GPR137B

Summary

GPR137B (G protein-coupled receptor 137B, HGNC:11862) is a protein-coding gene on chromosome 1q42.3, encoding Integral membrane protein GPR137B (O60478). Lysosomal integral membrane protein that regulates the localization and activity of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids.

Involved in positive regulation of TORC1 signaling; positive regulation of protein localization to lysosome; and regulation of autophagy. Located in lysosomal membrane.

Source: NCBI Gene 7107 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 61 total — 2 pathogenic
• MANE Select transcript: NM_003272

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11862
Approved symbol	GPR137B
Name	G protein-coupled receptor 137B
Location	1q42.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000077585
Ensembl biotype	protein_coding
OMIM	604658
Entrez	7107

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000366591, ENST00000366592, ENST00000419162, ENST00000454895, ENST00000477559, ENST00000889782, ENST00000889783, ENST00000889784, ENST00000889785, ENST00000889786, ENST00000972103, ENST00000972104, ENST00000972105

RefSeq mRNA: 1 — MANE Select: NM_003272 NM_003272

CCDS: CCDS1609

Canonical transcript exons

ENST00000366592 — 7 exons

Exon	Start	End
ENSE00000961594	236168706	236168755
ENSE00001022688	236208050	236208907
ENSE00001442134	236142539	236143036
ENSE00003465477	236205126	236205250
ENSE00003577777	236178414	236178636
ENSE00003694495	236183778	236183906
ENSE00003741263	236179879	236180028

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 96.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0933 / max 411.4252, expressed in 1723 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9215	30.8420	1720
9214	1.2514	792

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	96.81	gold quality
trigeminal ganglion	UBERON:0001675	96.01	gold quality
medial globus pallidus	UBERON:0002477	95.55	gold quality
oocyte	CL:0000023	95.50	gold quality
corpus epididymis	UBERON:0004359	95.30	gold quality
nephron tubule	UBERON:0001231	94.68	gold quality
globus pallidus	UBERON:0001875	94.64	gold quality
dorsal root ganglion	UBERON:0000044	94.26	gold quality
secondary oocyte	CL:0000655	94.05	gold quality
nucleus accumbens	UBERON:0001882	93.64	gold quality
caudate nucleus	UBERON:0001873	93.59	gold quality
putamen	UBERON:0001874	93.27	gold quality
tibial nerve	UBERON:0001323	92.86	gold quality
germinal epithelium of ovary	UBERON:0001304	92.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.62	gold quality
spinal cord	UBERON:0002240	92.50	gold quality
buccal mucosa cell	CL:0002336	92.48	gold quality
heart right ventricle	UBERON:0002080	91.77	gold quality
periodontal ligament	UBERON:0008266	91.76	gold quality
ventricular zone	UBERON:0003053	91.73	gold quality
lateral globus pallidus	UBERON:0002476	91.71	gold quality
olfactory bulb	UBERON:0002264	91.64	gold quality
amygdala	UBERON:0001876	91.62	gold quality
stromal cell of endometrium	CL:0002255	91.25	gold quality
adult mammalian kidney	UBERON:0000082	91.06	gold quality
cranial nerve II	UBERON:0000941	90.84	gold quality
substantia nigra	UBERON:0002038	90.78	gold quality
adult organism	UBERON:0007023	90.54	gold quality
caput epididymis	UBERON:0004358	90.48	gold quality
midbrain	UBERON:0001891	90.37	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	20.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting GPR137B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606

Literature-anchored findings (GeneRIF, showing 1)

• PR137B-knockout cells exhibited defective autophagy and an expanded lysosome compartment, similar to Rag-knockout cells. Like zebrafish RagA mutants, GPR137B-mutant zebrafish had upregulated TFEB target gene expression and an expanded lysosome compartment in microglia. (PMID:31036939)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr137bb	ENSDARG00000077608
danio_rerio	gpr137ba	ENSDARG00000078448
mus_musculus	Gpr137b	ENSMUSG00000021306
rattus_norvegicus	Gpr137b	ENSRNOG00000002480

Paralogs (2): GPR137 (ENSG00000173264), GPR137C (ENSG00000180998)

Protein

Protein identifiers

Integral membrane protein GPR137B — O60478 (reviewed: O60478)

Alternative names: Transmembrane 7 superfamily member 1 protein

All UniProt accessions (3): O60478, H0Y509, Q5TAF0

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal integral membrane protein that regulates the localization and activity of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Interacts with Rag GTPases and increases the lysosomial localization and activity of Rag GTPases and thereby regulates mTORC1 translocation and activity in lysosome. Involved in the regulation of lysosomal morphology and autophagy. Also acts as a negative regulator of osteoclast activity. Involved in interleukin-4-induced M2 macrophage polarization.

Subunit / interactions. Interaction with RRAGA; increases RRAGA recruitment to lysosomes. Interacts with MTOR; this interaction is amino acid sensitive.

Subcellular location. Lysosome membrane.

Tissue specificity. Expressed in kidney, heart, brain and placenta.

Similarity. Belongs to the GPR137 family.

RefSeq proteins (1): NP_003263* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029723	GPR137	Family

UniProt features (23 total): topological domain 8, transmembrane region 7, glycosylation site 3, sequence conflict 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60478-F1	69.47	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (3): 26, 263, 275

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 337 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, FREAC2_01, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_VACUOLAR_MEMBRANE, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION

GO Biological Process (8): autophagy (GO:0006914), regulation of autophagy (GO:0010506), regulation of macrophage activation (GO:0043030), regulation of GTPase activity (GO:0043087), negative regulation of osteoclast differentiation (GO:0045671), negative regulation of bone resorption (GO:0045779), positive regulation of protein localization to lysosome (GO:0150032), positive regulation of TORC1 signaling (GO:1904263)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), membrane (GO:0016020), lysosome (GO:0005764)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
autophagy	1
regulation of catabolic process	1
regulation of leukocyte activation	1
macrophage activation	1
GTPase activity	1
regulation of hydrolase activity	1
negative regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
regulation of bone resorption	1
bone resorption	1
negative regulation of bone remodeling	1
protein localization to lysosome	1
regulation of protein localization to lysosome	1
positive regulation of protein localization	1
positive regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
binding	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
cellular anatomical structure	1
lytic vacuole	1

Protein interactions and networks

STRING

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR137B	GPR108	Q9NPR9	552
GPR137B	GPR107	Q5VW38	520
GPR137B	GPR155	Q7Z3F1	483
GPR137B	GPR152	Q8TDT2	437
GPR137B	TM7SF3	Q9NS93	432
GPR137B	GPR82	Q96P67	413
GPR137B	GPR143	P51810	412
GPR137B	CHST8	Q9H2A9	395
GPR137B	GPRC5C	Q9NQ84	390
GPR137B	COPS5	Q92905	380
GPR137B	SLC26A9	Q7LBE3	349
GPR137B	PAQR9	Q6ZVX9	346
GPR137B	OPN3	Q9H1Y3	344
GPR137B	GPR153	Q6NV75	338
GPR137B	GPR171	O14626	333

IntAct

20 interactions, top by confidence:

A	B	Type	Score
GPR137B	USP20	psi-mi:“MI:0915”(physical association)	0.600
USP20	GPR137B	psi-mi:“MI:0407”(direct interaction)	0.600
GPR137B	TRIM32	psi-mi:“MI:0915”(physical association)	0.560
GPR137B	DOC2A	psi-mi:“MI:0914”(association)	0.530
USP33	GPR137B	psi-mi:“MI:0915”(physical association)	0.520
GPR137B	GPR137B	psi-mi:“MI:0915”(physical association)	0.400
GPR137B	HIF1A	psi-mi:“MI:0915”(physical association)	0.400
APP	GPR137B	psi-mi:“MI:0915”(physical association)	0.370
GPR137B	SMC2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
TRIM32	GPR137B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): NCAPD2 (Affinity Capture-MS), SMC2 (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), NCAPH (Affinity Capture-MS), DOC2A (Affinity Capture-MS), NCAPG (Affinity Capture-MS), DOC2A (Affinity Capture-MS), NCAPD2 (Affinity Capture-MS), NCAPH (Affinity Capture-MS), NCAPG (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), SMC2 (Affinity Capture-MS), GPR137B (Affinity Capture-RNA), GPR137B (Two-hybrid), TRIM32 (Two-hybrid)

ESM2 similar proteins: A2BGS3, A6NGA9, E7F594, O36364, O60478, O60883, O95800, O95838, P03208, P16849, P31389, P34590, P35367, P49219, Q03613, Q09351, Q09964, Q09965, Q14439, Q16950, Q16951, Q2KI97, Q3U3F9, Q5FVG1, Q5IXF8, Q5UAW9, Q60755, Q64017, Q66615, Q66H29, Q6P7G9, Q6SW98, Q6X632, Q7TSN5, Q7TSN6, Q80W35, Q80WT4, Q8BNQ3, Q8C206, Q8CIM5

Diamond homologs: E7F594, E9Q343, O60478, Q17QQ5, Q6DCW7, Q80ZU9, Q8BNQ3, Q8N3F9, Q96N19

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

61 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	54
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
625533	GRCh37/hg19 1q42.3-43(chr1:234742890-239475761)	Pathogenic
814181	GRCh37/hg19 1q42.2-43(chr1:233843930-237971511)x1	Pathogenic

SpliceAI

1653 predictions. Top by Δscore:

Variant	Effect	Δscore
1:236143033:GCAG:G	donor_gain	1.0000
1:236143034:CAGG:C	donor_loss	1.0000
1:236143035:AGGT:A	donor_loss	1.0000
1:236143036:GGT:G	donor_loss	1.0000
1:236143037:GTGA:G	donor_loss	1.0000
1:236143038:T:A	donor_loss	1.0000
1:236179873:TTCCA:T	acceptor_loss	1.0000
1:236179874:TCCAG:T	acceptor_loss	1.0000
1:236179875:CCA:C	acceptor_loss	1.0000
1:236179876:CA:C	acceptor_loss	1.0000
1:236179877:A:AT	acceptor_loss	1.0000
1:236179877:AG:A	acceptor_gain	1.0000
1:236179878:GG:G	acceptor_gain	1.0000
1:236183777:GGCA:G	acceptor_gain	1.0000
1:236183903:CCTT:C	donor_gain	1.0000
1:236183907:G:GG	donor_gain	1.0000
1:236220826:TCTTA:T	donor_loss	1.0000
1:236220827:CTTA:C	donor_loss	1.0000
1:236220828:TTAC:T	donor_loss	1.0000
1:236220829:TA:T	donor_loss	1.0000
1:236220830:A:AG	donor_loss	1.0000
1:236220862:T:TA	donor_gain	1.0000
1:236220961:TGAGT:T	acceptor_gain	1.0000
1:236220962:GAGT:G	acceptor_gain	1.0000
1:236220964:GT:G	acceptor_gain	1.0000
1:236220966:C:CC	acceptor_gain	1.0000
1:236143032:CGCAG:C	donor_gain	0.9900
1:236143033:GCAGG:G	donor_gain	0.9900
1:236143037:G:GG	donor_gain	0.9900
1:236168700:TTGCA:T	acceptor_loss	0.9900

AlphaMissense

2575 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:236183841:T:A	W301R	0.999
1:236183841:T:C	W301R	0.999
1:236142884:T:A	W88R	0.998
1:236142884:T:C	W88R	0.998
1:236142965:T:A	W115R	0.998
1:236142965:T:C	W115R	0.998
1:236142998:T:C	F126L	0.998
1:236143000:T:A	F126L	0.998
1:236143000:T:G	F126L	0.998
1:236178445:A:C	S166R	0.998
1:236178447:C:A	S166R	0.998
1:236178447:C:G	S166R	0.998
1:236178454:T:C	F169L	0.998
1:236178456:C:A	F169L	0.998
1:236178456:C:G	F169L	0.998
1:236178468:T:A	N173K	0.998
1:236178468:T:G	N173K	0.998
1:236180008:T:A	W273R	0.998
1:236180008:T:C	W273R	0.998
1:236183845:A:T	E302V	0.998
1:236142984:C:A	P121H	0.997
1:236178544:G:C	D199H	0.997
1:236178553:T:C	F202L	0.997
1:236178555:C:A	F202L	0.997
1:236178555:C:G	F202L	0.997
1:236179953:C:A	N254K	0.997
1:236179953:C:G	N254K	0.997
1:236180010:G:C	W273C	0.997
1:236180010:G:T	W273C	0.997
1:236183820:T:C	F294L	0.997

dbSNP variants (sampled 300 via entrez): RS1000033289 (1:236196529 T>C), RS1000039683 (1:236188531 G>A,T), RS1000051492 (1:236157771 A>C), RS1000107230 (1:236157575 G>A), RS1000195671 (1:236181252 G>A), RS1000199317 (1:236170766 A>G), RS1000210833 (1:236168282 C>A), RS1000258518 (1:236162435 A>G), RS1000362456 (1:236167844 C>A), RS1000385901 (1:236194590 C>G), RS1000437957 (1:236169927 C>T), RS1000452881 (1:236196932 C>T), RS1000538559 (1:236161497 A>T), RS1000570321 (1:236165444 C>T), RS1000601480 (1:236165699 T>A)

Disease associations

OMIM: gene MIM:604658 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000883_6	Response to antipsychotic treatment in schizophrenia (working memory)	5.000000e-07
GCST007094_191	Diastolic blood pressure	3.000000e-11
GCST007098_34	Diastolic blood pressure	6.000000e-06
GCST007099_202	Systolic blood pressure	5.000000e-07
GCST008161_59	Waist circumference adjusted for body mass index	1.000000e-06
GCST009391_753	Metabolite levels	3.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004335	short-term memory
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0007789	BMI-adjusted waist circumference
EFO:0010390	sphingomyelin 14:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

61 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
Cyclosporine	affects expression, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Testosterone	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	affects methylation, decreases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
quercitrin	increases expression	1
terbufos	decreases methylation	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
vanadyl sulfate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0E1	Ubigene HeLa GPR137B KO	Cancer cell line	Female
CVCL_SQ44	HAP1 GPR137B (-) 1	Cancer cell line	Male
CVCL_SQ45	HAP1 GPR137B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.