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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RASSF8
Ras association domain family member 8
Chromosome 12 · 12p12.1
NCBI Gene: 11228Ensembl: ENSG00000123094.17HGNC: HGNC:13232UniProt: A8K8G8
63PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsignal transductionsmoking initiationatrial fibrillationneuroendocrine neoplasmpost term pregnancy
✦AI Summary

RASSF8 (Ras association domain family member 8) functions as a tumor suppressor protein that regulates cell growth, migration, and apoptosis through multiple signaling pathways. The protein localizes to both the nucleus and cell membrane at adherens junctions, where it co-localizes with β-catenin and binds to E-cadherin to maintain epithelial cell-cell adhesions 1. RASSF8 contains an N-terminal Ras association domain and lacks the SARAH domain characteristic of classical RASSF family members 1. Mechanistically, RASSF8 suppresses tumor progression by inhibiting Wnt and NF-κB signaling pathways - its depletion leads to β-catenin and p65 nuclear translocation with increased transcriptional activity 1. RASSF8 also activates the p53-p21 pathway to induce apoptosis 2. The gene demonstrates significant clinical relevance across multiple cancers. RASSF8 expression is frequently downregulated in various malignancies through promoter hypermethylation 2 or transcriptional repression by E4BP4 via histone methyltransferases G9a and SUV39H1 3. Higher RASSF8 expression correlates with advanced tumor stages and metastasis in thyroid carcinoma 4, while loss of expression promotes cancer cell invasion, migration, and anchorage-independent growth 1. These findings establish RASSF8 as an important tumor suppressor with therapeutic potential.

Sources cited
1
RASSF8 localizes to adherens junctions, regulates Wnt/NF-κB signaling, and suppresses tumor growth
PMID: 20514026
2
RASSF8 activates p53-p21 pathway, is downregulated by promoter methylation in melanoma
PMID: 26334503
3
Higher RASSF8 expression correlates with advanced tumor stages in thyroid carcinoma
PMID: 24516056
4
E4BP4 represses RASSF8 through histone methyltransferases G9a and SUV39H1
PMID: 29467226
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
smoking initiationOpen Targets
0.41Moderate
atrial fibrillationOpen Targets
0.31Weak
neuroendocrine neoplasmOpen Targets
0.27Weak
post term pregnancyOpen Targets
0.24Weak
neurodegenerative diseaseOpen Targets
0.24Weak
Non-Neoplastic Bile Duct DisorderOpen Targets
0.13Weak
esophageal squamous cell carcinomaOpen Targets
0.10Suggestive
gastric cancerOpen Targets
0.09Suggestive
melanomaOpen Targets
0.08Suggestive
laryngeal squamous cell carcinomaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
46,XY disorder of sex development due to 5-alpha-reductase 2 deficiencyOpen Targets
0.06Suggestive
cervical cancerOpen Targets
0.05Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.05Suggestive
46,XX ovotesticular disorder of sex developmentOpen Targets
0.05Suggestive
hypogonadotropic hypogonadism 11 with or without anosmiaOpen Targets
0.05Suggestive
Testicular regression syndromeOpen Targets
0.05Suggestive
cryptorchidismOpen Targets
0.04Suggestive
Crandall syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FBLN1Protein interaction93%TP53BP2Protein interaction92%PPP1R13BProtein interaction92%FRMD6Protein interaction90%PARD3Protein interaction86%
Tissue Expression6 tissues
Heart
100%
Ovary
86%
Lung
41%
Brain
38%
Liver
16%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
RASSF8FBLN1TP53BP2PPP1R13BFRMD6PARD3
PROTEIN STRUCTURE
Preparing viewer…
PDB2CS4 · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.66LoF Tolerant
pLIⓘ
0.03Tolerant
Observed/Expected LoF0.46 [0.32–0.66]
RankingsWhere RASSF8 stands among ~20K protein-coding genes
  • #7,399of 20,598
    Most Researched63
  • #4,809of 17,882
    Most Constrained (LOEUF)0.66
Genes detectedRASSF8
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
RASSF7 and RASSF8 proteins are predictive factors for development and metastasis in malignant thyroid neoplasms.
PMID: 24516056
J Cancer Res Ther · 2013
1.00
2
RASSF8-AS1 displays low expression in colorectal cancer and up-regulates RASSF8 to suppress cell invasion and migration.
PMID: 35839610
Pathol Res Pract · 2022
0.90
3
The RASSF8 candidate tumor suppressor inhibits cell growth and regulates the Wnt and NF-kappaB signaling pathways.
PMID: 20514026
Oncogene · 2010
0.80
4
PMID: 36846012
Ann Transl Med · 2023
0.70
5
RASSF8 regulates progression of cutaneous melanoma through nuclear factor-κb.
PMID: 26334503
Oncotarget · 2015
0.60