RXFP2

Chr 13

relaxin family peptide receptor 2

Also known as: GPR106, GREAT, INSL3R, LGR8, LGR8.1, RXFPR2

NCBI Gene: 122042 ENSG00000133105 UniProt: Q8WXD0

The protein is a G protein-coupled receptor that serves as a receptor for relaxin and Leydig insulin-like peptide (INSL3), activating adenylyl cyclase and increasing cAMP levels. Mutations cause cryptorchidism, which presents at birth as undescended testes. The gene shows extremely low constraint to loss-of-function variation (pLI near zero), suggesting tolerance to protein-truncating variants.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the GPCR (G protein-coupled, 7-transmembrane receptor) family. Mutations in this gene are associated with cryptorchidism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCryptorchidism

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.00

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.000

Z-score 1.54

OE 0.74 (0.55–1.00)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.89Z-score

OE missense 0.87 (0.80–0.95)

345 obs / 395.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.55–1.00)

0≤0.351.4

Missense OE?0.87 (0.80–0.95)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 29 / 39.4Missense obs/exp: 345 / 395.0Syn Z: 0.23

Background carrier burden — how many people carry a rare variant somewhere in RXFP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 85

858 rare PASS variants

Rare truncating (LoF)

1 in 380

141 rare PASS variants

Rare synonymous (reference)

1 in 160

348 rare PASS variants

Rare missense and truncating variants are carried at similar rates in RXFP2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 360
South Asian	~43k	1 in 84	1 in 480
Remaining (unassigned)	~30k	1 in 63	1 in 520
European (Finnish)	~27k	1 in 260	1 in 1,300
Admixed American	~22k	1 in 70	1 in 500
African / African American	~21k	1 in 90	1 in 340
East Asian	~20k	1 in 79	1 in 440
Ashkenazi Jewish	~13k	1 in 390	1 in 790
Middle Eastern	~2,884	1 in 74	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 18 coding exons well covered in gnomAD exomes; exons 1, 4, 5, 6, 9 and 3 more marginal. Genomes: all 18.? see exons ↓