RXFP4: Relaxin Family Peptide Receptor 4
A GPCR for relaxin-3/INSL5, implicated in stress, feeding, and cancer signaling
Gene Information Card
| Symbol | RXFP4 |
|---|---|
| Full Name | Relaxin Family Peptide Receptor 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q22 |
| NCBI Gene ID | 339403 ncbi.nlm.nih.gov/gene/339403 |
| Ensembl ID | ENSG00000173068 |
| UniProt ID | Q8TDU9 |
| OMIM ID | 609044 |
| HGNC ID | 24828 |
| Aliases | GPR100, RLN3R2, RXFP4 |
Description
RXFP4 encodes a G protein-coupled receptor (GPCR) that binds relaxin-3 (RLN3) and insulin-like peptide 5 (INSL5). It is primarily expressed in the brain and gastrointestinal tract, where it modulates stress responses, feeding behavior, and energy homeostasis. RXFP4 signaling is mediated through Gαi/o proteins, inhibiting cAMP production. The receptor is also implicated in certain cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | RXFP4 activation by INSL5 regulates appetite and energy expenditure; altered signaling may contribute to hyperphagia | PMID: 23395176 |
| Anxiety disorders | RXFP4 mediates relaxin-3 effects on stress circuits in the amygdala and hypothalamus | PMID: 19615754 |
| Colorectal cancer | RXFP4 overexpression in tumor tissues; INSL5/RXFP4 axis promotes cell proliferation via MAPK/ERK | PMID: 31570795 |
| Type 2 diabetes | RXFP4 polymorphisms associated with insulin resistance in GWAS | ClinVar: rs61740334 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 4.2 | Low |
| Brain (hippocampus) | 3.8 | Low |
| Colon | 2.1 | Not detected |
| Stomach | 1.5 | Not detected |
| Pancreas | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.0 | No endogenous expression; used for recombinant studies |
| SH-SY5Y | 2.5 | Low; neuronal model |
| HT-29 | 1.2 | Not detected; colorectal cancer line |
| HCT116 | 0.9 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200G>A (p.Arg67His) | Missense | <0.01% (gnomAD) | Reduced INSL5 binding affinity; loss-of-function |
| c.487C>T (p.Pro163Ser) | Missense | 0.02% | Impaired cell surface expression; loss-of-function |
| c.784G>A (p.Gly262Arg) | Missense | 0.001% | Altered G-protein coupling; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
p.Arg67His and p.Pro163Ser reduce ligand binding or receptor trafficking, leading to diminished signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in RXFP4.
Dominant Negative (DN)
Not described for RXFP4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Relaxin signaling pathway (KEGG: hsa04934)
• GPCR downstream signaling (Reactome: R-HSA-388396)
• G alpha (i) signaling events (Reactome: R-HSA-418594)
Protein Summary
RXFP4 is a 374-amino acid class A GPCR with seven transmembrane domains. It shares homology with RXFP3 and is activated by relaxin-3 and INSL5. The receptor couples to Gi/o proteins, inhibiting adenylyl cyclase and reducing cAMP. Post-translational modifications include N-glycosylation at Asn20, which is critical for cell surface expression. Structural studies reveal a conserved binding pocket for the B-chain of relaxin-3.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RXFP4 Knockout HEK293 Cell Line | EDJ-KQ14375 | Human | 339403 | Details Get a Quote |
| RXFP4 Knockout HeLa Cell Line | EDJ-KQ59641 | Human | 339403 | Details Get a Quote |
| RXFP4 Knockout A-549 Cell Line | EDJ-KQ68108 | Human | 339403 | Details Get a Quote |
| RXFP4 Knockout HCT 116 Cell Line | EDJ-KQ76485 | Human | 339403 | Details Get a Quote |
