LGR6

Summary

LGR6 (leucine rich repeat containing G protein-coupled receptor 6, HGNC:19719) is a protein-coding gene on chromosome 1q32.1, encoding Leucine-rich repeat-containing G-protein coupled receptor 6 (Q9HBX8). Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a marker of multipotent stem cells in the epidermis.

This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane protein superfamily. The encoded protein is a glycoprotein hormone receptor with a large N-terminal extracellular domain that contains leucine-rich repeats important for the formation of a horseshoe-shaped interaction motif for ligand binding. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 59352 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 174 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001017403

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19719
Approved symbol	LGR6
Name	leucine rich repeat containing G protein-coupled receptor 6
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14471
Ensembl gene	ENSG00000133067
Ensembl biotype	protein_coding
OMIM	606653
Entrez	59352

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 30 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000255432, ENST00000308543, ENST00000367278, ENST00000423542, ENST00000439764, ENST00000487787, ENST00000503519, ENST00000506931, ENST00000904632, ENST00000904633, ENST00000904634, ENST00000904635, ENST00000904636, ENST00000904637, ENST00000904638, ENST00000904639, ENST00000904640, ENST00000904641, ENST00000904642, ENST00000904643, ENST00000904644, ENST00000904645, ENST00000904646, ENST00000904647, ENST00000904648, ENST00000904649, ENST00000904650, ENST00000904651, ENST00000904652, ENST00000904653, ENST00000956147, ENST00000956148, ENST00000956149, ENST00000956150

RefSeq mRNA: 3 — MANE Select: NM_001017403 NM_001017403, NM_001017404, NM_021636

CCDS: CCDS1424, CCDS30971, CCDS30972

Canonical transcript exons

ENST00000367278 — 18 exons

Exon	Start	End
ENSE00000962212	202235922	202235993
ENSE00001138667	202276306	202276521
ENSE00001954339	202193799	202194201
ENSE00002376019	202306868	202306939
ENSE00003471012	202303279	202303347
ENSE00003471871	202225423	202225494
ENSE00003476178	202297508	202297576
ENSE00003485774	202304559	202304630
ENSE00003507755	202227936	202228007
ENSE00003545565	202280781	202280852
ENSE00003546588	202307330	202307401
ENSE00003640413	202301164	202301235
ENSE00003643490	202300849	202300920
ENSE00003665010	202309051	202309176
ENSE00003681358	202314802	202314882
ENSE00003694518	202310197	202310357
ENSE00003784292	202305684	202305749
ENSE00003915749	202317952	202319761

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 96.75.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0601 / max 61.5416, expressed in 256 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7788	0.2750	112
7793	0.2540	54
7795	0.1444	50
7790	0.1171	64
7792	0.0920	34
7794	0.0665	26
7791	0.0548	27
7789	0.0449	26
7797	0.0076	3
7796	0.0037	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	96.75	gold quality
descending thoracic aorta	UBERON:0002345	96.59	gold quality
thoracic aorta	UBERON:0001515	94.72	gold quality
ascending aorta	UBERON:0001496	94.50	gold quality
left coronary artery	UBERON:0001626	92.09	gold quality
coronary artery	UBERON:0001621	91.63	gold quality
granulocyte	CL:0000094	88.76	gold quality
aorta	UBERON:0000947	88.72	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.59	silver quality
mucosa of stomach	UBERON:0001199	84.89	gold quality
popliteal artery	UBERON:0002250	84.37	gold quality
tibial artery	UBERON:0007610	84.29	gold quality
adenohypophysis	UBERON:0002196	84.27	gold quality
right uterine tube	UBERON:0001302	84.22	gold quality
right atrium auricular region	UBERON:0006631	83.24	gold quality
cardiac atrium	UBERON:0002081	82.94	gold quality
left ventricle myocardium	UBERON:0006566	81.15	gold quality
pituitary gland	UBERON:0000007	81.02	gold quality
gall bladder	UBERON:0002110	80.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.58	gold quality
mammary duct	UBERON:0001765	79.02	gold quality
epithelium of mammary gland	UBERON:0003244	78.98	gold quality
tibia	UBERON:0000979	78.35	gold quality
medial globus pallidus	UBERON:0002477	78.02	gold quality
sperm	CL:0000019	77.80	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.31	gold quality
gingival epithelium	UBERON:0001949	77.22	silver quality
pancreatic ductal cell	CL:0002079	76.17	silver quality
gingiva	UBERON:0001828	75.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting LGR6, 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-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
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-7152-3P	99.97	67.47	849
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-6792-5P	98.39	68.16	1330

Literature-anchored findings (GeneRIF, showing 17)

• Overexpression of wild-type LGR6 in HeLa cells leads to increased cell migration. (PMID:22615920)
• Lgr6 marks mammary gland progenitor cells that can initiate tumours, and cells of luminal breast tumours required for efficient tumour maintenance. (PMID:27798604)
• LGR6 expression is significantly downregulated in human masticatory mucosa during wound healing (PMID:28005267)
• Two of the three monoclonal antibodies recognized the large N-terminal extracellular domain of leucine rich repeat containing G protein-coupled receptor 6 (LGR6), and competitively blocked the binding of R-spondin 1, which is known to be the ligand for LGR6. (PMID:28013222)
• Inhibition of LGR6 promoted the osteogenic differentiation of bone marrow stromal cells in vitro. (PMID:29625528)
• Lgr6 has a tumorpromoting role in the development of colorectal cancer. (PMID:29693156)
• The expression levels of LGR6 in colon adenoma and adenocarcinoma were significantly higher than those in normal colon epithelial tissues. Low LGR6 expression predicted a short overall survival in patients with colon adenocarcinoma. (PMID:29971639)
• LGR6 has a role in stimulating maresin 1’s key proresolving functions of phagocytes (PMID:31657786)
• LGR6 is a potential diagnostic and prognostic marker for esophageal squamous cell carcinoma. (PMID:31917882)
• Epithelial stem cell marker LGR6 expression identifies a low-risk subgroup in human papillomavirus positive oropharyngeal squamous cell carcinoma. (PMID:32244172)
• WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer. (PMID:33109540)
• LGR6 activates the Wnt/beta-catenin signaling pathway and forms a beta-catenin/TCF7L2/LGR6 feedback loop in LGR6(high) cervical cancer stem cells. (PMID:34489551)
• [Expression and Significance of Leucine-rich Repeat-containing G-protein Coupled Receptor 5/6 in Wnt Pathway in Children with Acute Lymphoblastic Leukemia]. (PMID:34494532)
• Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases. (PMID:34943945)
• WNT enhancing signals in pancreatic cancer are transmitted by LGR6. (PMID:37770230)
• DNA methylation and expression of LGR6 gene in ankylosing spondylitis: A case-control study. (PMID:37802707)
• The oncogenic role of LGR6 overexpression induced by aberrant Wnt/beta-catenin signaling in lung cancer. (PMID:38014454)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lgr6	ENSMUSG00000042793
rattus_norvegicus	Lgr6	ENSRNOG00000005093
drosophila_melanogaster	Con	FBGN0005775
drosophila_melanogaster	kek3	FBGN0028370
caenorhabditis_elegans	lron-9	WBGENE00011971
caenorhabditis_elegans		WBGENE00020649

Paralogs (22): CHADL (ENSG00000100399), LGI1 (ENSG00000108231), CHAD (ENSG00000136457), LRIG3 (ENSG00000139263), LGR5 (ENSG00000139292), LRIG1 (ENSG00000144749), LRRTM2 (ENSG00000146006), LRIT1 (ENSG00000148602), LGI2 (ENSG00000153012), LGI4 (ENSG00000153902), LRRC52 (ENSG00000162763), ELFN2 (ENSG00000166897), LGI3 (ENSG00000168481), LRG1 (ENSG00000171236), CPN2 (ENSG00000178772), LRIT3 (ENSG00000183423), LRRC26 (ENSG00000184709), LRIG2 (ENSG00000198799), LGR4 (ENSG00000205213), ELFN1 (ENSG00000225968), LRRC24 (ENSG00000254402), TRIL (ENSG00000255690)

Protein

Protein identifiers

Leucine-rich repeat-containing G-protein coupled receptor 6 — Q9HBX8 (reviewed: Q9HBX8)

All UniProt accessions (3): D6R9F0, Q9HBX8, Q5T508

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a marker of multipotent stem cells in the epidermis. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. May act as a tumor suppressor.

Subcellular location. Cell membrane.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HBX8-3	3	yes
Q9HBX8-1	1
Q9HBX8-2	2

RefSeq proteins (3): NP_001017403, NP_001017404, NP_067649 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000372	LRRNT	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR002131	Gphrmn_rcpt_fam	Family
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF13855

UniProt features (47 total): repeat 15, topological domain 8, transmembrane region 7, sequence variant 5, splice variant 3, sequence conflict 3, glycosylation site 2, signal peptide 1, chain 1, domain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HBX8-F1	77.94	0.54

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): 642–717

Glycosylation sites (2): 77, 208

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-4641263	Regulation of FZD by ubiquitination
R-HSA-162582	Signal Transduction
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT

MSigDB gene sets: 107 (showing top): BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_GROWTH, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_TAXIS, MODULE_205, GOCC_TRANS_GOLGI_NETWORK, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, NF1_Q6_01, MARTIN_VIRAL_GPCR_SIGNALING_DN, GOBP_TISSUE_REGENERATION, LEE_METASTASIS_AND_ALTERNATIVE_SPLICING_DN, RICKMAN_HEAD_AND_NECK_CANCER_A, GOMF_GLYCOSAMINOGLYCAN_BINDING

GO Biological Process (11): G protein-coupled receptor signaling pathway (GO:0007186), axon guidance (GO:0007411), cell population proliferation (GO:0008283), Wnt signaling pathway (GO:0016055), positive regulation of Wnt signaling pathway (GO:0030177), positive regulation of cell migration (GO:0030335), negative chemotaxis (GO:0050919), positive regulation of canonical Wnt signaling pathway (GO:0090263), bone regeneration (GO:1990523), signal transduction (GO:0007165), tissue regeneration (GO:0042246)

GO Molecular Function (6): transmembrane signaling receptor activity (GO:0004888), heparin binding (GO:0008201), protein-hormone receptor activity (GO:0016500), Roundabout binding (GO:0048495), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), vesicle (GO:0031982), trans-Golgi network membrane (GO:0032588), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	1
Signal Transduction	1
Signaling by WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
signaling receptor activity	2
G protein-coupled receptor activity	1
signal transduction	1
axonogenesis	1
neuron projection guidance	1
cell surface receptor signaling pathway	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
chemotaxis	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
tissue regeneration	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regeneration	1
developmental growth	1
glycosaminoglycan binding	1
sulfur compound binding	1
signaling receptor binding	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
membrane	1
cell periphery	1
membrane-bounded organelle	1
trans-Golgi network	1
organelle membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LGR6	RSPO1	Q2MKA7	987
LGR6	RSPO4	Q2I0M5	829
LGR6	ZNRF3	Q9ULT6	764
LGR6	RLN1	P04808	727
LGR6	RLN2	P04090	718
LGR6	LRP6	O75581	644
LGR6	RSPO2	Q6UXX9	637
LGR6	GPR18	Q14330	628
LGR6	KRT15	P19012	615
LGR6	AXIN2	Q9Y2T1	610
LGR6	RSPO3	Q9BXY4	599
LGR6	RNF43	Q68DV7	580
LGR6	PLET1	Q6UQ28	572
LGR6	CTNNB1	P35222	554
LGR6	GPR32	O75388	548

IntAct

4 interactions, top by confidence:

A	B	Type	Score
LGR6	RSPO1	psi-mi:“MI:0915”(physical association)	0.400
LGR6	Rspo2	psi-mi:“MI:0915”(physical association)	0.400
LGR6	Rspo3	psi-mi:“MI:0915”(physical association)	0.400
LGR6	RSPO4	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): LGR6 (Negative Genetic), LGR6 (Affinity Capture-MS), LGR6 (Affinity Capture-MS), LGR6 (Co-localization), LGR6 (Two-hybrid)

ESM2 similar proteins: A1A4H9, A2ARI4, A4IIW9, B0BLW3, B1H234, D3ZAL8, D3ZTV3, D4A6D8, D4A7P2, D4AC13, E5DHB5, E7FE13, F1MLX5, F1MT22, F1NUK7, F7D3V9, O43155, O43300, O75473, P0DM44, P21463, P47750, P56495, Q27987, Q3UVD5, Q5R6B1, Q5R6T0, Q5RDJ4, Q66HV9, Q6RKD8, Q80ZD7, Q80ZD8, Q86UE6, Q86VH5, Q86WK6, Q8BGA3, Q8BGT1, Q8BLU0, Q8BZ81, Q8K377

Diamond homologs: A2ARI4, A8WHP9, B0BLW3, D4AC13, E5DHB5, E7FE13, F1MLX5, F1MT22, F7D3V9, O02833, O75473, P0DM44, P70193, Q3UVD5, Q5NVQ6, Q8BGX3, Q8N967, Q96JA1, Q9BXB1, Q9HBX8, Q9Z1P4, Q9Z2H4, P14763, P16473, P56495, Q27987, Q8SPP9, Q9BGN4, A6NJW4, O35103, O42235, O43822, O75093, O77742, O88280, O94769, O94898, P23820, P24014, P35409

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	140
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
929630	NM_014176.3(UBE2T):c.-65+1253_*12383del	Pathogenic

SpliceAI

3125 predictions. Top by Δscore:

Variant	Effect	Δscore
1:202194201:TG:T	donor_loss	1.0000
1:202194202:G:GG	donor_gain	1.0000
1:202225418:ACCAG:A	acceptor_gain	1.0000
1:202225421:A:AG	acceptor_gain	1.0000
1:202225421:A:C	acceptor_loss	1.0000
1:202225421:AG:A	acceptor_gain	1.0000
1:202225422:G:GG	acceptor_gain	1.0000
1:202225422:GG:G	acceptor_gain	1.0000
1:202225490:GAGCT:G	donor_gain	1.0000
1:202225491:AGCT:A	donor_gain	1.0000
1:202225492:GCT:G	donor_gain	1.0000
1:202225492:GCTG:G	donor_gain	1.0000
1:202225494:TGT:T	donor_loss	1.0000
1:202225495:G:GG	donor_gain	1.0000
1:202225495:G:T	donor_loss	1.0000
1:202225496:T:A	donor_loss	1.0000
1:202228008:G:GG	donor_gain	1.0000
1:202235994:G:GG	donor_gain	1.0000
1:202276304:A:AG	acceptor_gain	1.0000
1:202276305:G:GG	acceptor_gain	1.0000
1:202276305:GGC:G	acceptor_gain	1.0000
1:202276517:GTGCT:G	donor_gain	1.0000
1:202276519:GCT:G	donor_gain	1.0000
1:202276520:CTGTG:C	donor_loss	1.0000
1:202276522:G:A	donor_loss	1.0000
1:202276522:G:GG	donor_gain	1.0000
1:202297572:G:GT	donor_gain	1.0000
1:202297572:GAACT:G	donor_gain	1.0000
1:202297573:A:T	donor_gain	1.0000
1:202297577:G:GG	donor_gain	1.0000

AlphaMissense

6207 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:202276377:T:C	L167P	0.997
1:202227951:C:A	N100K	0.996
1:202227951:C:G	N100K	0.996
1:202276383:T:C	L169P	0.996
1:202225437:A:T	N76I	0.995
1:202225438:C:A	N76K	0.995
1:202225438:C:G	N76K	0.995
1:202276521:T:C	L215P	0.995
1:202225494:T:C	L95P	0.994
1:202228007:T:C	L119P	0.994
1:202235927:T:C	L121P	0.994
1:202235993:T:C	L143P	0.994
1:202276321:C:A	N148K	0.994
1:202276321:C:G	N148K	0.994
1:202276393:T:A	N172K	0.994
1:202276393:T:G	N172K	0.994
1:202297513:T:C	L241P	0.994
1:202309056:T:C	L429P	0.994
1:202225428:T:C	L73P	0.993
1:202227941:T:C	L97P	0.993
1:202235937:T:A	N124K	0.993
1:202235937:T:G	N124K	0.993
1:202276311:T:C	L145P	0.993
1:202276465:C:A	N196K	0.993
1:202276465:C:G	N196K	0.993
1:202280796:C:A	N220K	0.993
1:202280796:C:G	N220K	0.993
1:202280852:T:C	L239P	0.993
1:202318211:G:C	W636C	0.993
1:202318211:G:T	W636C	0.993

dbSNP variants (sampled 300 via entrez): RS1000003836 (1:202289578 T>A), RS1000032040 (1:202250270 C>A), RS1000074149 (1:202198572 C>T), RS1000076339 (1:202201776 G>T), RS1000089101 (1:202243542 A>G), RS1000104629 (1:202220601 A>G), RS1000128143 (1:202201974 G>A), RS1000132622 (1:202224397 G>A), RS1000173615 (1:202225413 T>C), RS1000189302 (1:202306071 C>T), RS1000248531 (1:202244028 C>T), RS1000250798 (1:202265800 C>A,T), RS1000295955 (1:202296203 T>C), RS1000367686 (1:202205684 C>A,T), RS1000405922 (1:202232433 G>A,C)

Disease associations

OMIM: gene MIM:606653 | disease phenotypes: MIM:616435

GenCC curated gene-disease

Mondo (1): Fanconi anemia complementation group T (MONDO:0014638)

Orphanet (1): Fanconi anemia (Orphanet:84)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001930_15	Breast cancer	1.000000e-08
GCST002681_4	Post-traumatic stress disorder	1.000000e-06
GCST003842_1	Breast cancer (estrogen-receptor negative)	9.000000e-10
GCST003845_2	Breast cancer	2.000000e-08
GCST005076_4	Breast cancer (estrogen-receptor negative)	3.000000e-12
GCST007234_2	Acne (severe)	9.000000e-09
GCST007540_1	PEG-asparaginase hypersensitivity without enzyme activity in childhood acute lymphoblastic leukaemia	7.000000e-06
GCST011710_1	Restless legs syndrome in migraine	3.000000e-07
GCST90002402_257	Platelet count	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004881	asparaginase hypersensitivity
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066413 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — LGR4, LGR5, LGR6

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
R-spondin-2	Full agonist	9.3	pIC50
R-spondin-3	Full agonist	8.77	pIC50
R-spondin-1	Full agonist	8.48	pIC50
R-spondin-4	Full agonist	8.15	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
Aflatoxin B1	affects methylation, increases methylation	2
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	decreases expression	1
MRK 003	increases expression	1
2,6-dichloro-(1,4)benzoquinone	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
S-Nitrosoglutathione	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5522537	Binding	Agonist activity at human LGR6 measured upto 100 uM by Discovery X assay	Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. — J Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7Y0	Abcam Raji LGR6 KO	Cancer cell line	Male
CVCL_B9YQ	Abcam THP-1 LGR6 KO	Cancer cell line	Male
CVCL_C7AH	Abcam PC-3 LGR6 KO	Cancer cell line	Male
CVCL_E0GH	Ubigene HeLa LGR6 KO	Cancer cell line	Female
CVCL_KX89	PathHunter CHO-K1 LGR6 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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