GPR19

Summary

GPR19 (G protein-coupled receptor 19, HGNC:4473) is a protein-coding gene on chromosome 12p13.1, encoding Probable G-protein coupled receptor 19 (Q15760). G-protein coupled receptor that plays a role in the regulation of circadian rhythms and energy metabolism.

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium.

Source: NCBI Gene 2842 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 62 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006143

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4473
Approved symbol	GPR19
Name	G protein-coupled receptor 19
Location	12p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183150
Ensembl biotype	protein_coding
OMIM	602927
Entrez	2842

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000332427, ENST00000537507, ENST00000540510, ENST00000540796, ENST00000545876, ENST00000651487, ENST00000859055, ENST00000859056, ENST00000859057, ENST00000859058, ENST00000912534, ENST00000912535, ENST00000912536, ENST00000912537

RefSeq mRNA: 1 — MANE Select: NM_006143 NM_006143

CCDS: CCDS8652

Canonical transcript exons

ENST00000651487 — 4 exons

Exon	Start	End
ENSE00001294881	12684351	12684507
ENSE00001791213	12695459	12695511
ENSE00002275546	12696065	12696183
ENSE00003850411	12660890	12662470

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 89.45.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6385 / max 348.0970, expressed in 563 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129757	2.8018	283
129759	0.5725	336
129756	0.1585	86
129758	0.1057	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.90	gold quality
endothelial cell	CL:0000115	83.38	gold quality
middle temporal gyrus	UBERON:0002771	83.21	gold quality
cortical plate	UBERON:0005343	79.92	gold quality
primary visual cortex	UBERON:0002436	77.17	gold quality
ganglionic eminence	UBERON:0004023	76.76	gold quality
cerebellar hemisphere	UBERON:0002245	76.65	gold quality
cerebellar cortex	UBERON:0002129	76.64	gold quality
pituitary gland	UBERON:0000007	76.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.06	gold quality
cerebellum	UBERON:0002037	75.74	gold quality
prefrontal cortex	UBERON:0000451	75.62	gold quality
nucleus accumbens	UBERON:0001882	75.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.18	gold quality
Brodmann (1909) area 46	UBERON:0006483	75.02	silver quality
hypothalamus	UBERON:0001898	74.84	gold quality
caudate nucleus	UBERON:0001873	74.61	gold quality
adenohypophysis	UBERON:0002196	74.27	gold quality
neocortex	UBERON:0001950	74.00	gold quality
cranial nerve II	UBERON:0000941	73.92	gold quality
frontal cortex	UBERON:0001870	73.85	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	73.78	gold quality
entorhinal cortex	UBERON:0002728	73.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.44	gold quality
cerebral cortex	UBERON:0000956	73.42	gold quality
cingulate cortex	UBERON:0003027	73.33	gold quality
right frontal lobe	UBERON:0002810	73.28	gold quality
anterior cingulate cortex	UBERON:0009835	73.02	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.53

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

34 targeting GPR19, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-6780B-3P	99.13	67.18	622
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-518C-5P	98.53	69.20	1640

Literature-anchored findings (GeneRIF, showing 4)

• G protein-coupled receptor 19 (GPR19) was found frequently overexpressed in tissue samples obtained from patients with small cell lung cancer. (PMID:22912338)
• GPR19 overexpression drives MDA-MB-231 cells towards an epithelial phenotype. GPR19 upregulates E-cadherin via MAPK/ERK1/2 pathway. (PMID:28476646)
• GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process. (PMID:37239845)
• Expression of G protein-coupled receptor GPR19 in normal and neoplastic human tissues. (PMID:37923782)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr19	ENSDARG00000102226
mus_musculus	Gpr19	ENSMUSG00000032641
rattus_norvegicus	Gpr19	ENSRNOG00000007126

Paralogs (33): TACR2 (ENSG00000075073), PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), TACR1 (ENSG00000115353), GPR75 (ENSG00000119737), PRLHR (ENSG00000119973), GPR83 (ENSG00000123901), MCHR1 (ENSG00000128285), OR11H1 (ENSG00000130538), MTNR1B (ENSG00000134640), MCHR2 (ENSG00000152034), NPY1R (ENSG00000164128), NPY5R (ENSG00000164129), MTNR1A (ENSG00000168412), PROKR1 (ENSG00000169618), TACR3 (ENSG00000169836), OR9G1 (ENSG00000174914), OR11H4 (ENSG00000176198), OR11H6 (ENSG00000176219), OR9A2 (ENSG00000179468), GPR88 (ENSG00000181656), NPY2R (ENSG00000185149), OR11G2 (ENSG00000196832), NPY4R (ENSG00000204174), OR11A1 (ENSG00000204694), OR9A1P (ENSG00000237621), OR11H12 (ENSG00000257115), OR9A4 (ENSG00000258083), OR11H2 (ENSG00000258453), OR11H7 (ENSG00000258806), NPY4R2 (ENSG00000264717), OR10X1 (ENSG00000279111), OR51F1 (ENSG00000280021)

Protein

Protein identifiers

Probable G-protein coupled receptor 19 — Q15760 (reviewed: Q15760)

Alternative names: GPR-NGA

All UniProt accessions (2): Q15760, F5GWU2

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor that plays a role in the regulation of circadian rhythms and energy metabolism. Participates in maintaining proper circadian gene expression in the suprachiasmatic nucleus (SCN), the locus of the master circadian clock in the brain. May function as a coordinator of aging-associated metabolic dysfunction, stress response, DNA integrity management, and eventual senescence. Upon binding to adropin, modulates mitochondrial energy metabolism via the p44/42-PDK4 signaling pathway, influencing pyruvate dehydrogenase activity.

Subcellular location. Cell membrane.

Tissue specificity. Abundant expression in the brain.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_006134* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR047829	GPR19_7tmA	Domain

Pfam: PF00001

UniProt features (20 total): topological domain 8, transmembrane region 7, glycosylation site 2, chain 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15760-F1	74.43	0.35

Functional residue map

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

Disulfide bonds (1): 138–210

Glycosylation sites (2): 25, 52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 166 (showing top): MORF_FLT1, CAR_TNFRSF25, MORF_MSH3, MORF_BRCA1, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MORF_ESR1, MORF_RAD51L3, MORF_CTSB, MORF_IL4, MORF_PRKCA, FISCHER_DREAM_TARGETS, HAND1E47_01, LEE_CALORIE_RESTRICTION_NEOCORTEX_UP, MORF_ATF2

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), MAPK cascade (GO:0000165), signal transduction (GO:0007165), glucose homeostasis (GO:0042593)

GO Molecular Function (1): G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (4): plasma membrane (GO:0005886), cilium (GO:0005929), neuron projection (GO:0043005), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane bounded cell projection	2
G protein-coupled receptor activity	1
signal transduction	1
intracellular signaling cassette	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
carbohydrate homeostasis	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

654 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR19	ENHO	Q6UWT2	902
GPR19	ETV6	P41212	736
GPR19	CDKN1B	P46527	569
GPR19	CREBL2	O60519	529
GPR19	MTFR1	Q15390	520
GPR19	GPR82	Q96P67	515
GPR19	GPR22	Q99680	467
GPR19	GPR88	Q9GZN0	456
GPR19	CNTN6	Q9UQ52	444
GPR19	ZNF396	Q96N95	433
GPR19	CMKLR2	P46091	416
GPR19	GPRC5B	Q9NZH0	409
GPR19	MANSC1	Q9H8J5	407
GPR19	DHX40	Q8IX18	403
GPR19	SLC35F4	A4IF30	389

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RAMP1	GPR19	psi-mi:“MI:0915”(physical association)	0.400
GPR19	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR19	psi-mi:“MI:0915”(physical association)	0.400
GPR19	RAMP3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): GPR19 (Affinity Capture-MS), GPR19 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A678XMK4, A6QLE7, O17899, O42384, O42574, O70528, O77680, P04274, P07550, P0C5J4, P10608, P17124, P18762, P18901, P21728, P25102, P30728, P42288, P42289, P42290, P42291, P47898, P49285, P49288, P50130, P51046, P53452, P54833, P70585, P97288, Q09638, Q13639, Q15760, Q16950, Q16951, Q28044, Q28509, Q28997, Q4KWL2, Q61121

Diamond homologs: A0A287A2K5, O02836, O08786, O35210, O42179, O43193, O57422, O60755, O77408, O77590, O88626, O88853, O97772, P08483, P08911, P11483, P20309, P22270, P25095, P25104, P29089, P29754, P30551, P30552, P30553, P30555, P30556, P30796, P32238, P32239, P34976, P41984, P43240, P46627, P49146, P49219, P49286, P49287, P49288, P49578

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	48
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2671607	Single allele	Pathogenic

SpliceAI

888 predictions. Top by Δscore:

Variant	Effect	Δscore
12:12687021:A:AC	donor_gain	0.9900
12:12687022:C:CC	donor_gain	0.9900
12:12687024:TTTG:T	donor_gain	0.9900
12:12696064:CGAG:C	donor_gain	0.9900
12:12663338:ATAGT:A	donor_gain	0.9800
12:12696063:A:AC	donor_gain	0.9800
12:12696064:C:CC	donor_gain	0.9800
12:12696147:C:CA	donor_gain	0.9800
12:12696148:C:A	donor_gain	0.9800
12:12687059:T:TA	donor_gain	0.9700
12:12663355:G:C	donor_gain	0.9600
12:12696013:C:A	donor_gain	0.9600
12:12696070:TGTGG:T	donor_gain	0.9600
12:12695453:TGGTA:T	donor_loss	0.9500
12:12695454:GGTAC:G	donor_loss	0.9500
12:12695455:GTAC:G	donor_loss	0.9500
12:12695456:TA:T	donor_loss	0.9500
12:12695457:ACCTT:A	donor_loss	0.9500
12:12695458:C:CT	donor_loss	0.9500
12:12695991:C:CT	donor_gain	0.9500
12:12695992:T:TT	donor_gain	0.9500
12:12695459:C:G	donor_loss	0.9400
12:12695996:T:TA	donor_gain	0.9400
12:12696055:A:AC	donor_gain	0.9400
12:12696057:G:T	donor_gain	0.9400
12:12688801:C:CA	donor_gain	0.9300
12:12696012:C:A	donor_gain	0.9300
12:12696081:G:A	donor_gain	0.9300
12:12663354:A:AC	donor_gain	0.9200
12:12685409:AGG:A	donor_gain	0.9200

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000020213 (12:12692762 T>C), RS1000042322 (12:12706118 C>A,T), RS1000240914 (12:12692525 G>A,T), RS1000268508 (12:12695481 A>G), RS1000373402 (12:12707026 T>C), RS1000399846 (12:12688422 C>A), RS1000533122 (12:12685549 C>A,T), RS1000549235 (12:12663734 G>A), RS1000559550 (12:12698326 T>C), RS1000570435 (12:12690912 A>G), RS1000677808 (12:12705758 C>T), RS1000708647 (12:12705319 GA>G,GAA,GAAA), RS1000843667 (12:12683372 T>C), RS1001024213 (12:12669641 A>G), RS1001122938 (12:12662976 C>T)

Disease associations

OMIM: gene MIM:602927 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001795_6	Systemic lupus erythematosus	4.000000e-17
GCST006190_48	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	9.000000e-14
GCST006190_86	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-07
GCST006192_35	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-09
GCST006192_69	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-15
GCST006193_31	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	9.000000e-11
GCST006195_13	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	9.000000e-08
GCST006195_62	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	5.000000e-13
GCST008161_58	Waist circumference adjusted for body mass index	5.000000e-06
GCST010002_209	Refractive error	4.000000e-34
GCST011038_9	Parkinson’s disease progression (motor)	8.000000e-06
GCST011426_30	Systemic lupus erythematosus	3.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0007789	BMI-adjusted waist circumference
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523870 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Class A Orphans with emerging pharmacology

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
adropin	Agonist	8.11	pEC50

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, increases expression	4
Valproic Acid	increases methylation, affects expression, decreases expression	3
Benzo(a)pyrene	affects methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Cyclosporine	increases methylation, increases expression	2
FR900359	affects phosphorylation	1
potassium perchlorate	decreases expression	1
quercitrin	increases expression	1
ferrous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Vorinostat	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cytarabine	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	increases expression	1
Testosterone	affects cotreatment, decreases expression	1
Sodium Selenite	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883437	Binding	PRESTO-Tango GPCRome screening (GPR19)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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