RASSF1 (Ras association (RalGDS/AF-6) domain family member)
2001-12-01 Debora Angeloni , Michael I. Lerman AffiliationLaboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research Facility Bldg. 560 Rm. 12 26 Frederick, MD 21702, USA
Identity
HGNC
LOCATION
3p21.31
IMAGE
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
123F2,NORE2A,RASSF1A,RDA32,REH3P21
FUSION GENES
DNA/RNA
Grey: exon 1a, green: exon 1b; blue: exon 2ab; yellow : exon 2g; brown: exons 3,4, 5, 6. Arrows: transcription start sites. CpG: location of CpG islands. RASSF1A and RASSF1B start with exon 1a and 1b respectively. The second exon (2ab) is common to both forms. Exon 2g is the first exon of RASSF1C and is present in this transcript only.
Description
the genomic size of the gene is about 7.6 kb.
Transcription
At least three alternative transcripts were identified (A, B and C) that originate from alternative splicing and promoter usage. Exons 3 to 6 are common to all forms. Transcript A has two 5 exons (designated 1a and 2ab), this cDNA is 1,873 bp (ORF: 340 amino acids). RASSF1B first exon is designated 1b and is different from RASSF1A. Exon two is 2ab as in transcript A. cDNA size: 1,664 bp. Transcript RASSF1C first exon is designated 2g, cDNA size 1700 bp (ORF 270 amino acids).
Pseudogene
no known pseudogenes.
Proteins
Schematic representation of RASSF1 protein variants, as deduced from the transcripts.
Description
The carboxy terminus of RASSF1A shows about 55% identity to the mouse protein Nore1 and the rat protein Maxp1, both are Ras effector proteins (Nore1 was shown to interact in vivo with Ras upon receptor activation in a GTP-dependent manner). RASSF1A N terminus has high homology with a domain known as protein kinase C conserved region 1 domain (a cysteine-rich diacylglycerol/phorbol ester binding domain). RASSF1B most likely is constituted only of the Ras association domain.
Expression
RASSF1A and RASSF1C are expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, small intestine, colon, peripheral blood leukocytes. RASSF1B is expressed predominantly in cells of hematopoietic origin.
Localisation
not determined.
Function
RASSF1 binds Ras in a GTP-dependent manner and may serve as the effector that mediates Ras apoptotic effects. Alternatively, it may sequester RAS proteins thereby regulating the availability of these proteins for signaling.
Mutations
Note
single nucleotide polymorphism (SNP) in exon 1a: AAG (Lys21)/CAG (Gln21).
Somatic
Mutations were rarely found. In non small cell lung cancer four were found: GAC (Asp129) to GAG (Glu129); ATT (Ile135) to ACT (Thr135); CGG (Arg257) to CAG (Gln257); GCC (Ala336) to ACC (Thr336).
Implicated in
Entity name
clear cell renal carcinoma and papillary renal carcinoma; lung cancer; ovarian cancer; prostate cancer, gastric adenocarcinoma; bladder carcinoma; nasopharingeal carcinoma; breast cancer.
Note
The mechanism of inactivation of this tumor suppressor consists in promoter hypermethylation. The gene promoter was found hypermetylated in 90 % of primary kidney tumors and 40 % of lung tumors. Hypermethylation and loss of transcription were causally related. Hypermethylation occurs in variable percentage in other tumors and indicate a role for this gene in malignant progression (62 % of bladder carcinoma; 49 % of breast tumors; 40 % of ovarian tumors; 12 % of colon cancer).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11313894 | 2001 | Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours. | Agathanggelou A et al |
| 11333291 | 2001 | Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. | Burbee DG et al |
| 11585730 | 2001 | Frequent epigenetic inactivation of RASSF1A by aberrant promoter hypermethylation in human gastric adenocarcinoma. | Byun DS et al |
| 10888881 | 2000 | Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. | Dammann R et al |
| 11429703 | 2001 | The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas. | Dammann R et al |
| 11306494 | 2001 | Hypermethylation of the cpG island of Ras association domain family 1A (RASSF1A), a putative tumor suppressor gene from the 3p21.3 locus, occurs in a large percentage of human breast cancers. | Dammann R et al |
| 11390984 | 2001 | The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. | Dreijerink K et al |
| 11559536 | 2001 | Frequent epigenetic inactivation of RASSF1A in human bladder carcinoma. | Lee MG et al |
| 11085536 | 2000 | The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. | Lerman MI et al |
| 11358799 | 2001 | High frequency of promoter hypermethylation of RASSF1A in nasopharyngeal carcinoma. | Lo KW et al |
| 11585766 | 2001 | Epigenetic inactivation of the RASSF1A 3p21.3 tumor suppressor gene in both clear cell and papillary renal cell carcinoma. | Morrissey C et al |
| 10998413 | 2000 | Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. | Vos MD et al |
| 11668500 | 2001 | Hypermethylation of the CpG island of the RASSF1A gene in ovarian and renal cell carcinomas. | Yoon JH et al |
Other Information
Locus ID:
NCBI: 11186
MIM: 605082
HGNC: 9882
Ensembl: ENSG00000068028
Variants:
dbSNP: 11186
ClinVar: 11186
TCGA: ENSG00000068028
COSMIC: RASSF1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA10040 | cetuximab | Chemical | ClinicalAnnotation, VariantAnnotation | ambiguous | PD | ||
| PA446108 | Colorectal Neoplasms | Disease | ClinicalAnnotation, VariantAnnotation | ambiguous | PD |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38203733 | 2024 | Expression of RASSF1A, DIRAS3, and AKAP9 Genes in Thyroid Lesions: Implications for Differential Diagnosis and Prognosis of Thyroid Carcinomas. | 0 |
| 38493315 | 2024 | Diagnostic Value of GSTP1, RASSF1, AND RASSF2 Methylation in Serum of Prostate Cancer Patients. | 0 |
| 38840077 | 2024 | Association of the SHOX2 and RASSF1A methylation levels with the pathological evolution of early-stage lung adenocarcinoma. | 0 |
| 38203733 | 2024 | Expression of RASSF1A, DIRAS3, and AKAP9 Genes in Thyroid Lesions: Implications for Differential Diagnosis and Prognosis of Thyroid Carcinomas. | 0 |
| 38493315 | 2024 | Diagnostic Value of GSTP1, RASSF1, AND RASSF2 Methylation in Serum of Prostate Cancer Patients. | 0 |
| 38840077 | 2024 | Association of the SHOX2 and RASSF1A methylation levels with the pathological evolution of early-stage lung adenocarcinoma. | 0 |
| 36404583 | 2023 | RASSF1A inhibits epithelial-mesenchymal transition of gastric cancer cells by downregulating P-JNK. | 0 |
| 36584330 | 2023 | Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients. | 1 |
| 36905106 | 2023 | WDR3 promotes stem cell-like properties in prostate cancer by inhibiting USF2-mediated transcription of RASSF1A. | 1 |
| 38093706 | 2023 | RASSF1A promotes ATM signaling and RASSF1A methylation is a synthetic lethal marker for ATR inhibitors. | 1 |
| 38115290 | 2023 | SEPT9, H4C6, and RASSF1A methylation in nasopharyngeal swabs: A reflection of potential minimally invasive biomarkers for early screening of nasopharyngeal cancer. | 0 |
| 36404583 | 2023 | RASSF1A inhibits epithelial-mesenchymal transition of gastric cancer cells by downregulating P-JNK. | 0 |
| 36584330 | 2023 | Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients. | 1 |
| 36905106 | 2023 | WDR3 promotes stem cell-like properties in prostate cancer by inhibiting USF2-mediated transcription of RASSF1A. | 1 |
| 38093706 | 2023 | RASSF1A promotes ATM signaling and RASSF1A methylation is a synthetic lethal marker for ATR inhibitors. | 1 |
Citation
Debora Angeloni ; Michael I. Lerman
RASSF1 (Ras association (RalGDS/AF-6) domain family member)
Atlas Genet Cytogenet Oncol Haematol. 2001-12-01
Online version: http://atlasgeneticsoncology.org/gene/377/rassf1
