ADGRG6

Summary

ADGRG6 (adhesion G protein-coupled receptor G6, HGNC:13841) is a protein-coding gene on chromosome 6q24.2, encoding Adhesion G-protein coupled receptor G6 (Q86SQ4). Adhesion G-protein coupled receptor (aGPCR) for steroid hormones, such as progesterone and 17alpha-hydroxyprogesterone (17OHP).

This gene, which is upregulated in human umbilical vein endothelial cells, encodes a G protein-coupled receptor. Variations in this gene can affect a person’s stature. Multiple transcript variants encoding different proteins have been found for this gene.

Source: NCBI Gene 57211 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lethal congenital contracture syndrome 9 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 104
• Clinical variants (ClinVar): 270 total — 4 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes
• MANE Select transcript: NM_198569

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13841
Approved symbol	ADGRG6
Name	adhesion G protein-coupled receptor G6
Location	6q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14937
Ensembl gene	ENSG00000112414
Ensembl biotype	protein_coding
OMIM	612243
Entrez	57211

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000230173, ENST00000296932, ENST00000367608, ENST00000367609, ENST00000415128, ENST00000435011, ENST00000463637, ENST00000472054, ENST00000497898, ENST00000508295, ENST00000538281, ENST00000540208, ENST00000541199, ENST00000545477, ENST00000968517, ENST00000968518

RefSeq mRNA: 4 — MANE Select: NM_198569 NM_001032394, NM_001032395, NM_020455, NM_198569

CCDS: CCDS47489, CCDS47490, CCDS47491, CCDS55064

Canonical transcript exons

ENST00000367609 — 25 exons

Exon	Start	End
ENSE00000764807	142411305	142411411
ENSE00000764808	142414969	142415096
ENSE00000764811	142415796	142416064
ENSE00000764812	142417273	142417369
ENSE00001294799	142381951	142382019
ENSE00001302165	142390258	142390343
ENSE00001304937	142400485	142400596
ENSE00001306787	142401994	142402058
ENSE00001314331	142402620	142402830
ENSE00001319408	142370170	142370793
ENSE00001325138	142392948	142393000
ENSE00001375310	142383760	142383843
ENSE00001428388	142302007	142302331
ENSE00002265917	142393896	142393958
ENSE00002297106	142403802	142403973
ENSE00002312511	142397613	142397755
ENSE00003463379	142367569	142367910
ENSE00003471491	142438212	142438364
ENSE00003540016	142409874	142409919
ENSE00003556874	142309544	142309644
ENSE00003563872	142437434	142437535
ENSE00003655604	142405688	142405828
ENSE00003687074	142443337	142446261
ENSE00003693888	142419821	142420104
ENSE00003694212	142408150	142408269

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 96.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3651 / max 665.7671, expressed in 1148 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70184	9.5121	1066
70189	1.7478	312
70182	0.3339	201
70178	0.3160	154
70183	0.3115	183
70188	0.2769	142
70181	0.1353	53
204226	0.1203	83
70187	0.1176	76
70177	0.1136	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	96.92	gold quality
amniotic fluid	UBERON:0000173	95.57	gold quality
placenta	UBERON:0001987	94.00	gold quality
liver	UBERON:0002107	92.97	gold quality
palpebral conjunctiva	UBERON:0001812	92.10	gold quality
jejunal mucosa	UBERON:0000399	91.60	gold quality
decidua	UBERON:0002450	90.88	gold quality
parietal pleura	UBERON:0002400	90.76	gold quality
right lobe of liver	UBERON:0001114	90.61	gold quality
colonic epithelium	UBERON:0000397	90.22	gold quality
duodenum	UBERON:0002114	89.62	gold quality
lower lobe of lung	UBERON:0008949	89.35	gold quality
pleura	UBERON:0000977	88.95	gold quality
pylorus	UBERON:0001166	88.76	gold quality
cartilage tissue	UBERON:0002418	87.74	gold quality
visceral pleura	UBERON:0002401	87.66	gold quality
tongue squamous epithelium	UBERON:0006919	87.50	gold quality
buccal mucosa cell	CL:0002336	87.46	gold quality
lung	UBERON:0002048	87.14	gold quality
tibia	UBERON:0000979	87.11	gold quality
right lung	UBERON:0002167	86.98	gold quality
trigeminal ganglion	UBERON:0001675	86.81	gold quality
upper leg skin	UBERON:0004262	86.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.98	gold quality
urethra	UBERON:0000057	84.92	gold quality
tibial nerve	UBERON:0001323	84.82	gold quality
germinal epithelium of ovary	UBERON:0001304	84.41	gold quality
urinary bladder	UBERON:0001255	84.25	gold quality
dorsal root ganglion	UBERON:0000044	84.05	gold quality
secondary oocyte	CL:0000655	83.95	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	456.93
E-GEOD-135922	yes	52.15
E-CURD-119	yes	20.20
E-ANND-3	yes	10.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

141 targeting ADGRG6, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-218-5P	99.93	72.22	2103

Literature-anchored findings (GeneRIF, showing 34)

• VIGR represents a novel G protein coupled receptors of the adhesion family, which is unique in its long extra-cellular domain. (PMID:15225624)
• APG1 formed an alpha-helical structure at the C-terminal site and a positive charge cluster at the N-terminal site. (PMID:17109822)
• The PS1TP2 gene was located at 6q24.1, and interacts with leukocyte proteins. (PMID:18304421)
• Possible new targets for GPCR modulation: allosteric interactions, plasma membrane domains, intercellular transfer and epigenetic mechanisms. (PMID:21929287)
• A single nucleotide polymorphism in the GPR126 gene is associated with increased susceptibility for adolescent idiopathic scoliosis. [Meta-analysis] (PMID:23666238)
• Gpr126 functions in Schwann cells for proper development and myelination through G-protein-signaling pathways. (PMID:24227709)
• GPR126 modulates both physiological and pathological angiogenesis through VEGF signaling (PMID:25217645)
• Genetic variants of GPR126 gene are associated with adolescent idiopathic scoliosis susceptibility in Chinese populations. (PMID:25479386)
• Together, these data uncover Gpr126 as a genetic cause for the pathogenesis of Adolescent idiopathic scoliosis (AIS) and pectus excavatum in a mouse model. (PMID:25954032)
• Mutations of GPR126 are responsible for severe arthrogryposis multiplex congenita. (PMID:26004201)
• The association of a single nucleotide polymorphism in GPR126 with aggressive periodontitis in a Japanese population. The role of GPR126 in maintaining the homeostasis of periodontal ligament tissues. (PMID:27509131)
• SNPs of the GPR126 gene were functionally associated with adolescent idiopathic scoliosis in a Chinese population. (PMID:28198779)
• The genetic variants in EPAS1, GPR126 may contribute to the physiological adaptations to hypobaric hypoxia, possibly by altering lung function. (PMID:29026132)
• GPR126 single nucleotide polymorphisms rs225694, rs7774095 and rs2294773 are significantly associated with adolescent idiopathic scoliosis in Northern Chinese Han patients. (PMID:29363878)
• Gene expression analysis of ADGRG6 in human lung tissue revealed a decreased expression in patients with chronic obstructive pulmonary disease (PMID:30049742)
• The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 x 10(-20); odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and adolescent idiopathic scoliosis susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus. (PMID:30069010)
• In NMIBC, somatic GPR126 noncoding mutations occurred in 47.7% of samples and were negatively associated with GPR126 mRNA levels. GPR126 mutations had higher frequencies in nonsmoker patients and were associated with a prior history of NMIBC. GPR126 overexpression was detected in 70.5% of samples. (PMID:30401719)
• The role of GPR126 in radial sorting and myelination in Schwann cells suggests a mechanism of pathogenesis for intellectual disability (ID). Involvement of GPR126 in lethal congenital contracture syndrome 9 has been identified previously, but this is the first report of a plausible candidate gene, GPR126, in ID. (PMID:30549416)
• Authors find recurrent ADGRG6 enhancer mutations and FRS2 duplications which are associated with higher protein expression in the tumor and poor prognosis. Functional assays demonstrate that depletion of ADGRG6 or FRS2 expression in UBC cells compromise their abilities to recruit endothelial cells and induce tube formation. (PMID:30755618)
• Chondrogenic differentiation experiment showed that GPR126-exon6(in) has a high expression level relative to GPR126-exon6(ex) during chondrogenic differentiation of hMSCs. Our findings indicate that newly discovered SNP is related to cartilage development and may provide valuable insights into the etiology and pathogenesis of adolescent idiopathic scoliosis. (PMID:30886859)
• Asymmetric expression of GPR126 in the convex/concave side of the spine is associated with spinal skeletal malformation in adolescent idiopathic scoliosis population (PMID:31079250)
• data demonstrate that the newly generated lacZ reporter mouse is a suitable model to study Gpr126 expression during development and adulthood, provide detailed insight into Gpr126 expression at the cellular level, and reveal that all identified Gpr126-expressing cells are known to be exposed to mechanical stimuli (PMID:31215653)
• modulation of gpr126 expression in zebrafish by injection of either miR-27b or miR-27b inhibitor in single cell-stage embryos resulted in hypo- or hypertrabeculation, respectively (PMID:31596512)
• Alternative splicing regulates ECR conformation and receptor signaling, while mutagenesis of the calcium-binding site abolishes Gpr126 function in vivo. These results demonstrate that Gpr126 ECR utilizes a multi-faceted dynamic approach to regulate receptor function and provide relevant insights for ECR-targeted drug design. (PMID:31924782)
• Genomic characterization of the adolescent idiopathic scoliosis-associated transcriptome and regulome. (PMID:33179741)
• A synthetic method to assay adhesion-family G-protein coupled receptors. Determination of the G-protein coupling profile of ADGRG6(GPR126). (PMID:33248691)
• GPR126 regulates colorectal cancer cell proliferation by mediating HDAC2 and GLI2 expression. (PMID:33629464)
• Functional genomics of GPR126 in airway smooth muscle and bronchial epithelial cells. (PMID:34165809)
• Progesterone activates GPR126 to promote breast cancer development via the Gi pathway. (PMID:35394864)
• Noncoding SNP at rs1663689 represses ADGRG6 via interchromosomal interaction and reduces lung cancer progression. (PMID:37154297)
• Analysis of GPR126 polymorphisms and their relationship with scoliosis in Marfan syndrome and Marfan-like syndrome in Mexican patients. (PMID:37270806)
• Adhesion GPCR Gpr126 (Adgrg6) Expression Profiling in Zebrafish, Mouse, and Human Kidney. (PMID:37566066)
• The COPD GWAS gene ADGRG6 instructs function and injury response in human iPSC-derived type II alveolar epithelial cells. (PMID:37734371)
• Adhesion G Protein-Coupled Receptor Gpr126 (Adgrg6) Expression Profiling in Diseased Mouse, Rat, and Human Kidneys. (PMID:38786096)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adgrg6	ENSDARG00000054137
mus_musculus	Adgrg6	ENSMUSG00000039116
rattus_norvegicus	Adgrg6	ENSRNOG00000011411

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), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), 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 G6 — Q86SQ4 (reviewed: Q86SQ4)

Alternative names: Developmentally regulated G-protein-coupled receptor, G-protein coupled receptor 126, Vascular inducible G protein-coupled receptor

All UniProt accessions (5): Q86SQ4, F5H054, F5H2L1, H0YFM8, H0YGP2

UniProt curated annotations — full annotation on UniProt →

Function. Adhesion G-protein coupled receptor (aGPCR) for steroid hormones, such as progesterone and 17alpha-hydroxyprogesterone (17OHP). Involved in many biological processes, such as myelination, sprouting angiogenesis, placenta, ear and cartilage development. 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. ADGRG6 is coupled to G(i) G alpha proteins and mediates inhibition of adenylate cyclase. Also able to couple to G(q) G proteins. Involved in myelination of the peripheral nervous system: required for differentiation of promyelinating Schwann cells and for normal myelination of axons. Also acts as a regulator of body length and bone mass. Acts as a regulator of blood-brain barrier formation in the central nervous system vie its association with LRP1 and ITGB1.

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 Laminin-2; this interaction stabilizes the receptor in an inactive state. Laminin-2 polymerization could facilitate ADGRG6-NTF removal, thereby exposing the tethered agonist to drive myelination. Interacts with PRNP. Interacts with ITGB1. Interacts with LRP1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in placenta and to a lower extent in pancreas and liver. Detected in aortic endothelial cells but not in skin microvascular endothelial cells.

Post-translational modifications. Proteolytically cleaved into 2 conserved sites: one in the GPS region of the GAIN-B domain (S1 site) and the other in the middle of the extracellular domain (S2 site). The proteolytic cleavage at S1 site generates an extracellular subunit and a seven-transmembrane subunit. Furin is involved in the cleavage of the S2 site generating a soluble fragment. Processing at the GPS region occurred independent of and probably prior to the cleavage at the S2 site. Proteolytic cleavage is required for activation of the receptor. Highly glycosylated.

Disease relevance. Lethal congenital contracture syndrome 9 (LCCS9) [MIM:616503] A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. The disease is caused by variants affecting the gene represented in this entry.

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.

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.

Induction. Up-regulated by bacterial lipopolysaccharides (LPS) and thrombin, but not by other inflammatory stimuli in primary umbilical veins.

Polymorphism. Genetic variations in ADGRG6 influences stature as a quantitative trait (STQTL) [MIM:606255]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q86SQ4-1	1	yes
Q86SQ4-2	2
Q86SQ4-3	3
Q86SQ4-4	4

RefSeq proteins (4): NP_001027566, NP_001027567, NP_065188, NP_940971* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000832	GPCR_2_secretin-like	Family
IPR000859	CUB_dom	Domain
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
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR057244	GAIN_B	Domain
IPR057333	SEA_Gpr126	Domain
IPR058857	GAIN_ADGRG2/6	Domain

Pfam: PF00002, PF00354, PF00431, PF01825, PF25307, PF26574

UniProt features (107 total): mutagenesis site 25, glycosylation site 25, topological domain 8, disulfide bond 8, transmembrane region 7, binding site 6, sequence variant 6, sequence conflict 5, region of interest 4, chain 3, domain 3, site 2, modified residue 2, splice variant 2, signal peptide 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
21DU	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SQ4-F1	73.96	0.17

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 (2): 467–468 (cleavage; by furin like-convertase); 840–841 (cleavage)

Ligand- & substrate-binding residues (6): 89; 97; 134; 136; 137; 1103

Post-translational modifications (2): 1165, 1168

Disulfide bonds (8): 41–67, 94–111, 186–254, 231–277, 525–560, 548–580, 803–835, 822–837

Glycosylation sites (25): 121, 143, 206, 258, 314, 324, 353, 438, 445, 452, 485, 488, 505, 563, 593, 600, 605, 667, 673, 695 …

Mutagenesis-validated functional residues (25):

Position	Phenotype
1099	decreased activation by 17alpha-hydroxyprogesterone.
1103	strongly decreased g-protein coupled receptor activity in response to 17alpha-hydroxyprogesterone (17ohp).
468	abolished cleavage by furin like-convertase without affecting localization to the cell surface.
469	no effect on cleavage.
803	no cleavage and not detected at the cell surface.
813	no effect on g-protein-mediated camp release.
815	abolishes g-protein-mediated camp release.
818	abolishes g-protein-mediated camp release.
819	abolishes g-protein-mediated camp release.
822	no cleavage and not detected at the cell surface.
835	no cleavage and not detected at the cell surface.
837	no cleavage and not detected at the cell surface.
841	no cleavage but detected at cell surface.
841	no cleavage and not detected at the cell surface.
915	strongly decreased g-protein coupled receptor activity in response to 17alpha-hydroxyprogesterone (17ohp).
916	does not impair g-protein coupled receptor activity in response to 17alpha-hydroxyprogesterone (17ohp).
937	does not impair g-protein coupled receptor activity in response to 17alpha-hydroxyprogesterone (17ohp).
941	strongly decreased g-protein coupled receptor activity in response to 17alpha-hydroxyprogesterone (17ohp).
1001	impaired conformational change in response to 17alpha-hydroxyprogesterone (17ohp) without affecting response to progeste
1012	impaired conformational change in response to 17alpha-hydroxyprogesterone (17ohp) without affecting response to progeste
1014	strongly decreased g-protein coupled receptor activity in response to 17alpha-hydroxyprogesterone (17ohp).
1081	strongly decreased g-protein coupled receptor activity in response to 17alpha-hydroxyprogesterone (17ohp).
1085	impaired response to progesterone, but not to17alpha-hydroxyprogesterone (17ohp).
1091	strongly decreased g-protein coupled receptor activity in response to 17alpha-hydroxyprogesterone (17ohp).
1099	strongly decreased g-protein coupled receptor activity in response to 17alpha-hydroxyprogesterone (17ohp).

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-1266738	Developmental Biology
R-HSA-9675108	Nervous system development

MSigDB gene sets: 332 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, LI_CISPLATIN_RESISTANCE_DN, GOBP_CARTILAGE_DEVELOPMENT, GOBP_HEART_TRABECULA_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, AREB6_03, GOBP_GLIAL_CELL_DEVELOPMENT, GOCC_CELL_SURFACE, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_NEUROGENESIS, GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (16): placenta development (GO:0001890), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), nervous system development (GO:0007399), Schwann cell differentiation (GO:0014037), myelination in peripheral nervous system (GO:0022011), regulation of bone mineralization (GO:0030500), myelination (GO:0042552), cartilage development (GO:0051216), heart trabecula formation (GO:0060347), establishment of blood-brain barrier (GO:0060856), regulation of sprouting angiogenesis (GO:1903670), signal transduction (GO:0007165)

GO Molecular Function (7): endopeptidase activity (GO:0004175), G protein-coupled receptor activity (GO:0004930), collagen binding (GO:0005518), laminin binding (GO:0043236), metal ion binding (GO:0046872), extracellular matrix binding (GO:0050840), transmembrane signaling receptor activity (GO:0004888)

GO Cellular Component (5): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
animal organ development	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
G protein-coupled receptor activity	1
adenylate cyclase activity	1
adenylate cyclase activator activity	1
adenylate cyclase inhibitor activity	1
system development	1
peripheral nervous system development	1
glial cell differentiation	1
Schwann cell development	1
peripheral nervous system axon ensheathment	1
myelination	1
regulation of ossification	1
bone mineralization	1
regulation of biomineral tissue development	1
axon ensheathment	1
skeletal system development	1
connective tissue development	1
cardiac chamber morphogenesis	1
trabecula formation	1
heart trabecula morphogenesis	1
central nervous system development	1
cell development	1
sprouting angiogenesis	1
regulation of angiogenesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
peptidase activity	1
transmembrane signaling receptor activity	1
protein-containing complex binding	1
protein binding	1
extracellular matrix binding	1
cation binding	1
binding	1

Protein interactions and networks

STRING

998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRG6	NAALADL1	Q9UQQ1	768
ADGRG6	SELL	P14151	768
ADGRG6	SBF2	Q86WG5	714
ADGRG6	NPR3	P17342	674
ADGRG6	LIN28B	Q6ZN17	667
ADGRG6	EGR2	P11161	645
ADGRG6	MCM6	Q14566	638
ADGRG6	UCHL1	P09936	626
ADGRG6	NPPC	P23582	588
ADGRG6	FLNB	O75369	583
ADGRG6	KCNN3	Q9UGI6	575
ADGRG6	PRNP	P04156	542
ADGRG6	CCR7	P32248	526
ADGRG6	LBX1	P52954	526
ADGRG6	GSTCD	Q8NEC7	523

IntAct

29 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
M		psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350
PCDHB3	ESYT2	psi-mi:“MI:0914”(association)	0.350
APOM	ESYT2	psi-mi:“MI:0914”(association)	0.350
CHRNA1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HLA-C	TMEM131L	psi-mi:“MI:0914”(association)	0.350
KLRD1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
UPK2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
NAAA	HAX1	psi-mi:“MI:0914”(association)	0.350
CHST8	NDUFS8	psi-mi:“MI:0914”(association)	0.350
PRTN3	MANBA	psi-mi:“MI:0914”(association)	0.350
LPAR1	GOSR2	psi-mi:“MI:0914”(association)	0.350
UGT1A7	ADAM10	psi-mi:“MI:0914”(association)	0.350
FZD7	EI24	psi-mi:“MI:0914”(association)	0.350
CLDND1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
CST8	HS3ST1	psi-mi:“MI:0914”(association)	0.350
GP5	MGST3	psi-mi:“MI:0914”(association)	0.350
TMPRSS5	CLGN	psi-mi:“MI:0914”(association)	0.350
CLRN2	CA12	psi-mi:“MI:0914”(association)	0.350
CD3D	TAP2	psi-mi:“MI:0914”(association)	0.350
NIPAL3	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC30A5	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (52): GPR126 (Affinity Capture-RNA), GPR126 (Affinity Capture-RNA), GPR126 (Affinity Capture-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS), GPR126 (Proximity Label-MS)

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

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	4
Uncertain significance	160
Likely benign	32
Benign	44

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1342704	NM_198569.3(ADGRG6):c.2219T>A (p.Leu740Ter)	Pathogenic
192347	NM_198569.3(ADGRG6):c.19C>T (p.Arg7Ter)	Pathogenic
192348	NM_198569.3(ADGRG6):c.2144dup (p.Gln716fs)	Pathogenic
504275	NM_198569.3(ADGRG6):c.738dup (p.Ala247fs)	Pathogenic
1527298	GRCh37/hg19 6q24.1-24.2(chr6:140486733-143341271)	Likely pathogenic
3064408	NM_198569.3(ADGRG6):c.672_681del (p.Ser225fs)	Likely pathogenic
3233964	NM_198569.3(ADGRG6):c.1424+2T>A	Likely pathogenic
4081094	NM_198569.3(ADGRG6):c.931C>T (p.Arg311Ter)	Likely pathogenic

SpliceAI

4079 predictions. Top by Δscore:

Variant	Effect	Δscore
6:142302332:G:GG	donor_gain	1.0000
6:142309540:GCAG:G	acceptor_loss	1.0000
6:142309541:CA:C	acceptor_loss	1.0000
6:142309542:A:AG	acceptor_gain	1.0000
6:142309542:AG:A	acceptor_gain	1.0000
6:142309542:AGGAT:A	acceptor_gain	1.0000
6:142309543:G:GA	acceptor_gain	1.0000
6:142309543:GG:G	acceptor_gain	1.0000
6:142309543:GGA:G	acceptor_gain	1.0000
6:142309543:GGAT:G	acceptor_gain	1.0000
6:142309543:GGATG:G	acceptor_gain	1.0000
6:142309586:G:GT	donor_gain	1.0000
6:142370168:A:AG	acceptor_gain	1.0000
6:142370169:G:GG	acceptor_gain	1.0000
6:142392942:TTCCA:T	acceptor_loss	1.0000
6:142392943:TCCAG:T	acceptor_loss	1.0000
6:142392944:CCAG:C	acceptor_loss	1.0000
6:142392945:CA:C	acceptor_loss	1.0000
6:142392946:A:AC	acceptor_loss	1.0000
6:142392946:A:AG	acceptor_gain	1.0000
6:142392947:G:GC	acceptor_gain	1.0000
6:142392947:GCTC:G	acceptor_gain	1.0000
6:142392947:GCTCA:G	acceptor_gain	1.0000
6:142392999:AGG:A	donor_loss	1.0000
6:142393001:G:GA	donor_loss	1.0000
6:142393002:T:G	donor_loss	1.0000
6:142393892:TTAGT:T	acceptor_loss	1.0000
6:142393894:A:AG	acceptor_gain	1.0000
6:142393894:AGTT:A	acceptor_loss	1.0000
6:142393895:G:A	acceptor_loss	1.0000

AlphaMissense

8312 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:142367670:T:A	W69R	0.999
6:142367670:T:C	W69R	0.999
6:142367672:G:C	W69C	0.999
6:142367672:G:T	W69C	0.999
6:142367745:T:A	C94S	0.999
6:142367745:T:C	C94R	0.999
6:142367746:G:A	C94Y	0.999
6:142367746:G:C	C94S	0.999
6:142367747:C:G	C94W	0.999
6:142367754:G:C	D97H	0.999
6:142367755:A:C	D97A	0.999
6:142367755:A:T	D97V	0.999
6:142367796:T:A	C111S	0.999
6:142367796:T:C	C111R	0.999
6:142367797:G:A	C111Y	0.999
6:142367797:G:C	C111S	0.999
6:142367797:G:T	C111F	0.999
6:142367798:T:G	C111W	0.999
6:142367857:T:C	F131S	0.999
6:142367862:A:C	S133R	0.999
6:142367864:T:A	S133R	0.999
6:142367864:T:G	S133R	0.999
6:142367890:T:C	F142S	0.999
6:142392949:T:C	L437P	0.999
6:142367664:T:C	C67R	0.998
6:142367713:T:C	F83S	0.998
6:142367731:A:T	E89V	0.998
6:142367732:A:C	E89D	0.998
6:142367732:A:T	E89D	0.998
6:142367746:G:T	C94F	0.998

dbSNP variants (sampled 300 via entrez): RS1000016930 (6:142320682 G>A), RS1000030051 (6:142364597 C>T), RS1000033830 (6:142407814 C>G,T), RS1000047954 (6:142321037 A>G), RS1000060184 (6:142431204 C>T), RS1000085071 (6:142437703 G>C), RS1000089324 (6:142408125 C>G), RS1000100843 (6:142306693 GT>G,GTT), RS1000121237 (6:142388471 G>A,C), RS1000140071 (6:142394079 T>G), RS1000152360 (6:142387249 A>G,T), RS1000168442 (6:142337115 A>T), RS1000184238 (6:142434611 G>A,T), RS1000192827 (6:142391165 G>A), RS1000222668 (6:142301177 C>T)

Disease associations

OMIM: gene MIM:612243 | disease phenotypes: MIM:616503, MIM:617468

GenCC curated gene-disease

Disease	Classification	Inheritance
lethal congenital contracture syndrome 9	Definitive	Autosomal recessive
intellectual disability	Limited	Autosomal recessive

Mondo (4): lethal congenital contracture syndrome 9 (MONDO:0014670), arthrogryposis multiplex congenita (MONDO:0015168), lung adenocarcinoma (MONDO:0005061), intellectual disability (MONDO:0001071)

Orphanet (2): Arthrogryposis multiplex congenita (Orphanet:1037), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000219	Thin upper lip vermilion
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000463	Anteverted nares
HP:0000775	Abnormality of the diaphragm
HP:0001060	Axillary pterygium
HP:0001181	Adducted thumb
HP:0001196	Short umbilical cord
HP:0001239	Wrist flexion contracture
HP:0001371	Flexion contracture
HP:0001511	Intrauterine growth retardation
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001762	Talipes equinovarus
HP:0002089	Pulmonary hypoplasia
HP:0002803	Congenital contracture
HP:0002804	Arthrogryposis multiplex congenita
HP:0003198	Myopathy
HP:0003557	Increased variability in muscle fiber diameter
HP:0003687	Centrally nucleated skeletal muscle fibers
HP:0005280	Depressed nasal bridge
HP:0005659	Thoracic kyphoscoliosis
HP:0006543	Cardiorespiratory arrest
HP:0009473	Joint contracture of the hand
HP:0009487	Ulnar deviation of the hand
HP:0009760	Antecubital pterygium
HP:0010963	Absence of stomach bubble on fetal sonography

GWAS associations

104 associations (top):

Study	Trait	p-value
GCST000175_52	Height	5.000000e-14
GCST000176_6	Height	2.000000e-18
GCST000372_19	Height	4.000000e-11
GCST000542_2	Pulmonary function	1.000000e-09
GCST000644_5	Height	2.000000e-07
GCST000817_104	Height	1.000000e-33
GCST000817_21	Height	1.000000e-07
GCST001621_25	Airflow obstruction	3.000000e-06
GCST001784_29	Pulmonary function (smoking interaction)	3.000000e-12
GCST001859_15	Thiazide-induced adverse metabolic effects in hypertensive patients	1.000000e-07
GCST001956_12	Height	1.000000e-20
GCST002020_1	Scoliosis	4.000000e-12
GCST002020_2	Scoliosis	1.000000e-14
GCST002644_5	Birth length	6.000000e-06
GCST002647_61	Height	3.000000e-55
GCST002702_122	Height	2.000000e-11
GCST002938_22	Copper levels	3.000000e-06
GCST002998_3	Lobe attachment	2.000000e-06
GCST002999_4	Lobe size	3.000000e-13
GCST003001_6	Ear morphology	5.000000e-09
GCST003052_4	Adolescent idiopathic scoliosis	3.000000e-09
GCST004063_109	Waist circumference adjusted for body mass index	5.000000e-07
GCST004063_147	Waist circumference adjusted for body mass index	6.000000e-11
GCST004063_153	Waist circumference adjusted for body mass index	2.000000e-06
GCST004067_140	Hip circumference adjusted for BMI	2.000000e-16
GCST004067_4	Hip circumference adjusted for BMI	3.000000e-16
GCST004067_97	Hip circumference adjusted for BMI	1.000000e-29
GCST004147_11	Chronic obstructive pulmonary disease	2.000000e-19
GCST004183_27	Lung function (FEV1)	2.000000e-10
GCST004185_35	Lung function (FEV1/FVC)	2.000000e-31

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0006784	body height at birth
EFO:0007667	lobe attachment
EFO:0007666	lobe size
EFO:0007664	outer ear morphology trait
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004314	forced expiratory volume
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0004341	body fat distribution
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:1001904	oral mucositis
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523884 (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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	7
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance	2
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
beta-Naphthoflavone	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases expression, decreases response to substance	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
quercitrin	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
1-nitropyrene	increases expression	1
triadimefon	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
rofecoxib	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
incobotulinumtoxinA	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
CHEMBL4883407	Binding	PRESTO-Tango GPCRome screening (GPR126)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
NCT00087412	PHASE2	COMPLETED	S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer
NCT00118144	PHASE2	COMPLETED	Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer
NCT00118183	PHASE2	COMPLETED	Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
NCT00126581	PHASE2	COMPLETED	Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer
NCT00334815	PHASE2	ACTIVE_NOT_RECRUITING	Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT00368992	PHASE2	COMPLETED	S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer
NCT00511485	PHASE2	COMPLETED	Study of Vintafolide (MK-8109, EC145) in Participants With Progressive Adenocarcinoma of the Lung (MK-8109-008, EC-FV-03)
NCT00950365	PHASE2	COMPLETED	Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer
NCT00955305	PHASE2	TERMINATED	Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
NCT01218516	PHASE2	COMPLETED	A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung