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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RASSF4
Ras association domain family member 4
Chromosome 10 · 10q11.21
NCBI Gene: 83937Ensembl: ENSG00000107551.22HGNC: HGNC:20793UniProt: Q9H2L5
30PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Tumor Suppressor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsignal transductionprostate carcinomaAbruptio Placentaepsoriatic arthritishepatocellular carcinoma
✦AI Summary

RASSF4 (Ras association domain family member 4) functions as a tumor suppressor gene that regulates apoptosis and cell cycle progression through multiple signaling pathways. The protein acts as a key regulator of the Hippo pathway, interacting with MST1 to inhibit YAP nuclear translocation, thereby suppressing cell proliferation and tumor growth 1. RASSF4 promotes apoptosis through activation of the Chk2-p53 signaling axis, stabilizing p53 and facilitating stress-induced apoptosis in response to genotoxic agents 2. The gene is frequently downregulated through epigenetic mechanisms in various cancers, including colorectal cancer 3, non-small cell lung cancer 4, and gastric cancer 2. In acute myeloid leukemia, RASSF4 expression is negatively regulated by GATA2, and its downregulation contributes to chemotherapy resistance by modulating the MDM2-p53 pathway 5. RASSF4 also plays a protective role in metabolic dysfunction-associated steatotic liver disease by preventing hepatic steatosis and fibrosis 1. Clinically, reduced RASSF4 expression correlates with advanced tumor stage, poor prognosis, and decreased overall survival in multiple cancer types, establishing it as both a prognostic biomarker and potential therapeutic target.

Sources cited
1
RASSF4 interacts with MST1 to inhibit YAP nuclear translocation through the Hippo pathway and prevents hepatic steatosis
PMID: 38697356
2
RASSF4 stabilizes p53 through Chk2 activation and facilitates stress-induced apoptosis
PMID: 40259805
3
RASSF4 is downregulated in colorectal cancer and regulates cell behavior through YAP/Bcl-2 pathway
PMID: 35611809
4
RASSF4 downregulation associates with advanced TNM stage and poor prognosis in non-small cell lung cancer
PMID: 26526576
5
GATA2 negatively regulates RASSF4 expression, contributing to chemotherapy resistance in acute myeloid leukemia
PMID: 39841459
Disease Associationsⓘ20
prostate carcinomaOpen Targets
0.29Weak
Abruptio PlacentaeOpen Targets
0.28Weak
psoriatic arthritisOpen Targets
0.27Weak
hepatocellular carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
eustachian tube diseaseOpen Targets
0.07Suggestive
osteosarcomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
abscessOpen Targets
0.06Suggestive
malignant renal pelvis neoplasmOpen Targets
0.05Suggestive
cellulitisOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
nasopharyngeal carcinomaOpen Targets
0.04Suggestive
hypertensionOpen Targets
0.04Suggestive
colorectal cancerOpen Targets
0.03Suggestive
juvenile idiopathic arthritisOpen Targets
0.03Suggestive
cardiovascular diseaseOpen Targets
0.03Suggestive
frozen shoulderOpen Targets
0.03Suggestive
oral squamous cell carcinomaOpen Targets
0.02Suggestive
corneal neovascularizationOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
STK3Protein interaction98%RASSF2Protein interaction91%STK4Protein interaction79%
Tissue Expression6 tissues
Heart
100%
Lung
46%
Liver
46%
Brain
36%
Bone Marrow
32%
Ovary
14%
Gene Interaction Network
Click a node to explore
RASSF4STK3RASSF2STK4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9H2L5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.36LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.01 [0.76–1.36]
RankingsWhere RASSF4 stands among ~20K protein-coding genes
  • #12,016of 20,598
    Most Researched30
  • #14,171of 17,882
    Most Constrained (LOEUF)1.36
Genes detectedRASSF4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Single-cell RNA sequencing reveals the transcriptomic landscape of kidneys in patients with ischemic acute kidney injury.
PMID: 37083129
Chin Med J (Engl) · 2023
1.00
2
GATA2 links stemness to chemotherapy resistance in acute myeloid leukemia.
PMID: 39841459
Blood · 2025
0.90
3
RASSF4 Attenuates Metabolic Dysfunction-Associated Steatotic Liver Disease Progression via Hippo Signaling and Suppresses Hepatocarcinogenesis.
PMID: 38697356
Cell Mol Gastroenterol Hepatol · 2024
0.80
4
RASSF4 inhibits cell proliferation and increases drug sensitivity in colorectal cancer through YAP/Bcl-2 pathway.
PMID: 35611809
J Cell Mol Med · 2022
0.70
5
RASSF4 Suppresses Gastric Tumor Growth through Activation of Chk2-p53 Signaling Axis.
PMID: 40259805
Cancer Res Treat · 2025
0.60