RLN3
Chr 19relaxin 3
Also known as: H3, RXN3, ZINS4, insl7
The RLN3 protein is a neuropeptide hormone that functions as a ligand for receptors LGR7, RXFP3, and RXFP4, regulating stress, memory, and appetite in the brain. Mutations in RLN3 cause neurodevelopmental disorders with intellectual disability and behavioral abnormalities, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants (low constraint), suggesting that complete loss of function may be required for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
44 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 12 | 0 | 12 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 21 | 4 | 0 | 25 |
Likely Benign | 0 | 2 | 2 | 0 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 2 | |||
| Total | 0 | 23 | 19 | 0 | 44 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RLN3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools