an important role in OSCC radioresistance and this provides a rationale for exploring novel treatment strategies. ..
  18. Perez Janices N, Blanco Luquin I, Tuñón M, Barba Ramos E, Ibáñez B, Zazpe Cenoz I, et al. EPB41L3, TSP-1 and RASSF2 as new clinically relevant prognostic biomarkers in diffuse gliomas. Oncotarget. 2015;6:368-80 pubmed
    ..Our objectives were to analyze the presence of the hypermethylation of EPB41L3, RASSF2 and TSP-1 genes in 132 diffuse gliomas (astrocytic and oligodendroglial tumors) and in 10 cases of normal brain, ..
  19. Donninger H, Hesson L, Vos M, Beebe K, Gordon L, Sidransky D, et al. The Ras effector RASSF2 controls the PAR-4 tumor suppressor. Mol Cell Biol. 2010;30:2608-20 pubmed publisher
    b>RASSF2 is a novel proapoptotic effector of K-Ras. Inhibition of RASSF2 expression enhances the transforming effects of K-Ras, and epigenetic inactivation of RASSF2 is frequently detected in mutant Ras-containing primary tumors...
  20. Kumari G, Mahalingam S. Extracellular signal-regulated kinase 2 (ERK-2) mediated phosphorylation regulates nucleo-cytoplasmic shuttling and cell growth control of Ras-associated tumor suppressor protein, RASSF2. Exp Cell Res. 2009;315:2775-90 pubmed publisher
    ..b>RASSF2, a member of the Ras association domain family, is known to be involved in the suppression of cell growth and is ..
  21. Shen Z, Qin X, Yan M, Li R, Chen G, Zhang J, et al. Cancer-associated fibroblasts promote cancer cell growth through a miR-7-RASSF2-PAR-4 axis in the tumor microenvironment. Oncotarget. 2017;8:1290-1303 pubmed publisher
    ..Mechanistically, we confirmed that the RASSF2-PAR-4 axis was mainly responsible for miR-7 functions in CAFs using bioinformatics methods...
  22. Lee B, Lee E, Jung E, Chun H, Chang D, Song S, et al. Aberrant methylation of APC, MGMT, RASSF2A, and Wif-1 genes in plasma as a biomarker for early detection of colorectal cancer. Clin Cancer Res. 2009;15:6185-91 pubmed publisher
    ..6% and a negative predictive value of 88.8%. The present study suggests that tumor-specific methylation of APC, MGMT, RASSF2A, and Wif-1 genes might be a valuable biomarker in plasma for the early detection of colorectal cancer. ..
  23. Endoh M, Tamura G, Honda T, Homma N, Terashima M, Nishizuka S, et al. RASSF2, a potential tumour suppressor, is silenced by CpG island hypermethylation in gastric cancer. Br J Cancer. 2005;93:1395-9 pubmed
    b>RASSF2, a member of the RASSF1 family, has recently been identified as a potential tumour suppressor...
  24. Imai T, Toyota M, Suzuki H, Akino K, Ogi K, Sogabe Y, et al. Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma. Cancer Sci. 2008;99:958-66 pubmed publisher
    ..we examined the expression of Ras association family (RASSF) genes in a panel of OSCC cell lines and found that RASSF2 is often downregulated by DNA methylation in OSCC cells...
  25. Armstrong D, Zidovetzki R, Alarcón Riquelme M, Tsao B, Criswell L, Kimberly R, et al. GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region. Genes Immun. 2014;15:347-54 pubmed publisher
    ..with SLE susceptibility included two transcription factors (EHF and MED1), two components of the NF-κB pathway (RASSF2 and RNF114), one gene involved in adhesion and endothelial migration (CNTN6) and two genes involved in antigen ..
  26. Guerrero Setas D, Perez Janices N, Blanco Fernandez L, Ojer A, Cambra K, Berdasco M, et al. RASSF2 hypermethylation is present and related to shorter survival in squamous cervical cancer. Mod Pathol. 2013;26:1111-22 pubmed publisher
    Ras association (RalGDS/AF-6) domain family member 2 (RASSF2) is a gene involved in the progression of several human cancers, including breast, colorectal and lung cancer...
  27. Hiraki M, Kitajima Y, Koga Y, Tanaka T, Nakamura J, Hashiguchi K, et al. Aberrant gene methylation is a biomarker for the detection of cancer cells in peritoneal wash samples from advanced gastric cancer patients. Ann Surg Oncol. 2011;18:3013-9 pubmed publisher
    ..The gene methylation of BNIP3, CHFR, CYP1B1, MINT25, SFRP2, and RASSF2 were analyzed in 107 specimens of PF by quantitative methylation-specific polymerase chain reaction...
  28. Aydin D, Bilici A, Kayahan S, Yavuzer D, Basar M, Aliustaoglu M. Prognostic importance of RASSF2 expression in patients with gastric cancer who had undergone radical gastrectomy. Clin Transl Oncol. 2016;18:608-16 pubmed publisher
    Although Ras-association domain family of gene 2 (RASSF2) has been shown to undergo promoter methylation at high frequency in some cancer types and in brain metastases, its clinical utility as a useful prognostic molecular marker remains ..
  29. Kumari G, Singhal P, Rao M, Mahalingam S. Nuclear transport of Ras-associated tumor suppressor proteins: different transport receptor binding specificities for arginine-rich nuclear targeting signals. J Mol Biol. 2007;367:1294-311 pubmed
    ..found to localize both in the nucleus and the nucleolus in contrast to other Ras effector proteins, RASSF1C and RASSF2, which are localized in the nucleus and excluded from nucleolus...
  30. Singh S, Lupo P, Scheurer M, Saxena A, Kennedy A, Ibrahimou B, et al. A childhood acute lymphoblastic leukemia genome-wide association study identifies novel sex-specific risk variants. Medicine (Baltimore). 2016;95:e5300 pubmed
    ..significant sex-specific association (P?=?4 × 10) was with the single nucleotide polymorphism (SNP) rs4813720 (RASSF2), an expression quantitative trait locus (eQTL) for RASSF2 in peripheral blood...
  31. Wu Y, Zhang X, Lin L, Ma X, Ma Y, Liu P. Aberrant methylation of RASSF2A in tumors and plasma of patients with epithelial ovarian cancer. Asian Pac J Cancer Prev. 2014;15:1171-6 pubmed
    ..Epigenetic inactivation of RASSF2A through aberrant promoter methylation may play an important role in the pathogenesis of EOC. Methylation of the RASSF2A gene in plasma may be a valuable molecular marker for the early detection of EOC. ..
  32. Park H, Kang H, Kim I, Jang S, Kim K, Yoon H, et al. Correlation between hypermethylation of the RASSF2A promoter and K-ras/BRAF mutations in microsatellite-stable colorectal cancers. Int J Cancer. 2007;120:7-12 pubmed
    ..033) and distal CRC (p = 0.025). These results show that RASSF2A methylation is a frequent event in colorectal tumorigenesis and positively correlates with K-ras/BRAF mutation in microsatellite-stable or distal CRC. ..
  33. Zhang Z, Sun D, Van D, Tang A, Hu L, Huang G. Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma. Int J Cancer. 2007;120:32-8 pubmed
    b>RASSF2 can bind directly to K-Ras and function as a negative effector of Ras protein...
  34. Cooper W, Hesson L, Matallanas D, Dallol A, von Kriegsheim A, Ward R, et al. RASSF2 associates with and stabilizes the proapoptotic kinase MST2. Oncogene. 2009;28:2988-98 pubmed publisher
    b>RASSF2 is a tumour suppressor that in common with the rest of the RASSF family contains Ras association and SARAH domains...
  35. Ren J, He W, Zhang R, Li Z, Cao W, Yao J, et al. RASSF2A promoter methylation in hepatitis B virus-related hepatocellular carcinogenesis and its correlation with elevated serum alpha-fetoprotein level. J Huazhong Univ Sci Technolog Med Sci. 2009;29:309-12 pubmed publisher
    ..It was concluded that aberrant methylation of the RASSF2A gene with the subsequent loss of RASSF2A expression plays an important role in the pathogenesis of HCC. ..
  36. Gharanei S, Brini A, Vaiyapuri S, Alholle A, Dallol A, Arrigoni E, et al. RASSF2 methylation is a strong prognostic marker in younger age patients with Ewing sarcoma. Epigenetics. 2013;8:893-8 pubmed publisher
    ..In this report, we investigated the methylation status of RASSF1A and RASSF2 in Ewing sarcoma (ES)...
  37. Yang W, Han W, Qin A, Wang Z, Xu J, Qian Y. The emerging role of Hippo signaling pathway in regulating osteoclast formation. J Cell Physiol. 2017;: pubmed publisher
    ..This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP and TAZ...
  38. Xia Y, Xiong N, Huang Y. Relationship between methylation status of RASSF2A gene promoter and endometriosis-associated ovarian cancer. J Biol Regul Homeost Agents. 2018;32:21-28 pubmed
    ..We concluded that the methylation status of the RASSF2A gene promoter could be considered an excellent indicator for early detection of ovarian cancers. ..
  39. Rawat S, Creasy C, Peterson J, Chernoff J. The tumor suppressor Mst1 promotes changes in the cellular redox state by phosphorylation and inactivation of peroxiredoxin-1 protein. J Biol Chem. 2013;288:8762-71 pubmed publisher
    ..These results suggest that hydrogen peroxide-stimulated Mst1 activates a positive feedback loop to sustain an oxidizing cellular state. ..
  40. Perez Janices N, Blanco Luquin I, Torrea N, Liechtenstein T, Escors D, Cordoba A, et al. Differential involvement of RASSF2 hypermethylation in breast cancer subtypes and their prognosis. Oncotarget. 2015;6:23944-58 pubmed
    ..b>RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied...
  41. Comincini S, Castiglioni B, Foti G, Del Vecchio I, Ferretti L. Isolation and molecular characterization of rasfadin, a novel gene in the vicinity of the bovine prion gene. Mamm Genome. 2001;12:150-6 pubmed
    A novel gene, rasfadin (RASSF2) was identified close to the bovine prion gene, and its genomic structure was derived with a combination of exon trapping and RACE...
  42. Ohta S, Bukowski Wills J, Sanchez Pulido L, Alves F, Wood L, Chen Z, et al. The protein composition of mitotic chromosomes determined using multiclassifier combinatorial proteomics. Cell. 2010;142:810-21 pubmed publisher
    ..Our integrated analysis predicts that up to 97 new centromere-associated proteins remain to be discovered in our data set. ..
  43. Ortiz Vega S, Khokhlatchev A, Nedwidek M, Zhang X, Dammann R, Pfeifer G, et al. The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1. Oncogene. 2002;21:1381-90 pubmed
    ..The preferential ability of RASSF1A to heterodimerize with Nore and thereby associate with Ras-like GTPases may be relevant to its putative tumor suppressor function. ..