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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RLN2
relaxin 2
Chromosome 9 · 9p24.1
NCBI Gene: 6019Ensembl: ENSG00000107014.9HGNC: HGNC:10027UniProt: P04090
115PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of catalytic activitypositive regulation of gene expressionpositive regulation of angiogenesisextracellular regioninfectious diseaseArthropathyneoplasmosteosarcoma
✦AI Summary

RLN2 (relaxin-2) is a peptide hormone with dual roles in reproductive physiology and pathological processes. In normal physiology, RLN2 mediates connective tissue remodeling during pregnancy, promoting cervical ripening and pubic ligament growth through collagen degradation and matrix metalloproteinase upregulation 1. RLN2 signals via the G protein-coupled receptor RXFP1 to trigger vasodilation, angiogenesis, and anti-inflammatory effects 2. In cancer pathogenesis, RLN2 expression is frequently elevated and contributes to aggressive phenotypes across multiple malignancies. In breast cancer, estrogen receptor-alpha directly regulates RLN2 transcription 3, and tumor-associated neutrophils secrete RLN2 to suppress the immune lncRNA C6orf99 via RXFP1, activating pro-tumoral STAT3 signaling 4. In osteosarcoma, RLN2 promotes cell invasion and chemoresistance through AKT/NF-κB pathway activation 5, and elevated RLN2 expression correlates with metastasis and poor survival 6. RLN2 is also upregulated in thyroid carcinoma tissues 7 and prostate cancer, where novel RLN1-RLN2 fusion transcripts are detected 8. Clinically, RLN2's antifibrotic properties show therapeutic promise: engineered long-acting RLN2 variants maintain RXFP1 agonist activity for heart failure and fibrotic disease treatment 2, while RLN2-secreting CAR-T cells enhance tumor infiltration in stroma-rich solid tumors 1. RLN2 represents both a cancer biomarker and potential therapeutic target.

Sources cited
1
Estrogen receptor-alpha directly regulates RLN2 transcription in breast cancer cells
PMID: 19416221
2
RLN2 promotes osteosarcoma cell invasion and chemoresistance via AKT/NF-κB signaling
PMID: 26229955
3
Novel RLN1-RLN2 fusion transcripts are expressed in prostate cancer cells and tissues
PMID: 26499396
4
RLN2 activates RXFP1 receptor and engineered Fc-fusion RLN2 maintains long serum half-life
PMID: 39134056
5
Tumor-associated neutrophil-derived RLN2 suppresses C6orf99 via RXFP1 to activate STAT3 in breast cancer
PMID: 40925207
6
RLN2 is highly expressed in differentiated thyroid carcinoma tissues and cell lines
PMID: 38815632
7
High RLN2 expression in osteosarcoma correlates with metastasis and poor overall survival
PMID: 25339476
8
RLN2 promotes collagen degradation and matrix metalloproteinase upregulation to enhance CAR-T cell infiltration
PMID: 40666525
Disease Associationsⓘ20
infectious diseaseOpen Targets
0.29Weak
ArthropathyOpen Targets
0.29Weak
neoplasmOpen Targets
0.10Weak
osteosarcomaOpen Targets
0.09Suggestive
atrial fibrillationOpen Targets
0.08Suggestive
prostate cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
cancerOpen Targets
0.06Suggestive
Isolated follicle stimulating hormone deficiencyOpen Targets
0.05Suggestive
myocardial infarctionOpen Targets
0.05Suggestive
azoospermiaOpen Targets
0.05Suggestive
prostate neoplasmOpen Targets
0.05Suggestive
Kallmann syndromeOpen Targets
0.05Suggestive
partial androgen insensitivity syndromeOpen Targets
0.05Suggestive
pernicious anemiaOpen Targets
0.04Suggestive
placenta praeviaOpen Targets
0.04Suggestive
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiencyOpen Targets
0.04Suggestive
ring chromosome YOpen Targets
0.04Suggestive
isochromosomy YpOpen Targets
0.04Suggestive
Leydig cell hypoplasiaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RXFP2Protein interaction99%INSL5Protein interaction99%RLN3Protein interaction99%INSL3Protein interaction98%INSL4Protein interaction98%RXFP3Protein interaction96%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
82%
Lung
55%
Brain
27%
Ovary
9%
Liver
0%
Gene Interaction Network
Click a node to explore
RLN2RXFP2INSL5RLN3INSL3INSL4RXFP3
PROTEIN STRUCTURE
Preparing viewer…
PDB6RLX · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.78LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.97 [0.50–1.78]
RankingsWhere RLN2 stands among ~20K protein-coding genes
  • #4,132of 20,598
    Most Researched115 · top quartile
  • #16,492of 17,882
    Most Constrained (LOEUF)1.78
Genes detectedRLN2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Estrogen and TCDD influence RLN2 gene activity in estrogen receptor-positive human breast cancer cells.
PMID: 19416221
Ann N Y Acad Sci · 2009
1.00
2
RLN2 Is a Positive Regulator of AKT-2-Induced Gene Expression Required for Osteosarcoma Cells Invasion and Chemoresistance.
PMID: 26229955
Biomed Res Int · 2015
0.90
3
Identification of a novel fusion transcript between human relaxin-1 (RLN1) and human relaxin-2 (RLN2) in prostate cancer.
PMID: 26499396
Mol Cell Endocrinol · 2016
0.80
4
Engineering and Characterization of a Long-Half-Life Relaxin Receptor RXFP1 Agonist.
PMID: 39134056
Mol Pharm · 2024
0.70
5
Tumor-associated neutrophils promote breast cancer progression via RLN2/RXFP1-C6orf99-STAT3 axis.
PMID: 40925207
Int Immunopharmacol · 2025
0.60