<i>GPR37L1</i> | Class A Orphans | IUPHAR/BPS Guide to PHARMACOLOGY

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Target not currently curated in GtoImmuPdb

Target id: 104

Nomenclature: GPR37L1

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

This receptor has a proposed ligand; see the Latest Pairings page for more information.

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 481 1q32.1 GPR37L1 G protein-coupled receptor 37 like 1 7
Mouse 7 481 1 E4 Gpr37l1 G protein-coupled receptor 37-like 1 3
Rat 7 481 13q13 Gpr37l1 G protein-coupled receptor 37-like 1 4
Previous and Unofficial Names
CAG-18 | endothelin B receptor-like protein 2 | ETBRLP2 | G-protein coupled receptor CNS2
Database Links
Specialist databases
GPCRDB etbr2_human (Hs), etbr2_mouse (Mm), etbr2_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands
prosaptide {Sp: Human}
Comments: Proposed ligand, single publication.

Download all structure-activity data for this target as a CSV file

Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
prosaptide {Sp: Human} Hs Agonist 8.3 pEC50 5
pEC50 8.3 (EC50 5x10-9 M) [5]
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Comments:  Pertussis toxin pre-treatment completely inhibited the ability of prosaptide to stimulate ERK phosphorylation in GPR37L-transfected cells [5].
Tissue Distribution
Cerebellum, cortex, medulla, spinal cord, putamen, occipital, frontal, temporal lobes
Species:  Human
Technique:  Northern blot.
References:  7
Highly expressed in cerebellar Bergmann glia of the Purkinje cell layer, internal capsule fibers of the caudate putamen and in temporal cortex
Species:  Human
Technique:  in situ hybridisation
References:  7
Muscle-myenteric nerve layer of gastrointestinal tract
Species:  Mouse
Technique:  RT-PCR
References:  1
Tissue Distribution Comments
No transcripts of GPR37L1 were detected in peripheral tissues such as heart, placenta, lung, liver, skeletal muscle, kidney and pancreas when examined by Northen blot [7].
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Ligand/receptor interaction.
Species:  Human
Tissue:  HEK-293T cells transfected with GPR37L1.
Response measured:  Internalisation of epitope-tagged receptor, ERK phosphorylation, 35S-GTPγS binding.
References:  5
Physiological Consequences of Altering Gene Expression
Mice with GPR37L1 knockout show high blood pressure and high heart weight/ body weight (HW/BW).
Species:  Mouse
Tissue:  Heart
Technique:  knockout by gene targeting in embryonic stem cells
References:  6
Overexpression of GPR37L1 induces apoptosis of cardiomyocytes.
Species:  Mouse
Tissue:  Cardiomyocytes
Technique:  Gene overexpression
References:  6
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gpr37l1tm1Lex Gpr37l1tm1Lex/Gpr37l1tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J
MGI:1928503  MP:0002169 no abnormal phenotype detected
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  G90D
Global MAF (%):  16
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 25|13|19|9
Minor allele count:  G=0.160/349
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
References:  7
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  P81A
Global MAF (%):  24
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 31|25|40|6
Minor allele count:  G=0.238/519
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
General Comments
It is shown that folic acid supplementation decreased the expression of GPR37L1 in a dose-dependent manner [2].


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1. Ito J, Ito M, Nambu H, Fujikawa T, Tanaka K, Iwaasa H, Tokita S. (2009) Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice. Cell Tissue Res., 338 (2): 257-69. [PMID:19763624]

2. Junaid MA, Kuizon S, Cardona J, Azher T, Murakami N, Pullarkat RK, Brown WT. (2011) Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem. Biophys. Res. Commun., 412 (4): 688-92. [PMID:21867686]

3. Kim SJ, Shon BH, Kang JH, Hahm KS, Yoo OJ, Park YS, Lee KK. (1997) Cloning of novel trinucleotide-repeat (CAG) containing genes in mouse brain. Biochem. Biophys. Res. Commun., 240 (1): 239-43. [PMID:9367917]

4. Leng N, Gu G, Simerly RB, Spindel ER. (1999) Molecular cloning and characterization of two putative G protein-coupled receptors which are highly expressed in the central nervous system. Brain Res. Mol. Brain Res., 69 (1): 73-83. [PMID:10350639]

5. Meyer RC, Giddens MM, Schaefer SA, Hall RA. (2013) GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin. Proc. Natl. Acad. Sci. U.S.A., 110 (23): 9529-34. [PMID:23690594]

6. Min KD, Asakura M, Liao Y, Nakamaru K, Okazaki H, Takahashi T, Fujimoto K, Ito S, Takahashi A, Asanuma H, Yamazaki S, Minamino T, Sanada S, Seguchi O, Nakano A, Ando Y, Otsuka T, Furukawa H, Isomura T, Takashima S, Mochizuki N, Kitakaze M. (2010) Identification of genes related to heart failure using global gene expression profiling of human failing myocardium. Biochem. Biophys. Res. Commun., 393 (1): 55-60. [PMID:20100464]

7. Valdenaire O, Giller T, Breu V, Ardati A, Schweizer A, Richards JG. (1998) A new family of orphan G protein-coupled receptors predominantly expressed in the brain. FEBS Lett., 424 (3): 193-6. [PMID:9539149]


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