ADGRD1

Summary

ADGRD1 (adhesion G protein-coupled receptor D1, HGNC:19893) is a protein-coding gene on chromosome 12q24.33, encoding Adhesion G-protein coupled receptor D1 (Q6QNK2). Adhesion G-protein coupled receptor (aGPCR) for androgen hormone 5alpha-dihydrotestosterone (5alpha-DHT), also named 17beta-hydroxy-5alpha-androstan-3-one, the most potent hormone among androgens.

The adhesion G-protein-coupled receptors (GPCRs), including GPR133, are membrane-bound proteins with long N termini containing multiple domains. GPCRs, or GPRs, contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins (summary by Bjarnadottir et al., 2004 [PubMed 15203201]).

Source: NCBI Gene 283383 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 130 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_198827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19893
Approved symbol	ADGRD1
Name	adhesion G protein-coupled receptor D1
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434B1272, PGR25
Ensembl gene	ENSG00000111452
Ensembl biotype	protein_coding
OMIM	613639
Entrez	283383

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 11 protein_coding, 8 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000261654, ENST00000335486, ENST00000376682, ENST00000446583, ENST00000535015, ENST00000536988, ENST00000537489, ENST00000537600, ENST00000540207, ENST00000541143, ENST00000541937, ENST00000542091, ENST00000543617, ENST00000543826, ENST00000544673, ENST00000545900, ENST00000881059, ENST00000881060, ENST00000881061, ENST00000881062, ENST00000881063, ENST00000964278

RefSeq mRNA: 2 — MANE Select: NM_198827 NM_001330497, NM_198827

CCDS: CCDS81753, CCDS9272

Canonical transcript exons

ENST00000261654 — 25 exons

Exon	Start	End
ENSE00001334702	131005972	131006047
ENSE00001423274	130992237	130992392
ENSE00001426022	130966463	130966546
ENSE00003467777	130981884	130982063
ENSE00003493889	131131725	131131816
ENSE00003514228	131105754	131105865
ENSE00003520245	130954624	130954660
ENSE00003528154	131104831	131104934
ENSE00003586781	131108724	131108877
ENSE00003587369	131118385	131118451
ENSE00003595107	131120847	131120913
ENSE00003596877	131138137	131138229
ENSE00003600167	130987095	130987349
ENSE00003623595	131136973	131137014
ENSE00003636799	130953907	130954531
ENSE00003640564	130971458	130971580
ENSE00003672981	131136037	131136163
ENSE00003679766	131076801	131076874
ENSE00003691336	131139168	131141469
ENSE00003732362	131003185	131003302
ENSE00003735025	131014199	131014340
ENSE00003738144	130991014	130991078
ENSE00003738461	131000383	131000442
ENSE00003745154	131084540	131084663
ENSE00003749645	131004186	131004296

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 97.60.

FANTOM5 (CAGE): breadth broad, TPM avg 7.1174 / max 381.2893, expressed in 723 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128743	4.0538	603
128744	1.7564	474
128742	0.8107	194
128745	0.1785	75
128751	0.1175	39
128746	0.1068	42
128750	0.0937	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	97.60	gold quality
right atrium auricular region	UBERON:0006631	96.58	gold quality
cardiac atrium	UBERON:0002081	96.40	gold quality
tibial nerve	UBERON:0001323	94.54	gold quality
decidua	UBERON:0002450	93.74	gold quality
right lung	UBERON:0002167	93.33	gold quality
sural nerve	UBERON:0015488	93.23	gold quality
upper lobe of left lung	UBERON:0008952	93.21	gold quality
left ventricle myocardium	UBERON:0006566	92.76	silver quality
upper lobe of lung	UBERON:0008948	92.55	gold quality
mucosa of stomach	UBERON:0001199	92.24	gold quality
apex of heart	UBERON:0002098	92.03	gold quality
heart left ventricle	UBERON:0002084	91.66	gold quality
cardiac ventricle	UBERON:0002082	91.27	gold quality
heart	UBERON:0000948	91.17	gold quality
lung	UBERON:0002048	90.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.58	gold quality
lower esophagus	UBERON:0013473	89.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.11	gold quality
gall bladder	UBERON:0002110	88.90	gold quality
endocervix	UBERON:0000458	88.82	gold quality
calcaneal tendon	UBERON:0003701	88.73	gold quality
right ovary	UBERON:0002118	88.68	gold quality
left uterine tube	UBERON:0001303	88.62	gold quality
parietal pleura	UBERON:0002400	87.59	gold quality
myocardium	UBERON:0002349	87.51	silver quality
secondary oocyte	CL:0000655	87.44	gold quality
omental fat pad	UBERON:0010414	86.91	gold quality
peritoneum	UBERON:0002358	86.79	gold quality
body of stomach	UBERON:0001161	86.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-111727	yes	133.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting ADGRD1, 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-3924	100.00	72.09	2394
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4428	99.73	66.41	1733

Literature-anchored findings (GeneRIF, showing 8)

• A role for GPR133 protein in affecting the length of the electrocardiographic RR interval and heart rate. (PMID:20031603)
• Cell adhesion receptor GPR133 couples to Gs protein (PMID:22025619)
• The results show that a broad spectrum of functionally relevant ADGRD1 variants is present in the human population which may cause clinically relevant phenotypes, while being compatible with life when heterozygous. (PMID:27516204)
• N(6) -methyladenosine (m(6) A) RNA modification of G protein-coupled receptor 133 increases proliferation of lung adenocarcinoma. (PMID:34185971)
• ADGRD1 as a Potential Prognostic and Immunological Biomarker in Non-Small-Cell Lung Cancer. (PMID:36457341)
• Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage. (PMID:38564758)
• Modulation of GPR133 (ADGRD1) signaling by its intracellular interaction partner extended synaptotagmin 1. (PMID:38758649)
• Upregulation of mRNA Expression of ADGRD1/GPR133 and ADGRG7/GPR128 in SARS-CoV-2-Infected Lung Adenocarcinoma Calu-3 Cells. (PMID:38786015)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adgrd1	ENSDARG00000053344
mus_musculus	Adgrd1	ENSMUSG00000044017
rattus_norvegicus	Adgrd1	ENSRNOG00000023536

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), SCTR (ENSG00000080293), VIPR2 (ENSG00000106018), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), VIPR1 (ENSG00000114812), ADGRL2 (ENSG00000117114), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), ADGRB3 (ENSG00000135298), PTH2R (ENSG00000144407), ADGRG7 (ENSG00000144820), ADGRL3 (ENSG00000150471), ADGRA3 (ENSG00000152990), ADGRF1 (ENSG00000153292), ADGRF4 (ENSG00000153294), ADGRG4 (ENSG00000156920), ADGRG5 (ENSG00000159618), PTH1R (ENSG00000160801), ADGRL4 (ENSG00000162618), EVA1C (ENSG00000166979), ADGRF3 (ENSG00000173567), ADGRG2 (ENSG00000173698), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Adhesion G-protein coupled receptor D1 — Q6QNK2 (reviewed: Q6QNK2)

Alternative names: G-protein coupled receptor 133, G-protein coupled receptor PGR25

All UniProt accessions (4): Q6QNK2, A0A087WYZ5, F5H7I3, H0Y2U9

UniProt curated annotations — full annotation on UniProt →

Function. Adhesion G-protein coupled receptor (aGPCR) for androgen hormone 5alpha-dihydrotestosterone (5alpha-DHT), also named 17beta-hydroxy-5alpha-androstan-3-one, the most potent hormone among androgens. Also activated by methenolone drug. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. ADGRD1 is coupled to G(s) G proteins and mediates activation of adenylate cyclase activity. Acts as a 5alpha-DHT receptor in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength.

Subunit / interactions. Heterodimer of 2 chains generated by proteolytic processing; the large extracellular N-terminal fragment and the membrane-bound C-terminal fragment predominantly remain associated and non-covalently linked. Interacts with ESYT1; interaction takes place in absence of cytosolic calcium and inhibits the G protein-coupled receptor activity of ADGRD1.

Subcellular location. Cell membrane.

Tissue specificity. Up-regulated in CD133(+) cell population of glioblastoma.

Post-translational modifications. Autoproteolytically processed at the GPS region of the GAIN-B domain; this cleavage modulates receptor activity. Cleavage takes place early in the secretory pathway before N-glycosylation.

Activity regulation. Forms a heterodimer of 2 chains generated by proteolytic processing that remain associated through non-covalent interactions mediated by the GAIN-B domain. In the inactivated receptor, the Stachel sequence (also named stalk) is embedded in the GAIN-B domain, where it adopts a beta-strand conformation. On activation, the Stachel moves into the 7 transmembrane region and adopts a twisted hook-shaped configuration that forms contacts within the receptor, leading to coupling of a G-alpha protein, which activates signaling. The cleaved GAIN-B and N-terminal domains can then dissociate from the rest of the receptor. Interaction with ESYT1 in absence of cytosolic calcium inhibits the G protein-coupled receptor activity; interaction and inhibition is relieved when cytosolic calcium increases. Activated by AP503, a small molecule that activates ADGRD1 without activating androgen nuclear receptors: AP503 enhances muscle strength without eliciting androgenic adverse effects. Activated by the 8E3E8 antibody that targets the N-terminus.

Domain organisation. The Stachel sequence (also named stalk) in the C-terminal part of the extracellular domain (ECD) functions as a tethered agonist. In the inactivated receptor, the Stachel sequence (also named stalk) is embedded in the GAIN-B domain, where it adopts a beta-strand conformation. On activation, the Stachel moves into the 7 transmembrane region and adopts a twisted hook-shaped configuration that forms contacts within the receptor, leading to coupling of a G-alpha protein, which activates signaling. The N-terminal domain and autocatalytic activity of ADGRD1 at the GPCR proteolysis site (GPS) are not required for G-protein coupling activity.

Induction. Up-regulated by hypoxia in hypoxia-inducible factor 1-alpha (HIF1A)-dependent manner.

Similarity. Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6QNK2-1	1	yes
Q6QNK2-2	2
Q6QNK2-3	3
Q6QNK2-4	4

RefSeq proteins (2): NP_001317426, NP_942122* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000832	GPCR_2_secretin-like	Family
IPR001759	PTX_dom	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR057244	GAIN_B	Domain

Pfam: PF00002, PF01825, PF13385

UniProt features (223 total): sequence variant 105, mutagenesis site 45, helix 15, glycosylation site 9, topological domain 8, strand 8, transmembrane region 7, splice variant 5, turn 4, chain 3, region of interest 3, disulfide bond 3, domain 2, binding site 2, signal peptide 1, sequence conflict 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8X9T	ELECTRON MICROSCOPY	2.75
7WU2	ELECTRON MICROSCOPY	2.8
8X9U	ELECTRON MICROSCOPY	2.88
9IV1	ELECTRON MICROSCOPY	2.98
7EPT	ELECTRON MICROSCOPY	3
8X9S	ELECTRON MICROSCOPY	3.49
9V0U	ELECTRON MICROSCOPY	3.51
9IV2	ELECTRON MICROSCOPY	3.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6QNK2-F1	72.06	0.19

Antibody-complex structures (SAbDab): 4 — 7EPT, 7WU2, 8X9T, 9IV1

Functional residue map

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

Catalytic / active sites (1): 544–545 (cleavage; by autolysis)

Ligand- & substrate-binding residues (2): 563; 795

Disulfide bonds (3): 510–539, 527–541, 632–704

Glycosylation sites (9): 90, 185, 282, 302, 319, 394, 476, 501, 533

Mutagenesis-validated functional residues (45):

Position	Phenotype
543	increased g protein-coupled receptor signaling.
543	does not affect membrane trafficking and basal activity. abolished autoproteolytic cleavage.
544	increased g protein-coupled receptor signaling.
545	decreased autoproteolytic cleavage and decreased g-protein coupled receptor activity; does not affect subcellular locati
546	strongly decreased g protein-coupled receptor signaling.
547	strongly decreased g protein-coupled receptor signaling.
549	strongly decreased g protein-coupled receptor signaling.
550	abolishes g-protein coupled receptor activity; does not affect subcellular location.
551	abolishes g-protein coupled receptor activity; does not affect subcellular location.
553	strongly decreased g protein-coupled receptor signaling.
554	abolishes g-protein coupled receptor activity; does not affect subcellular location.
563	decreased activation by 5alpha-dihydrotestosterone.
605	strongly decreased g protein-coupled receptor signaling.
619	decreased activation by 5alpha-dihydrotestosterone.
623	decreased activation by 5alpha-dihydrotestosterone.
640	increased affinity to 5alpha-dihydrotestosterone.
643	decreased activation by 5alpha-dihydrotestosterone.
647	strongly decreased g protein-coupled receptor signaling.
650	strongly decreased g protein-coupled receptor signaling.
653	strongly decreased g protein-coupled receptor signaling.
656	strongly decreased g protein-coupled receptor signaling.
657	strongly decreased g protein-coupled receptor signaling.
658	strongly decreased g protein-coupled receptor signaling.
705	strongly decreased g protein-coupled receptor signaling.
713	strongly decreased g protein-coupled receptor signaling.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GGGTGGRR_PAX4_03, GOBP_SKELETAL_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CONTRACTION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_CONTRACTION, WONG_ENDMETRIUM_CANCER_DN, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, GOBP_REGULATION_OF_SYSTEM_PROCESS, AACTTT_UNKNOWN, GOBP_MUSCLE_SYSTEM_PROCESS, GOBP_REGULATION_OF_SKELETAL_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_MUSCLE_SYSTEM_PROCESS, GOBP_NEUROMUSCULAR_PROCESS

GO Biological Process (5): cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), regulation of skeletal muscle contraction (GO:0014819), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), nuclear speck (GO:0016607)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
G protein-coupled receptor activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
skeletal muscle contraction	1
regulation of striated muscle contraction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
signaling receptor activity	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRD1	SBF2	Q86WG5	719
ADGRD1	NPR3	P17342	711
ADGRD1	LIN28B	Q6ZN17	682
ADGRD1	MCM6	Q14566	648
ADGRD1	NPPC	P23582	633
ADGRD1	FLNB	O75369	589
ADGRD1	ADRB1	P08588	550
ADGRD1	ADGRG5	Q8IZF4	488
ADGRD1	GPR157	Q5UAW9	461
ADGRD1	MYH6	P13533	455
ADGRD1	ACE	P12821	428
ADGRD1	MCRIP2	Q9BUT9	401
ADGRD1	ADGRG6	Q86SQ4	400
ADGRD1	AGTR1	P30556	392
ADGRD1	PLXDC2	Q6UX71	386

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PRAF2	ADGRD1	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	ADGRD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): GPR133 (Affinity Capture-RNA), GPR133 (Affinity Capture-MS), PRAF2 (Two-hybrid), GPR133 (Affinity Capture-MS), GPR133 (Cross-Linking-MS (XL-MS)), GPR133 (Proximity Label-MS), GPR133 (Affinity Capture-RNA), GPR133 (Affinity Capture-RNA)

ESM2 similar proteins: A6QLU6, A8WCC4, B8JK39, F1MLX5, J3S6Y1, O94955, P07224, P07225, P13612, P51810, P57097, P59822, P70259, P98118, Q12866, Q13797, Q14246, Q28520, Q2TBA3, Q3TDN0, Q3URE9, Q5M900, Q5R5V8, Q5Y4N8, Q60805, Q61549, Q61730, Q63621, Q6F3F9, Q6NRQ1, Q6QNK2, Q6R6I6, Q6R6I7, Q7L985, Q7TT36, Q7Z443, Q80T32, Q86SQ4, Q8IWK6, Q8NFZ0

Diamond homologs: A6QLU6, C0HL12, D4A3T6, E9Q4J9, G5ECX0, G5EDW2, O14514, O35161, O60242, O88278, O88917, O88923, O94910, O95490, O97817, O97827, O97831, P30083, P48960, Q14246, Q2Q421, Q2Q426, Q3UHD1, Q54MC6, Q58Y75, Q59I63, Q5T601, Q5Y4N8, Q61549, Q6F3F9, Q6QNK2, Q7SY09, Q7Z7M1, Q80T32, Q80TR1, Q80TS3, Q80ZF8, Q86SQ3, Q86SQ4, Q8IZF2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	90
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59847	GRCh38/hg38 12q24.32-24.33(chr12:126403612-133166920)x3	Pathogenic

SpliceAI

6325 predictions. Top by Δscore:

Variant	Effect	Δscore
12:130954659:AGGT:A	donor_loss	1.0000
12:130954660:GGTAA:G	donor_loss	1.0000
12:130954661:G:C	donor_loss	1.0000
12:130954662:T:A	donor_loss	1.0000
12:130966461:A:G	acceptor_gain	1.0000
12:130966544:G:GT	donor_gain	1.0000
12:130971454:TTAG:T	acceptor_loss	1.0000
12:130971456:A:AG	acceptor_gain	1.0000
12:130971457:G:GA	acceptor_gain	1.0000
12:130971457:GA:G	acceptor_gain	1.0000
12:130971457:GAT:G	acceptor_gain	1.0000
12:130971457:GATA:G	acceptor_gain	1.0000
12:130971457:GATAT:G	acceptor_gain	1.0000
12:130971581:G:GC	donor_loss	1.0000
12:130971582:T:A	donor_loss	1.0000
12:130987350:GTCA:G	donor_gain	1.0000
12:130987354:G:GG	donor_gain	1.0000
12:130992235:A:AG	acceptor_gain	1.0000
12:130992235:AGAT:A	acceptor_gain	1.0000
12:130992236:G:GA	acceptor_gain	1.0000
12:130992236:GA:G	acceptor_gain	1.0000
12:130992236:GAT:G	acceptor_gain	1.0000
12:130992236:GATG:G	acceptor_gain	1.0000
12:130992352:G:GG	donor_gain	1.0000
12:131004179:A:AG	acceptor_gain	1.0000
12:131004180:C:G	acceptor_gain	1.0000
12:131004181:C:A	acceptor_gain	1.0000
12:131004184:A:AG	acceptor_gain	1.0000
12:131004185:G:GG	acceptor_gain	1.0000
12:131004185:GA:G	acceptor_gain	1.0000

AlphaMissense

5713 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:131108781:T:A	W649R	0.998
12:131108781:T:C	W649R	0.998
12:131137008:T:A	N810K	0.998
12:131137008:T:G	N810K	0.998
12:131105801:T:C	L608P	0.997
12:131108806:T:C	L657P	0.997
12:131120884:T:C	F716L	0.997
12:131120886:T:A	F716L	0.997
12:131120886:T:G	F716L	0.997
12:131131730:C:A	N727K	0.997
12:131131730:C:G	N727K	0.997
12:131136069:C:G	P767R	0.997
12:131136086:T:A	W773R	0.997
12:131136086:T:C	W773R	0.997
12:131136973:G:A	G799R	0.997
12:131136973:G:C	G799R	0.997
12:131076861:T:C	F512L	0.996
12:131076863:C:A	F512L	0.996
12:131076863:C:G	F512L	0.996
12:131084558:G:C	W522C	0.996
12:131084558:G:T	W522C	0.996
12:131104897:T:C	C580R	0.996
12:131136140:T:C	F791L	0.996
12:131136142:T:A	F791L	0.996
12:131136142:T:G	F791L	0.996
12:131136997:T:C	C807R	0.996
12:131137013:A:T	E812V	0.996
12:131084556:T:A	W522R	0.995
12:131084556:T:C	W522R	0.995
12:131108796:G:A	G654R	0.995

dbSNP variants (sampled 300 via entrez): RS1000013637 (12:131093050 C>A,T), RS1000039402 (12:130990328 A>C), RS1000062474 (12:131057381 C>T), RS1000081860 (12:131051298 C>G), RS1000083750 (12:130996090 G>T), RS1000087202 (12:131110207 A>G), RS1000087392 (12:130980603 G>A), RS1000116704 (12:131110539 A>G), RS1000143124 (12:131017020 C>G), RS1000150566 (12:131114640 G>A), RS1000175245 (12:131002864 A>G), RS1000178746 (12:130995833 A>G), RS1000206453 (12:131002679 G>T), RS1000209969 (12:131073128 C>T), RS1000212034 (12:131035270 G>A)

Disease associations

OMIM: gene MIM:613639 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000189_18	Protein quantitative trait loci	1.000000e-06
GCST000451_4	RR interval (heart rate)	4.000000e-08
GCST000475_1	Height	5.000000e-08
GCST000785_6	Longevity	1.000000e-06
GCST002337_98	Amyotrophic lateral sclerosis (sporadic)	8.000000e-10
GCST006979_1087	Heel bone mineral density	3.000000e-12
GCST009259_7	Amygdala volume	2.000000e-06
GCST90000025_1035	Appendicular lean mass	6.000000e-37
GCST90006988_3	Gut microbiota relative abundance (Bacteroides)	5.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008391	erythropoetin measurement
EFO:0004831	RR interval
EFO:0009270	heel bone mineral density
EFO:0004980	appendicular lean mass
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523877 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adhesion Class GPCRs

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Valproic Acid	affects expression, decreases expression, increases methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
bufotalin	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Copper	affects binding, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	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
CHEMBL4883409	Binding	PRESTO-Tango GPCRome screening (GPR133)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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