RXFP1

Chr 4

relaxin family peptide receptor 1

Also known as: LGR7, RXFPR1

NCBI Gene: 59350ENSG00000171509UniProt: Q9HBX9

The protein functions as a G protein-coupled receptor for relaxin hormones, stimulating adenylate cyclase to increase cAMP levels and playing critical roles in sperm motility, pregnancy, and parturition. RXFP1 mutations cause cryptorchidism (autosomal dominant inheritance), affecting male reproductive development. The gene shows minimal constraint against loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
30
Pubs (1 yr)
35
P/LP submissions
0%
P/LP missense
0.90
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— RXFP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 100 VUS of 145 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.000
Z-score 2.08
OE 0.64 (0.47–0.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.12Z-score
OE missense 0.84 (0.77–0.92)
329 obs / 391.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.47–0.90)
0≤0.351.4
Missense OE0.84 (0.77–0.92)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 25 / 39.0Missense obs/exp: 329 / 391.4Syn Z: 1.25
DN
0.80top 25%
GOF
0.80top 10%
LOF
0.2189th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

145 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic3
VUS100
Likely Benign3
32
Pathogenic
3
Likely Pathogenic
100
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
3
0
3
VUS
0
92
8
0
100
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total094431138

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RXFP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Ednrb-driven ET-1/RXFP1 underlies TXA-induced exacerbation of acute cartilage injury-related PTOA.
Li M et al.·Biochem Biophys Res Commun
2026
Phase 2b trial of an oral RXFP1 agonist in patients with chronic heart failure: rationale and design.
Quintana-Hayashi MP et al.·ESC Heart Fail
2026Cohort
Description of a Large Family with Periodic Fever Carrying a Variant in RXFP1 Gene: A Possible Novel Modulator of Inflammation in Autoinflammatory Diseases.
Buttarelli M et al.·Int J Mol Sci
2026Open Access
The simultaneous targeting of RXFP1 and RXFP3 improves motor function and reduces brain inflammation, apoptosis and glial scarring following photothrombotic stroke in male mice.
Knezic A et al.·Biochem Pharmacol
2026
The role of relaxins in blood cell modulation: interactions with relaxin family peptide receptor 1 (RXFP1) and glucocorticoid receptor (GR).
Broszkiewicz W et al.·Clin Sci (Lond)
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients