• Gene id: 122042

Gene Summary

• Gene Symbol: RXFP2   Gene   UCSC   Ensembl
• Aliases: GPR106, GREAT, INSL3R, LGR8, LGR8.1, RXFPR2
• Gene name: relaxin family peptide receptor 2
• Alternate names: relaxin receptor 2, G protein coupled receptor affecting testicular descent, G-protein coupled receptor 106, leucine-rich repeat-containing G-protein coupled receptor 8, relaxin/insulin like family peptide receptor 2,
• Gene location: 13q13.1 (31739541: 31802871)     Exons: 18     NC_000013.11
• Gene summary(Entrez): 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.[pr
• OMIM: 606655

SNPs

rs1555633

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000013.11   g.31781295T>A
NC_000013.11   g.31781295T>G
NC_000013.10   g.32355432T>A
NC_000013.10   g.32355432T>G
NG_015819.1   g.46754T>A
NG_015819.1   g.46754T>G|SEQ=[T/A/G]|GENE=RXFP2

rs7325513

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000013.11   g.31786410A>C
NC_000013.11   g.31786410A>G
NC_000013.11   g.31786410A>T
NC_000013.10   g.32360547A>C
NC_000013.10   g.32360547A>G
NC_000013.10   g.32360547A>T
NG_015819.1   g.51869A>C
NG_015819.1   g.51869A>G
NG_015819.1   g.51869A>T
NM_130806.5   c.957A>

Protein Summary

• Protein general information: Q8WXD0  
  • Name: Relaxin receptor 2 (G protein coupled receptor 106) (G protein coupled receptor affecting testicular descent) (Leucine rich repeat containing G protein coupled receptor 8) (Relaxin family peptide receptor 2)
  • Length: 754  
  • Mass: 86,453
• Sequence:

  MIVFLVFKHLFSLRLITMFFLLHFIVLINVKDFALTQGSMITPSCQKGYFPCGNLTKCLPRAFHCDGKDDCGNGA
  DEENCGDTSGWATIFGTVHGNANSVALTQECFLKQYPQCCDCKETELECVNGDLKSVPMISNNVTLLSLKKNKIH
  SLPDKVFIKYTKLKKIFLQHNCIRHISRKAFFGLCNLQILYLNHNCITTLRPGIFKDLHQLTWLILDDNPITRIS
  QRLFTGLNSLFFLSMVNNYLEALPKQMCAQMPQLNWVDLEGNRIKYLTNSTFLSCDSLTVLFLPRNQIGFVPEKT
  FSSLKNLGELDLSSNTITELSPHLFKDLKLLQKLNLSSNPLMYLHKNQFESLKQLQSLDLERIEIPNINTRMFQP
  MKNLSHIYFKNFRYCSYAPHVRICMPLTDGISSFEDLLANNILRIFVWVIAFITCFGNLFVIGMRSFIKAENTTH
  AMSIKILCCADCLMGVYLFFVGIFDIKYRGQYQKYALLWMESVQCRLMGFLAMLSTEVSVLLLTYLTLEKFLVIV
  FPFSNIRPGKRQTSVILICIWMAGFLIAVIPFWNKDYFGNFYGKNGVCFPLYYDQTEDIGSKGYSLGIFLGVNLL
  AFLIIVFSYITMFCSIQKTALQTTEVRNCFGREVAVANRFFFIVFSDAICWIPVFVVKILSLFRVEIPDTMTSWI
  VIFFLPVNSALNPILYTLTTNFFKDKLKQLLHKHQRKSIFKIKKKSLSTSIVWIEDSSSLKLGVLNKITLGDSIM
  KPVS

• Structural information:
  • Protein Domains: LDL-receptor (44-81)
  • Interpro: IPR000276  IPR017452  IPR036055  IPR023415  IPR002172   IPR001611  IPR003591  IPR032675  IPR008112  
  • Prosite: PS50262 PS01209 PS50068 PS51450
  • CDD: cd00112
  • PDB: 2M96
  • PDBsum: 2M96
  • STRING: ENSP00000298386
• Other Databases: GeneCards:  RXFP2  Malacards:  RXFP2

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0001556	oocyte maturation	IEA	biological process
GO:0004930	G-protein coupled receptor activity	IBA	molecular function
GO:0005886	plasma membrane	IBA	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0007188	adenylate cyclase-modulating G-protein coupled receptor signaling pathway	IBA	biological process
GO:0007189	adenylate cyclase-activating G-protein coupled receptor signaling pathway	IEA	biological process
GO:0007193	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway	IEA	biological process
GO:0008285	negative regulation of cell proliferation	IEA	biological process
GO:0008584	male gonad development	IEA	biological process
GO:0016021	integral component of membrane	IEA	cellular component
GO:0016500	protein-hormone receptor activity	IEA	molecular function
GO:0017046	peptide hormone binding	IEA	molecular function
GO:0030819	positive regulation of cAMP biosynthetic process	IEA	biological process
GO:0043066	negative regulation of apoptotic process	IEA	biological process
GO:0001556	oocyte maturation	IEA	biological process
GO:0004871	signal transducer activity	IEA	molecular function
GO:0004930	G-protein coupled receptor activity	IEA	molecular function
GO:0004930	G-protein coupled receptor activity	IBA	molecular function
GO:0004930	G-protein coupled receptor activity	IEA	molecular function
GO:0005886	plasma membrane	IEA	cellular component
GO:0005886	plasma membrane	IBA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0007165	signal transduction	IEA	biological process
GO:0007165	signal transduction	IEA	biological process
GO:0007186	G-protein coupled receptor signaling pathway	IEA	biological process
GO:0007186	G-protein coupled receptor signaling pathway	IEA	biological process
GO:0007188	adenylate cyclase-modulating G-protein coupled receptor signaling pathway	IBA	biological process
GO:0007189	adenylate cyclase-activating G-protein coupled receptor signaling pathway	IEA	biological process
GO:0007193	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway	IEA	biological process
GO:0008285	negative regulation of cell proliferation	IEA	biological process
GO:0008584	male gonad development	IEA	biological process
GO:0016020	membrane	IEA	cellular component
GO:0016020	membrane	IEA	cellular component
GO:0016021	integral component of membrane	IEA	cellular component
GO:0016021	integral component of membrane	IEA	cellular component
GO:0016500	protein-hormone receptor activity	IEA	molecular function
GO:0017046	peptide hormone binding	IEA	molecular function
GO:0030819	positive regulation of cAMP biosynthetic process	IEA	biological process
GO:0043066	negative regulation of apoptotic process	IEA	biological process
GO:0004930	G-protein coupled receptor activity	IBA	molecular function
GO:0005886	plasma membrane	IBA	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0007188	adenylate cyclase-modulating G-protein coupled receptor signaling pathway	IBA	biological process

KEGG pathways

Pathway id	Pathway name
hsa04080	Neuroactive ligand-receptor interaction
hsa04926	Relaxin signaling pathway

Diseases

Associated diseases	References
Noonan syndrome	KEGG: H00523
Cryptorchidism	MIK: 12970298
Azoospermia	MIK: 12970298
Nonsyndromic cryptorchidism	MIK: 26209787
Testicular dysgenesis syndrome (TDS)	MIK: 16687567
Testicular functions	MIK: 15353080
Normozoospermia	MIK: 12970298
Retractile testes	MIK: 12970298
Male factor infertility	MIK: 15956751
Maldescended testes	MIK: 16687567
Male factor infertility	MIK: 15533513
Klinefelter syndrome	MIK: 19017913
Cryptorchidism	GAD: 17028442
Anorchia	MIK: 15579790
Bilateral cryptorchidism	MIK: 31167797
Cryptorchidism	MIK: 18772597
Klienfelter syndrome	MIK: 19017913
Testicular functions	MIK: 15353080
Male Infertility	MIK: 12970298
Testicular dysgenesis syndrome	MIK: 16687567
Azoospermia	MIK: 12970298

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
20636340	Infertility	T222P	Spanish , Itali an	741 controls ( 390 Spanish, 351 Italian), 187 Spanish patients (113 unilateral cryptorchidism, 74 bilateral cryptorchidism), 199 Italianpatients (132 unilateral cryptorchidism, 67 bilateral cryptorchidism)	Male infertility
19416190	Infertility	Five RXFP2 mutations		300 noncryptorchid subjects, 600 newborns with cryptorchidism (396 unilateral and 204 bilateral)	Male infertility	RXFP2
19017913	Infertility	T222P		300 controls, 600 patients (396 unilateral cryptorchidism, 204 bilateral cryptorchidism)	Male infertility	RXFP2 AR
18772597	Infertility	T222P	Morocca n	359 (109 patients with cryptorchidism, 250 controls)	Male infertility	INSL3
18433302	Infertility	T222P	Italian	25 ( 17 unilateral cryptorchidism, 8 bilateral cryptorchidism)	Male infertility	INSL3
18073304	Infertility	T222P	Italy, Spain, Hungary , and E gypt	822(359 with a history of cryptorchidism ( Italian (98 unilateral, 61 bilateral), Hungarian patients (51 unilateral, 19 bilateral), Egyptian origin ( 45 unilateral, 8 bilateral), 77 Spanish patients) and 463 controls)	Male infertility
17028442	Infertility	Thr/Thr genotype of Ala60Thr	Japanes e	60 controls, 62 cryptorchidism patients	Male infertility	INSL3
16926383	Infertility	T222P, R223K	Italian	1048 (241 bilateral cryptorchidism, 357 unilateral cryptorchidism, 450 controls)	Male infertility
15579790	Infertility			14 patients with anorchia	Male infertility	INSL3 SRY
15533513	Infertility	A missense (A60T) substitution in exon 1 of INSL3 and two silent substitutions in exon 12 and one missense (I604V) substitution in exon 17 of GREAT		13 familial cryptorchidism	Male infertility	INSL3
15353080	Infertility			100 controls, 135 ex-cryptorchid patients	Male infertility	LGR8/GREAT
14656401	Infertility	957A->G , 993A->G, 1810A->G => I604V	Finnish	56 (23 cryptorchid patients, 33 controls)	Male infertility
12970298	Infertility	INSL3 (L9L (27G->A), A60T (178G>A), L42L (126G>A), 278C>T (P93L), 304C>T(R102C), and 305G>A (R102H)), LGR8 (T222P, INV2(+15)C >T, Exon 3 (261G> A A87A), INV4(+17)T>A), Exon 12 957G> A E319E, Exon 12 993A-> G L331L, INV12( -2)A9> A13, Exon 17 1810A> G I604		80 controls, 87 ex-cryptorchid patients	Male infertility	INSL3
19017913	Cryptorchidism, Klienfelter syndrome	AR (H382Y, T558S), INSL3 (R102C, T86M), RXFP2(T222P)	Italian	900 (600 male infants (396 had unilateral cryptorchidism, 204 bilateral cryptorchidism ) with cryptorchidism, 300 noncryptorchid male children)	Male infertility	INSL3R RXFP2 AR
19017913	Cryptorchidism, Klienfelter syndrome	AR (H382Y, T558S), INSL3 (R102C, T86M), RXFP2(T222P)	Italian	900 (600 male infants (396 had unilateral cryptorchidism, 204 bilateral cryptorchidism ) with cryptorchidism, 300 noncryptorchid male children)	Male infertility	INSL3R RXFP2 AR
15353080	Cryptorchidism, Testicular functions			235 (135 ex-cryptorchid patients, 100 controls)	Male infertility	INSL3 LGR8/GREAT
26209787	Nonsyndromic cryptorchidism		Europea n	3562 (844 boys with nonsyndromic cryptorchidism, 2718 control subjects without syndromes or genital anomalies)	Male infertility	INSL3 RXFP2
18772597	Cryptorchidism	T222P in LGR8	Morocca n	359 (109 patients with cryptorchidism, 250 controls)	Male infertility
17437853	Cryptorchidism	INSL3 variants (C-19G, V18M and R105H)		454 (184 patients (52 presented with unilateral cryptorchidism, 37 presented with bilateral cryptorchidism, 19 presented with cryptorchidism and hypospadias, 1 presented with bilateral cryptorchidism and micropenis, and 75 presented with isolated hypospad	Male infertility	INSL3 LGR8 receptor
16687567	Maldescended testes, infertility, testicular dysgenesis syndrome	LGR8 receptor (R4H, W69R, and R72K)		1417 (967 subjects with a history of maldescended testes and/or infertility and/or testicular cancer, 450 controls)	Male infertility	INSL3 LGR8
15533513	Familial cryptorchidism	One missense (A60T) substitution in exon 1 of INSL3 and two silent substitutions in exon 12 and one missense (I604V) substitution in exon 17 of GREAT		13 individuals with personal and family histories of cryptorchidism	Male infertiltiy	INSL3 LGR8/GREAT
12970298	Normozoospermia, complete azoospermia, bilateral cryptorchidism			167 (87 ex-cryptorchid patients, 80 controls)	Male infertility	INSL3 LGR8/GREAT
23100620	Important for testicular descent				Male infertility
31167797	Bilateral cryptorchidism	c.1496G>A .p.Gly499Glu		4 bilateral cryptorchidism	Male infertility	NGS
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq