RLN1

Chr 9

relaxin 1

Also known as: H1, H1RLX, RLXH1, bA12D24.3.1, bA12D24.3.2

NCBI Gene: 6013 ENSG00000107018 OMIM: 179730

The protein encoded by this gene is relaxin, a hormone that acts with estrogen to dilate the birth canal by remodeling connective tissues during pregnancy, promoting growth of pubic ligaments and ripening of the cervix. No disease associations with RLN1 mutations have been established in the provided data. The gene shows low constraint to loss-of-function variation (pLI = 0.007, LOEUF = 1.86), suggesting tolerance to inactivating variants.

OMIM ResearchSummary from RefSeq, UniProt

Relaxins are known endocrine and autocrine/paracrine hormones, belonging to the insulin gene superfamily. In humans there are three non-allelic relaxin genes, RLN1, RLN2 and RLN3, where RLN1 and RLN2 share high sequence homology. The protein encoded by this gene is synthesized as a single-chain polypeptide but the active form consists of an A chain and a B chain linked by disulfide bonds. Relaxin is produced by the ovary, and targets the mammalian reproductive system to ripen the cervix, elongate the pubic symphysis and inhibit uterine contraction. It may have additional roles in enhancing sperm motility, regulating blood pressure, controlling heart rate and releasing oxytocin and vasopressin. [provided by RefSeq, Jan 2013]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.85

Clinical Summary— RLN1

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

42 VUS of 51 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?

1.85LOEUF

pLI 0.007

Z-score 0.01

OE 0.99 (0.43–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.64Z-score

OE missense 1.46 (1.28–1.68)

146 obs / 99.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.99 (0.43–1.85)

0≤0.351.4

Missense OE?1.46 (1.28–1.68)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 3 / 3.0Missense obs/exp: 146 / 99.9Syn Z: -0.84

This gene — mechanism propensity

0.85top 5%

GOF

0.4874th %ile

LOF

0.1796th %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

51 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign5

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	42	0	42
Likely Benign	5	0	5
Benign	0	1	1
Total	47	1	48

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

View in ClinVar →

164 pathogenic / likely-pathogenic (of 175) ClinVar copy-number / structural variants overlap RLN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →