GNAI2

Summary

GNAI2 (G protein subunit alpha i2, HGNC:4385) is a protein-coding gene on chromosome 3p21.31, encoding Guanine nucleotide-binding protein G(i) subunit alpha-2 (P04899). Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.

The protein encoded by this gene is an alpha subunit of guanine nucleotide binding proteins (G proteins). The encoded protein contains the guanine nucleotide binding site and is involved in the hormonal regulation of adenylate cyclase. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2771 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ventricular tachycardia, familial (Moderate, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 51 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_002070

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4385
Approved symbol	GNAI2
Name	G protein subunit alpha i2
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	GIP
Ensembl gene	ENSG00000114353
Ensembl biotype	protein_coding
OMIM	139360
Entrez	2771

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000266027, ENST00000313601, ENST00000422163, ENST00000440628, ENST00000441156, ENST00000446079, ENST00000451956, ENST00000468422, ENST00000480090, ENST00000490122, ENST00000491100, ENST00000492383, ENST00000869096, ENST00000918110, ENST00000918111

RefSeq mRNA: 6 — MANE Select: NM_002070 NM_001166425, NM_001282617, NM_001282618, NM_001282619, NM_001282620, NM_002070

CCDS: CCDS2813, CCDS54587, CCDS63642, CCDS63644

Canonical transcript exons

ENST00000313601 — 9 exons

Exon	Start	End
ENSE00001858906	50258368	50259362
ENSE00003508048	50256723	50256852
ENSE00003516686	50253024	50253184
ENSE00003524043	50257500	50257714
ENSE00003533037	50256937	50257090
ENSE00003571970	50256192	50256320
ENSE00003583830	50236204	50236453
ENSE00003638869	50252397	50252538
ENSE00003691130	50252100	50252142

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 373.6504 / max 15142.5565, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36702	369.1011	1828
36705	1.6186	1028
36700	1.3217	831
36706	0.7844	475
202758	0.3674	144
36701	0.3187	140
36703	0.1384	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.51	gold quality
monocyte	CL:0000576	99.47	gold quality
right lung	UBERON:0002167	99.35	gold quality
leukocyte	CL:0000738	99.34	gold quality
mononuclear cell	CL:0000842	99.32	gold quality
stromal cell of endometrium	CL:0002255	99.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.15	gold quality
right coronary artery	UBERON:0001625	99.14	gold quality
upper lobe of left lung	UBERON:0008952	99.13	gold quality
ascending aorta	UBERON:0001496	99.07	gold quality
thoracic aorta	UBERON:0001515	99.07	gold quality
descending thoracic aorta	UBERON:0002345	99.07	gold quality
left uterine tube	UBERON:0001303	99.03	gold quality
endocervix	UBERON:0000458	99.02	gold quality
aorta	UBERON:0000947	99.00	gold quality
popliteal artery	UBERON:0002250	98.98	gold quality
tibial artery	UBERON:0007610	98.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.95	gold quality
nerve	UBERON:0001021	98.94	gold quality
tibial nerve	UBERON:0001323	98.94	gold quality
body of uterus	UBERON:0009853	98.94	gold quality
lower esophagus	UBERON:0013473	98.94	gold quality
left coronary artery	UBERON:0001626	98.93	gold quality
omental fat pad	UBERON:0010414	98.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.93	gold quality
coronary artery	UBERON:0001621	98.91	gold quality
gall bladder	UBERON:0002110	98.91	gold quality
peritoneum	UBERON:0002358	98.90	gold quality
spinal cord	UBERON:0002240	98.88	gold quality
lymph node	UBERON:0000029	98.87	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	78.16
E-GEOD-135922	yes	38.94
E-MTAB-8410	yes	27.63
E-CURD-112	yes	20.69
E-CURD-88	yes	19.75
E-MTAB-8271	yes	18.22
E-HCAD-1	yes	17.47
E-MTAB-8498	yes	10.00
E-HCAD-13	yes	8.21
E-MTAB-10485	no	668.94
E-MTAB-7051	no	152.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPG, FOXC1, MTA1, NFE2L2, SP1, SPI1, SREBF1

miRNA regulators (miRDB)

86 targeting GNAI2, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-12136	99.98	72.81	5713
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-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-548AU-3P	99.70	68.22	1373

Literature-anchored findings (GeneRIF, showing 40)

• CXCL12 upregulated T-cell activation, and an alpha(i) G-coupled protein mediated signaling pathway was necessary for stimulation of T cells by CXCL12. (PMID:12088413)
• Modulation of G(ialpha(2)) signaling by the axonal guidance molecule UNC5H2 (PMID:12359238)
• valproic acid-induced expression of Galphai2 is regulated by Sp1 transcription factor (PMID:12624107)
• Cholesterol lowering by pravastatin might increase the response of the heart to parasympathetic stimulation and changes in Galpha(i2) expression might serve as a molecular marker for this effect (PMID:14623802)
• Galphai2 has a role in calcium-sensing receptor-mediated ERK1/2 activation (PMID:14701866)
• Abnormal regulation of GNAI2 was studied in cultured skin fibroblasts from insulin-resistant hypertensive individuals. (PMID:15126921)
• in elderly subjects of similar ages, those with diabetes have 1.7-fold higher levels of Galpha(i2) and twofold higher levels of Gbeta(1). (PMID:15331550)
• the Galphai2 gene promoter is transcriptionally activated through nuclear factor-kappaB and antioxidant response elements (PMID:15640523)
• a GNAI2 -318 C>G SNP impairs transcriptional activity through specific binding of Sp1 and is associated with high SBP in Caucasians from Italy (PMID:16565233)
• These results suggest that Galphai2 is involved specifically in the activation of TRPC4. (PMID:18854172)
• These results show that G(i2) protein is involved in D(2)R-mediated ERK activation but beta-arrestins 1 and 2 are either not involved or play minor role. (PMID:18940181)
• This suggests a novel set of candidate genes for NS (GNAI2 and RGS proteins) and if validated could have important implications for therapy as well. (PMID:19282110)
• Data support the notion that oligomerization of the mu-opioid receptor is not required for agonist and antagonist binding in regard to allosteric regulation of agonist binding by Gi2. (PMID:19542234)
• Study identified a number of high-confident miR-138 target genes, including proto-oncogene GNAI2, which may play an important role in tongue squamous cell carcinoma. initiation and progression. (PMID:21079996)
• SDF-1 treatment of T cells induced the formation of a novel molecular signaling complex containing RasGRP1, Galphai2, and ZAP-70. (PMID:21856938)
• Suggest that Gnia2 is involved in endothelial TLR pathways along a signaling cascade that is distinct from MyD88. (PMID:21949112)
• Galphai2 as a novel claudin-5 partner required for TJ integrity in brain endothelial cells. (PMID:22333621)
• Gialpha2 plays an essential role in OXT and EGF signaling to induce prostate cancer cell migration. (PMID:22936789)
• HIV-1 Nef impairs heterotrimeric G-protein signaling by targeting Galpha(i2) for degradation through ubiquitination (PMID:23071112)
• These results suggest that the extent of G-protein-mediated inhibition is significantly reduced in the K1336E mutant CaV2.1 Ca(2+) channels (PMID:23430985)
• There is an interaction between the activated Gsalpha subunit and membrane lipid microdomains in the pathophysiology of some major depressive disorders. (PMID:23490066)
• The ubiquitination of Galphai2 and Galphaq is suppressed by expression of Ric-8A. The suppression likely requires Ric-8A interaction with these Galpha proteins; the C-terminal truncation of Galphaq and Galphai2 completely abrogates their interaction with Ric-8A. (PMID:23665327)
• Changes in ion selectivity and pore dilation of the TRPC4 channel elicited by the Galphai2 subunit, were studied. (PMID:24011658)
• Galphai2(Q205L) regulates satellite cell differentiation into myotubes in a protein kinase C - and histone deacetylase -dependent manner (PMID:24298018)
• Data strongly implicate GNAI2 as a critical regulator of oncogenesis and an upstream driver of cancer progression in ovarian carcinoma. (PMID:24423449)
• We observed increased expression of Galphai1/3 in wounded human skin and keloid skin tissues, suggesting the possible involvement of Galphai1/3 in wound healing and keloid formation. (PMID:25078664)
• Galpha(i2) activates the TRPC4 channel by direct binding. (PMID:25788576)
• Kinocilium is essential for proper localization of Lgn, as well as Gai and aPKC, suggesting that cilium function plays a role in positioning of apical proteins critical for hearing. (PMID:26662512)
• MicroRNA-222-3p/GNAI2/AKT signaling axis inhibits epithelial ovarian cancer cell growth and is associated with good overall survival. (PMID:27811362)
• These data indicate that, unlike in taste cells, TAS2Rs couple to the prevalent G proteins, Galphai1, Galphai2, and Galphai3, with no evidence for functional coupling to Galphagust. (PMID:28145731)
• The data show that the nonpalmitoylated CB1 receptor significantly reduced its association with Galphai2 . (PMID:28722168)
• genotyping at GNAI2 may be a useful biomarker in identifying individuals at risk for developing salt-sensitive blood pressure. (PMID:29906209)
• 3.6 A structure of the human A1R in complex with adenosine and heterotrimeric Gi2 protein determined by Volta phase plate cryo-electron microscopy (PMID:29925945)
• We conclude that Gia2 protein acts at two different levels which are both dependent and independent of GPCR signaling to induce cell migration and invasion in prostate cancer cells and its action is downstream of PI3-kinase-AKT-Rac1 axis. (PMID:30078221)
• CXCL2-CXCR2 axis mediates through Galphai-2 and Galphaq/11 to promote tumorigenesis and contributes to cancer stem cell properties of CPT-11-resistant LoVo cells. (PMID:30552676)
• Preferential Coupling of Dopamine D2S and D2L Receptor Isoforms with Gi1 and Gi2 Proteins-In Silico Study. (PMID:31936673)
• The Galphai protein subclass selectivity to the dopamine D2 receptor is also decided by their location at the cell membrane. (PMID:33308256)
• Increased functional coupling of the mu opioid receptor in the anterior insula of depressed individuals. (PMID:33531622)
• S-nitrosylation-mediated coupling of G-protein alpha-2 with CXCR5 induces Hippo/YAP-dependent diabetes-accelerated atherosclerosis. (PMID:34294713)
• Guanine Nucleotide-Binding Protein G(i) Subunit Alpha 2 Exacerbates NASH Progression by Regulating Peroxiredoxin 1-Related Inflammation and Lipophagy. (PMID:34322898)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnai2b	ENSDARG00000017294
danio_rerio	gnai2a	ENSDARG00000018174
mus_musculus	Gnai2	ENSMUSG00000032562
rattus_norvegicus	Gnai2	ENSRNOG00000016592
drosophila_melanogaster	Galphaf	FBGN0010223
caenorhabditis_elegans		WBGENE00001664
caenorhabditis_elegans		WBGENE00001665
caenorhabditis_elegans		WBGENE00001667
caenorhabditis_elegans		WBGENE00001668
caenorhabditis_elegans		WBGENE00001670
caenorhabditis_elegans		WBGENE00001671
caenorhabditis_elegans		WBGENE00001673
caenorhabditis_elegans		WBGENE00001675
caenorhabditis_elegans	gpa-14	WBGENE00001676
caenorhabditis_elegans	gsa-1	WBGENE00001745

Paralogs (15): GNA15 (ENSG00000060558), GNAI3 (ENSG00000065135), GNAO1 (ENSG00000087258), GNAS (ENSG00000087460), GNA11 (ENSG00000088256), GNAT1 (ENSG00000114349), GNA13 (ENSG00000120063), GNAI1 (ENSG00000127955), GNAZ (ENSG00000128266), GNAT2 (ENSG00000134183), GNAL (ENSG00000141404), GNA12 (ENSG00000146535), GNA14 (ENSG00000156049), GNAQ (ENSG00000156052), GNAT3 (ENSG00000214415)

Protein

Protein identifiers

Guanine nucleotide-binding protein G(i) subunit alpha-2 — P04899 (reviewed: P04899)

Alternative names: Adenylate cyclase-inhibiting G alpha protein

All UniProt accessions (3): P04899, F8WBG4, F8WE78

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. Examples of interacting GPCRs include the adenosine A1 receptor/ADORA1, CNR1, and FPR2. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase: inhibits adenylate cyclase activity of ADCY1, ADCY5 and ADCY6, leading to decreased intracellular cAMP levels. Plays an important role in the activation of the transcription factor NFAT in endothelial cells to promote angiogenesis. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. Plays an essential role for neutrophil recruitment in the context of acute inflammation suggesting a linked function of both GNAI2 in neutrophils and endothelial cells for polymorphonuclear neutrophils transmigration. Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool.

Subunit / interactions. G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. In this context, forms a complex with the beta subunit GNB1 and the gamma subunit GNG2. Interacts with GPSM1. Interacts with RGS12 and RGS14. Interacts with UNC5B; this interaction inhibits GNAI2 inhibition of adenylyl cyclase. Interacts (inactive GDP-bound form) with NUCB1 (via GBA motif); the interaction leads to activation of GNAI3. Interacts (inactive GDP-bound form) with CCDC88C/DAPLE (via GBA motif). Interacts (inactive GDP-bound form) with CCDC8A/GIV (via GBA motif). Interacts with CXCR1 and CXCR2. Interacts with ADORA1. Interacts with CNR1. Interacts with FPR2.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cell membrane. Membrane.

Tissue specificity. Highly expressed in endothelial cells.

Post-translational modifications. (Microbial infection) Deamidated at Gln-205 by Photorhabdus asymbiotica toxin PAU_02230, blocking GTP hydrolysis of heterotrimeric GNAQ or GNA11 and G-alphai (GNAI1, GNAI2 or GNAI3) proteins, thereby activating RhoA.

Similarity. Belongs to the G-alpha family. G(i/o/t/z) subfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
P04899-1	1	yes
P04899-2	2
P04899-3	3
P04899-4	sGi2, sGalphai2
P04899-5	5
P04899-6	6

RefSeq proteins (6): NP_001159897, NP_001269546, NP_001269547, NP_001269548, NP_001269549, NP_002061* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001019	Gprotein_alpha_su	Family
IPR001408	Gprotein_alpha_I	Family
IPR011025	GproteinA_insert	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00503

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (53 total): strand 10, helix 9, turn 8, binding site 7, splice variant 5, region of interest 5, modified residue 3, lipid moiety-binding region 2, initiator methionine 1, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8ZBW	ELECTRON MICROSCOPY	2.58
8THK	ELECTRON MICROSCOPY	2.6
7YK7	ELECTRON MICROSCOPY	2.75
9K6L	ELECTRON MICROSCOPY	2.77
7WVX	ELECTRON MICROSCOPY	2.8
8W8A	ELECTRON MICROSCOPY	2.8
8ZSJ	ELECTRON MICROSCOPY	2.8
7WVV	ELECTRON MICROSCOPY	2.9
9DQJ	ELECTRON MICROSCOPY	2.9
9KFI	ELECTRON MICROSCOPY	2.91
9KFK	ELECTRON MICROSCOPY	2.95
8ZSV	ELECTRON MICROSCOPY	2.96
7WVY	ELECTRON MICROSCOPY	3
7XXI	ELECTRON MICROSCOPY	3
8W89	ELECTRON MICROSCOPY	3
7YK6	ELECTRON MICROSCOPY	3.03
8KGG	ELECTRON MICROSCOPY	3.06
8ZSS	ELECTRON MICROSCOPY	3.07
7WVW	ELECTRON MICROSCOPY	3.1
8THL	ELECTRON MICROSCOPY	3.1
8WPU	ELECTRON MICROSCOPY	3.1
9KFJ	ELECTRON MICROSCOPY	3.1
8ZSP	ELECTRON MICROSCOPY	3.14
7YJ4	ELECTRON MICROSCOPY	3.19
8ZH8	ELECTRON MICROSCOPY	3.19
7LD3	ELECTRON MICROSCOPY	3.2
8K6N	ELECTRON MICROSCOPY	3.2
7F8V	ELECTRON MICROSCOPY	3.3
7LD4	ELECTRON MICROSCOPY	3.3
8K6M	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04899-F1	94.25	0.89

Antibody-complex structures (SAbDab): 22 — 7WV9, 7YJ4, 7YK6, 7YK7, 8K6M, 8K6N, 8K6O, 8KGG, 8THK, 8THL, 8W89, 8W8A, 8WPU, 8ZH8, 8ZSJ, 8ZSP, 8ZSS, 8ZSV, 9K6L, 9KFI, 9KFJ, 9KFK

Functional residue map

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

Ligand- & substrate-binding residues (7): 176–182; 182; 201–205; 270–273; 327; 40–47; 47

Post-translational modifications (5): 179, 205, 352, 2, 3

Mutagenesis-validated functional residues (1):

Position	Phenotype
205	constitutively activated gtpase deficient mutant.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-170670	Adenylate cyclase inhibitory pathway
R-HSA-392170	ADP signalling through P2Y purinoceptor 12
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-418555	G alpha (s) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events
R-HSA-422356	Regulation of insulin secretion
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9634597	GPER1 signaling
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production

MSigDB gene sets: 560 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_MEMORY, GOBP_G_PROTEIN_COUPLED_PURINERGIC_RECEPTOR_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, PID_S1P_S1P1_PATHWAY, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, GOBP_COGNITION, GOBP_BEHAVIOR, CCAWYNNGAAR_UNKNOWN, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, GOCC_SECRETORY_GRANULE, AAGTCCA_MIR422B_MIR422A, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GOBP_ADULT_BEHAVIOR

GO Biological Process (25): G protein-coupled adenosine receptor signaling pathway (GO:0001973), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), negative regulation of adenylate cyclase activity (GO:0007194), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), gamma-aminobutyric acid signaling pathway (GO:0007214), response to nutrient (GO:0007584), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), positive regulation of cell migration (GO:0030335), positive regulation of superoxide anion generation (GO:0032930), positive regulation of urine volume (GO:0035810), negative regulation of calcium ion-dependent exocytosis (GO:0045955), negative regulation of synaptic transmission (GO:0050805), cell division (GO:0051301), regulation of calcium ion transport (GO:0051924), positive regulation of ERK1 and ERK2 cascade (GO:0070374), negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071878), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), positive regulation of neural precursor cell proliferation (GO:2000179), negative regulation of apoptotic signaling pathway (GO:2001234), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (8): G protein-coupled receptor binding (GO:0001664), GTPase activity (GO:0003924), GTP binding (GO:0005525), G-protein beta/gamma-subunit complex binding (GO:0031683), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), guanyl nucleotide binding (GO:0019001)

GO Cellular Component (16): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), membrane (GO:0016020), dendrite (GO:0030425), midbody (GO:0030496), ciliary basal body (GO:0036064), cell body (GO:0044297), extracellular exosome (GO:0070062), hippocampal mossy fiber to CA3 synapse (GO:0098686), neuronal dense core vesicle (GO:0098992), extracellular vesicle (GO:1903561), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
GPCR downstream signalling	3
G-protein mediated events	1
Activation of GABAB receptors	1
Signal amplification	1
Regulation of insulin secretion	1
Integration of energy metabolism	1
ESR-mediated signaling	1
G alpha (s) signalling events	1
Anti-inflammatory response favouring Leishmania parasite infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cellular process	3
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
microtubule organizing center	2
G protein-coupled purinergic receptor signaling pathway	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase activator activity	1
adenylate cyclase inhibitor activity	1
adenylate cyclase activity	1
negative regulation of catalytic activity	1
regulation of adenylate cyclase activity	1
G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
cell-cell signaling	1
GABA receptor activity	1
response to nutrient levels	1
response to chemical	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of superoxide anion generation	1
superoxide anion generation	1
positive regulation of reactive oxygen species metabolic process	1
regulation of urine volume	1
calcium-ion regulated exocytosis	1
regulation of calcium ion-dependent exocytosis	1
negative regulation of regulated secretory pathway	1
chemical synaptic transmission	1
negative regulation of cell communication	1
negative regulation of signaling	1
modulation of chemical synaptic transmission	1

Protein interactions and networks

STRING

2766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNAI2	GNB1	P04697	773
GNAI2	DRD2	P14416	745
GNAI2	GNB2	P11016	732
GNAI2	GPSM2	P81274	671
GNAI2	FPR1	P21462	657
GNAI2	FSHR	P23945	631
GNAI2	ADCY9	O60503	620
GNAI2	GPSM1	Q86YR5	612
GNAI2	RIC8A	Q9NPQ8	609
GNAI2	GNB5	O14775	592
GNAI2	SEMA4B	Q9NPR2	590
GNAI2	PKD1L1	Q8TDX9	586
GNAI2	C5AR1	P21730	583
GNAI2	GNG12	Q9UBI6	565
GNAI2	SUCLG1	P53597	564

IntAct

186 interactions, top by confidence:

A	B	Type	Score
CXCR5	GNAI2	psi-mi:“MI:2364”(proximity)	0.720
CXCR5	GNAI2	psi-mi:“MI:0915”(physical association)	0.720
GNAI2	CXCR5	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
GNAI2	CXCR5	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MDFI	GNAI2	psi-mi:“MI:0915”(physical association)	0.700
GNAI2	MDFI	psi-mi:“MI:0915”(physical association)	0.700
GNAI2	GPSM3	psi-mi:“MI:0915”(physical association)	0.670
GPSM3	GNAI2	psi-mi:“MI:0915”(physical association)	0.670
GNAI2	GNB1	psi-mi:“MI:0915”(physical association)	0.670
PAK5	AURKA	psi-mi:“MI:0914”(association)	0.640
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
GNG8	GNB5	psi-mi:“MI:0914”(association)	0.640
CD81	EGFR	psi-mi:“MI:0914”(association)	0.600
NCF2	GNAI2	psi-mi:“MI:0915”(physical association)	0.580

BioGRID (359): KRT31 (Two-hybrid), MDFI (Two-hybrid), TRIP6 (Two-hybrid), RGS20 (Two-hybrid), GPSM3 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-8 (Two-hybrid), NOTCH2NL (Two-hybrid), GNAI2 (Affinity Capture-Western), CXCR5 (Affinity Capture-Western), GNAI2 (Affinity Capture-MS), GNAI2 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), RIC8B (Affinity Capture-MS), RIC8A (Affinity Capture-MS)

ESM2 similar proteins: A8MTJ3, B2RSH2, G1XJZ0, O13055, O14438, O15976, P04695, P04696, P04897, P04899, P08752, P08753, P08754, P0C7Q4, P10824, P10825, P11488, P16894, P19087, P20353, P20612, P27044, P28052, P29348, P38400, P38401, P38402, P38403, P38407, P38408, P41776, P50146, P50147, P50149, P51876, P63096, P63097, P87034, P87383, Q18434

Diamond homologs: A2Y3B5, A8MTJ3, B0XRA0, B2RSH2, O04278, O04279, O13055, O13315, O14438, O15976, O42784, O74227, O74259, O95837, P04695, P04696, P04897, P04899, P08239, P08752, P08753, P08754, P09471, P0C7Q4, P0CN96, P0CN97, P10824, P10825, P11488, P16378, P16894, P18064, P18872, P19087, P20353, P20612, P26981, P27044, P27045, P28051

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
SMO	“up-regulates activity”	GNAI2	binding
GNAI2	“up-regulates activity”	TNFAIP8	binding
GNAI2	“down-regulates activity”	ADCY1	binding
GNAI2	down-regulates	Adenylate_cyclase	binding
hsa-miR-138-5p	“down-regulates quantity by repression”	GNAI2	“post transcriptional regulation”
hsa-miR-30d-5p	“down-regulates quantity by repression”	GNAI2	“post transcriptional regulation”
CXCR4	“up-regulates activity”	GNAI2	binding
GNAI2	down-regulates	Cell_invasion
GNAI2	down-regulates	Cell_migration
GNAI2	down-regulates	ADCY1	binding
GNAI2	“down-regulates activity”	ADCY5	binding
GNAI2	“down-regulates activity”	ADCY6	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Prostacyclin signalling through prostacyclin receptor	9	47.5×	1e-11
G beta:gamma signalling through BTK	8	44.5×	4e-10
ADP signalling through P2Y purinoceptor 12	10	43.5×	2e-12
G beta:gamma signalling through PLC beta	8	40.1×	6e-10
G beta:gamma signalling through CDC42	8	40.1×	6e-10
Presynaptic function of Kainate receptors	8	38.2×	8e-10
G-protein activation	8	33.4×	2e-09
Thromboxane signalling through TP receptor	8	33.4×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
G protein-coupled receptor signaling pathway	15	3.9×	1e-02

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — NHL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	22
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
15904	NM_002070.4(GNAI2):c.536G>A (p.Arg179His)	Pathogenic
15905	NM_002070.4(GNAI2):c.535C>G (p.Arg179Gly)	Pathogenic
15906	NM_002070.4(GNAI2):c.600T>A (p.Phe200Leu)	Pathogenic
4278646	NM_002070.4(GNAI2):c.545C>T (p.Thr182Ile)	Pathogenic
1803978	NM_002070.4(GNAI2):c.544A>C (p.Thr182Pro)	Likely pathogenic

SpliceAI

1413 predictions. Top by Δscore:

Variant	Effect	Δscore
3:50236432:G:GT	donor_gain	1.0000
3:50252143:G:GG	donor_gain	1.0000
3:50252387:T:TA	acceptor_gain	1.0000
3:50252392:A:AG	acceptor_gain	1.0000
3:50252392:ATCAG:A	acceptor_gain	1.0000
3:50252396:GGATC:G	acceptor_gain	1.0000
3:50252534:GAGCG:G	donor_gain	1.0000
3:50252535:AGCGG:A	donor_loss	1.0000
3:50252536:GCG:G	donor_gain	1.0000
3:50252537:CG:C	donor_gain	1.0000
3:50252537:CGG:C	donor_loss	1.0000
3:50252538:GG:G	donor_gain	1.0000
3:50252539:G:GA	donor_loss	1.0000
3:50252539:G:GG	donor_gain	1.0000
3:50253180:GCCTA:G	donor_gain	1.0000
3:50253185:G:GG	donor_gain	1.0000
3:50256187:CCCAG:C	acceptor_loss	1.0000
3:50256189:CAG:C	acceptor_loss	1.0000
3:50256190:A:AG	acceptor_gain	1.0000
3:50256190:AG:A	acceptor_loss	1.0000
3:50256191:G:GG	acceptor_gain	1.0000
3:50256191:GC:G	acceptor_gain	1.0000
3:50256191:GCT:G	acceptor_gain	1.0000
3:50256191:GCTA:G	acceptor_gain	1.0000
3:50256191:GCTAC:G	acceptor_gain	1.0000
3:50256307:G:GT	donor_gain	1.0000
3:50256321:G:GG	donor_gain	1.0000
3:50256720:CAG:C	acceptor_loss	1.0000
3:50256721:A:AG	acceptor_gain	1.0000
3:50256721:AG:A	acceptor_gain	1.0000

AlphaMissense

2384 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:50236403:T:C	L23P	1.000
3:50236442:T:C	L36S	1.000
3:50236445:T:A	L37Q	1.000
3:50236445:T:C	L37P	1.000
3:50236448:T:C	L38P	1.000
3:50236453:G:A	G40S	1.000
3:50236453:G:C	G40R	1.000
3:50236453:G:T	G40C	1.000
3:50252100:G:A	G40D	1.000
3:50252100:G:T	G40V	1.000
3:50252105:G:T	G42W	1.000
3:50252111:T:C	S44P	1.000
3:50252114:G:A	G45R	1.000
3:50252114:G:C	G45R	1.000
3:50252114:G:T	G45W	1.000
3:50252115:G:A	G45E	1.000
3:50252115:G:C	G45A	1.000
3:50252115:G:T	G45V	1.000
3:50252117:A:C	K46Q	1.000
3:50252118:A:T	K46M	1.000
3:50252119:G:C	K46N	1.000
3:50252119:G:T	K46N	1.000
3:50252120:A:C	S47R	1.000
3:50252120:A:T	S47C	1.000
3:50252121:G:T	S47I	1.000
3:50252122:C:A	S47R	1.000
3:50252122:C:G	S47R	1.000
3:50252124:C:A	T48N	1.000
3:50252124:C:T	T48I	1.000
3:50252134:G:C	K51N	1.000

dbSNP variants (sampled 300 via entrez): RS1000061614 (3:50241529 G>T), RS1000215613 (3:50252676 C>G), RS1000468909 (3:50229782 C>G), RS1000759932 (3:50254162 T>G), RS1000774471 (3:50262297 A>T), RS1000862074 (3:50235440 C>A,T), RS1000882759 (3:50228336 G>A,T), RS1001021451 (3:50228648 C>T), RS1001054477 (3:50260409 C>G,T), RS1001181133 (3:50254465 C>T), RS1001381572 (3:50263761 G>A,T), RS1001431728 (3:50257385 C>T), RS1001726687 (3:50263392 G>A), RS1001866999 (3:50230001 C>T), RS1001980154 (3:50238057 C>G,T)

Disease associations

OMIM: gene MIM:139360 | disease phenotypes: MIM:219090, MIM:192605, MIM:102200

GenCC curated gene-disease

Disease	Classification	Inheritance
ventricular tachycardia, familial	Moderate	Autosomal dominant

Mondo (6): ovarian granulosa cell tumor (MONDO:0023283), Cushing disease due to pituitary adenoma (MONDO:0009050), hypopituitarism (MONDO:0005152), ventricular tachycardia, familial (MONDO:0008648), long QT syndrome (MONDO:0002442), familial isolated pituitary adenoma (MONDO:0017824)

Orphanet (2): Cushing disease (Orphanet:96253), Familial isolated pituitary adenoma (Orphanet:314777)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0001638	Cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0003581	Adult onset
HP:0004751	Paroxysmal ventricular tachycardia
HP:0011712	Complete right bundle branch block

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST005951_49	Body mass index	1.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST007565_77	Morning person	2.000000e-16
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST010989_218	Body size at age 10	4.000000e-10
GCST011124_15	Caffeine consumption from tea	1.000000e-08
GCST90002388_195	Lymphocyte count	1.000000e-12
GCST90002389_20	Lymphocyte percentage of white cells	7.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0010091	tea consumption measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D049913	ACTH-Secreting Pituitary Adenoma	C04.557.470.035.012; C04.588.322.609.145; C10.228.140.617.738.675.149; C19.344.609.145; C19.700.734.145
D007018	Hypopituitarism	C10.228.140.617.738.300; C19.700.482
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
C537296	Granulosa cell tumor of the ovary (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105887 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,843 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 6 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.93	Kd	118.7	nM	CHEMBL5653589
6.89	ED50	129.5	nM	CHEMBL5653589
6.74	Kd	184	nM	ALISERTIB
6.51	Kd	307.1	nM	CHEMBL3752910
6.47	ED50	335.2	nM	CHEMBL3752910
5.90	IC50	1270	nM	MOLIBRESIB

PubChem BioAssay actives

4 with measured affinity, of 188 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148441: Binding affinity to human GNAI2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1187	uM
4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid	1425011: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1840	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148441: Binding affinity to human GNAI2 incubated for 45 mins by Kinobead based pull down assay	kd	0.3071	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179028: Inhibition of GNAI2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.2700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, affects expression	4
Particulate Matter	affects cotreatment, increases abundance, increases expression, affects expression	3
perfluorooctanoic acid	decreases expression, affects cotreatment, affects expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
bisphenol F	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	affects binding, decreases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
CMF regimen	increases response to substance	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
seocalcitol	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
thifluzamide	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991724	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01794793	PHASE4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT02060383	PHASE4	COMPLETED	Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing’s Disease or Acromegaly
NCT03080181	PHASE4	COMPLETED	Adipokine Profile in Patients With Cushing’s Disease on Pasireotide Treatment
NCT00140413	PHASE4	COMPLETED	Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia
NCT00360074	PHASE4	COMPLETED	Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation
NCT00490191	PHASE4	COMPLETED	Comparison of Two Growth Hormone Dosing Methods in Adults With Growth Hormone Deficiency
NCT00851942	PHASE4	COMPLETED	Determination of Method-specific Normal Cortisol and Adrenal Hormone Responses to the Short Synacthen Test
NCT04897802	PHASE4	COMPLETED	Identification and Clinical Relevance of an Oxytocin Deficient State (GLP1 Study)
NCT04902235	PHASE4	COMPLETED	Identification and Clinical Relevance of an Oxytocin Deficient State (CRH Study)
NCT05188131	PHASE4	COMPLETED	Acute Neuroendocrine Response to Intravenous Infusion of Diclofenac Sodium
NCT05206149	PHASE4	COMPLETED	Stimulation Test With Intranasal Glucagon for Corticotroph, Somatotroph and Antidiuretic Axes
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00434148	PHASE3	COMPLETED	Safety and Efficacy of Different Dose Levels of Pasireotide in Patients With de Novo, Persistent or Recurrent Cushing’s Disease
NCT00889525	PHASE3	COMPLETED	Study of Cabergoline in Treatment of Corticotroph Pituitary Tumor
NCT01371565	PHASE3	COMPLETED	Compassionate Use of CORLUX® (Mifepristone) in the Treatment of Signs and Symptoms of Endogenous Cushing’s Syndrome
NCT01374906	PHASE3	COMPLETED	Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing’s Disease
NCT01582061	PHASE3	COMPLETED	An Open-label, Multi-center, Expanded Access Study of Pasireotide s.c. in Patients With Cushing’s Disease.
NCT01925092	PHASE3	WITHDRAWN	Mifepristone in Children With Refractory Cushing’s Disease
NCT02697734	PHASE3	COMPLETED	Efficacy and Safety Evaluation of Osilodrostat in Cushing’s Disease
NCT03621280	PHASE3	COMPLETED	Open-label Treatment in Cushing’s Syndrome
NCT01007071	PHASE3	COMPLETED	Effects of Growth Hormone on Cognition and Cerebral Metabolism in Adults With Growth Hormone Deficiency
NCT00748657	PHASE2	COMPLETED	Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary
NCT01042522	PHASE2	UNKNOWN	Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors
NCT01584297	PHASE2	TERMINATED	Ketoconazole as Inhibitor of the Enzyme CYP17 in Locally Advanced or Disseminated Granulosa Cell Tumour of Ovary
NCT05348356	PHASE2	COMPLETED	Nirogacestat in Ovarian Granulosa Cell Tumors
NCT00171951	PHASE2	COMPLETED	Extension Study to Assess the Safety and Efficacy of Pasireotide in Participants With Cushing’s Disease
NCT00612066	PHASE2	TERMINATED	Rosiglitazone in Treating Patients With Newly Diagnosed ACTH-Secreting Pituitary Tumor (Cushing Disease)
NCT01331239	PHASE2	COMPLETED	Safety and Efficacy of LCI699 in Cushing’s Disease Patients
NCT02484755	PHASE2	UNKNOWN	Targeted Therapy With Gefitinib in Patients With USP8-mutated Cushing’s Disease
NCT03774446	PHASE2	RECRUITING	Multicenter Study of Seliciclib (R-roscovitine) for Cushing Disease
NCT04339751	PHASE2	WITHDRAWN	Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease
NCT05971758	PHASE2	RECRUITING	Fimepinostat, Combination HDAC and Pi3-kinase Inhibitor Tumor-Directed Therapy for Cushing Disease
NCT06471829	PHASE2	RECRUITING	A Trial of Lu AG13909 in Adult Participants With Cushing’s Disease
NCT00080483	PHASE2	COMPLETED	Testosterone and Growth Hormone for Bone Loss in Men
NCT04121780	PHASE2	RECRUITING	Growth Hormone Replacement Therapy for Retried Professional Football Players
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns