GPR108

Summary

GPR108 (G protein-coupled receptor 108, HGNC:17829) is a protein-coding gene on chromosome 19p13.3, encoding Protein GPR108 (Q9NPR9). May play a role in intracellular immune modulation by activating NF-kappaB response and attenuating Toll-like-receptor response.

Predicted to be involved in negative regulation of toll-like receptor signaling pathway. Predicted to act upstream of or within defense response to virus; protein catabolic process; and type I interferon-mediated signaling pathway. Located in trans-Golgi network.

Source: NCBI Gene 56927 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 115 total
• MANE Select transcript: NM_001080452

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17829
Approved symbol	GPR108
Name	G protein-coupled receptor 108
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	LUSTR2
Ensembl gene	ENSG00000125734
Ensembl biotype	protein_coding
OMIM	618491
Entrez	56927

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 17 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000264080, ENST00000430424, ENST00000537722, ENST00000594034, ENST00000594500, ENST00000595108, ENST00000595620, ENST00000595908, ENST00000597043, ENST00000597298, ENST00000597706, ENST00000598052, ENST00000598626, ENST00000598955, ENST00000600773, ENST00000601402, ENST00000601716, ENST00000863578, ENST00000863579, ENST00000863580, ENST00000863581, ENST00000863582, ENST00000863583, ENST00000938366, ENST00000969484, ENST00000969485, ENST00000969486

RefSeq mRNA: 17 — MANE Select: NM_001080452 NM_001080452, NM_001394714, NM_001394715, NM_001394716, NM_001394717, NM_001394718, NM_001394719, NM_001394720, NM_001394721, NM_001394722, NM_001394723, NM_001394724, NM_001394725, NM_001394726, NM_001394727, NM_001394728, NM_020171

CCDS: CCDS42479, CCDS45940

Canonical transcript exons

ENST00000264080 — 18 exons

Exon	Start	End
ENSE00000667848	6732987	6733062
ENSE00000667863	6737457	6737580
ENSE00002851040	6729914	6730384
ENSE00003483479	6732476	6732549
ENSE00003505129	6734183	6734307
ENSE00003516808	6733168	6733301
ENSE00003533292	6732263	6732380
ENSE00003537334	6731891	6731934
ENSE00003575518	6733845	6733913
ENSE00003594167	6735908	6735958
ENSE00003612696	6731473	6731522
ENSE00003643597	6730987	6731111
ENSE00003658489	6732025	6732155
ENSE00003667574	6735622	6735704
ENSE00003679637	6736592	6736711
ENSE00003685440	6734005	6734054
ENSE00003690263	6731199	6731282
ENSE00003786616	6733570	6733674

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5718 / max 163.6229, expressed in 1813 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178812	10.0674	1783
178809	3.5284	1349
178811	0.9814	712
178810	0.5853	341
178808	0.4093	234

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.96	gold quality
right uterine tube	UBERON:0001302	97.72	gold quality
mucosa of transverse colon	UBERON:0004991	97.61	gold quality
right lobe of thyroid gland	UBERON:0001119	97.36	gold quality
metanephros cortex	UBERON:0010533	97.27	gold quality
left lobe of thyroid gland	UBERON:0001120	97.22	gold quality
body of pancreas	UBERON:0001150	97.02	gold quality
right adrenal gland	UBERON:0001233	96.95	gold quality
right ovary	UBERON:0002118	96.94	gold quality
left ovary	UBERON:0002119	96.94	gold quality
right adrenal gland cortex	UBERON:0035827	96.89	gold quality
granulocyte	CL:0000094	96.82	gold quality
ileal mucosa	UBERON:0000331	96.78	gold quality
endocervix	UBERON:0000458	96.73	gold quality
left adrenal gland cortex	UBERON:0035825	96.72	gold quality
left adrenal gland	UBERON:0001234	96.69	gold quality
minor salivary gland	UBERON:0001830	96.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.57	gold quality
thyroid gland	UBERON:0002046	96.53	gold quality
ectocervix	UBERON:0012249	96.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.24	gold quality
body of uterus	UBERON:0009853	96.20	gold quality
adrenal cortex	UBERON:0001235	96.06	gold quality
transverse colon	UBERON:0001157	96.00	gold quality
apex of heart	UBERON:0002098	96.00	gold quality
gall bladder	UBERON:0002110	95.96	gold quality
spleen	UBERON:0002106	95.94	gold quality
saliva-secreting gland	UBERON:0001044	95.93	gold quality
right lobe of liver	UBERON:0001114	95.93	gold quality
body of stomach	UBERON:0001161	95.93	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.87
E-MTAB-6142	no	286.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting GPR108, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-3190-3P	97.61	66.95	1406

Literature-anchored findings (GeneRIF, showing 4)

• The 18-exon human GPR107 gene is located at 9q34.2-3 and spans 86.4 kb and the cDNA encodes a 552 residue protein; murine Gpr108 cDNA encodes a 562 residue protein that has 49% identity to human GPR107. (PMID:17454009)
• GPR108, an NF-kappaB activator suppressed by TIRAP, negatively regulates TLR-triggered immune responses. (PMID:30332431)
• GPR108 is required for gambogic acid inhibiting NF-kappaB signaling in cancer. (PMID:35659621)
• A Golgi-resident GPR108 cooperates with E3 ubiquitin ligase Smurf1 to suppress antiviral innate immunity. (PMID:37330913)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr108	ENSDARG00000096651
mus_musculus	Gpr108	ENSMUSG00000005823
rattus_norvegicus	Gpr108	ENSRNOG00000046128
drosophila_melanogaster	CG12121	FBGN0030109
drosophila_melanogaster	CG17660	FBGN0031356
caenorhabditis_elegans		WBGENE00015801
caenorhabditis_elegans		WBGENE00016867

Paralogs (3): TMEM87A (ENSG00000103978), GPR107 (ENSG00000148358), TMEM87B (ENSG00000153214)

Protein

Protein identifiers

Protein GPR108 — Q9NPR9 (reviewed: Q9NPR9)

Alternative names: Lung seven transmembrane receptor 2

All UniProt accessions (10): Q9NPR9, G5E9L6, M0QYF6, M0QZ03, M0QZW9, M0QZY1, M0R1G1, M0R1Q3, M0R2E1, M0R3H4

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in intracellular immune modulation by activating NF-kappaB response and attenuating Toll-like-receptor response. (Microbial infection) Plays an essential function in adeno-associated virus (AAV) transduction across multiple serotypes except AAV5. May play a critical role in mediating the endosomal virus escape or in the AAV virions trafficking from endosomes to the nucleus.

Subcellular location. Golgi apparatus. cis-Golgi network membrane. trans-Golgi network membrane. Golgi apparatus membrane.

Domain organisation. (Microbial infection) N- and C-terminal domains are required for AAV transduction.

Similarity. Belongs to the LU7TM family.

RefSeq proteins (17): NP_001073921, NP_001381643, NP_001381644, NP_001381645, NP_001381646, NP_001381647, NP_001381648, NP_001381649, NP_001381650, NP_001381651, NP_001381652, NP_001381653, NP_001381654, NP_001381655, NP_001381656, NP_001381657, NP_064556 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009637	GPR107/GPR108-like	Family
IPR053937	GOST_TM	Domain

Pfam: PF06814

UniProt features (18 total): transmembrane region 7, glycosylation site 6, sequence variant 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPR9-F1	76.08	0.29

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 (6): 57, 109, 200, 204, 228, 534

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 126 (showing top): GOBP_RESPONSE_TO_PEPTIDE, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOCC_TRANS_GOLGI_NETWORK, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (4): negative regulation of toll-like receptor signaling pathway (GO:0034122), regulation of immune response (GO:0050776), defense response to virus (GO:0051607), type I interferon-mediated signaling pathway (GO:0060337)

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

GO Cellular Component (5): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), membrane (GO:0016020), cis-Golgi network membrane (GO:0033106)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
bounding membrane of organelle	2
toll-like receptor signaling pathway	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
regulation of toll-like receptor signaling pathway	1
regulation of immune system process	1
immune response	1
regulation of response to stimulus	1
defense response	1
response to virus	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
binding	1
Golgi apparatus	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
cellular anatomical structure	1
cis-Golgi network	1

Protein interactions and networks

STRING

702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR108	KIAA0319L	Q8IZA0	644
GPR108	GPR152	Q8TDT2	632
GPR108	GPR137B	O60478	552
GPR108	GPR137	Q96N19	544
GPR108	GPR137C	Q8N3F9	529
GPR108	GPR171	O14626	493
GPR108	TPRA1	Q86W33	476
GPR108	TM9SF2	Q99805	447
GPR108	GPR158	Q5T848	431
GPR108	TTC16	Q8NEE8	417
GPR108	OR4K5	Q8NGD3	414
GPR108	GPR157	Q5UAW9	412
GPR108	GPR162	Q16538	411
GPR108	GPR82	Q96P67	411
GPR108	GPR63	Q9BZJ6	399

IntAct

37 interactions, top by confidence:

A	B	Type	Score
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
MUC1	GPR108	psi-mi:“MI:0915”(physical association)	0.560
GJA8	GPR108	psi-mi:“MI:0915”(physical association)	0.560
TMEM243	GPR108	psi-mi:“MI:0915”(physical association)	0.560
MTERF3	GPR108	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	GPR108	psi-mi:“MI:0915”(physical association)	0.560
CD53	GPR108	psi-mi:“MI:0915”(physical association)	0.560
KIR2DL3	GPR108	psi-mi:“MI:0915”(physical association)	0.560
NEMP1	GPR108	psi-mi:“MI:0915”(physical association)	0.560
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
GPR108	PCNA	psi-mi:“MI:0915”(physical association)	0.370
GPR108	CLPTM1	psi-mi:“MI:0914”(association)	0.350
REEP5	ESYT2	psi-mi:“MI:0914”(association)	0.350
STARD3NL	GPAA1	psi-mi:“MI:0914”(association)	0.350
MFSD5	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC16A4	APP	psi-mi:“MI:0914”(association)	0.350
SLC7A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TMEM216	SNAP23	psi-mi:“MI:2364”(proximity)	0.270
GJA8	GPR108	psi-mi:“MI:0915”(physical association)	0.000
TMEM243	GPR108	psi-mi:“MI:0915”(physical association)	0.000
GPR108	MTERF3	psi-mi:“MI:0915”(physical association)	0.000
GPR108	FAM209A	psi-mi:“MI:0915”(physical association)	0.000
GPR108	CD53	psi-mi:“MI:0915”(physical association)	0.000
GPR108	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.000
GPR108	NEMP1	psi-mi:“MI:0915”(physical association)	0.000
GPR108	MUC1	psi-mi:“MI:0915”(physical association)	0.000
GPR108	GJA8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): GPR108 (Proximity Label-MS), GPR108 (Proximity Label-MS), GPR108 (PCA), GPR108 (Affinity Capture-MS), GPR108 (Two-hybrid), GPR108 (Two-hybrid), GPR108 (Two-hybrid), GPR108 (Two-hybrid), TMEM243 (Two-hybrid), CD53 (Two-hybrid), MTERF3 (Two-hybrid), TMEM194A (Two-hybrid), MUC1 (Two-hybrid), KIR2DL3 (Two-hybrid), GPR108 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IMY7, A0JPA0, A2AP18, A8DYE2, J9SQF3, O00329, O35904, O75038, P0C1Q3, P0C588, P19687, P33402, P48736, P97557, Q02108, Q09M05, Q148L1, Q1LWG4, Q2TV84, Q2WEA5, Q3USB7, Q4ZHS0, Q502J0, Q5EBA1, Q60565, Q62688, Q69ZF7, Q6P4Q7, Q6PA06, Q7L5N7, Q7TN37, Q7Z2W7, Q7Z4N2, Q80YD1, Q8BTI9, Q8BYI6, Q8BZN2, Q8CIR4, Q8NHH9, Q8R455

Diamond homologs: D3ZWZ9, F4JY11, Q148L1, Q5VW38, Q6P6V6, Q8BUV8, Q91WD0, Q9LZ39, Q9NPR9, Q8N769

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2663 predictions. Top by Δscore:

Variant	Effect	Δscore
19:6730981:G:C	donor_gain	1.0000
19:6730985:A:AC	donor_gain	1.0000
19:6730986:C:CC	donor_gain	1.0000
19:6730986:CA:C	donor_gain	1.0000
19:6730987:A:AC	donor_gain	1.0000
19:6730988:C:CC	donor_gain	1.0000
19:6730988:CTTG:C	donor_gain	1.0000
19:6730994:C:CA	donor_gain	1.0000
19:6731005:T:TA	donor_gain	1.0000
19:6731008:T:TA	donor_gain	1.0000
19:6731017:T:TA	donor_gain	1.0000
19:6731108:AGAG:A	acceptor_gain	1.0000
19:6731109:GAG:G	acceptor_gain	1.0000
19:6731109:GAGC:G	acceptor_loss	1.0000
19:6731110:AG:A	acceptor_gain	1.0000
19:6731110:AGCTG:A	acceptor_loss	1.0000
19:6731111:GCTG:G	acceptor_loss	1.0000
19:6731112:C:CA	acceptor_loss	1.0000
19:6731112:C:CC	acceptor_gain	1.0000
19:6731113:T:C	acceptor_loss	1.0000
19:6731120:C:CT	acceptor_gain	1.0000
19:6731197:A:AC	donor_gain	1.0000
19:6731198:C:CC	donor_gain	1.0000
19:6731315:C:CC	acceptor_gain	1.0000
19:6731523:C:CC	acceptor_gain	1.0000
19:6731889:AC:A	donor_gain	1.0000
19:6731890:CC:C	donor_gain	1.0000
19:6731895:C:A	donor_gain	1.0000
19:6732019:CCTCA:C	donor_loss	1.0000
19:6732020:CTCAC:C	donor_loss	1.0000

AlphaMissense

3548 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:6731058:G:C	F496L	0.997
19:6731058:G:T	F496L	0.997
19:6731060:A:G	F496L	0.997
19:6731059:A:G	F496S	0.992
19:6731491:G:C	F444L	0.991
19:6731491:G:T	F444L	0.991
19:6731493:A:G	F444L	0.991
19:6731059:A:C	F496C	0.989
19:6733008:G:C	S304R	0.989
19:6733008:G:T	S304R	0.989
19:6733010:T:G	S304R	0.989
19:6735951:A:G	F83S	0.988
19:6736653:A:G	L60P	0.988
19:6736676:G:C	F52L	0.988
19:6736676:G:T	F52L	0.988
19:6736678:A:G	F52L	0.988
19:6733622:A:G	F224S	0.987
19:6733628:A:G	L222P	0.986
19:6736670:G:C	F54L	0.986
19:6736670:G:T	F54L	0.986
19:6736672:A:G	F54L	0.986
19:6736671:A:G	F54S	0.985
19:6731492:A:C	F444C	0.983
19:6733212:G:C	F271L	0.979
19:6733212:G:T	F271L	0.979
19:6733214:A:G	F271L	0.979
19:6733635:A:C	Y220D	0.979
19:6733672:G:C	F207L	0.979
19:6733672:G:T	F207L	0.979
19:6733674:A:G	F207L	0.979

dbSNP variants (sampled 300 via entrez): RS1000322717 (19:6734364 C>T), RS1000435496 (19:6736435 T>C), RS1000812686 (19:6729761 C>T), RS1001119347 (19:6729523 T>C), RS1001460123 (19:6737957 A>G), RS1001478757 (19:6729683 C>A), RS1001577580 (19:6738245 G>A), RS1002112122 (19:6737689 A>C,G), RS1002387540 (19:6732923 T>A,G), RS1002597488 (19:6734513 T>C), RS1002651251 (19:6734869 T>C), RS1003552979 (19:6730724 G>A,T), RS1003593944 (19:6736255 C>G,T), RS1003679397 (19:6731724 G>A), RS1004276741 (19:6735787 C>A,T)

Disease associations

OMIM: gene MIM:618491 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, decreases methylation	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
Temozolomide	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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