ARHGDIB

Summary

ARHGDIB (Rho GDP dissociation inhibitor beta, HGNC:679) is a protein-coding gene on chromosome 12p12.3, encoding Rho GDP-dissociation inhibitor 2 (P52566). Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them.

Members of the Rho (or ARH) protein family (see MIM 165390) and other Ras-related small GTP-binding proteins (see MIM 179520) are involved in diverse cellular events, including cell signaling, proliferation, cytoskeletal organization, and secretion. The GTP-binding proteins are active only in the GTP-bound state. At least 3 classes of proteins tightly regulate cycling between the GTP-bound and GDP-bound states: GTPase-activating proteins (GAPs), guanine nucleotide-releasing factors (GRFs), and GDP-dissociation inhibitors (GDIs). The GDIs, including ARHGDIB, decrease the rate of GDP dissociation from Ras-like GTPases (summary by Scherle et al., 1993 [PubMed 8356058]).

Source: NCBI Gene 397 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 30 total
• Druggable target: yes
• MANE Select transcript: NM_001175

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:679
Approved symbol	ARHGDIB
Name	Rho GDP dissociation inhibitor beta
Location	12p12.3
Locus type	gene with protein product
Status	Approved
Aliases	Ly-GDI, RhoGDI2
Ensembl gene	ENSG00000111348
Ensembl biotype	protein_coding
OMIM	602843
Entrez	397

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000228945, ENST00000535676, ENST00000536592, ENST00000539131, ENST00000541380, ENST00000541546, ENST00000541644, ENST00000542276, ENST00000545895, ENST00000880005, ENST00000880006, ENST00000880007, ENST00000880008, ENST00000880009, ENST00000880010, ENST00000880011, ENST00000970038

RefSeq mRNA: 5 — MANE Select: NM_001175 NM_001175, NM_001321420, NM_001321421, NM_001321422, NM_001321423

CCDS: CCDS8671

Canonical transcript exons

ENST00000228945 — 6 exons

Exon	Start	End
ENSE00000999867	14942031	14942721
ENSE00002271391	14961537	14961601
ENSE00003467352	14944776	14944839
ENSE00003565003	14950532	14950724
ENSE00003611072	14947873	14947949
ENSE00003790402	14949802	14949885

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 263.3287 / max 5475.5919, expressed in 1582 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129908	252.6748	1311
129900	4.7374	1098
129907	1.9010	348
129905	1.7404	387
129911	1.1831	453
129910	0.4819	261
129904	0.2894	165
129909	0.1900	116
129901	0.1307	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.80	gold quality
monocyte	CL:0000576	99.77	gold quality
leukocyte	CL:0000738	99.76	gold quality
mononuclear cell	CL:0000842	99.76	gold quality
bone marrow	UBERON:0002371	99.71	gold quality
granulocyte	CL:0000094	99.70	gold quality
trabecular bone tissue	UBERON:0002483	99.63	gold quality
bone marrow cell	CL:0002092	99.55	gold quality
lymph node	UBERON:0000029	99.55	gold quality
spleen	UBERON:0002106	99.55	gold quality
vermiform appendix	UBERON:0001154	99.54	gold quality
thymus	UBERON:0002370	99.46	gold quality
right lung	UBERON:0002167	99.12	gold quality
caecum	UBERON:0001153	99.11	gold quality
gall bladder	UBERON:0002110	98.93	gold quality
palpebral conjunctiva	UBERON:0001812	98.90	gold quality
superficial temporal artery	UBERON:0001614	98.81	gold quality
upper lobe of left lung	UBERON:0008952	98.76	gold quality
epithelium of nasopharynx	UBERON:0001951	98.75	gold quality
upper lobe of lung	UBERON:0008948	98.74	gold quality
lower lobe of lung	UBERON:0008949	98.63	gold quality
descending thoracic aorta	UBERON:0002345	98.54	gold quality
omental fat pad	UBERON:0010414	98.52	gold quality
peritoneum	UBERON:0002358	98.51	gold quality
right coronary artery	UBERON:0001625	98.50	gold quality
nasal cavity epithelium	UBERON:0005384	98.48	gold quality
visceral pleura	UBERON:0002401	98.46	gold quality
thoracic aorta	UBERON:0001515	98.44	gold quality
ascending aorta	UBERON:0001496	98.43	gold quality
tonsil	UBERON:0002372	98.43	gold quality

Single-cell (SCXA)

Detected in 46 experiment(s), a significant marker in 38.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	4138.98
E-GEOD-130473	yes	2432.47
E-MTAB-8221	yes	1440.80
E-MTAB-8142	yes	1405.66
E-HCAD-10	yes	1326.54
E-CURD-98	yes	1188.49
E-HCAD-1	yes	1134.04
E-MTAB-10662	yes	1032.04
E-MTAB-9906	yes	1015.69
E-MTAB-7381	yes	989.19
E-MTAB-9435	yes	960.70
E-MTAB-5061	yes	875.53
E-GEOD-125970	yes	794.45
E-GEOD-114530	yes	661.05
E-MTAB-10287	yes	611.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, ETS1

miRNA regulators (miRDB)

47 targeting ARHGDIB, 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-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6895-3P	98.79	65.69	996

Literature-anchored findings (GeneRIF, showing 40)

• These data suggest that D4-GDI of Rho family GTPase may be regulated during apoptosis through the caspase-3 mediated cleavage of the GDI protein. (PMID:11989976)
• Results demonstrate that modification of Rho guanine nucleotide dissociation inhibitor (GDI) 2 during apoptosis is often accompanied by their relocalisation between cellular compartments [Rho GDI 2 ] (PMID:12203895)
• the interaction of Vav1 and Ly-GDI creates a fine tuning mechanism for the regulation of intracellular signaling pathways leading to NFAT stimulation (PMID:12386169)
• RhoGDI2 has a role in progression of bladder cancer (PMID:15173088)
• RhoGDI2 may be implicated in the progress of malignancy. (PMID:17487395)
• One gene identified by microarray gene expression analysis, RhoGDI2, was tested and confirmed to be metastasis supressor gene; results from cells expressing RhoG-two molecular effectors of RhoGDI2 signaling were identified: endothelin-1 and Neuromedin U. (PMID:17826660)
• Rho-GDI beta has two roles: one that suppresses tumor progression by inhibiting migration and the other that stimulates it by enhancing Cox-2 expression (PMID:18006811)
• D4-GDI with two mutations (V68L & V69A) inhibited GDP dissociation from Rho in a dominant negative manner. It accelerates invasion via regulation of cytoskeletal machinery. (PMID:18037226)
• Transgenic mice with T cell-specific expression display altered cellular immunity against cytozoic pathogens (PMID:18689726)
• Overexpression of D4-GDI is associated with breast cancer. (PMID:19269969)
• RhoGDI2 metastasis inhibition works through Rho GTPases but via a mechanism distinct from inhibition of membrane association. (PMID:19276387)
• phosphorylation by Src enhances RhoGDI2 metastasis suppression and loss of Src relieves metastasis suppression in tumor cells that maintain RhoGDI2 expression. (PMID:19321744)
• RhoGDI2 is involved in gastric tumor growth and metastasis, and that RhoGDI2 may be a useful marker for tumor progression of human gastric cancer. (PMID:19351766)
• Results show that the established nerve invasion model and the consensus signature of perineural invasion could be instrumental in the identification of novel therapeutic targets of pancreatic cancer as exemplified by KIF14 and ARHGDIbeta. (PMID:19509238)
• RhoGDI2 is associated with c-Src in bladder tumors, where the expression of both is diminished as a function of stage. c-Src binds to and phosphorylates RhoGDI2 resulting in enhanced metastasis suppressive potency. Review. (PMID:20013033)
• High LyGDI serum levels are associated with ovarian cancer. (PMID:20375790)
• RhoGDI2 is likely to be involved in lung tumor malignancy and metastasis. (PMID:20596634)
• This study has revealed that Rho GDP-dissociation inhibitor 2, Y-box binding protein 1, and the HSP70/90 organizing protein have a critical role to play in resistance to cyclin-depedent kinases inhibitor. (PMID:21067243)
• identification of LyGDI as a binding partner of SHIP, associating inducibly with the SHIP/Grb2/Shc complex (PMID:21695085)
• Overexpression of RhoGDI2 correlates with tumor progression in colorectal carcinoma. (PMID:21861235)
• The ARHGDIB is a lymphoid-specific intrinsic negative regulator of HIV-1 replication that acts by simultaneously inhibiting RhoA and Rac1 functions. (PMID:21936715)
• PLCgamma plays a key role in RhoGDI2-mediated cisplatin resistance and cell invasion in gastric cancer cells. (PMID:21986528)
• activation of the Src family members and downstream signalling proteins are associated with a good prognosis in transitional cell carcinoma of the bladder, and activated Src has a positive relationship with RhoGD12. (PMID:22353809)
• We delineate the mechanism by which RhoGDI2 promotes gastric cancer cell invasion and chemoresistance. In total, 47 differential protein spots were identified; 33 were upregulated, and 14 were downregulated by RhoGDI2 overexpression. (PMID:22364609)
• RhoGDI2 suppresses lung metastasis in mouse models by reducing the expression of isoforms V1 and V3 of the proteoglycan versican. RhoGDI2 suppressed metastasis by altering inflammation in the tumor microenvironment. (PMID:22406535)
• RhoGDI2 becomes rapidly phosphorylated at Ser31 in response to phorbol 12-myristate 13-acetate stimulation. Conventional type PKCalpha is responsible for this phosphorylation. (PMID:22469974)
• Results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis. (PMID:22674302)
• Rictor regulates cell migration by suppressing RhoGDI2. (PMID:22777355)
• Expression of ARHGDIB variants 6a, 6b, and 6c appears to be restricted to cancer cells and normal placental tissue, suggesting that these variants possess cancer-specific functions. (PMID:23206989)
• These results suggest that RhoGDIbeta has mitotic functions, including regulation of cytokinesis and bipolar spindle formation (PMID:23232495)
• 14-3-3sigma is a RhoGDI2-regulated gene that appears to be important for suppressing the chemoresistance of gastric cancer cells. (PMID:24185104)
• RhoGDI2 inhibits trophoblast cell migration, and this function may involve suppression of RAC1 activation. (PMID:24554735)
• RhoGDI2 overexpression is associated with tumor growth, metastasis, and chemoresistance in gastric cancer. (PMID:24721928)
• Depletion of RhoGDI2 expression inhibits the ability of invasion and migration in pancreatic carcinoma. (PMID:24788627)
• Short hairpin RNA-mediated knockdown of RhoGDI2 induces the invasion and migration of lung cancer due to cross-talk with the PI3K/Akt pathway and MMP-9. (PMID:25266803)
• Results show that RhoGDI2 suppresses bladder cancer metastatic colonization via negative regulation of RhoC activity, providing a rationale for the development of therapeutics that target RhoC signaling. (PMID:25516960)
• These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be involved in the rearrangement of cytoskeleton in lung cancer cells. (PMID:25562149)
• Our interpretation of these contradictions is that truncation and/or mutation of RhoGDI2 perturbs its conformation to expose a site that adventitiously binds FLNA and is not a bona-fide interaction. (PMID:26707877)
• The caspase-3-cleaved RhoGDIbeta is a possible determinant to promote cancer spreading. (PMID:26919575)
• Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. (PMID:27721047)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arhgdib	ENSMUSG00000030220
rattus_norvegicus	Arhgdib	ENSRNOG00000005809
drosophila_melanogaster	RhoGDI	FBGN0036921
caenorhabditis_elegans		WBGENE00004356

Paralogs (2): ARHGDIA (ENSG00000141522), ARHGDIG (ENSG00000242173)

Protein

Protein identifiers

Rho GDP-dissociation inhibitor 2 — P52566 (reviewed: P52566)

Alternative names: Ly-GDI, Rho-GDI beta

All UniProt accessions (5): P52566, F5H2R5, F5H3P3, F5H6Q0, H0YGX7

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Regulates reorganization of the actin cytoskeleton mediated by Rho family members.

Subunit / interactions. Interacts with RHOA. Interacts with RAC1. Interacts with RAC2. Interacts with CDC42.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Detected in bone marrow, thymus and spleen.

Similarity. Belongs to the Rho GDI family.

RefSeq proteins (5): NP_001166, NP_001308349, NP_001308350, NP_001308351, NP_001308352 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000406	Rho_GDI	Family
IPR014756	Ig_E-set	Homologous_superfamily
IPR024792	RhoGDI_dom_sf	Homologous_superfamily

Pfam: PF02115

UniProt features (31 total): strand 11, modified residue 10, helix 4, sequence conflict 2, initiator methionine 1, chain 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5H1D	X-RAY DIFFRACTION	1.49
9X59	X-RAY DIFFRACTION	1.65
9X56	X-RAY DIFFRACTION	1.7
9X53	X-RAY DIFFRACTION	1.85
9X54	X-RAY DIFFRACTION	2.13
1DS6	X-RAY DIFFRACTION	2.35
9X55	X-RAY DIFFRACTION	2.37

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52566-F1	87.94	0.72

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 (10): 124, 145, 175, 2, 21, 24, 25, 40, 47, 102

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013407	RHOH GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle

MSigDB gene sets: 381 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, TSUNODA_CISPLATIN_RESISTANCE_UP, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, CHIBA_RESPONSE_TO_TSA_UP, MCLACHLAN_DENTAL_CARIES_UP, GCM_MSN, MODULE_45, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, HSIAO_HOUSEKEEPING_GENES, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MODULE_16, GOMF_GTPASE_BINDING, GGGTGGRR_PAX4_03

GO Biological Process (4): Rho protein signal transduction (GO:0007266), regulation of Rho protein signal transduction (GO:0035023), cellular response to redox state (GO:0071461), negative regulation of trophoblast cell migration (GO:1901164)

GO Molecular Function (5): GTPase activity (GO:0003924), Rho GDP-dissociation inhibitor activity (GO:0005094), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	6

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
small GTPase-mediated signal transduction	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
response to redox state	1
negative regulation of cell migration	1
negative regulation of multicellular organismal process	1
trophoblast cell migration	1
regulation of trophoblast cell migration	1
negative regulation of reproductive process	1
ribonucleoside triphosphate phosphatase activity	1
GDP-dissociation inhibitor activity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
GTPase binding	1
binding	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intracellular vesicle	1
extracellular vesicle	1

Protein interactions and networks

STRING

1764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGDIB	RHOA	P06749	911
ARHGDIB	CDC42	P21181	827
ARHGDIB	AKT1	P31749	776
ARHGDIB	RAC2	P15153	650
ARHGDIB	RHOC	P08134	633
ARHGDIB	GDI2	P50395	599
ARHGDIB	CFL1	P23528	562
ARHGDIB	LAPTM5	Q13571	556
ARHGDIB	IQGAP1	P46940	476
ARHGDIB	NTRK2	Q16620	462
ARHGDIB	SRGN	P10124	451
ARHGDIB	LCP2	Q13094	438
ARHGDIB	DOCK11	Q5JSL3	438
ARHGDIB	TYROBP	O43914	437
ARHGDIB	RHOB	P01121	435

IntAct

39 interactions, top by confidence:

A	B	Type	Score
FOS	ARHGDIB	psi-mi:“MI:0915”(physical association)	0.560
GRB2	ARHGDIB	psi-mi:“MI:0915”(physical association)	0.560
UQCRC1	ARHGDIB	psi-mi:“MI:0915”(physical association)	0.560
CASP7	ARHGDIB	psi-mi:“MI:0194”(cleavage reaction)	0.440
CASP3	ARHGDIB	psi-mi:“MI:0194”(cleavage reaction)	0.440
RAC2	ARHGDIB	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM8B	ARHGDIB	psi-mi:“MI:0915”(physical association)	0.400
ARHGDIB		psi-mi:“MI:0915”(physical association)	0.370
ARHGDIB	htpG	psi-mi:“MI:0915”(physical association)	0.370
FCN1	ARHGDIB	psi-mi:“MI:0915”(physical association)	0.370
RAC1	ARHGDIB	psi-mi:“MI:0915”(physical association)	0.370
ARHGDIB	RAC3	psi-mi:“MI:0915”(physical association)	0.370
UFM1	ARHGDIB	psi-mi:“MI:0915”(physical association)	0.370
RHOG	COPE	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
SLC26A6	SLC25A17	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SARAF	A2ML1	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (49): ARHGDIB (Co-fractionation), RHOC (Co-fractionation), SUMO4 (Co-fractionation), ARHGDIB (Affinity Capture-Western), WSB1 (Affinity Capture-Western), ARHGDIB (Reconstituted Complex), ARHGDIB (Affinity Capture-MS), ARHGDIB (Affinity Capture-Western), FBXL5 (Affinity Capture-Western), ARHGDIB (Proximity Label-MS), ARHGDIB (Two-hybrid), ARHGDIB (Two-hybrid), VAV1 (Affinity Capture-Western), VAV1 (Reconstituted Complex), ARHGDIB (Co-crystal Structure)

ESM2 similar proteins: A7YW45, O14744, P08168, P10523, P15372, P15887, P19107, P19108, P20443, P25455, P32122, P36575, P51432, P51477, P51478, P51479, P51481, P51482, P51483, P51484, P51485, P51486, P51487, P52566, P55274, P79260, Q0VCA2, Q1JQD4, Q28281, Q498D9, Q4R4K0, Q4R5M3, Q5DRQ4, Q5FWL4, Q5R5L7, Q5R698, Q61599, Q66KM2, Q6NUA1, Q6TXF1

Diamond homologs: O14224, P19803, P52565, P52566, P80237, Q0II80, Q12434, Q20496, Q4R4J0, Q5XI73, Q61599, Q62160, Q95UQ1, Q99819, Q99PT1, Q9SFC6, Q9TU03

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SRC	unknown	ARHGDIB	phosphorylation
PRKCA	down-regulates	ARHGDIB	phosphorylation
RNF128	“up-regulates quantity by stabilization”	ARHGDIB	polyubiquitination
MAP3K20	“down-regulates activity”	ARHGDIB	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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
actin filament organization	5	19.1×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

672 predictions. Top by Δscore:

Variant	Effect	Δscore
12:14942717:ATCCA:A	acceptor_gain	1.0000
12:14942718:TCCA:T	acceptor_gain	1.0000
12:14942719:CCA:C	acceptor_gain	1.0000
12:14942719:CCAC:C	acceptor_gain	1.0000
12:14942720:CA:C	acceptor_gain	1.0000
12:14942720:CAC:C	acceptor_gain	1.0000
12:14942721:ACTAA:A	acceptor_loss	1.0000
12:14942722:C:CC	acceptor_gain	1.0000
12:14942723:T:G	acceptor_loss	1.0000
12:14947867:ACTT:A	donor_loss	1.0000
12:14947869:TTA:T	donor_loss	1.0000
12:14947870:TACTT:T	donor_loss	1.0000
12:14947871:A:AC	donor_gain	1.0000
12:14947871:ACTTT:A	donor_loss	1.0000
12:14947872:C:CA	donor_gain	1.0000
12:14947872:CT:C	donor_gain	1.0000
12:14947872:CTT:C	donor_gain	1.0000
12:14947872:CTTT:C	donor_gain	1.0000
12:14947872:CTTTG:C	donor_gain	1.0000
12:14947947:CTC:C	acceptor_gain	1.0000
12:14947948:TC:T	acceptor_gain	1.0000
12:14947949:CC:C	acceptor_gain	1.0000
12:14947950:C:CC	acceptor_gain	1.0000
12:14947950:CT:C	acceptor_loss	1.0000
12:14947951:T:G	acceptor_loss	1.0000
12:14950528:ATACC:A	donor_loss	1.0000
12:14950529:TA:T	donor_loss	1.0000
12:14950530:ACCTG:A	donor_loss	1.0000
12:14950531:CCTG:C	donor_gain	1.0000
12:14950575:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000092671 (12:14952305 G>A,T), RS1000177338 (12:14942060 G>C), RS1000681706 (12:14952362 A>G), RS1000922005 (12:14952578 G>T), RS1000980259 (12:14951911 T>C), RS1001136863 (12:14946537 A>G), RS1001150631 (12:14956467 C>T), RS1001357175 (12:14950744 C>A,T), RS1001438605 (12:14952157 G>A,C), RS1001454067 (12:14945072 T>C), RS1001492673 (12:14946148 C>T), RS1001522401 (12:14962641 C>T), RS1001688670 (12:14950955 T>C,G), RS1001763557 (12:14956270 G>A), RS1002046362 (12:14960395 C>T)

Disease associations

OMIM: gene MIM:602843 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066872 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects splicing, decreases expression, affects cotreatment, increases abundance	6
Valproic Acid	increases expression, decreases expression, affects cotreatment	5
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	4
(+)-JQ1 compound	decreases expression	3
Quercetin	affects cotreatment, increases expression, increases cleavage	3
Tobacco Smoke Pollution	decreases expression, affects expression	3
Tretinoin	increases expression	3
Cadmium Chloride	increases abundance, increases expression	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cisplatin	decreases expression, affects cotreatment	2
Methyl Methanesulfonate	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, decreases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
diallyl disulfide	decreases expression, increases expression, decreases reaction, affects reaction	1
9-deoxy-delta-9-prostaglandin D2	increases cleavage	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
CHEMBL5650927	Binding	Binding affinity to human ARHGDIB 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 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1QM	HyCyte HL-60 KO-hARHGDIB	Cancer cell line	Female

Clinical trials (associated diseases)

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