GNG2

Summary

GNG2 (G protein subunit gamma 2, HGNC:4404) is a protein-coding gene on chromosome 14q22.1, encoding Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (P59768). Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems.

This gene encodes one of the gamma subunits of a guanine nucleotide-binding protein. Such proteins are involved in signaling mechanisms across membranes. Various subunits forms heterodimers which then interact with the different signal molecules.

Source: NCBI Gene 54331 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 10 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_053064

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4404
Approved symbol	GNG2
Name	G protein subunit gamma 2
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186469
Ensembl biotype	protein_coding
OMIM	606981
Entrez	54331

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 22 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000335281, ENST00000553299, ENST00000553432, ENST00000553560, ENST00000554736, ENST00000554832, ENST00000554840, ENST00000554875, ENST00000555472, ENST00000556471, ENST00000556522, ENST00000556752, ENST00000556766, ENST00000557208, ENST00000557376, ENST00000615906, ENST00000889630, ENST00000889631, ENST00000889632, ENST00000889633, ENST00000889634, ENST00000889635, ENST00000889636, ENST00000938421, ENST00000938422, ENST00000938423, ENST00000954512, ENST00000954513

RefSeq mRNA: 7 — MANE Select: NM_053064 NM_001243773, NM_001243774, NM_001389707, NM_001389708, NM_001389709, NM_001389710, NM_053064

CCDS: CCDS32082

Canonical transcript exons

ENST00000556766 — 4 exons

Exon	Start	End
ENSE00002430221	51860612	51860790
ENSE00002533715	51966559	51969795
ENSE00003500243	51877617	51877657
ENSE00003644323	51950650	51950765

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.2714 / max 3798.6657, expressed in 1422 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139569	31.9317	1314
139570	14.6207	1236
139572	13.4888	1287
139571	6.5367	1007
139568	0.7261	164
139567	0.2144	75
139575	0.1712	39
139574	0.1697	44
139561	0.1165	5
139562	0.1076	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.52	gold quality
secondary oocyte	CL:0000655	99.31	gold quality
ganglionic eminence	UBERON:0004023	98.81	gold quality
left testis	UBERON:0004533	97.66	gold quality
right testis	UBERON:0004534	97.64	gold quality
bone marrow cell	CL:0002092	96.93	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.90	gold quality
middle temporal gyrus	UBERON:0002771	96.89	gold quality
testis	UBERON:0000473	96.85	gold quality
colonic epithelium	UBERON:0000397	96.75	gold quality
blood	UBERON:0000178	96.44	gold quality
dorsal root ganglion	UBERON:0000044	96.16	gold quality
leukocyte	CL:0000738	96.08	gold quality
monocyte	CL:0000576	95.96	gold quality
granulocyte	CL:0000094	95.61	gold quality
bone marrow	UBERON:0002371	95.58	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.35	gold quality
trigeminal ganglion	UBERON:0001675	95.34	gold quality
amygdala	UBERON:0001876	95.11	gold quality
prefrontal cortex	UBERON:0000451	95.10	gold quality
parietal pleura	UBERON:0002400	94.97	gold quality
anterior cingulate cortex	UBERON:0009835	94.59	gold quality
temporal lobe	UBERON:0001871	94.53	gold quality
islet of Langerhans	UBERON:0000006	94.35	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.30	gold quality
hypothalamus	UBERON:0001898	94.25	gold quality
entorhinal cortex	UBERON:0002728	94.22	gold quality
vermiform appendix	UBERON:0001154	94.12	gold quality
endothelial cell	CL:0000115	94.04	gold quality
cerebral cortex	UBERON:0000956	93.64	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	420.48
E-CURD-122	yes	54.56
E-MTAB-9467	yes	35.28
E-GEOD-135922	yes	24.74
E-GEOD-93593	yes	20.81
E-ANND-3	yes	16.00
E-CURD-46	yes	11.42
E-GEOD-125970	yes	6.77
E-MTAB-4850	no	1646.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MITF

miRNA regulators (miRDB)

210 targeting GNG2, 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-656-3P	100.00	72.15	2788
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 16)

• Data show that G protein inhibition of N-type calcium channels is critically dependent on two separate but adjacent approximately 20-amino acid regions of the Gbeta subunit, as examined with Gbetas 1 and 5 and Ggamma2. (PMID:15105422)
• 10 genes were down-regulated following treatment of the T-ALL cells with 0.15 and 1.5 microg/mL of metal ores at 72 h (PMID:15747776)
• Fission of transport carriers at the trans-Golgi network is dependent on specifically PLCbeta3, which is necessary to activate PKCeta and PKD in that Golgi compartment, via diacylglycerol production. (PMID:17492941)
• signaling pathway by which G(i)-coupled receptor specifically induces Rac and Cdc42 activation through direct interaction of Gbetagamma with FLJ00018. (PMID:18045877)
• Data show that activation of PLCbeta(2) by alpha(q) and beta1gamma2 differ from activation by Rac2 and from each other. (PMID:20007712)
• Data implicate the domain I-II linker region as an important contributor to voltage dependent Gbeta1/Ggamma2 modulation of Cav2.2 calcium channels. (PMID:20181083)
• Gbetagamma inhibits Epac-induced Ca 2+ elevation in melanoma cells. Cross talk of Ca 2+ signaling between Gbetagamma & Epac plays a major role in melanoma cell migration. (PMID:21679469)
• presence of Gng2 and Netrin-G2 immunoreactive elements in the insular cortex, but not in the putamen, suggests a possible common ontogeny of the claustrum and insula (PMID:22957104)
• increased protein expression level of GNG2 alone inhibits proliferation of malignant melanoma cells in vitro and in vivo (PMID:23031273)
• Data indicate that endogenous mTOR interacts with Gbetagamma. (PMID:24462769)
• Alteration of gene expression profiling including GPR174 and GNG2 is associated with vasovagal syncope. (PMID:25367286)
• G-protein betagamma subunits are positive regulators of Kv7.4 and native vascular Kv7 channel activity. (PMID:25941381)
• High GNG2 expression is associated with alcoholic hepatitis. (PMID:28818508)
• this paper shows that GNG2 gene polymorphism is associated with IgA nephropathy risk in Chinese Han population (PMID:30928649)
• Low GNG2 expression is associated with Abdominal Aortic Aneurysm. (PMID:31730405)
• Interference with KCNJ2 inhibits proliferation, migration and EMT progression of apillary thyroid carcinoma cells by upregulating GNG2 expression. (PMID:34212982)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gng2	ENSDARG00000056831
mus_musculus	Gng2	ENSMUSG00000043004
rattus_norvegicus	Gng2	ENSRNOG00000048980

Paralogs (11): GNG11 (ENSG00000127920), GNGT1 (ENSG00000127928), GNG5B (ENSG00000133136), GNG3 (ENSG00000162188), GNGT2 (ENSG00000167083), GNG8 (ENSG00000167414), GNG4 (ENSG00000168243), GNG12 (ENSG00000172380), GNG5 (ENSG00000174021), GNG7 (ENSG00000176533), GNG10 (ENSG00000242616)

Protein

Protein identifiers

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 — P59768 (reviewed: P59768)

Alternative names: G gamma-I

All UniProt accessions (6): P59768, G3V2C9, G3V2N0, G3V2W5, G3V3J9, G3V415

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.

Subunit / interactions. G proteins are composed of 3 units, alpha, beta and gamma. In this context, interacts with GNB2. The heterodimer formed by GNB1 and GNG2 interacts with ARHGEF5. The heterodimer formed by GNB1 and GNG2 interacts with GRK2. The heterodimer formed by GNB1 and GNG2 interacts with the ghrelin receptor GHSR. Forms complexes with TAS2R14 and G-proteins; these complexes play a role in the perception of bitterness. Component of the TAS2R14-GNAI1 complex, consisting of TAS2R14, GNAI1, GNB1 and GNG2. Component of the TAS2R14-GNAT3 complex, consisting of TAS2R14, GNAT3, GNB1 and GNG2. Component of the TAS2R14-GNAS2 complex, consisting of TAS2R14, GNAS2, GNB1 and GNG2. Component of a complex composed of FPR1 or FPR2 receptor and G(i) protein subunits GNAI1, GNB1 and GNG2; this complex is involved in innate recognition of N-formyl-methionyl peptides derived from invading microbes and host mitochondria as pathogen- and damage-associated molecular patterns (PAMPs and DAMPs).

Subcellular location. Cell membrane.

Tissue specificity. Expressed in fetal tissues, including testis, adrenal gland, brain, white blood cells and brain.

Similarity. Belongs to the G protein gamma family.

RefSeq proteins (7): NP_001230702, NP_001230703, NP_001376636, NP_001376637, NP_001376638, NP_001376639, NP_444292* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001770	G-protein_gamma	Family
IPR015898	G-protein_gamma-like_dom	Domain
IPR036284	GGL_sf	Homologous_superfamily

Pfam: PF00631

UniProt features (14 total): turn 4, helix 4, modified residue 2, initiator methionine 1, chain 1, propeptide 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1252 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8QEH	X-RAY DIFFRACTION	1.43
8QEG	X-RAY DIFFRACTION	1.7
8F0K	ELECTRON MICROSCOPY	1.9
9YDQ	ELECTRON MICROSCOPY	1.94
7MBX	ELECTRON MICROSCOPY	1.95
9YDP	ELECTRON MICROSCOPY	1.95
6CRK	X-RAY DIFFRACTION	2
8F0J	ELECTRON MICROSCOPY	2
8F2B	ELECTRON MICROSCOPY	2
9XXT	ELECTRON MICROSCOPY	2
9EJZ	ELECTRON MICROSCOPY	2.06
6X18	ELECTRON MICROSCOPY	2.1
6X19	ELECTRON MICROSCOPY	2.1
9P7Z	ELECTRON MICROSCOPY	2.1
7RTB	ELECTRON MICROSCOPY	2.14
9YDR	ELECTRON MICROSCOPY	2.14
5UKL	X-RAY DIFFRACTION	2.15
7TYF	ELECTRON MICROSCOPY	2.2
8F2A	ELECTRON MICROSCOPY	2.2
9BP3	ELECTRON MICROSCOPY	2.2
9MZE	ELECTRON MICROSCOPY	2.2
9N05	ELECTRON MICROSCOPY	2.2
9VAW	ELECTRON MICROSCOPY	2.24
6UVA	ELECTRON MICROSCOPY	2.3
6WZG	ELECTRON MICROSCOPY	2.3
8E3X	ELECTRON MICROSCOPY	2.3
8E3Y	ELECTRON MICROSCOPY	2.3
8YN9	ELECTRON MICROSCOPY	2.3
9BUB	ELECTRON MICROSCOPY	2.3
9HYI	ELECTRON MICROSCOPY	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59768-F1	89.49	0.71

Antibody-complex structures (SAbDab): 796 — 5UZ7, 6B3J, 6CRK, 6DDE, 6E3Y, 6GDG, 6K41, 6K42, 6KPF, 6KPG, 6LFM, 6LFO, 6LI3, 6LMK, 6LML, 6M1H, 6M1I, 6N4B, 6NI3, 6NIY, 6OIJ, 6OIK, 6OMM, 6OS9, 6OT0 (+771 more)

Functional residue map

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

Post-translational modifications (3): 2, 68, 68

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-1296041	Activation of G protein gated Potassium channels
R-HSA-163359	Glucagon signaling in metabolic regulation
R-HSA-202040	G-protein activation
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-392170	ADP signalling through P2Y purinoceptor 12
R-HSA-392451	G beta:gamma signalling through PI3Kgamma
R-HSA-392851	Prostacyclin signalling through prostacyclin receptor
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-4086398	Ca2+ pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-418217	G beta:gamma signalling through PLC beta
R-HSA-418555	G alpha (s) signalling events
R-HSA-418592	ADP signalling through P2Y purinoceptor 1
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events
R-HSA-420092	Glucagon-type ligand receptors
R-HSA-428930	Thromboxane signalling through TP receptor
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-500657	Presynaptic function of Kainate receptors
R-HSA-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
R-HSA-8964315	G beta:gamma signalling through BTK
R-HSA-8964616	G beta:gamma signalling through CDC42
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9634597	GPER1 signaling
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-997272	Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits

MSigDB gene sets: 387 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, LU_IL4_SIGNALING, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GOBP_CELLULAR_RESPONSE_TO_PROSTAGLANDIN_STIMULUS, REACTOME_GLUCAGON_SIGNALING_IN_METABOLIC_REGULATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP

GO Biological Process (6): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating dopamine receptor signaling pathway (GO:0007191), fibroblast proliferation (GO:0048144), cellular response to prostaglandin E stimulus (GO:0071380), cellular response to catecholamine stimulus (GO:0071870), signal transduction (GO:0007165)

GO Molecular Function (2): G-protein beta-subunit binding (GO:0031681), protein binding (GO:0005515)

GO Cellular Component (5): heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), membrane (GO:0016020), synapse (GO:0045202), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
GPCR downstream signalling	5
Signal amplification	3
Regulation of insulin secretion	2
G-protein beta:gamma signalling	2
G protein gated Potassium channels	1
Integration of energy metabolism	1
Opioid Signalling	1
Platelet homeostasis	1
Beta-catenin independent WNT signaling	1
Class B/2 (Secretin family receptors)	1
Aquaporin-mediated transport	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
G protein-coupled dopamine receptor signaling pathway	1
cell population proliferation	1
response to prostaglandin E	1
cellular response to prostaglandin stimulus	1
cellular response to alcohol	1
cellular response to ketone	1
cellular response to monoamine stimulus	1
response to catecholamine	1
cellular response to oxygen-containing compound	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein binding	1
binding	1
extrinsic component of cytoplasmic side of plasma membrane	1
plasma membrane protein complex	1
GTPase complex	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cell junction	1
extracellular vesicle	1

Protein interactions and networks

STRING

1574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNG2	GNB1	P04697	955
GNG2	GNB2	P11016	896
GNG2	SUCLG2	Q96I99	798
GNG2	PLCB2	Q00722	765
GNG2	CACNA1H	O95180	763
GNG2	PIK3R5	Q8WYR1	760
GNG2	CACNA1G	O43497	754
GNG2	GNB4	Q9HAV0	736
GNG2	GNAS	Q5JWF2	693
GNG2	GNG13	Q9P2W3	687
GNG2	GNB5	O14775	678
GNG2	GNAI1	P04898	669
GNG2	PLCB1	Q9NQ66	663
GNG2	PIK3R6	Q5UE93	661
GNG2	FNDC1	Q4ZHG4	650

IntAct

76 interactions, top by confidence:

A	B	Type	Score
GNG2	GNB1	psi-mi:“MI:0914”(association)	0.940
GNB1	GNG2	psi-mi:“MI:0407”(direct interaction)	0.940
GNB1	GNG2	psi-mi:“MI:0915”(physical association)	0.940
GNG2	GNB1	psi-mi:“MI:0915”(physical association)	0.910
GNG2	GNB1	psi-mi:“MI:0407”(direct interaction)	0.910
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
KCTD12	GNG2	psi-mi:“MI:0915”(physical association)	0.740
GNG2	GNAS	psi-mi:“MI:0914”(association)	0.620
GNG2	GNAI1	psi-mi:“MI:0914”(association)	0.610
CALCA	RAMP1	psi-mi:“MI:0915”(physical association)	0.610
GNG2	GNAI1	psi-mi:“MI:2364”(proximity)	0.610
GNG2	GNB2	psi-mi:“MI:0914”(association)	0.530
GNG2	GNB3	psi-mi:“MI:0914”(association)	0.530
GNG2	GNB5	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530

BioGRID (126): GNG2 (Affinity Capture-MS), GNG2 (Affinity Capture-MS), GNG2 (Affinity Capture-MS), GNG2 (Affinity Capture-MS), GNG2 (Affinity Capture-MS), GNG2 (Affinity Capture-MS), GNG2 (Affinity Capture-MS), GNG2 (Phenotypic Enhancement), GNG2 (Phenotypic Enhancement), GNB2L1 (Affinity Capture-Western), FYN (Affinity Capture-Western), PTK2 (Affinity Capture-Western), GNG2 (Affinity Capture-Western), GNB2 (Affinity Capture-Western), GNG2 (Affinity Capture-MS)

ESM2 similar proteins: A0A804HLA8, O14610, O60262, O97564, P02698, P30671, P38040, P43425, P50150, P50151, P50153, P50154, P54406, P59768, P61952, P61953, P61954, P63077, P63078, P63210, P63211, P63212, P63213, P63214, P63215, P63216, P63217, P63218, P63219, Q28024, Q4VT26, Q5E9F0, Q5R639, Q5R7U4, Q5RBQ0, Q5REH7, Q61012, Q61016, Q61017, Q6CPB4

Diamond homologs: A0A1W2PPG7, O60262, P30671, P43425, P50150, P50153, P59768, P63212, P63213, P63214, P63215, P63216, Q28024, Q5R639, Q5R7U4, Q5RBQ0, Q61016, Q9DAS9, Q9UBI6, A0A804HLA8, P38040, P50151, P63077, P63078, P63217, P63218, P63219, Q4VT26, Q5REH7, Q80SZ7, Q9CXP8, Q9UK08, O14610, O97564, P02698, P50154, P54406, P61952, P61953, P61954

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
GNG2	up-regulates	PIK3CA	binding
SMO	up-regulates	GNG2	binding
GNG2	up-regulates	PLCG1	binding
GNG2	up-regulates	PI3K	binding
GNG2	“form complex”	GNB/GNG	binding
GPER1	“up-regulates activity”	GNG2	binding
GNB1	“up-regulates activity”	GNG2	binding
GNG2	“up-regulates activity”	GNB1	binding
GNG2	“up-regulates activity”	SRC

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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	5	88.4×	3e-08
ADP signalling through P2Y purinoceptor 12	6	87.6×	1e-09
Adrenaline,noradrenaline inhibits insulin secretion	7	81.1×	1e-10
Glucagon-type ligand receptors	7	71.2×	2e-10
Activation of G protein gated Potassium channels	5	57.9×	2e-07
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	5	57.9×	2e-07
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	7	54.7×	1e-09
ADORA2B mediated anti-inflammatory cytokines production	7	52.2×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	6	28.6×	9e-06
adenylate cyclase-activating G protein-coupled receptor signaling pathway	8	19.7×	3e-06
G protein-coupled receptor signaling pathway	11	8.7×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1278 predictions. Top by Δscore:

Variant	Effect	Δscore
14:51950648:A:AG	acceptor_gain	1.0000
14:51950648:AGT:A	acceptor_gain	1.0000
14:51950649:G:GA	acceptor_gain	1.0000
14:51950649:GT:G	acceptor_gain	1.0000
14:51950649:GTG:G	acceptor_gain	1.0000
14:51950649:GTGT:G	acceptor_gain	1.0000
14:51950649:GTGTT:G	acceptor_gain	1.0000
14:51950763:AAGG:A	donor_loss	1.0000
14:51950766:G:GG	donor_gain	1.0000
14:51847306:G:T	donor_gain	0.9900
14:51847376:CAGG:C	donor_loss	0.9900
14:51847377:AGGT:A	donor_loss	0.9900
14:51847378:G:GC	donor_loss	0.9900
14:51847379:G:GA	donor_loss	0.9900
14:51877616:GCCA:G	acceptor_gain	0.9900
14:51950644:TTCTA:T	acceptor_gain	0.9900
14:51950645:TCTA:T	acceptor_gain	0.9900
14:51950646:CTAG:C	acceptor_gain	0.9900
14:51950647:TAGTG:T	acceptor_gain	0.9900
14:51950648:A:T	acceptor_gain	0.9900
14:51950649:G:T	acceptor_gain	0.9900
14:51950717:G:GT	donor_gain	0.9900
14:51950759:GA:G	donor_gain	0.9900
14:51847306:G:GT	donor_gain	0.9800
14:51847375:GCAG:G	donor_gain	0.9800
14:51877615:A:AG	acceptor_gain	0.9800
14:51877616:G:GG	acceptor_gain	0.9800
14:51877654:AGAG:A	donor_loss	0.9800
14:51877655:GAGG:G	donor_loss	0.9800
14:51877656:AG:A	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000009935 (14:51827604 C>G), RS1000025234 (14:51869528 G>C), RS1000068383 (14:51884711 T>A,C), RS1000074609 (14:51833348 A>C), RS1000082234 (14:51903936 C>A,T), RS1000082809 (14:51863704 TC>T), RS1000085235 (14:51911493 G>A), RS1000119273 (14:51846996 C>A,G,T), RS1000120764 (14:51966134 C>A,T), RS1000126572 (14:51833060 A>T), RS1000127370 (14:51965418 A>G), RS1000175499 (14:51956889 T>C), RS1000179355 (14:51876056 G>A), RS1000247165 (14:51835661 C>G), RS1000314806 (14:51877597 T>C)

Disease associations

OMIM: gene MIM:606981 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST001940_3	Non-melanoma skin cancer	7.000000e-08
GCST002392_2	Lung cancer (smoking interaction)	7.000000e-06
GCST002750_3	Chronic obstructive pulmonary disease	4.000000e-06
GCST003075_46	Cognitive decline rate in late mild cognitive impairment	1.000000e-06
GCST003075_52	Cognitive decline rate in late mild cognitive impairment	2.000000e-06
GCST003264_102	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003264_801	Post bronchodilator FEV1/FVC ratio	4.000000e-07
GCST004412_11	Craniofacial microsomia	1.000000e-07
GCST006005_23	High density lipoprotein cholesterol levels	1.000000e-08
GCST008150_7	Triglyceride levels	6.000000e-08
GCST009615_14	Triglyceride levels x loop diuretics use interaction	3.000000e-07
GCST009615_15	Triglyceride levels x loop diuretics use interaction	6.000000e-06
GCST90020024_768	A body shape index	3.000000e-08
GCST90020024_769	A body shape index	3.000000e-08
GCST90020025_297	Waist-to-hip ratio adjusted for BMI	9.000000e-12
GCST90020025_298	Waist-to-hip ratio adjusted for BMI	6.000000e-09
GCST90020027_674	Waist-hip index	2.000000e-12
GCST90020027_675	Waist-hip index	3.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006527	smoking status measurement
EFO:0007710	cognitive decline measurement
EFO:0004713	FEV/FVC ratio
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3883319 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,372 (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
CHEMBL87223	AMINOQUINURIDE	2	1,372

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

ChEMBL bioactivities

24 potent at pChembl≥5 of 44 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.00	IC50	100	nM	CHEMBL3728058
7.00	IC50	100	nM	CHEMBL487046
6.89	IC50	130	nM	CHEMBL1723511
6.70	IC50	200	nM	CHEMBL502775
6.70	IC50	200	nM	CHEMBL3733064
6.70	IC50	200	nM	CHEMBL3728757
6.70	IC50	200	nM	CHEMBL3732105
6.70	IC50	200	nM	CHEMBL4469620
6.70	IC50	200	nM	CHEMBL487046
6.60	IC50	250	nM	CHEMBL4443974
6.16	IC50	700	nM	CHEMBL3727794
6.16	IC50	700	nM	CHEMBL471004
5.70	IC50	2000	nM	CHEMBL203722
5.70	IC50	2000	nM	CHEMBL3728876
5.60	IC50	2500	nM	CHEMBL1208090
5.52	IC50	3000	nM	CHEMBL487046
5.30	IC50	5000	nM	CHEMBL3728247
5.30	IC50	5000	nM	AMINOQUINURIDE
5.30	IC50	5000	nM	CHEMBL1178292
5.22	IC50	6000	nM	CHEMBL1208442
5.10	IC50	8000	nM	CHEMBL487046
5.00	IC50	1e+04	nM	CHEMBL471225

PubChem BioAssay actives

6 with measured affinity, of 7 total; 6 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
8-(3,4,5-trihydroxy-6-oxoxanthen-9-yl)naphthalene-1-carboxylic acid	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	0.1300	uM
2-(3,4,5-trihydroxy-6-oxoxanthen-9-yl)cyclohexane-1-carboxylic acid	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	0.2000	uM
3’,4’,5’,6’-tetrahydroxyspiro[2-benzofuran-3,9’-xanthene]-1-one	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	0.2000	uM
7,8,9,10,11,11-hexachloro-4-(3,4,5-trihydroxy-6-oxoxanthen-9-yl)tricyclo[4.4.1.01,6]undec-8-ene-3-carboxylic acid	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	0.2500	uM
7-amino-1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	5.0000	uM
1,3-bis(4-amino-2-methylquinolin-6-yl)urea	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	5.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects methylation	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Aflatoxin B1	affects methylation, decreases methylation, increases expression	3
entinostat	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
bisphenol F	decreases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
trichostatin A	decreases expression, increases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
dorsomorphin	decreases expression, affects cotreatment	1
5-amino-2-methylsulfanyl-4-(3-(2-morpholin-4-ylacetylamino)phenyl)thieno(2,3-d)pyrimidine-6-carboxylic acid tert-butylamide	affects binding	1
asparanin A	decreases expression	1
bisphenol S	affects cotreatment, increases methylation	1
LDN 193189	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Barium	affects binding, decreases reaction, increases transport	1
Cadmium	decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3734300	Binding	Inhibition of SIGKAFKILGYPDYD binding to biotinylated Gbeta1gamma2 (unknown origin) incubated for 1 hr by phage ELISA	Compositions and methods for inhibiting g protein signaling

Clinical trials (associated diseases)

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