GPR137

Summary

GPR137 (G protein-coupled receptor 137, HGNC:24300) is a protein-coding gene on chromosome 11q13.1, encoding Integral membrane protein GPR137 (Q96N19). Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes.

Predicted to be involved in several processes, including negative regulation of bone resorption; negative regulation of osteoclast differentiation; and positive regulation of TORC1 signaling. Located in lysosomal membrane.

Source: NCBI Gene 56834 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_001170880

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24300
Approved symbol	GPR137
Name	G protein-coupled receptor 137
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	C11orf4, GPR137A, TM7SF1L1
Ensembl gene	ENSG00000173264
Ensembl biotype	protein_coding
Entrez	56834

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000313074, ENST00000377702, ENST00000411458, ENST00000438980, ENST00000535675, ENST00000536017, ENST00000536282, ENST00000536667, ENST00000538032, ENST00000538244, ENST00000539833, ENST00000540370, ENST00000541952, ENST00000542190, ENST00000543383, ENST00000545366, ENST00000546139, ENST00000546201, ENST00000853979, ENST00000853980, ENST00000853981, ENST00000853982, ENST00000853983, ENST00000853984, ENST00000853986, ENST00000938885, ENST00000938886, ENST00000954779

RefSeq mRNA: 18 — MANE Select: NM_001170880 NM_001170880, NM_001170881, NM_001177358, NM_001378076, NM_001378077, NM_001378078, NM_001378079, NM_001378080, NM_001378081, NM_001378082, NM_001378083, NM_001378084, NM_001378085, NM_001378086, NM_001378087, NM_001378088, NM_001378089, NM_020155

CCDS: CCDS53656, CCDS53658, CCDS8066

Canonical transcript exons

ENST00000438980 — 7 exons

Exon	Start	End
ENSE00001195497	64288603	64288721
ENSE00001195525	64288065	64288214
ENSE00001195536	64287721	64287946
ENSE00002209799	64285848	64286881
ENSE00002311079	64289037	64289494
ENSE00003598802	64288340	64288468
ENSE00003673168	64286965	64287014

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 99.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1886 / max 222.3849, expressed in 1810 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114922	7.4822	1699
114929	5.0819	1579
114925	2.4869	1149
114924	1.4675	720
114921	1.2346	786
114926	0.7118	362
114928	0.4315	224
114923	0.1323	43
114927	0.1097	26
114932	0.0502	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.09	gold quality
left testis	UBERON:0004533	99.08	gold quality
testis	UBERON:0000473	95.28	gold quality
right frontal lobe	UBERON:0002810	95.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.98	gold quality
lower esophagus mucosa	UBERON:0035834	94.92	gold quality
apex of heart	UBERON:0002098	94.67	gold quality
anterior cingulate cortex	UBERON:0009835	94.38	gold quality
cerebellar hemisphere	UBERON:0002245	94.30	gold quality
cingulate cortex	UBERON:0003027	94.26	gold quality
cerebellar cortex	UBERON:0002129	94.14	gold quality
prefrontal cortex	UBERON:0000451	93.64	gold quality
mucosa of transverse colon	UBERON:0004991	93.02	gold quality
cortical plate	UBERON:0005343	92.62	gold quality
right uterine tube	UBERON:0001302	92.49	gold quality
right lobe of thyroid gland	UBERON:0001119	92.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.35	gold quality
metanephros cortex	UBERON:0010533	92.29	gold quality
caudate nucleus	UBERON:0001873	92.14	gold quality
right adrenal gland	UBERON:0001233	92.07	gold quality
nucleus accumbens	UBERON:0001882	91.79	gold quality
left lobe of thyroid gland	UBERON:0001120	91.72	gold quality
stromal cell of endometrium	CL:0002255	91.59	gold quality
adenohypophysis	UBERON:0002196	91.57	gold quality
amygdala	UBERON:0001876	91.53	gold quality
cerebellum	UBERON:0002037	91.49	gold quality
putamen	UBERON:0001874	91.26	gold quality
right adrenal gland cortex	UBERON:0035827	91.25	gold quality
left adrenal gland	UBERON:0001234	91.20	gold quality
body of stomach	UBERON:0001161	91.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting GPR137, 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-4481	100.00	66.42	1669
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-134-3P	96.83	66.22	1001
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6865-5P	96.05	65.58	675
HSA-MIR-1238-5P	94.82	67.52	493
HSA-MIR-4758-5P	94.82	67.06	499
HSA-MIR-6767-5P	90.00	62.41	97

Literature-anchored findings (GeneRIF, showing 9)

• Our results indicated that GPR137 is involved in the progression of human glioma (PMID:24870220)
• Knockdown of GPR137 in HepG2 cells led to cell cycle arrest at G0/G1 phase and G2/M phase, and induced cell apoptosis, as determined by flow cytometry analysis, which contributed to cell growth inhibition. (PMID:25490967)
• GPR137 as an essential player in urinary bladder cancer cell growth (PMID:25496438)
• findings imply that GPR137 plays an important role in the occurrence and progression of PCa and may prove to be a potential therapeutic target for the treatment of advanced PCa (PMID:26669804)
• In humans, ESRP1 is downregulated in inflamed biopsies from inflammatory bowel disease patients. ESRP1 loss is an adverse prognostic factor in colorectal cancer. Furthermore, generation of ESRP1-dependent GPR137 isoforms is altered in colorectal cancer and expression of a specific GPR137 isoform predicts colorectal cancer patient survival. (PMID:28975893)
• High GRP137 expression is associated with metastasis in ovarian cancer. (PMID:29739299)
• Results show the expression of GPR137 in patients with bladder cancer was significantly higher than that in normal tissues at both mRNA and protein levels. The expression of GPR137 was associated with tumor size and low survival rate. (PMID:31464892)
• ALKBH1 contributes to renal cell carcinoma progression by reducing N6-methyladenine of GPR137. (PMID:36920340)
• GPR137 inactivates Hippo signaling to promote gastric cancer cell malignancy. (PMID:38163861)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr137	ENSDARG00000037244
mus_musculus	Gpr137	ENSMUSG00000024958
rattus_norvegicus	Gpr137	ENSRNOG00000021145

Paralogs (2): GPR137B (ENSG00000077585), GPR137C (ENSG00000180998)

Protein

Protein identifiers

Integral membrane protein GPR137 — Q96N19 (reviewed: Q96N19)

Alternative names: Transmembrane 7 superfamily member 1-like 1 protein

All UniProt accessions (13): Q96N19, F5GXD9, F5GXI8, F5GXW8, F5H097, F5H0Q1, F5H1T3, F5H1V9, F5H234, F5H4R8, F5H6Y8, F5H7S0, H0YGJ1

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes. May play a role in autophagy. May activate Wnt/beta-catenin signaling to modulate epithelial cell function.

Subcellular location. Lysosome membrane.

Similarity. Belongs to the GPR137 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96N19-1	1	yes
Q96N19-2	2
Q96N19-3	3
Q96N19-4	4
Q96N19-5	5

RefSeq proteins (18): NP_001164351, NP_001164352, NP_001170829, NP_001365005, NP_001365006, NP_001365007, NP_001365008, NP_001365009, NP_001365010, NP_001365011, NP_001365012, NP_001365013, NP_001365014, NP_001365015, NP_001365016, NP_001365017, NP_001365018, NP_064540 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029723	GPR137	Family

UniProt features (27 total): topological domain 8, transmembrane region 7, splice variant 5, compositionally biased region 2, glycosylation site 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N19-F1	66.31	0.18

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 (2): 4, 257

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 119 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, chr11q13, GALE_APL_WITH_FLT3_MUTATED_DN, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_TISSUE_REMODELING, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_HEMOPOIESIS

GO Biological Process (5): autophagy (GO:0006914), regulation of autophagy (GO:0010506), negative regulation of osteoclast differentiation (GO:0045671), negative regulation of bone resorption (GO:0045779), positive regulation of TORC1 signaling (GO:1904263)

GO Molecular Function (0):

GO Cellular Component (3): lysosomal membrane (GO:0005765), lysosome (GO:0005764), membrane (GO:0016020)

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
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
positive regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
lysosome	1
lytic vacuole membrane	1
lytic vacuole	1
cellular anatomical structure	1

Protein interactions and networks

STRING

622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR137	GPR158	Q5T848	624
GPR137	GPR108	Q9NPR9	544
GPR137	CCDC88B	A6NC98	496
GPR137	KCNK4	Q9NYG8	488
GPR137	NUDT22	Q9BRQ3	470
GPR137	TRMT112	Q9UI30	467
GPR137	FERD3L	Q96RJ6	463
GPR137	GPR155	Q7Z3F1	450
GPR137	GPRC5C	Q9NQ84	450
GPR137	GPR152	Q8TDT2	446
GPR137	HSPA12B	Q96MM6	443
GPR137	GPR82	Q96P67	442
GPR137	SSR4	P51571	437
GPR137	TM7SF3	Q9NS93	436
GPR137	MEX3C	Q5U5Q3	420

IntAct

7 interactions, top by confidence:

A	B	Type	Score
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
GPR137	DRD2	psi-mi:“MI:0915”(physical association)	0.370
CSNK2A2	VWA8	psi-mi:“MI:0914”(association)	0.350
LAMP1	DST	psi-mi:“MI:0914”(association)	0.350
MAPRE1	SCAMP1	psi-mi:“MI:0914”(association)	0.350
MFSD3	NME4	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): GPR137 (Affinity Capture-MS), GPR137 (Affinity Capture-MS), GPR137 (Affinity Capture-MS), GPR137 (Two-hybrid), GPR137 (Affinity Capture-MS), GPR137 (Affinity Capture-MS), GPR137 (Affinity Capture-MS), GPR137 (Affinity Capture-MS), GPR137 (Affinity Capture-MS)

ESM2 similar proteins: A1L134, A6NH21, A6NM10, A6QP75, A7MBM2, E1BE10, E2RD63, F6S3G9, O15554, O43292, O89109, P70295, Q17QQ5, Q32PG7, Q3ZCD2, Q4FZD7, Q5F2F2, Q5GH56, Q5GH64, Q5PQL3, Q60850, Q66K66, Q6IQX7, Q6PIS1, Q6UXT9, Q71RH2, Q7TN60, Q7TNV1, Q7Z403, Q863Y7, Q863Y8, Q8BHH1, Q8CHJ2, Q8CHM1, Q8IU68, Q8IXF9, Q8IZ52, Q8N2A8, Q8N9H8, Q8NBQ7

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1734 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64270335:CTT:C	acceptor_gain	1.0000
11:64270338:C:CC	acceptor_gain	1.0000
11:64271608:CTCA:C	donor_loss	1.0000
11:64271610:CA:C	donor_loss	1.0000
11:64271612:C:CA	donor_loss	1.0000
11:64271799:AGCGC:A	acceptor_gain	1.0000
11:64271800:GCGC:G	acceptor_gain	1.0000
11:64271801:CGC:C	acceptor_gain	1.0000
11:64271801:CGCC:C	acceptor_gain	1.0000
11:64271802:GC:G	acceptor_gain	1.0000
11:64271803:CC:C	acceptor_gain	1.0000
11:64271803:CCTG:C	acceptor_loss	1.0000
11:64271804:C:CC	acceptor_gain	1.0000
11:64271816:A:T	acceptor_gain	1.0000
11:64284178:TTA:T	donor_loss	1.0000
11:64284179:TA:T	donor_loss	1.0000
11:64284180:A:AC	donor_gain	1.0000
11:64284180:AC:A	donor_gain	1.0000
11:64284180:ACCT:A	donor_gain	1.0000
11:64284180:ACCTC:A	donor_gain	1.0000
11:64284181:C:CA	donor_gain	1.0000
11:64284181:CC:C	donor_gain	1.0000
11:64284181:CCT:C	donor_gain	1.0000
11:64284181:CCTC:C	donor_gain	1.0000
11:64284181:CCTCC:C	donor_gain	1.0000
11:64286878:CCAG:C	donor_loss	1.0000
11:64286879:CAGG:C	donor_loss	1.0000
11:64286882:G:C	donor_loss	1.0000
11:64287015:G:GG	donor_gain	1.0000
11:64288059:T:TA	acceptor_gain	1.0000

AlphaMissense

2521 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64288122:A:C	S231R	0.999
11:64288124:C:A	S231R	0.999
11:64288124:C:G	S231R	0.999
11:64286729:T:A	W69R	0.998
11:64286729:T:C	W69R	0.998
11:64286843:T:C	F107L	0.998
11:64286845:C:A	F107L	0.998
11:64286845:C:G	F107L	0.998
11:64288403:T:A	W283R	0.998
11:64288403:T:C	W283R	0.998
11:64288407:A:T	E284V	0.998
11:64288382:T:C	F276L	0.997
11:64288384:T:A	F276L	0.997
11:64288384:T:G	F276L	0.997
11:64288406:G:A	E284K	0.996
11:64286810:T:A	W96R	0.995
11:64286810:T:C	W96R	0.995
11:64286866:C:A	N114K	0.995
11:64286866:C:G	N114K	0.995
11:64287761:T:C	F150L	0.995
11:64287763:T:A	F150L	0.995
11:64287763:T:G	F150L	0.995
11:64288416:C:A	P287H	0.995
11:64288416:C:G	P287R	0.995
11:64286724:T:C	L67P	0.994
11:64286741:C:A	R73S	0.994
11:64286844:T:C	F107S	0.994
11:64288407:A:C	E284A	0.994
11:64286731:G:C	W69C	0.993
11:64286731:G:T	W69C	0.993

dbSNP variants (sampled 300 via entrez): RS1000009542 (11:64272887 G>C), RS1000679595 (11:64276575 C>T), RS1000873868 (11:64270016 C>A,T), RS1000999174 (11:64286294 T>A,C,G), RS1001012410 (11:64273643 G>A), RS1001263214 (11:64286888 A>G), RS1001278622 (11:64268976 T>C,G), RS1001486418 (11:64287582 C>T), RS1001687847 (11:64285813 A>G), RS1001709977 (11:64268766 C>G,T), RS1002055697 (11:64287348 A>G), RS1002127223 (11:64285932 C>A,G,T), RS1002257584 (11:64280816 C>T), RS1002405235 (11:64275144 A>G), RS1002535512 (11:64282499 C>T)

Disease associations

OMIM: gene `` | 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
GCST001622_1	Sarcoidosis	3.000000e-18
GCST004132_98	Crohn’s disease	5.000000e-06
GCST004785_38	Vitiligo	5.000000e-08
GCST010988_419	Adult body size	8.000000e-12
GCST90020025_1875	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020027_1492	Waist-hip index	4.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs671976	BAD, GPR137		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Other non-GPCR 7TM proteins

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	increases expression, affects methylation, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases abundance, increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, affects cotreatment, decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Urethane	increases expression	1
Cyclosporine	decreases expression	1
Gold Compounds	increases expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1GK	Abcam U2OS GPR137 KO	Cancer cell line	Female
CVCL_KX31	PathHunter CHO-K1 GPR137 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_SQ40	HAP1 GPR137 (-) 1	Cancer cell line	Male
CVCL_SQ41	HAP1 GPR137 (-) 2	Cancer cell line	Male
CVCL_SQ42	HAP1 GPR137 (-) 3	Cancer cell line	Male
CVCL_SQ43	HAP1 GPR137 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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