RLN2

Chr 9

relaxin 2

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

NCBI Gene: 6019 ENSG00000107014 UniProt: P04090 OMIM: 179740

This gene encodes relaxin, a peptide hormone that promotes dilatation of the birth canal and remodeling of connective tissues during pregnancy, and also regulates cardiovascular function including blood pressure and heart rate. The gene shows low constraint to loss-of-function variation (pLI 0.0009, LOEUF 1.905), and no pediatric neurological disorders have been definitively associated with RLN2 mutations in current medical literature. Based on available data, this gene does not appear to be relevant for pediatric neurogenetics practice.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.91

Clinical Summary— RLN2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

59 VUS of 69 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-1.32Z-score

OE missense 1.37 (1.19–1.58)

136 obs / 99.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.27 (0.58–1.91)

0≤0.351.4

Missense OE?1.37 (1.19–1.58)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 4 / 3.2Missense obs/exp: 136 / 99.1Syn Z: -0.75

This gene — mechanism propensity

0.93top 5%

GOF

0.3491th %ile

LOF

0.1499th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

69 submitted variants in ClinVar

ClinVar

Classification Summary

VUS59

Likely Benign7

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	58	0	59
Likely Benign	0	7	0	7
Benign	0	1	1	2
Total	1	66	1	68

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

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164 pathogenic / likely-pathogenic (of 177) ClinVar copy-number / structural variants overlap RLN2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →