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): 63 total — 1 pathogenic
• GTEx eGene: eQTL in 45 tissues, sQTL in 6 (q < 0.05)
• Constraint (gnomAD): pLI 0.48 (intermediate), LOEUF 0.77 (unconstrained)
• MANE Select transcript: NM_001494
• Interaction hub: 2,078 STRING partners (top 7% of genes corpus-wide)
• Notable: 63 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 31 — 25 protein_coding, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000380191

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 4, TSL 5: 2

ENST00000380191, ENST00000380127, ENST00000380181, ENST00000418688, ENST00000447751, ENST00000456041, ENST00000479928, ENST00000608581, ENST00000609712, ENST00000865639, ENST00000865640, ENST00000925479, ENST00000925480, ENST00000925481, ENST00000925482, ENST00000925483, ENST00000925484, ENST00000925485, ENST00000972136, ENST00000972137, ENST00000972138, ENST00000991541, ENST00001012274, ENST00001012275, ENST00001012278, ENST00001012280, ENST00001082739, ENST00001115160, ENST00001115161, ENST00001122220, ENST00001136342

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.

Highest expression (Bgee): jejunal mucosa, ileal mucosa, mucosa of sigmoid colon, colonic mucosa, corpus epididymis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GDI2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 51 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.8e-50	-0.28	10:5813440:G:C
Artery Tibial	eqtl	4.8e-50	-0.43	10:5813440:G:C
Adipose Subcutaneous	eqtl	1.0e-43	-0.35	10:5813440:G:C
Nerve Tibial	eqtl	4.4e-32	-0.26	10:5813440:G:C
Adipose Visceral Omentum	eqtl	1.3e-31	-0.30	10:5813440:G:C
Skin Not Sun Exposed Suprapubic	eqtl	2.3e-31	-0.33	10:5813440:G:C
Skin Sun Exposed Lower leg	eqtl	2.0e-30	-0.28	10:5813440:G:C
Pancreas	eqtl	5.8e-30	-0.37	10:5813440:G:C
Breast Mammary Tissue	eqtl	3.0e-29	-0.26	10:5813440:G:C
Artery Aorta	eqtl	7.6e-28	-0.36	10:5813440:G:C
Thyroid	eqtl	2.3e-26	-0.28	10:5813440:G:C
Esophagus Muscularis	eqtl	1.2e-25	-0.22	10:5813440:G:C
Esophagus Gastroesophageal Junction	eqtl	2.1e-23	-0.28	10:5813440:G:C
Colon Sigmoid	eqtl	1.5e-22	-0.32	10:5813440:G:C
Stomach	eqtl	2.2e-19	-0.27	10:5807954:C:G
Lung	eqtl	1.1e-18	-0.20	10:5813440:G:C
Heart Atrial Appendage	eqtl	5.9e-18	-0.27	10:5813440:G:C
Prostate	eqtl	1.3e-15	-0.39	10:5813440:G:C
Brain Nucleus accumbens basal ganglia	eqtl	1.4e-15	-0.36	10:5813440:G:C
Testis	eqtl	4.0e-15	-0.18	10:5813440:G:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
108117	224.5416	1827

Top tissues by expression

showing 100 of 295 tissues 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
ganglionic eminence	UBERON:0004023	99.07	gold quality
upper arm skin	UBERON:0004263	99.07	gold quality
bronchial epithelial cell	CL:0002328	99.03	gold quality
ventricular zone	UBERON:0003053	99.03	gold quality
oviduct epithelium	UBERON:0004804	98.98	gold quality
epithelium of mammary gland	UBERON:0003244	98.97	gold quality
cortical plate	UBERON:0005343	98.97	gold quality
gingiva	UBERON:0001828	98.96	gold quality
duodenum	UBERON:0002114	98.95	gold quality
endometrium	UBERON:0001295	98.94	gold quality
parotid gland	UBERON:0001831	98.94	gold quality
seminal vesicle	UBERON:0000998	98.93	gold quality
mammary duct	UBERON:0001765	98.92	gold quality
pigmented layer of retina	UBERON:0001782	98.92	gold quality
squamous epithelium	UBERON:0006914	98.90	gold quality
epithelium of bronchus	UBERON:0002031	98.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.89	gold quality
tendon	UBERON:0000043	98.88	gold quality
bronchus	UBERON:0002185	98.86	gold quality
nasal cavity epithelium	UBERON:0005384	98.86	gold quality
amniotic fluid	UBERON:0000173	98.85	gold quality
vermiform appendix	UBERON:0001154	98.85	gold quality
mammary gland	UBERON:0001911	98.82	gold quality
gingival epithelium	UBERON:0001949	98.82	gold quality
thoracic mammary gland	UBERON:0005200	98.81	gold quality
epithelial cell of pancreas	CL:0000083	98.80	gold quality
islet of Langerhans	UBERON:0000006	98.80	gold quality
lymph node	UBERON:0000029	98.79	gold quality
caecum	UBERON:0001153	98.75	gold quality
tonsil	UBERON:0002372	98.74	gold quality
pancreas	UBERON:0001264	98.71	gold quality
adrenal tissue	UBERON:0018303	98.68	gold quality
rectum	UBERON:0001052	98.67	gold quality
body of pancreas	UBERON:0001150	98.67	gold quality
placenta	UBERON:0001987	98.67	gold quality
layer of synovial tissue	UBERON:0007616	98.66	gold quality
heart right ventricle	UBERON:0002080	98.61	gold quality
smooth muscle tissue	UBERON:0001135	98.59	gold quality
tendon of biceps brachii	UBERON:0008188	98.58	gold quality
germinal epithelium of ovary	UBERON:0001304	98.54	gold quality
myocardium	UBERON:0002349	98.53	gold quality
lower lobe of lung	UBERON:0008949	98.52	gold quality
penis	UBERON:0000989	98.50	gold quality
nephron tubule	UBERON:0001231	98.50	gold quality
periodontal ligament	UBERON:0008266	98.49	gold quality
jejunum	UBERON:0002115	98.47	gold quality
adult organism	UBERON:0007023	98.46	gold quality
tibialis anterior	UBERON:0001385	98.45	gold quality
bone marrow	UBERON:0002371	98.40	gold quality
fallopian tube	UBERON:0003889	98.40	gold quality
gall bladder	UBERON:0002110	98.39	gold quality
oocyte	CL:0000023	98.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.35	gold quality
hair follicle	UBERON:0002073	98.32	gold quality
nasal cavity mucosa	UBERON:0001826	98.31	gold quality
kidney epithelium	UBERON:0004819	98.30	gold quality
bone marrow cell	CL:0002092	98.29	gold quality
synovial joint	UBERON:0002217	98.28	gold quality
buccal mucosa cell	CL:0002336	98.27	gold quality
cranial nerve II	UBERON:0000941	98.27	gold quality
pharyngeal mucosa	UBERON:0000355	98.26	gold quality
urinary bladder	UBERON:0001255	98.25	gold quality
cervix epithelium	UBERON:0004801	98.25	gold quality
pericardium	UBERON:0002407	98.24	gold quality
deltoid	UBERON:0001476	98.23	gold quality
left ventricle myocardium	UBERON:0006566	98.19	gold quality
uterus	UBERON:0000995	98.18	gold quality
type B pancreatic cell	CL:0000169	98.16	gold quality
stromal cell of endometrium	CL:0002255	98.16	gold quality
colonic epithelium	UBERON:0000397	98.12	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	250.7
Frontal cortex	tissue	247.2
Liver	tissue	225.4	low
Tonsil	tissue	224.1	medium
Spinal cord	tissue	217.9
Thalamus	tissue	205.4
Lymph node	tissue	203.1	low
Pons	tissue	199.2
Midbrain	tissue	195.0
Medulla oblongata	tissue	190.7
Superior colliculi	tissue	188.1
Cerebral cortex	tissue	183.9	medium
Somatosensory cortex	tissue	183.9
Substantia nigra	tissue	181.0
Hippocampal formation	tissue	173.5
Occipital cortex	tissue	173.0
Corpus callosum	tissue	172.9
Putamen	tissue	172.8
Prefrontal cortex	tissue	170.3
Motor cortex	tissue	165.6
Duodenum	tissue	165.1	medium
Ventral forebrain	tissue	160.5
Hypothalamus	tissue	160.0
Pancreas	tissue	155.7	high
Septum	tissue	152.9
Basal ganglia	tissue	152.8	medium
Rectum	tissue	150.9	medium
Small intestine	tissue	150.9	medium
Temporal cortex	tissue	150.4
Entorhinal cortex	tissue	149.7
Retrosplenial and cingulate cortex	tissue	149.1
Periaqueductal gray	tissue	147.2
Colon	tissue	143.2	medium
Appendix	tissue	143.0	medium
Retrosplenial cortex	tissue	141.6
Thymus	tissue	139.0
Kidney	tissue	136.2	medium
Urinary bladder	tissue	136.0	medium
Insular cortex	tissue	133.2
Spleen	tissue	130.7	medium
Ovary	tissue	130.2	high
Breast	tissue	129.1	medium
Placenta	tissue	127.3	low
Cerebellum	tissue	127.0	low
Amygdala	tissue	125.9
Esophagus	tissue	123.1	low
Bone marrow	tissue	119.5	medium
Adipose tissue	tissue	117.3	not detected
Smooth muscle	tissue	115.9	low
Olfactory bulb	tissue	113.6
Cervix	tissue	113.4	low
Locus coeruleus	tissue	112.9
Epididymis	tissue	108.8	medium
Thyroid gland	tissue	106.8	low
Gallbladder	tissue	105.6	medium
Adrenal gland	tissue	105.4	medium
Stomach 1	tissue	102.4	medium
Skin 1	tissue	101.6	low
Choroid plexus	tissue	96.4
Tongue	tissue	93.1

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (217.9), Dorsal spinal cord (191.3), Dorsal hippocampus (173.5), White matter (172.9), Ventral hippocampus (160.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GDI2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 56 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.481, LOEUF 0.774, missense Z 0.788 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000380191 — one region, missense o/e 0.77.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99845) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal lens morphology	1
cataract	1
abnormal retina morphology	1
abnormal vitreous body morphology	1
abnormal retina vasculature morphology	1
embryonic growth retardation	1
impaired glucose tolerance	1
abnormal retina blood vessel morphology	1
embryonic lethality during organogenesis, complete penetrance	1
preweaning lethality, complete penetrance	1
increased embryonic tissue cell apoptosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	P60028	100.0%	Diamond
Pongo pygmaeus	Q7YQM0	99.8%	Diamond
Macaca fascicularis	Q8HXX7	99.8%	Diamond
Pongo abelii	Q5RCE1	99.6%	Diamond
Canis lupus familiaris	O97555	99.3%	Diamond
Bos taurus	P21856	98.9%	Diamond
Sus scrofa	Q6Q7J2	97.8%	Diamond
Arabidopsis thaliana	O24653	91.9%	Diamond
Saccharomyces cerevisiae S288C	P39958	61.4%	Diamond
Schizosaccharomyces pombe 972h-	Q10305	61.4%	Diamond
Pyricularia oryzae 70-15	G4MT60	58.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TRV-TAC3-1	tRNA	100189342
TASOR2	protein-coding	54906
ASB13	protein-coding	79754
ANKRD16	protein-coding	54522
FBH1	protein-coding	84893
IL15RA	protein-coding	3601
LINC02677	ncRNA	102723629

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane

Antibody reliability (HPA): IH supported · IF approved

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)

Type	Positions
N-acetylmethionine	1
N6-succinyllysine	57
Phosphoserine	61, 130, 382
N6-acetyllysine	112, 269

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-6798695	Neutrophil degranulation	—
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs	—
R-HSA-9007101	Rab regulation of trafficking	—
R-HSA-5653656	Vesicle-mediated transport	—

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), regulation of protein localization (GO:0032880)

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

5 top-level categories:

Category	Pathways
Innate Immune System	1
Rab regulation of trafficking	1
Immune System	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

39 GO namespaces:

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 localization	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of cilium assembly	BP	mutant phenotype
negative regulation of protein localization to cilium	BP	mutant phenotype
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
vesicle	CC	high-throughput assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 2,078 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GDI2	RAB1A	P11476	818
GDI2	AGFG1	P52594	808
GDI2	RAB3A	P20336	700
GDI2	ATP6AP1	Q15904	569
GDI2	ARHGDIB	P52566	534
GDI2	ARHGDIA	P52565	511
GDI2	RAB5A	P20339	450
GDI2	RAB6A	P20340	439
GDI2	RAB10	P61026	424
GDI2	RAB8A	P24407	422
GDI2	GDI1	P31150	418
GDI2	RAB11A	P24410	417
GDI2	VPS26A	O75436	417
GDI2	RAB29	O14966	409
GDI2	LRRN2	O75325	409

IntAct

Human interaction partners of GDI2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

23 partners by confidence:

Partner	Interaction type	MIscore	Records
RAB8A	association	0.760	3
RAB24	physical association	0.710	1
RAB4A	physical association	0.690	2
RAB2B	physical association	0.560	1
FN1	association	0.530	1
RAB1A	physical association	0.400	2
HSPB1	physical association	0.370	2
GLRA2	physical association	0.370	1
MACROH2A1	association	0.350	1
RAB18	association	0.350	1
SGTA	association	0.350	1
ACTR6	physical association	0.000	1
ARF6	physical association	0.000	1
ATG5	physical association	0.000	1
EIF1B	physical association	0.000	1
EIF6	physical association	0.000	1
GH1	physical association	0.000	1
PAK2	physical association	0.000	1
PRKAB1	physical association	0.000	1
SGK1	physical association	0.000	1
TNFRSF14	physical association	0.000	1
TRAF6	physical association	0.000	1
VHL	physical association	0.000	1

BioGRID (316 interactions; top human partners by supporting records): GDI1 (Affinity Capture-MS; 10 records), RAB9A (Affinity Capture-MS; 8 records), RAB1A (Co-fractionation; 7 records), RAB5A (Affinity Capture-MS; 7 records), RAB1B (Affinity Capture-MS; 6 records), RAB4A (Reconstituted Complex; 6 records), RAB24 (Affinity Capture-MS; 5 records), RAB2A (Reconstituted Complex; 4 records), RAB5C (Affinity Capture-MS; 4 records), RAB6B (Affinity Capture-MS; 4 records), RAB7A (Co-fractionation; 4 records), RAB8B (Co-fractionation; 4 records), FN1 (Affinity Capture-MS; 3 records), RAB10 (Co-fractionation; 3 records), RAB11A (Reconstituted Complex; 3 records)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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	6	54.6×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
autophagy	5	23.9×	6e-04

Disease & clinical

Genetic variants

Variant evidence for GDI2: 63 ClinVar records (1 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
58710	GRCh38/hg38 10p15.3-15.1(chr10:69260-6209368)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore GDI2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 1,089):

Position(s)	Effect	Δscore	Sites
10:5766153–5766154	acceptor_loss	1.0000	3
10:5766239–5766240	donor_loss	1.0000	4
10:5766296–5766297	acceptor_loss	1.0000	5
10:5766492–5766493	donor_loss	1.0000	3
10:5766639–5766640	acceptor_loss	1.0000	4
10:5768211–5768212	donor_loss	1.0000	5
10:5768385–5768386	acceptor_loss	1.0000	5
10:5785140–5785141	donor_loss	1.0000	5
10:5785851	donor_loss	1.0000	2
10:5785855	donor_gain	1.0000

AlphaMissense

1,661 missense substitutions predicted likely pathogenic (of 2,943 scored), across 360 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M250	9	0.970	0.999
D34	8	0.998	0.999
D75	8	0.998	1.000
D331	8	0.998	0.999
H187	8	0.997	0.999
F102	8	0.996	1.000
F238	8	0.995	1.000
D405	8	0.990	0.998
H409	8	0.988	0.997
H32	8	0.986	0.998
F184	8	0.978	0.999
F410	8	0.977	0.998
D6	8	0.964	0.995
F135	8	0.962	0.988
D283	8	0.959	0.992
S222	8	0.957	0.999
S108	8	0.940	0.999
F140	8	0.939	0.994
D416	8	0.928	0.985
F80	8	0.926	0.996

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.19e-09
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	9e-08
Glioblastoma Multiforme (validation)	favorable	2.96e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000667

Disease associations

OMIM: gene MIM:600767 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST006585_1975	Blood protein levels	9e-14
GCST012489_7	Heel bone mineral density x serum urate levels interaction	1e-8
GCST010304_51	Cutaneous malignant melanoma	4e-6
GCST002056_5	Osteosarcoma	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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 (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	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	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GDI2 across ~30M SureChEMBL compounds — explore on Sugi Predict.