RLN2

Chr 9

relaxin 2

Also known as: H2, H2-RLX, RLXH2, bA12D24.1.1, bA12D24.1.2

NCBI Gene: 6019ENSG00000107014UniProt: P04090

This gene encodes a member of the relaxin subfamily and insulin superfamily of peptide hormones. In humans there are three non-allelic relaxin genes. This gene encodes multiple protein isoforms, at least one of which undergoes proteolytic processing. This processing generates relaxin A and B chains that are linked by disulfide bonds to form the mature peptide hormone. This hormone plays a role in the male and female reproductive systems and was initially noted for its role in pregnancy. This protein also plays broader roles in the cardiovascular system, including in the regulation of blood pressure and control of heart rate, and data from animal models shows that this protein may have anti-fibrotic and cardioprotective effects. [provided by RefSeq, Jul 2016]

243
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RLN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
243 total variants — no pathogenic classifications of 243 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.91LOEUF
pLI 0.001
Z-score -0.44
OE 1.27 (0.58–1.91)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.32Z-score
OE missense 1.37 (1.19–1.58)
136 obs / 99.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.27 (0.58–1.91)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.37 (1.19–1.58)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 4 / 3.2Missense obs/exp: 136 / 99.1Syn Z: -0.75

ClinVar Variant Classifications

243 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

RLN2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
RELAXIN 2; RLN2
MIM #179740 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Relaxin-2-secreting CAR-T cells exhibit enhanced efficacy in stromal-rich xenograft tumors.
Ogawa H et al.·Front Immunol
2025
Role of Relaxin Signaling in Cancer: A Review.
Kotwal A et al.·Biochem Pharmacol
2024Review
Prognostic significance of relaxin-2 and S100A4 expression in osteosarcoma.
Huang H et al.·Eur Rev Med Pharmacol Sci
2014
Healthy Donors Exhibit a CD4 T Cell Repertoire Specific to the Immunogenic Human Hormone H2-Relaxin before Injection.
Azam A et al.·J Immunol
2019
Relaxin-2 is a novel biomarker for differentiated thyroid carcinoma in humans.
Kotwal A et al.·Biochem Pharmacol
2024
Identification and validation of molecular subtypes and a 9-gene risk model for breast cancer.
Feng J·Medicine (Baltimore)
2023Functional
Interaction between angiotensin II and relaxin 2 in the progress of growth and spread of prostate cancer cells.
Domińska K et al.·Int J Oncol
2016
Preterm premature rupture of membranes: prediction of risks in women of Zaporizhzhia region of Ukraine.
Lyubomirskaya K et al.·Pol Merkur Lekarski
2020
Relaxin-2 Inhibits Cervical Cancer Growth by Downregulating Kruppel-Like Factor 5 (KLF5) Through the Inhibition of Hippo-YAP and JAK2/STAT3 Signaling Pathways.
Li H et al.·J Biochem Mol Toxicol
2026
SNPs and transcriptional activity of genes of innate and adaptive immunity at the maternal-fetal interface in woman with preterm labour, associated with preterm premature rupture of membranes.
Lyubomirskaya ES et al.·Wiad Lek
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools