G3BP2

Summary

G3BP2 (G3BP stress granule assembly factor 2, HGNC:30291) is a protein-coding gene on chromosome 4q21.1, encoding Ras GTPase-activating protein-binding protein 2 (Q9UN86). Scaffold protein that plays an essential role in cytoplasmic stress granule formation which acts as a platform for antiviral signaling.

Enables molecular condensate scaffold activity. Involved in positive regulation of stress granule assembly; protein homooligomerization; and stress granule assembly. Located in cytoplasmic stress granule and cytosol.

Source: NCBI Gene 9908 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 47 total
• Druggable target: yes
• MANE Select transcript: NM_203505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30291
Approved symbol	G3BP2
Name	G3BP stress granule assembly factor 2
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0660
Ensembl gene	ENSG00000138757
Ensembl biotype	protein_coding
OMIM	620020
Entrez	9908

Gene structure

Transcript identifiers

Ensembl transcripts: 120 — 81 protein_coding, 18 protein_coding_CDS_not_defined, 13 nonsense_mediated_decay, 8 retained_intron

ENST00000357854, ENST00000359707, ENST00000395719, ENST00000499709, ENST00000502654, ENST00000503660, ENST00000507133, ENST00000507252, ENST00000507701, ENST00000507745, ENST00000507947, ENST00000508510, ENST00000509100, ENST00000509561, ENST00000510902, ENST00000511146, ENST00000511868, ENST00000513927, ENST00000515457, ENST00000676470, ENST00000676485, ENST00000676493, ENST00000676579, ENST00000676580, ENST00000676584, ENST00000676641, ENST00000676666, ENST00000676689, ENST00000676702, ENST00000676761, ENST00000676839, ENST00000676926, ENST00000676974, ENST00000677003, ENST00000677060, ENST00000677094, ENST00000677125, ENST00000677145, ENST00000677162, ENST00000677171, ENST00000677192, ENST00000677201, ENST00000677265, ENST00000677278, ENST00000677333, ENST00000677426, ENST00000677489, ENST00000677515, ENST00000677520, ENST00000677566, ENST00000677583, ENST00000677597, ENST00000677606, ENST00000677620, ENST00000677727, ENST00000677733, ENST00000677794, ENST00000677876, ENST00000677888, ENST00000677889, ENST00000677952, ENST00000677970, ENST00000678062, ENST00000678100, ENST00000678122, ENST00000678123, ENST00000678244, ENST00000678265, ENST00000678273, ENST00000678326, ENST00000678329, ENST00000678389, ENST00000678447, ENST00000678552, ENST00000678578, ENST00000678620, ENST00000678642, ENST00000678670, ENST00000678732, ENST00000678798, ENST00000678843, ENST00000678875, ENST00000678908, ENST00000678932, ENST00000678958, ENST00000678971, ENST00000679281, ENST00000679294, ENST00000679325, ENST00000679329, ENST00000908073, ENST00000908074, ENST00000908075, ENST00000908076, ENST00000908077, ENST00000908078, ENST00000908079, ENST00000908080, ENST00000908081, ENST00000932842, ENST00000932843, ENST00000932844, ENST00000932845, ENST00000932846, ENST00000932847, ENST00000932848, ENST00000932849, ENST00000932850, ENST00000932851, ENST00000932852, ENST00000932853, ENST00000932854, ENST00000944684, ENST00000944685, ENST00000944686, ENST00000944687, ENST00000944688, ENST00000944689, ENST00000944690, ENST00000944691

RefSeq mRNA: 21 — MANE Select: NM_203505 NM_001400004, NM_001400005, NM_001400006, NM_001400007, NM_001400008, NM_001400010, NM_001400011, NM_001400012, NM_001400013, NM_001400014, NM_001400015, NM_001400016, NM_001400017, NM_001400018, NM_001400019, NM_001400020, NM_001400021, NM_001400022, NM_012297, NM_203504, NM_203505

CCDS: CCDS3571, CCDS3572, CCDS93544, CCDS93545

Canonical transcript exons

ENST00000359707 — 12 exons

Exon	Start	End
ENSE00000722530	75646338	75646456
ENSE00000722784	75653983	75654081
ENSE00000935618	75648639	75648741
ENSE00001284875	75661931	75662049
ENSE00003528532	75656924	75657014
ENSE00003561222	75655768	75655870
ENSE00003586028	75655066	75655246
ENSE00003599344	75647029	75647157
ENSE00003684719	75657557	75657730
ENSE00003790993	75658843	75658924
ENSE00003905513	75673208	75673411
ENSE00003905900	75642786	75645702

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 99.6476 / max 1248.7644, expressed in 1826 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52601	76.4058	1824
52602	14.3456	1720
52600	4.1955	1424
52597	1.7788	817
52598	1.1046	546
52599	0.5837	203
52594	0.5027	199
52592	0.4260	211
52596	0.1531	56
52593	0.1517	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.33	gold quality
adrenal tissue	UBERON:0018303	98.13	gold quality
medial globus pallidus	UBERON:0002477	97.99	gold quality
islet of Langerhans	UBERON:0000006	97.97	gold quality
calcaneal tendon	UBERON:0003701	97.91	gold quality
frontal pole	UBERON:0002795	97.78	gold quality
pons	UBERON:0000988	97.62	gold quality
substantia nigra pars compacta	UBERON:0001965	97.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.52	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.52	gold quality
germinal epithelium of ovary	UBERON:0001304	97.46	gold quality
colonic epithelium	UBERON:0000397	97.45	gold quality
tendon	UBERON:0000043	97.39	gold quality
globus pallidus	UBERON:0001875	97.38	gold quality
superior vestibular nucleus	UBERON:0007227	97.32	gold quality
prefrontal cortex	UBERON:0000451	97.18	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.15	gold quality
biceps brachii	UBERON:0001507	97.01	gold quality
ganglionic eminence	UBERON:0004023	96.86	gold quality
tendon of biceps brachii	UBERON:0008188	96.79	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.61	gold quality
paraflocculus	UBERON:0005351	96.61	gold quality
rectum	UBERON:0001052	96.45	gold quality
muscle of leg	UBERON:0001383	96.44	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.43	gold quality
embryo	UBERON:0000922	96.41	gold quality
stromal cell of endometrium	CL:0002255	96.40	gold quality
gastrocnemius	UBERON:0001388	96.38	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	9.27
E-MTAB-6678	yes	5.13
E-MTAB-7606	no	547.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

271 targeting G3BP2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-5692A	100.00	74.40	6850
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-4692	100.00	67.32	2066
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548C-3P	99.99	74.01	7587
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-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-19A-3P	99.98	75.33	2762

Literature-anchored findings (GeneRIF, showing 26)

• Both G3BP1 and G3BP2 isoforms may act as negative regulators of tumor suppressor protein p53. (PMID:17297477)
• We showed that just four genes, G3BP2, SCARB2, CSNK1A1 and SPRR2B, can classify patients as presence of lymph node metastasis negative or positive, with 80.0% accuracy. (PMID:21985131)
• first evidence of direct interactions between PKCalpha and G3BP2 and that PKCalpha can phosphorylate G3BP2. (PMID:22536444)
• Data show that the nsP3/G3BP interaction also blocks stress granules (SGs) induced by other stresses than virus infection. (PMID:23087212)
• both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses. (PMID:23279204)
• G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA. (PMID:24992036)
• Stress granule components G3BP1 and G3BP2 play a proviral role early in Chikungunya virus replication. (PMID:25653451)
• Reveal a TWIST1-G3BP2 mechanotransduction pathway that responds to biomechanical signals from the tumour microenvironment to drive EMT, invasion and metastasis. (PMID:25893917)
• FGDF peptide binds and changes conformation of the protruding N-terminal residues by providing hydrophobic interactions to a symmetry related molecule that facilitated crystallization of the G3BP2 isoform. (PMID:26410532)
• G3BP mediates the condensation of stress granules by shifting between two different states that are controlled by the phosphorylation of S149 and by binding to Caprin1 or USP10. (PMID:27022092)
• High G3BP2 levels worsened prognosis in breast cancer. Cell lines with lower G3BP2 levels required substantially higher cell numbers to form tumors in NOD/SCID mice. G3BP2 regulates SART3, Nanog, and Oct-4 expression levels and may be responsible for the maintenance of subpopulations of breast cancer cells with long-term proliferative properties.G3BP2 is important in breast tumor initiation. (PMID:28096337)
• Translocation of p53 is regulated by androgen-dependent sumoylation mediated by the G3BP2-interacting SUMO-E3 ligase, RanBP2. G3BP2 knockdown results in reduced tumor growth and increased nuclear p53 accumulation in mouse xenograft models of prostate cancer with or without long-term androgen deprivation. (PMID:28692047)
• USP10 was expressed primarily in the cytoplasm of prostate cancer tissues. High levels of USP10 expression were strongly correlated with high levels of AR, G3BP2, and p53 in the cytoplasm. High expression of USP10 was significantly associated with poor prognosis of patients with prostate cancer. (PMID:29378906)
• Overexpression of TRIM25 promoted prostate cancer cell proliferation and cell survival by modulating p53 nuclear export mechanism with G3BP2 interaction. (PMID:29379164)
• Results found that H. pylori upregulates G3BP2 in human gastric epithelium. In addition, the level of G3BP2 expression increases with severity of gastric malignant lesions in vivo. (PMID:30455363)
• A novel signaling pathway consisting of alpha-parvin, G3BP2, and TWIST1 regulates breast cancer progression and metastasis, this suggests that the activation of this signaling pathway is a key factor for driving the progression and poor clinical outcome of human ER-negative breast cancer. (PMID:30804457)
• These data confirm that G3BP is a ribosomal binding protein and reveal that alphaviral nsP3 uses G3BP to concentrate viral replication complexes and to recruit the translation initiation machinery, promoting the efficient translation of viral mRNAs. (PMID:31199850)
• BAALC-AS1/G3BP2/c-Myc feedback loop promotes cell proliferation in esophageal squamous cell carcinoma. (PMID:33476486)
• G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. (PMID:33497611)
• Genomics-guided targeting of stress granule proteins G3BP1/2 to inhibit SARS-CoV-2 propagation. (PMID:34517025)
• MG53 suppresses tumor progression and stress granule formation by modulating G3BP2 activity in non-small cell lung cancer. (PMID:34521423)
• EBF1-mediated up-regulation of lncRNA FGD5-AS1 facilitates osteosarcoma progression by regulating miR-124-3p/G3BP2 axis as a ceRNA. (PMID:35761386)
• USP7- and PRMT5-dependent G3BP2 stabilization drives de novo lipogenesis and tumorigenesis of HNSC. (PMID:36878903)
• Chemotherapy-induced exosomal circBACH1 promotes breast cancer resistance and stemness via miR-217/G3BP2 signaling pathway. (PMID:37461019)
• Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2. (PMID:38640983)
• Exosomal microRNA-363 mediates the destructive effect of M1 macrophages on chondrocytes by repressing G3BP2. (PMID:39413984)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	g3bp2a	ENSDARG00000014790
danio_rerio	g3bp2b	ENSDARG00000074572
mus_musculus	G3bp2	ENSMUSG00000029405
rattus_norvegicus	G3bp2	ENSRNOG00000002433
drosophila_melanogaster	rin	FBGN0015778
caenorhabditis_elegans		WBGENE00010677

Paralogs (1): G3BP1 (ENSG00000145907)

Protein

Protein identifiers

Ras GTPase-activating protein-binding protein 2 — Q9UN86 (reviewed: Q9UN86)

Alternative names: GAP SH3 domain-binding protein 2

All UniProt accessions (25): Q9UN86, A0A7I2V2R0, A0A7I2V382, A0A7I2V3E2, A0A7I2V3I4, A0A7I2V3P9, A0A7I2V3R7, A0A7I2V3Z6, A0A7I2V481, A0A7I2V513, A0A7I2V547, A0A7I2V572, A0A7I2V647, A0A7I2YQD9, A0A7I2YQG8, A0A7I2YQL7, A0A7I2YQS2, D6R9A4, D6RAC7, D6RB17, D6RBR0, D6RBW8, D6RE13, D6RGJ4, H0YAE3

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold protein that plays an essential role in cytoplasmic stress granule formation which acts as a platform for antiviral signaling. Plays an essential role in stress granule formation. Stress granules are membraneless compartments that store mRNAs and proteins, such as stalled translation pre-initiation complexes, in response to stress. Promotes formation of stress granules phase-separated membraneless compartment by undergoing liquid-liquid phase separation (LLPS) upon unfolded RNA-binding: functions as a molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA concentrations.

Subunit / interactions. Forms homooligomers. Forms heterodimers with G3BP1. Interacts with NFKBIA (via N-terminus). Interacts (via NTF2 domain) with USP10; inhibiting stress granule formation. Interacts (via NTF2 domain) with CAPRIN1; promoting stress granule formation. Associates (via RG-rich region) with 40S ribosome subunits. Interacts with PABPC1. (Microbial infection) Interacts with non-structural protein 3 (via C-terminus) of Sindbis virus and Semliki forest virus; this interaction inhibits the formation of host stress granules on viral mRNAs and the nsp3-G3BP2 complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes.

Subcellular location. Cytoplasm. Stress granule.

Post-translational modifications. (Microbial infection) Cleaved by foot-and-mouth disease virus leader protease; this cleavage suppresses the formation of cytoplasmic stress granules.

Activity regulation. Under physiological conditions, G3BP2 adopts a compact state that is stabilized by intramolecular interactions between the RG-rich and the acidic regions that inhibit phase separation. Upon stress, polysomes disassemble and mRNAs are released in an unfolded protein-free state. Binding of unfolded mRNA to G3BP2 outcompetes the intramolecular interactions and RNA-bound G3BP2 adopts an expanded conformation in which the RG-rich region becomes exposed to engage in protein-protein and protein-RNA interactions, allowing physical cross-linking of RNA molecules to form protein-RNA condensates, leading to liquid-liquid phase separation (LLPS).

Domain organisation. Can mediate both protein-protein and protein-RNA interactions via the NTF2 domain and RNA-binding domain RRM; protein-protein and protein-RNA interactions are essential for undergoing liquid-liquid phase separation (LLPS). The acidic disordered region acts as a negative regulator of phase separation. The NTF2 domain mediates interaction with CAPRIN1 and USP10 regulators, thereby regulating assembly of stress granules.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UN86-1	A	yes
Q9UN86-2	B

RefSeq proteins (21): NP_001386933, NP_001386934, NP_001386935, NP_001386936, NP_001386937, NP_001386939, NP_001386940, NP_001386941, NP_001386942, NP_001386943, NP_001386944, NP_001386945, NP_001386946, NP_001386947, NP_001386948, NP_001386949, NP_001386950, NP_001386951, NP_036429, NP_987100, NP_987101* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002075	NTF2_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR018222	Nuclear_transport_factor_2_euk	Domain
IPR032710	NTF2-like_dom_sf	Homologous_superfamily
IPR034376	G3BP2_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR039539	Ras_GTPase_bind_prot	Family

Pfam: PF00076, PF02136

UniProt features (49 total): modified residue 10, sequence variant 8, compositionally biased region 6, strand 6, helix 5, region of interest 5, sequence conflict 3, domain 2, initiator methionine 1, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9OS2	ELECTRON MICROSCOPY	2.5
5DRV	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UN86-F1	66.29	0.29

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 (11): 141, 149, 225, 227, 392, 457, 466, 468, 281, 227, 235

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses

MSigDB gene sets: 384 (showing top): MYAATNNNNNNNGGC_UNKNOWN, MODULE_97, MORF_SMC1L1, KAAB_FAILED_HEART_ATRIUM_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MORF_RRM1, MORF_HDAC1, AREB6_01, MODULE_182, MORF_HDAC2, GTACAGG_MIR486, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, SRF_Q5_01, CREB_Q4, GTGCCTT_MIR506

GO Biological Process (6): stress granule assembly (GO:0034063), innate immune response (GO:0045087), mRNA transport (GO:0051028), protein homooligomerization (GO:0051260), immune system process (GO:0002376), positive regulation of stress granule assembly (GO:0062029)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA binding (GO:0003729), molecular condensate scaffold activity (GO:0140693), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), cytoplasm (GO:0005737), cytoplasmic ribonucleoprotein granule (GO:0036464)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cytoplasm	2
cellular anatomical structure	2
membraneless organelle assembly	1
immune response	1
defense response to symbiont	1
RNA transport	1
protein complex oligomerization	1
biological_process	1
stress granule assembly	1
regulation of stress granule assembly	1
positive regulation of organelle assembly	1
nucleic acid binding	1
RNA binding	1
protein-macromolecule adaptor activity	1
cytoplasmic ribonucleoprotein granule	1
intracellular anatomical structure	1
ribonucleoprotein granule	1

Protein interactions and networks

STRING

2474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
G3BP2	CAPRIN1	Q14444	953
G3BP2	TWIST1	Q15672	946
G3BP2	G3BP1	Q13283	898
G3BP2	TIA1	P31483	830
G3BP2	PABPC1	P11940	699
G3BP2	SH2D3C	Q8N5H7	696
G3BP2	TIAL1	Q01085	669
G3BP2	RASA1	P20936	667
G3BP2	DDX6	P26196	660
G3BP2	NFKBIA	P25963	649
G3BP2	FXR2	P51116	649
G3BP2	FXR1	P51114	649
G3BP2	YBX1	P16990	634
G3BP2	USP10	Q14694	624
G3BP2	PRRC2B	Q5JSZ5	623

IntAct

232 interactions, top by confidence:

A	B	Type	Score
N	G3BP1	psi-mi:“MI:0914”(association)	0.980
N	G3BP2	psi-mi:“MI:0915”(physical association)	0.970
G3BP2	N	psi-mi:“MI:0407”(direct interaction)	0.970
G3BP2	N	psi-mi:“MI:0915”(physical association)	0.970
G3BP2	USP10	psi-mi:“MI:0915”(physical association)	0.940
USP10	G3BP2	psi-mi:“MI:0915”(physical association)	0.940
N	G3BP1	psi-mi:“MI:0914”(association)	0.920
N	EIF2AK2	psi-mi:“MI:0914”(association)	0.820
N	G3BP1	psi-mi:“MI:0914”(association)	0.760
CAPRIN1	N	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (751): G3BP2 (Two-hybrid), G3BP2 (Affinity Capture-MS), G3BP2 (Affinity Capture-MS), G3BP2 (Affinity Capture-MS), G3BP1 (Affinity Capture-MS), NUP214 (Affinity Capture-MS), NUFIP2 (Affinity Capture-MS), POM121 (Affinity Capture-MS), USP10 (Affinity Capture-MS), ATXN2L (Affinity Capture-MS), NUP153 (Affinity Capture-MS), NUP88 (Affinity Capture-MS), NUP62 (Affinity Capture-MS), G3BP2 (Affinity Capture-MS), ADSL (Co-fractionation)

ESM2 similar proteins: B2GV05, B5FXN8, G3V9R8, O08583, O75525, O77768, P07910, P19600, P23588, P52756, P55795, P70333, P97379, P97855, Q08DJ0, Q0VFL7, Q13148, Q13283, Q1RMU5, Q28FB9, Q32LC7, Q3SZF3, Q3T0I4, Q58EA2, Q5R5W2, Q5R9L3, Q5RA82, Q5RB87, Q5RD26, Q5SRX1, Q5VWX1, Q5ZLN5, Q60HC3, Q64012, Q6AY09, Q6GLW1, Q86SE5, Q86V81, Q8BGD9, Q8BTF8

Diamond homologs: O94260, P97379, P97855, Q13283, Q32LC7, Q5R9L3, Q5RB87, Q9C7F5, Q9FME2, Q9FZK4, Q9UN86, A0A0D1DZT6, A0A2R8Y4L2, A0JM51, A5A6H4, A7VJC2, O14979, O57437, O88569, P04256, P07909, P09651, P09867, P17130, P21522, P22626, P28644, P48810, P49312, P51989, P51990, P51992, Q00916, Q02926, Q04836, Q13242, Q14103, Q22037, Q28521, Q2HJ60

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
G3BP1	“up-regulates activity”	G3BP2	binding
G3BP2	“up-regulates activity”	G3BP1	binding
G3BP2	up-regulates	Stress_granules
G3BP2	“down-regulates activity”	NFKBIA	relocalization
G3BP2	“down-regulates activity”	MDM2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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.

GO biological processes:

GO term	Partners	Fold	FDR
mRNA stabilization	5	15.4×	5e-03
translational initiation	5	15.1×	5e-03
negative regulation of translation	8	13.2×	1e-04
protein phosphorylation	12	6.8×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1588 predictions. Top by Δscore:

Variant	Effect	Δscore
4:75645698:ATCGG:A	acceptor_gain	1.0000
4:75645699:TCGG:T	acceptor_gain	1.0000
4:75645700:CGG:C	acceptor_gain	1.0000
4:75645700:CGGC:C	acceptor_gain	1.0000
4:75645701:G:T	acceptor_gain	1.0000
4:75645701:GG:G	acceptor_gain	1.0000
4:75645701:GGCT:G	acceptor_loss	1.0000
4:75645703:C:CC	acceptor_gain	1.0000
4:75645704:T:C	acceptor_gain	1.0000
4:75645704:T:TC	acceptor_gain	1.0000
4:75645705:T:C	acceptor_gain	1.0000
4:75645705:T:TC	acceptor_gain	1.0000
4:75645707:A:AC	acceptor_gain	1.0000
4:75645707:A:C	acceptor_gain	1.0000
4:75646333:CTTA:C	donor_gain	1.0000
4:75646334:TTACT:T	donor_loss	1.0000
4:75646335:TA:T	donor_loss	1.0000
4:75646336:A:AC	donor_gain	1.0000
4:75646336:AC:A	donor_loss	1.0000
4:75646337:C:CT	donor_gain	1.0000
4:75646337:CT:C	donor_gain	1.0000
4:75646337:CTT:C	donor_gain	1.0000
4:75646337:CTTT:C	donor_gain	1.0000
4:75646337:CTTTT:C	donor_gain	1.0000
4:75646453:AAAC:A	acceptor_gain	1.0000
4:75646454:AAC:A	acceptor_gain	1.0000
4:75646454:AACCT:A	acceptor_loss	1.0000
4:75646455:AC:A	acceptor_gain	1.0000
4:75646456:CC:C	acceptor_gain	1.0000
4:75646456:CCTGT:C	acceptor_loss	1.0000

AlphaMissense

3164 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:75645655:T:A	K408N	1.000
4:75645655:T:G	K408N	1.000
4:75645657:T:C	K408E	1.000
4:75645658:T:A	K407N	1.000
4:75645658:T:G	K407N	1.000
4:75645659:T:A	K407I	1.000
4:75645660:T:C	K407E	1.000
4:75645660:T:G	K407Q	1.000
4:75645668:A:T	V404E	1.000
4:75645670:A:C	N403K	1.000
4:75645670:A:T	N403K	1.000
4:75645672:T:C	N403D	1.000
4:75645674:A:G	L402S	1.000
4:75646360:A:T	V385D	1.000
4:75646377:A:C	F379L	1.000
4:75646377:A:T	F379L	1.000
4:75646378:A:C	F379C	1.000
4:75646378:A:G	F379S	1.000
4:75646379:A:C	F379V	1.000
4:75646379:A:G	F379L	1.000
4:75646379:A:T	F379I	1.000
4:75646381:A:T	V378D	1.000
4:75646384:A:T	V377E	1.000
4:75646386:A:C	F376L	1.000
4:75646386:A:T	F376L	1.000
4:75646387:A:C	F376C	1.000
4:75646387:A:G	F376S	1.000
4:75646388:A:C	F376V	1.000
4:75646388:A:G	F376L	1.000
4:75646388:A:T	F376I	1.000

dbSNP variants (sampled 300 via entrez): RS1000033236 (4:75700245 G>A), RS1000059936 (4:75664172 G>A), RS1000087813 (4:75657484 T>C), RS1000130565 (4:75705296 C>T), RS1000173991 (4:75700830 A>C), RS1000247700 (4:75708072 C>T), RS1000288885 (4:75663295 C>T), RS1000330009 (4:75706427 G>C), RS1000341006 (4:75686983 T>C), RS1000453956 (4:75701013 T>C), RS1000467812 (4:75706599 C>A), RS1000476824 (4:75687198 G>A,T), RS1000479255 (4:75651921 C>G,T), RS10004891 (4:75712482 G>T), RS1000526021 (4:75656157 ATTTTT>A,AT,ATTT,ATTTT,ATTTTTT)

Disease associations

OMIM: gene MIM:620020 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003160_4	Subjective response to lithium treatment in bipolar disorder	7.000000e-07
GCST004635_8	Testicular germ cell tumor	2.000000e-11
GCST009172_1	Response to (pegylated) interferon in HBeAg-negative hepatitis B	2.000000e-06
GCST010242_118	HDL cholesterol levels	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007859	response to interferon
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066456 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.84	Kd	1429	nM	CHEMBL5653589
5.84	ED50	1429	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2148408: Binding affinity to human G3BP2 incubated for 45 mins by Kinobead based pull down assay	kd	1.4293	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, decreases methylation	3
bisphenol A	decreases expression, increases expression	2
trichostatin A	affects cotreatment, decreases expression	2
arsenite	affects localization, affects binding, increases reaction	2
sodium arsenite	increases activity, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Nickel	increases expression	2
Tretinoin	affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sulforaphane	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
nutlin 3	increases secretion, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Air Pollutants, Occupational	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651450	Binding	Binding affinity to human G3BP2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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