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7 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RNFT2
ring finger protein, transmembrane 2
Chromosome 12 · 12q24.22
NCBI Gene: 84900Ensembl: ENSG00000135119.15HGNC: HGNC:25905UniProt: Q96EX2
13PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ubiquitin protein ligase activitypositive regulation of ERAD pathwaymembranemiddle ear disorderinjuryplacenta praevialung cancer
✦AI Summary

RNFT2 (ring finger protein, transmembrane 2) is an E3 ubiquitin ligase that functions as a negative regulator of interleukin-3 (IL-3) signaling through IL-3 receptor α (IL-3Rα) ubiquitination and proteasomal degradation 1. This mechanism confers anti-inflammatory properties, as RNFT2 overexpression reduces lung inflammation in LPS-induced injury models, while RNFT2 knockdown exacerbates inflammatory responses 1. Despite this regulatory role in immunity, RNFT2 paradoxically functions as an oncogene in multiple cancers. RNFT2 is significantly upregulated in gastric cancer 23, where knockdown inhibits cell proliferation, migration, and invasion through the mTORC1 signaling pathway 3. In gastric cancer, high RNFT2 expression predicts peritoneal recurrence and poor overall survival 2. Similarly, RNFT2 promotes triple-negative breast cancer malignancy and angiogenesis, with elevated expression correlating with poor survival and advanced clinicopathological features 4. RNFT2 is also included in prognostic models for hepatocellular carcinoma 5. Additionally, RNFT2 has been identified as a pharmacogenetic locus associated with differential responsiveness to inhaled corticosteroids in African descent asthma populations 6. These findings establish RNFT2 as a potential therapeutic target in cancer while highlighting its immunoregulatory functions.

Sources cited
1
RNFT2 is an E3 ubiquitin ligase that negatively regulates IL-3Rα through ubiquitination and proteasomal degradation, with anti-inflammatory effects in lung injury models
PMID: 31990690
2
RNFT2 knockdown in gastric cancer cells inhibits proliferation, migration, and invasion through mTORC1 signaling pathway
PMID: 40097779
3
RNFT2 is upregulated in gastric cancer tissues and metastases; high expression correlates with peritoneal recurrence and poor overall survival
PMID: 33517265
4
RNFT2 is elevated in triple-negative breast cancer and promotes cell proliferation, invasion, and angiogenesis; high expression predicts poor outcomes
PMID: 40632345
5
RNFT2 is included as a key alternative splice gene in a seven-gene prognostic model for hepatocellular carcinoma
PMID: 37542549
6
A locus adjacent to RNFT2 on chromosome 12 is associated with differential responsiveness to inhaled corticosteroids in children of African descent with asthma
PMID: 34762840
7
RNFT2 is identified as a target of miR-627-5p in smoking-induced changes in human airway epithelium
PMID: 31568004
Disease Associationsⓘ20
middle ear disorderOpen Targets
0.27Weak
injuryOpen Targets
0.27Weak
placenta praeviaOpen Targets
0.25Weak
lung cancerOpen Targets
0.24Weak
respiratory system diseaseOpen Targets
0.20Weak
gastric cancerOpen Targets
0.08Suggestive
breast benign neoplasmOpen Targets
0.05Suggestive
triple-negative breast cancerOpen Targets
0.05Suggestive
snowflake vitreoretinal degenerationOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
pericarditisOpen Targets
0.04Suggestive
X-linked retinal dysplasiaOpen Targets
0.04Suggestive
isolated ectopia lentisOpen Targets
0.03Suggestive
lung carcinomaOpen Targets
0.01Suggestive
urinary bladder carcinomaOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
esophageal squamous cell carcinomaOpen Targets
0.01Suggestive
ataxia telangiectasiaOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
myxosarcomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TMEM259Shared pathway50%RNFT1Shared pathway50%TMX1Shared pathway25%ATXN3LShared pathway20%SIK2Shared pathway20%SGTAShared pathway14%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
7%
Ovary
7%
Heart
5%
Lung
4%
Liver
4%
Gene Interaction Network
Click a node to explore
RNFT2TMEM259RNFT1TMX1ATXN3LSIK2SGTA
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96EX2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.26LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.95 [0.73–1.26]
RankingsWhere RNFT2 stands among ~20K protein-coding genes
  • #16,281of 20,598
    Most Researched13
  • #13,346of 17,882
    Most Constrained (LOEUF)1.26
Genes detectedRNFT2
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Identification of gene and microRNA changes in response to smoking in human airway epithelium by bioinformatics analyses.
PMID: 31568004
Medicine (Baltimore) · 2019
1.00
2
Comprehensive analysis of CPSF4-related alternative splice genes in hepatocellular carcinoma.
PMID: 37542549
J Cancer Res Clin Oncol · 2023
0.86
3
Silencing of RNFT2 suppresses cell proliferation and migration through mTORC1 signaling pathway in gastric cancer.
PMID: 40097779
Amino Acids · 2025
0.71
4
Tissue
PMID: 33517265
Anticancer Res · 2021
0.57
5
Pharmacogenetic studies of long-acting beta agonist and inhaled corticosteroid responsiveness in randomised controlled trials of individuals of African descent with asthma.
PMID: 34762840
Lancet Child Adolesc Health · 2021
0.43