GPR85

Summary

GPR85 (G protein-coupled receptor 85, HGNC:4536) is a protein-coding gene on chromosome 7q31.1, encoding Probable G-protein coupled receptor 85 (P60893). Orphan receptor.

Members of the G protein-coupled receptor (GPCR) family, such as GPR85, have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli, such as neurotransmitters, hormones, or light, induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins (Matsumoto et al., 2000 [PubMed 10833454]).

Source: NCBI Gene 54329 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 52 total
• Druggable target: yes
• MANE Select transcript: NM_001146267

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4536
Approved symbol	GPR85
Name	G protein-coupled receptor 85
Location	7q31.1
Locus type	gene with protein product
Status	Approved
Aliases	SREB2
Ensembl gene	ENSG00000164604
Ensembl biotype	protein_coding
OMIM	605188
Entrez	54329

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000297146, ENST00000424100, ENST00000438062, ENST00000449591, ENST00000449735, ENST00000487573, ENST00000610164, ENST00000962376, ENST00000962377

RefSeq mRNA: 4 — MANE Select: NM_001146267 NM_001146265, NM_001146266, NM_001146267, NM_018970

CCDS: CCDS5758

Canonical transcript exons

ENST00000424100 — 3 exons

Exon	Start	End
ENSE00001085791	113085992	113086109
ENSE00001762400	113082285	113084891
ENSE00001779128	113086322	113086827

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 96.96.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1360 / max 111.3472, expressed in 458 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85781	0.5372	264
85779	0.2815	107
85780	0.1701	80
85782	0.0874	35
85778	0.0599	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.96	gold quality
endothelial cell	CL:0000115	95.85	gold quality
caudate nucleus	UBERON:0001873	85.71	gold quality
primary visual cortex	UBERON:0002436	85.05	gold quality
putamen	UBERON:0001874	84.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.54	gold quality
ganglionic eminence	UBERON:0004023	83.49	gold quality
prefrontal cortex	UBERON:0000451	83.41	gold quality
lateral nuclear group of thalamus	UBERON:0002736	83.28	gold quality
nucleus accumbens	UBERON:0001882	83.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.61	gold quality
right frontal lobe	UBERON:0002810	82.48	gold quality
anterior cingulate cortex	UBERON:0009835	82.48	gold quality
cingulate cortex	UBERON:0003027	82.34	gold quality
Ammon’s horn	UBERON:0001954	82.18	gold quality
neocortex	UBERON:0001950	81.98	gold quality
telencephalon	UBERON:0001893	81.75	gold quality
cerebral cortex	UBERON:0000956	81.66	gold quality
frontal cortex	UBERON:0001870	81.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.77	gold quality
cerebellar cortex	UBERON:0002129	80.76	gold quality
cerebellar hemisphere	UBERON:0002245	80.70	gold quality
amygdala	UBERON:0001876	80.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.51	gold quality
middle temporal gyrus	UBERON:0002771	80.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.94	gold quality
occipital lobe	UBERON:0002021	79.90	gold quality
cerebellum	UBERON:0002037	79.83	gold quality
sperm	CL:0000019	79.81	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ENAD-17	yes	228.85
E-ANND-3	yes	5.87
E-MTAB-10137	no	869.49
E-MTAB-6379	no	34.52
E-MTAB-7249	no	5.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

242 targeting GPR85, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6778-3P	99.96	67.29	2693

Literature-anchored findings (GeneRIF, showing 3)

• The areas expressing high levels of SREB2 mRNA overlap with brain structures known to possess high levels of plasticity, namely, the hippocampal formation, olfactory system, and supraoptic and paraventricular nuclei. (PMID:15893849)
• Theses data implicate SREB2 as a potential risk factor for psychiatric disorders. (PMID:18413613)
• Risk-associated variants in GPR85 are associated with phenotypes similar to those found in patients with schizophrenia. (PMID:22968816)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr85	ENSDARG00000068701
mus_musculus	Gpr85	ENSMUSG00000048216
rattus_norvegicus	Gpr85	ENSRNOG00000024636

Paralogs (2): GPR27 (ENSG00000170837), GPR173 (ENSG00000184194)

Protein

Protein identifiers

Probable G-protein coupled receptor 85 — P60893 (reviewed: P60893)

Alternative names: Super conserved receptor expressed in brain 2

All UniProt accessions (4): A4D0T8, C9JBQ9, C9JDK8, P60893

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor.

Subunit / interactions. Interacts with DLG4 and DLG3.

Subcellular location. Cell membrane. Endoplasmic reticulum.

Tissue specificity. Highly expressed in brain and testis. Lower levels in small intestine, placenta and spleen. In brain regions, detected in all regions tested, but somewhat lower levels in the corpus callosum, medulla and spinal cord.

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

RefSeq proteins (4): NP_001139737, NP_001139738, NP_001139739, NP_061843 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR051509	GPCR_Orphan/Phoenixin	Family

Pfam: PF00001

UniProt features (22 total): topological domain 8, transmembrane region 7, glycosylation site 3, sequence variant 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60893-F1	82.93	0.57

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): 94–172

Glycosylation sites (3): 3, 83, 182

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 233 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, AAGCCAT_MIR135A_MIR135B, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, CEBPB_01, CATTTCA_MIR203, GATA3_01, TGCTGAY_UNKNOWN, GTGTTGA_MIR505, TGTGTGA_MIR377, OCT1_07, ATTCTTT_MIR186, TGACATY_UNKNOWN

GO Biological Process (2): signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR85	CXCL14	O95715	778
GPR85	INSIG2	Q9Y5U4	775
GPR85	INSIG1	O15503	683
GPR85	ALDH18A1	P54886	641
GPR85	SREBF2	Q12772	640
GPR85	SREBF1	P36956	586
GPR85	SCARF1	Q14162	557
GPR85	SNX33	Q8WV41	515
GPR85	PLAGL2	Q9UPG8	490
GPR85	ENC1	O14682	483
GPR85	GPR176	Q14439	478
GPR85	SMIM20	Q8N5G0	457
GPR85	GPR52	Q9Y2T5	450
GPR85	GPR82	Q96P67	442
GPR85	TMEM168	Q9H0V1	438

IntAct

3 interactions, top by confidence:

A	B	Type	Score
GPR85	ACP2	psi-mi:“MI:0915”(physical association)	0.400
GPR85	H1-4	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): GPR85 (Affinity Capture-RNA), CXCL14 (Reconstituted Complex), GPR85 (Affinity Capture-Western), GPR85 (Proximity Label-MS), SH3BP4 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A5A4K9, A5A4L1, B2ZI34, F1MV99, O08725, O08786, O42329, O43193, O62709, O97772, P11616, P21451, P21729, P24053, P25099, P26684, P28088, P28190, P28646, P30542, P30550, P30551, P30872, P30873, P32238, P33534, P34970, P34975, P35342, P41144, P41145, P47745, P47751, P48302, P52500, P60893, P60894, P60895, Q2KIP6, Q49LX5

Diamond homologs: O54897, P60893, P60894, P60895, Q5E9H8, Q5RBG7, Q6PI62, Q9I918, Q9I919, Q9JJH2, Q9JJH3, Q9NS66, Q9NS67, A0A287A2K5, C3ZQF9, O08786, O15354, O42574, O43613, O62709, O62729, O70342, O97661, O97772, O97969, P08913, P17124, P18871, P21451, P22909, P24530, P25931, P28088, P28566, P30552, P30553, P30796, P32229, P32239, P34997

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

707 predictions. Top by Δscore:

Variant	Effect	Δscore
7:113084856:T:TA	donor_gain	1.0000
7:113084801:CATT:C	donor_gain	0.9900
7:113084807:A:AC	donor_gain	0.9900
7:113084808:C:CC	donor_gain	0.9900
7:113084837:T:C	donor_gain	0.9900
7:113084889:TAT:T	acceptor_gain	0.9900
7:113086896:C:A	donor_gain	0.9900
7:113084842:T:C	donor_gain	0.9800
7:113084892:C:CC	acceptor_gain	0.9800
7:113086450:AGTG:A	donor_gain	0.9800
7:113086895:T:TA	donor_gain	0.9800
7:113084889:TATCT:T	acceptor_loss	0.9700
7:113084891:TCTGA:T	acceptor_loss	0.9700
7:113084893:T:A	acceptor_loss	0.9700
7:113087439:CA:C	donor_gain	0.9700
7:113087438:A:AC	donor_gain	0.9600
7:113087439:C:CC	donor_gain	0.9600
7:113085983:A:AC	donor_gain	0.9400
7:113085990:A:AC	donor_gain	0.9400
7:113085991:C:CC	donor_gain	0.9400
7:113086880:C:A	donor_gain	0.9400
7:113086892:T:A	donor_gain	0.9400
7:113087437:TAC:T	donor_gain	0.9400
7:113087438:ACA:A	donor_gain	0.9400
7:113087439:CAC:C	donor_gain	0.9400
7:113080730:A:C	acceptor_gain	0.9300
7:113085757:T:TA	donor_gain	0.9300
7:113085991:CG:C	donor_gain	0.9300
7:113086879:T:TA	donor_gain	0.9300
7:113087439:CACCA:C	donor_gain	0.9300

AlphaMissense

2417 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:113083746:A:G	W326R	0.999
7:113083746:A:T	W326R	0.999
7:113084032:A:C	F230L	0.999
7:113084032:A:T	F230L	0.999
7:113084034:A:G	F230L	0.999
7:113084207:C:G	C172S	0.999
7:113084208:A:G	C172R	0.999
7:113084208:A:T	C172S	0.999
7:113084201:A:C	F174C	0.998
7:113084206:G:C	C172W	0.998
7:113084207:C:T	C172Y	0.998
7:113084227:G:C	F165L	0.998
7:113084227:G:T	F165L	0.998
7:113084229:A:G	F165L	0.998
7:113084276:G:A	S149F	0.998
7:113084276:G:T	S149Y	0.998
7:113084286:A:G	W146R	0.998
7:113084286:A:T	W146R	0.998
7:113084374:A:C	S116R	0.998
7:113084374:A:T	S116R	0.998
7:113084376:T:G	S116R	0.998
7:113084429:G:T	A98D	0.998
7:113084613:C:G	G37R	0.998
7:113084620:G:C	S34R	0.998
7:113084620:G:T	S34R	0.998
7:113084622:T:G	S34R	0.998
7:113083738:A:C	S328R	0.997
7:113083738:A:T	S328R	0.997
7:113083740:T:G	S328R	0.997
7:113083830:A:G	W298R	0.997

dbSNP variants (sampled 300 via entrez): RS1000158609 (7:113089657 C>A), RS1000858246 (7:113081920 C>T), RS1000938943 (7:113086843 C>T), RS1001531956 (7:113089203 A>G), RS1002157413 (7:113085032 T>A), RS1002254531 (7:113088735 G>T), RS1003060112 (7:113087056 T>A), RS1003121578 (7:113087594 G>A,T), RS1003564683 (7:113086801 T>C), RS1004492133 (7:113083831 C>A,T), RS1005092609 (7:113082438 G>A), RS1005123709 (7:113081940 A>G), RS1005494765 (7:113085711 T>A,C), RS1006121700 (7:113088727 C>T), RS1006216191 (7:113087084 G>T)

Disease associations

OMIM: gene MIM:605188 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000253_8	Attention deficit hyperactivity disorder and conduct disorder	5.000000e-06
GCST002897_14	Triglycerides	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523868 (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 only surrogate ligands

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sulforaphane	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Diethylhexyl Phthalate	increases abundance, decreases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Serpentine	increases methylation	1
Antirheumatic Agents	decreases expression	1
Acrylamide	decreases 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
CHEMBL4883472	Binding	PRESTO-Tango GPCRome screening (GPR85)	Data for DCP probe UCSF924

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX76	PathHunter CHO-K1 GPR85 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA46	PathHunter U2OS GPR85 beta-arrestin	Cancer cell line	Female

Clinical trials (associated diseases)

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