GDI2

Summary

GDI2 (GDP dissociation inhibitor 2, HGNC:4227) is a protein-coding gene on chromosome 10p15.1, encoding Rab GDP dissociation inhibitor beta (P50395). GDP-dissociation inhibitor preventing the GDP to GTP exchange of most Rab proteins.

GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI2 is ubiquitously expressed. The GDI2 gene contains many repetitive elements indicating that it may be prone to inversion/deletion rearrangements. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 2665 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 62 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001494

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4227
Approved symbol	GDI2
Name	GDP dissociation inhibitor 2
Location	10p15.1
Locus type	gene with protein product
Status	Approved
Aliases	RABGDIB
Ensembl gene	ENSG00000057608
Ensembl biotype	protein_coding
OMIM	600767
Entrez	2665

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 20 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000380127, ENST00000380181, ENST00000380191, ENST00000418688, ENST00000447751, ENST00000456041, ENST00000479928, ENST00000608581, ENST00000609712, ENST00000865639, ENST00000865640, ENST00000925479, ENST00000925480, ENST00000925481, ENST00000925482, ENST00000925483, ENST00000925484, ENST00000925485, ENST00000972136, ENST00000972137, ENST00000972138

RefSeq mRNA: 2 — MANE Select: NM_001494 NM_001115156, NM_001494

CCDS: CCDS44352, CCDS7071

Canonical transcript exons

ENST00000380191 — 11 exons

Exon	Start	End
ENSE00001641353	5768213	5768384
ENSE00001647202	5800598	5800705
ENSE00001666686	5785142	5785273
ENSE00001675403	5796763	5796862
ENSE00001699249	5794885	5795019
ENSE00001734505	5766494	5766638
ENSE00001814394	5765223	5766152
ENSE00002146447	5785852	5786050
ENSE00002707809	5813214	5813434
ENSE00003529451	5766241	5766295
ENSE00003785974	5773842	5773941

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 224.5416 / max 2193.8198, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108117	224.5416	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.54	gold quality
ileal mucosa	UBERON:0000331	99.53	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.51	gold quality
colonic mucosa	UBERON:0000317	99.46	gold quality
corpus epididymis	UBERON:0004359	99.40	gold quality
trabecular bone tissue	UBERON:0002483	99.38	gold quality
visceral pleura	UBERON:0002401	99.37	gold quality
parietal pleura	UBERON:0002400	99.36	gold quality
secondary oocyte	CL:0000655	99.35	gold quality
epithelium of nasopharynx	UBERON:0001951	99.34	gold quality
oral cavity	UBERON:0000167	99.32	gold quality
cartilage tissue	UBERON:0002418	99.31	gold quality
pleura	UBERON:0000977	99.30	gold quality
superficial temporal artery	UBERON:0001614	99.30	gold quality
palpebral conjunctiva	UBERON:0001812	99.30	gold quality
tibia	UBERON:0000979	99.29	gold quality
calcaneal tendon	UBERON:0003701	99.29	gold quality
esophagus squamous epithelium	UBERON:0006920	99.25	gold quality
caput epididymis	UBERON:0004358	99.24	gold quality
endometrium epithelium	UBERON:0004811	99.24	gold quality
cauda epididymis	UBERON:0004360	99.23	gold quality
upper leg skin	UBERON:0004262	99.19	gold quality
embryo	UBERON:0000922	99.17	gold quality
skin of hip	UBERON:0001554	99.15	gold quality
monocyte	CL:0000576	99.13	gold quality
mononuclear cell	CL:0000842	99.13	gold quality
epithelium of esophagus	UBERON:0001976	99.13	gold quality
mammalian vulva	UBERON:0000997	99.12	gold quality
leukocyte	CL:0000738	99.09	gold quality
tongue squamous epithelium	UBERON:0006919	99.08	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	34.00
E-CURD-122	yes	22.91
E-MTAB-8410	yes	14.20
E-CURD-88	yes	12.47
E-MTAB-6678	yes	8.35
E-MTAB-10042	yes	5.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting GDI2, 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-4776-3P	100.00	68.73	1340
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429

Literature-anchored findings (GeneRIF, showing 6)

• Reduction of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down syndrome brain. (PMID:11771757)
• The increased levels of cyclin I and GDI2 found to be associated with pancreatic carcinoma were further confirmed by Western blot analyses in an independent series of serum samples and/or pancreatic juice samples (PMID:17507299)
• MicroRNA15b5p exerts its tumor repressive role via targeting GDI2: A novel insight into the pathogenesis of thyroid carcinoma. (PMID:32945458)
• GDI2 is a target of paclitaxel that affects tumorigenesis of prostate cancer via the p75NTR signaling pathway. (PMID:34051575)
• ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling. (PMID:34556814)
• GDI2 is a novel diagnostic and prognostic biomarker in hepatocellular carcinoma. (PMID:34894398)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gdi2	ENSDARG00000005451
mus_musculus	Gdi2	ENSMUSG00000021218
rattus_norvegicus	Gdi2	ENSRNOG00000018091
drosophila_melanogaster	Gdi	FBGN0004868
caenorhabditis_elegans		WBGENE00001558

Paralogs (3): CHM (ENSG00000188419), CHML (ENSG00000203668), GDI1 (ENSG00000203879)

Protein

Protein identifiers

Rab GDP dissociation inhibitor beta — P50395 (reviewed: P50395)

Alternative names: Guanosine diphosphate dissociation inhibitor 2

All UniProt accessions (8): P50395, Q5SX86, Q5SX87, Q5SX90, Q5SX91, Q6IAT1, V9GYF8, V9GYJ7

UniProt curated annotations — full annotation on UniProt →

Function. GDP-dissociation inhibitor preventing the GDP to GTP exchange of most Rab proteins. By keeping these small GTPases in their inactive GDP-bound form regulates intracellular membrane trafficking. Negatively regulates protein transport to the cilium and ciliogenesis through the inhibition of RAB8A.

Subunit / interactions. Interacts with RHOH. Interacts with the GDP-bound inactive forms of RAB3A, RAB3B, RAB3C, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43; binds RAB3D to a lesser extent. Interacts with DZIP1; this interaction negatively regulates the interaction of GDI2 with GDP-bound RAB8A.

Subcellular location. Cytoplasm. Membrane. Golgi apparatus. trans-Golgi network.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the Rab GDI family.

Isoforms (2)

UniProt ID	Names	Canonical?
P50395-1	1	yes
P50395-2	2

RefSeq proteins (2): NP_001108628, NP_001485* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000806	RabGDI	Family
IPR018203	GDP_dissociation_inhibitor	Family
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily

Pfam: PF00996

UniProt features (10 total): modified residue 7, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50395-F1	93.71	0.88

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 (7): 1, 57, 61, 112, 130, 269, 382

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 287 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_SMC1L1, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GNF2_BNIP2, GOCC_SECRETORY_GRANULE, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, MORF_UBE2I, MORF_HDAC1, MORF_RAD21, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, HSIAO_HOUSEKEEPING_GENES, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (7): signal transduction (GO:0007165), small GTPase-mediated signal transduction (GO:0007264), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), negative regulation of cilium assembly (GO:1902018), negative regulation of protein localization to cilium (GO:1903565), negative regulation of protein localization (GO:1903828)

GO Molecular Function (6): RNA binding (GO:0003723), Rab GDP-dissociation inhibitor activity (GO:0005093), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), GDP-dissociation inhibitor activity (GO:0005092), protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), vesicle (GO:0031982), secretory granule lumen (GO:0034774), azurophil granule lumen (GO:0035578), synapse (GO:0045202), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	2
transport	2
intracellular protein localization	2
GTPase regulator activity	2
cytoplasm	2
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signaling cassette	1
establishment of protein localization	1
cilium assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
negative regulation of organelle assembly	1
protein localization to cilium	1
regulation of protein localization to cilium	1
negative regulation of protein localization	1
regulation of protein localization	1
negative regulation of biological process	1
nucleic acid binding	1
GDP-dissociation inhibitor activity	1
GTPase activity	1
enzyme activator activity	1
GTPase binding	1
GDP binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cell-substrate junction	1
membrane-bounded organelle	1
secretory granule	1
cytoplasmic vesicle lumen	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
cell junction	1
extracellular vesicle	1

Protein interactions and networks

STRING

2430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GDI2	AGFG1	P52594	899
GDI2	RAB1A	P11476	896
GDI2	RAB3A	P20336	725
GDI2	RAB10	P61026	658
GDI2	RAB6A	P20340	632
GDI2	RAB6D	Q53S08	609
GDI2	ARHGDIB	P52566	599
GDI2	USO1	O60763	598
GDI2	NSF	P46459	588
GDI2	ATP6AP1	Q15904	585
GDI2	ARHGDIA	P52565	550
GDI2	SCFD1	Q8WVM8	543
GDI2	RAB7A	P51149	521
GDI2	YWHAG	P35214	518
GDI2	VPS33B	Q9H267	518

IntAct

191 interactions, top by confidence:

A	B	Type	Score
RAB8A	GDI1	psi-mi:“MI:0914”(association)	0.860
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
RAB12	GDI1	psi-mi:“MI:0914”(association)	0.790
RAB10	GDI1	psi-mi:“MI:0914”(association)	0.790
GDI2	RAB8A	psi-mi:“MI:0914”(association)	0.760
RAB5A	GDI1	psi-mi:“MI:0914”(association)	0.730
RAB6B	GDI1	psi-mi:“MI:0914”(association)	0.730
RAB9A	GDI1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RAB24	GDI2	psi-mi:“MI:0915”(physical association)	0.710
RAB4A	GDI2	psi-mi:“MI:0915”(physical association)	0.690
GDI2	RAB4A	psi-mi:“MI:2364”(proximity)	0.690
RAB31	CHM	psi-mi:“MI:0914”(association)	0.640
DNAJC8	SF3B1	psi-mi:“MI:0914”(association)	0.640
RAB8B	GDI1	psi-mi:“MI:0914”(association)	0.640
RAB9A	CHM	psi-mi:“MI:0914”(association)	0.610
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
RAB2B	GDI2	psi-mi:“MI:0915”(physical association)	0.560
GDI2	Rab10	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (312): GDI2 (Affinity Capture-MS), GDI2 (Affinity Capture-MS), GDI2 (Affinity Capture-MS), GDI2 (Affinity Capture-MS), GDI2 (Two-hybrid), GDI2 (Affinity Capture-RNA), CLIC3 (Co-fractionation), EZR (Co-fractionation), FH (Co-fractionation), GDI2 (Co-fractionation), GDI2 (Co-fractionation), GDI2 (Co-fractionation), GDI2 (Co-fractionation), GDI2 (Co-fractionation), GDI2 (Co-fractionation)

ESM2 similar proteins: A0A0K9RL25, A0A0U1WZ18, A0A1S4A695, A4FV08, A4IHW6, O15305, O35621, O80840, O88958, O97555, O97556, P21856, P31150, P38024, P46926, P50395, P50396, P50397, P50398, P50399, P60028, Q1W374, Q1W375, Q1W376, Q1W377, Q259G4, Q3SZJ9, Q42521, Q4R5Y2, Q5E982, Q5R8T8, Q5RCE1, Q5ZID6, Q5ZJL4, Q60HD6, Q61598, Q64422, Q6IA69, Q6PA43, Q6Q7J2

Diamond homologs: G4MT60, O24653, O97555, O97556, P21856, P31150, P39958, P50395, P50396, P50397, P50398, P50399, P60028, Q10305, Q5RCE1, Q61598, Q6Q7J2, Q7YQM0, Q8HXX7, Q96254, Q9LXC0, O93831, P24386, P26374, P37727, Q9QXG2, Q9QZD5, Q9V8W3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 186 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
RAB geranylgeranylation	34	42.6×	3e-46
TBC/RABGAPs	14	26.3×	2e-14
RAB GEFs exchange GTP for GDP on RABs	27	24.3×	3e-28
Signaling by high-kinase activity BRAF mutants	5	11.5×	7e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	10	11.2×	4e-06
MAP2K and MAPK activation	5	10.3×	8e-03
Selective autophagy	5	10.1×	8e-03
Signaling by moderate kinase activity BRAF mutants	5	9.2×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
Rab protein signal transduction	7	41.8×	6e-08
antigen processing and presentation	9	38.1×	6e-10
autophagosome assembly	11	14.9×	6e-08
endocytic recycling	8	12.9×	3e-05
exocytosis	11	10.1×	3e-06
endosomal transport	6	8.8×	4e-03
macroautophagy	6	8.7×	4e-03
intracellular protein transport	21	8.2×	2e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	39
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
58710	GRCh38/hg38 10p15.3-15.1(chr10:69260-6209368)x1	Pathogenic

SpliceAI

2043 predictions. Top by Δscore:

Variant	Effect	Δscore
10:5766148:AAGAT:A	acceptor_gain	1.0000
10:5766152:TCTGA:T	acceptor_loss	1.0000
10:5766153:C:CC	acceptor_gain	1.0000
10:5766237:TCACC:T	donor_loss	1.0000
10:5766238:CACCT:C	donor_loss	1.0000
10:5766239:A:AC	donor_gain	1.0000
10:5766239:A:T	donor_loss	1.0000
10:5766240:C:CA	donor_loss	1.0000
10:5766240:C:CC	donor_gain	1.0000
10:5766240:CCTGG:C	donor_gain	1.0000
10:5766291:CAAAT:C	acceptor_gain	1.0000
10:5766296:C:CC	acceptor_gain	1.0000
10:5766296:C:CG	acceptor_loss	1.0000
10:5766297:T:A	acceptor_loss	1.0000
10:5766488:ACT:A	donor_loss	1.0000
10:5766490:TCACT:T	donor_loss	1.0000
10:5766491:CACT:C	donor_loss	1.0000
10:5766492:A:AC	donor_gain	1.0000
10:5766492:ACT:A	donor_loss	1.0000
10:5766492:ACTT:A	donor_gain	1.0000
10:5766493:C:CA	donor_gain	1.0000
10:5766493:C:G	donor_loss	1.0000
10:5766493:CT:C	donor_gain	1.0000
10:5766493:CTT:C	donor_gain	1.0000
10:5766493:CTTC:C	donor_gain	1.0000
10:5766493:CTTCT:C	donor_gain	1.0000
10:5766495:T:TA	donor_gain	1.0000
10:5766636:TAT:T	acceptor_gain	1.0000
10:5766636:TATCT:T	acceptor_loss	1.0000
10:5766637:ATC:A	acceptor_loss	1.0000

AlphaMissense

2943 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:5768373:A:C	C277W	1.000
10:5773933:G:T	A243D	1.000
10:5773939:A:G	L241P	1.000
10:5773941:C:A	R240S	1.000
10:5773941:C:G	R240S	1.000
10:5785142:C:A	R240M	1.000
10:5785142:C:G	R240T	1.000
10:5785147:A:C	F238L	1.000
10:5785147:A:T	F238L	1.000
10:5785149:A:G	F238L	1.000
10:5785153:T:A	Q236H	1.000
10:5785153:T:G	Q236H	1.000
10:5785172:C:A	G230V	1.000
10:5785172:C:T	G230D	1.000
10:5785173:C:G	G230R	1.000
10:5785218:A:G	S215P	1.000
10:5794914:G:T	P120H	1.000
10:5794967:A:C	F102L	1.000
10:5794967:A:T	F102L	1.000
10:5794968:A:G	F102S	1.000
10:5794969:A:G	F102L	1.000
10:5795001:A:G	L91P	1.000
10:5796793:C:G	D75H	1.000
10:5796795:A:T	V74D	1.000
10:5796802:A:G	W72R	1.000
10:5796802:A:T	W72R	1.000
10:5800632:C:T	G40E	1.000
10:5800636:A:G	Y39H	1.000
10:5800659:A:G	L31P	1.000
10:5800662:A:T	V30D	1.000

dbSNP variants (sampled 300 via entrez): RS1000056388 (10:5802869 A>G), RS1000108169 (10:5784832 CAG>C), RS1000147074 (10:5774536 G>A), RS1000161819 (10:5813680 G>A,C), RS1000219904 (10:5806748 T>TC), RS1000225898 (10:5797801 C>G), RS1000278113 (10:5798029 C>G), RS1000289302 (10:5790532 A>G), RS1000346166 (10:5791913 C>T), RS1000360577 (10:5796270 A>G), RS1000445131 (10:5786790 G>A), RS1000586476 (10:5805549 T>C), RS1000654541 (10:5781481 C>A,G,T), RS1000723410 (10:5794785 A>G), RS1000742877 (10:5773191 A>T)

Disease associations

OMIM: gene MIM:600767 | 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
GCST002056_5	Osteosarcoma	8.000000e-06
GCST006585_247	Blood protein levels	9.000000e-14
GCST010304_51	Cutaneous malignant melanoma	4.000000e-06
GCST012489_50	Heel bone mineral density x serum urate levels interaction	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066507 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.29	Kd	513.7	nM	CHEMBL5653589
6.29	ED50	513.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 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	2148424: Binding affinity to human GDI2 incubated for 45 mins by Kinobead based pull down assay	kd	0.5137	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	3
Air Pollutants	increases abundance, increases oxidation, affects expression, affects cotreatment	2
Ozone	increases oxidation, increases abundance, affects expression, affects cotreatment	2
Smoke	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression, increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
pyrogallol 1,3-dimethyl ether	increases expression, decreases expression, affects cotreatment, affects localization	1
arsenite	affects binding, decreases reaction, increases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
chloropicrin	increases expression	1
nickel acetate	affects expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	affects methylation	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	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
CHEMBL5651466	Binding	Binding affinity to human GDI2 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

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2XL	Abcam HEK293T GDI2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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