GPR137C

Summary

GPR137C (G protein-coupled receptor 137C, HGNC:25445) is a protein-coding gene on chromosome 14q22.1, encoding Integral membrane protein GPR137C (Q8N3F9). Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes.

Predicted to be involved in positive regulation of TORC1 signaling. Located in lysosomal membrane.

Source: NCBI Gene 283554 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_001099652

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25445
Approved symbol	GPR137C
Name	G protein-coupled receptor 137C
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp762F0713, TM7SF1L2
Ensembl gene	ENSG00000180998
Ensembl biotype	protein_coding
Entrez	283554

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000321662, ENST00000542169, ENST00000555369, ENST00000555622, ENST00000866179

RefSeq mRNA: 2 — MANE Select: NM_001099652 NM_001099652, NM_001353361

CCDS: CCDS45106

Canonical transcript exons

ENST00000321662 — 7 exons

Exon	Start	End
ENSE00001282160	52600113	52600341
ENSE00001282168	52598272	52598315
ENSE00001282180	52552836	52553591
ENSE00003509328	52633828	52633946
ENSE00003514909	52634938	52637713
ENSE00003518278	52632160	52632309
ENSE00003571193	52633530	52633655

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 89.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.2448 / max 119.9929, expressed in 1030 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139614	2.2715	580
139615	0.9727	579
139613	0.6264	345
139616	0.3743	161

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	89.49	gold quality
cerebellar cortex	UBERON:0002129	89.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.80	gold quality
cerebellum	UBERON:0002037	88.39	gold quality
ganglionic eminence	UBERON:0004023	85.36	gold quality
cortical plate	UBERON:0005343	83.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.88	gold quality
prefrontal cortex	UBERON:0000451	81.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.12	gold quality
ventricular zone	UBERON:0003053	80.64	gold quality
hypothalamus	UBERON:0001898	78.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.67	gold quality
anterior cingulate cortex	UBERON:0009835	77.31	gold quality
right frontal lobe	UBERON:0002810	77.28	gold quality
frontal cortex	UBERON:0001870	77.04	gold quality
neocortex	UBERON:0001950	76.80	gold quality
spinal cord	UBERON:0002240	74.92	gold quality
cerebral cortex	UBERON:0000956	74.63	gold quality
caudate nucleus	UBERON:0001873	74.56	gold quality
brain	UBERON:0000955	74.00	gold quality
amygdala	UBERON:0001876	73.70	gold quality
putamen	UBERON:0001874	73.01	gold quality
stromal cell of endometrium	CL:0002255	72.68	gold quality
forebrain	UBERON:0001890	72.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.33	gold quality
cerebellar vermis	UBERON:0004720	72.33	gold quality
nucleus accumbens	UBERON:0001882	72.24	gold quality
endothelial cell	CL:0000115	69.37	silver quality
substantia nigra	UBERON:0002038	69.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

179 targeting GPR137C, 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-9-5P	100.00	72.28	2361
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr137c	ENSDARG00000045289
mus_musculus	Gpr137c	ENSMUSG00000049092
rattus_norvegicus	Gpr137c	ENSRNOG00000026328

Paralogs (2): GPR137B (ENSG00000077585), GPR137 (ENSG00000173264)

Protein

Protein identifiers

Integral membrane protein GPR137C — Q8N3F9 (reviewed: Q8N3F9)

Alternative names: Transmembrane 7 superfamily member 1-like 2 protein

All UniProt accessions (3): Q8N3F9, H0YFL6, H0YJZ7

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes.

Subcellular location. Lysosome membrane.

Similarity. Belongs to the GPR137 family.

RefSeq proteins (2): NP_001093122, NP_001340290 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029723	GPR137	Family

UniProt features (21 total): topological domain 8, transmembrane region 7, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3F9-F1	67.87	0.31

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 (1): 285

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOCC_VACUOLAR_MEMBRANE, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, TERAMOTO_OPN_TARGETS_CLUSTER_3, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_TOR_SIGNALING, FISCHER_DREAM_TARGETS, NIKOLSKY_BREAST_CANCER_14Q22_AMPLICON, GEORGES_TARGETS_OF_MIR192_AND_MIR215, IVANOVSKA_MIR106B_TARGETS, GOBP_TORC1_SIGNALING, GOBP_POSITIVE_REGULATION_OF_TORC1_SIGNALING, E2F3_UP.V1_UP, STK33_SKM_UP

GO Biological Process (1): 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
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

372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR137C	TXNDC16	Q9P2K2	640
GPR137C	TMEM221	A6NGB7	630
GPR137C	LRRC42	Q9Y546	568
GPR137C	GPR157	Q5UAW9	558
GPR137C	STYX	Q8WUJ0	548
GPR137C	TMEM171	Q8WVE6	530
GPR137C	GPR108	Q9NPR9	529
GPR137C	DDHD1	Q8NEL9	526
GPR137C	HAUS8	Q9BT25	522
GPR137C	GPR107	Q5VW38	519
GPR137C	SYCE2	Q6PIF2	488
GPR137C	LHFPL7	Q6ICI0	488
GPR137C	HSF2BP	O75031	486
GPR137C	OVOL3	O00110	477
GPR137C	TCP11L2	Q8N4U5	472

IntAct

3 interactions, top by confidence:

A	B	Type	Score
GPR137C		psi-mi:“MI:0915”(physical association)	0.370
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): GPR137C (Affinity Capture-RNA), GPR137C (Affinity Capture-MS), GPR137C (Affinity Capture-RNA)

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1334 predictions. Top by Δscore:

Variant	Effect	Δscore
14:52598266:TTATA:T	acceptor_loss	1.0000
14:52598267:TATA:T	acceptor_loss	1.0000
14:52598268:ATAGG:A	acceptor_loss	1.0000
14:52598269:TAG:T	acceptor_loss	1.0000
14:52598270:AGGT:A	acceptor_loss	1.0000
14:52598271:G:GC	acceptor_loss	1.0000
14:52598315:AGT:A	donor_loss	1.0000
14:52598316:G:A	donor_loss	1.0000
14:52598316:G:GG	donor_gain	1.0000
14:52598317:T:A	donor_loss	1.0000
14:52599062:G:GT	donor_gain	1.0000
14:52599101:G:GT	donor_gain	1.0000
14:52633616:G:GA	donor_gain	1.0000
14:52633944:A:T	donor_gain	1.0000
14:52553589:GAG:G	donor_gain	0.9900
14:52553590:AGG:A	donor_loss	0.9900
14:52553592:GTA:G	donor_loss	0.9900
14:52553593:T:A	donor_loss	0.9900
14:52590166:GCC:G	donor_gain	0.9900
14:52590173:C:G	donor_gain	0.9900
14:52598270:A:AG	acceptor_gain	0.9900
14:52598271:G:GG	acceptor_gain	0.9900
14:52598311:CACAA:C	donor_gain	0.9900
14:52598313:CAA:C	donor_gain	0.9900
14:52598313:CAAG:C	acceptor_loss	0.9900
14:52598318:AAGTT:A	donor_loss	0.9900
14:52599070:A:G	donor_gain	0.9900
14:52600107:TTTCA:T	acceptor_loss	0.9900
14:52600108:TTCAG:T	acceptor_loss	0.9900
14:52600109:TCAGA:T	acceptor_loss	0.9900

AlphaMissense

2768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:52553434:G:T	R96M	0.998
14:52553553:T:C	F136L	0.998
14:52553555:C:A	F136L	0.998
14:52553555:C:G	F136L	0.998
14:52633879:T:C	F349L	0.998
14:52633881:C:A	F349L	0.998
14:52633881:C:G	F349L	0.998
14:52553434:G:C	R96T	0.997
14:52633590:T:A	W310R	0.997
14:52633590:T:C	W310R	0.997
14:52633883:A:T	D350V	0.997
14:52553554:T:C	F136S	0.996
14:52600144:A:C	S174R	0.996
14:52600146:C:A	S174R	0.996
14:52600146:C:G	S174R	0.996
14:52600252:A:C	S210R	0.996
14:52600254:C:A	S210R	0.996
14:52600254:C:G	S210R	0.996
14:52633880:T:G	F349C	0.996
14:52633903:A:C	S357R	0.996
14:52633905:T:A	S357R	0.996
14:52633905:T:G	S357R	0.996
14:52553421:T:A	W92R	0.995
14:52553421:T:C	W92R	0.995
14:52553435:G:C	R96S	0.994
14:52553435:G:T	R96S	0.994
14:52553520:T:A	W125R	0.994
14:52553520:T:C	W125R	0.994
14:52600153:T:C	F177L	0.994
14:52600155:T:A	F177L	0.994

dbSNP variants (sampled 300 via entrez): RS1000022750 (14:52600238 C>G), RS1000069859 (14:52574325 C>T), RS1000120838 (14:52588895 T>C), RS1000132589 (14:52566965 T>C), RS1000148230 (14:52630575 G>A), RS1000245300 (14:52579612 T>C), RS1000247083 (14:52597971 C>T), RS1000264284 (14:52571986 A>G), RS1000293300 (14:52586011 C>T), RS1000310319 (14:52560553 G>T), RS1000315275 (14:52628727 C>T), RS1000318072 (14:52597669 A>G), RS1000324212 (14:52585757 C>T), RS1000360974 (14:52561242 G>A), RS1000362849 (14:52594201 A>G)

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

1 associations (top):

Study	Trait	p-value
GCST001942_15	Prostate cancer	2.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Valproic Acid	affects expression, increases expression	3
sodium arsenite	affects expression, increases expression	2
Acetaminophen	increases expression	2
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
sulforaphane	decreases expression	1
potassium chromate(VI)	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Fluorouracil	affects expression	1
Silver	increases expression	1
Theophylline	increases expression	1
Vanadates	increases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SQ46	HAP1 GPR137C (-) 1	Cancer cell line	Male
CVCL_SQ47	HAP1 GPR137C (-) 2	Cancer cell line	Male
CVCL_XP33	HAP1 GPR137C (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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