RXFP4

Chr 1

relaxin family peptide/INSL5 receptor 4

Also known as: GPCR142, GPR100, RLN3R2, RXFPR4

NCBI Gene: 339403 ENSG00000173080 UniProt: Q8TDU9 OMIM: 609043

GPR100 is a member of the rhodopsin family of G protein-coupled receptors (GPRs) (Fredriksson et al., 2003 [PubMed 14623098]).[supplied by OMIM, Mar 2008]

OMIM Research

GPR100 is a member of the rhodopsin family of G protein-coupled receptors (GPRs) (Fredriksson et al., 2003 [PubMed 14623098]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.70

Clinical Summary— RXFP4

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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

70 VUS of 75 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?

1.70LOEUF

pLI 0.000

Z-score 0.04

OE 0.98 (0.57–1.70)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.66Z-score

OE missense 0.88 (0.79–0.99)

209 obs / 237.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.98 (0.57–1.70)

0≤0.351.4

Missense OE?0.88 (0.79–0.99)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 8 / 8.1Missense obs/exp: 209 / 237.4Syn Z: 1.61

This gene — mechanism propensity

0.6937th %ile

GOF

0.81top 10%

LOF

0.3259th %ile

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

GOFprediction above median

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

75 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	70	70
Likely Benign	5	5
Benign	0	0
Total	75	75

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap RXFP4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →