ARPC2

Summary

ARPC2 (actin related protein 2/3 complex subunit 2, HGNC:705) is a protein-coding gene on chromosome 2q35, encoding Actin-related protein 2/3 complex subunit 2 (O15144). Actin-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). It is a selective cancer dependency (DepMap: 39.0% of cell lines).

This gene encodes one of seven subunits of the human Arp2/3 protein complex. The Arp2/3 protein complex has been implicated in the control of actin polymerization in cells and has been conserved through evolution. The exact role of the protein encoded by this gene, the p34 subunit, has yet to be determined. Two alternatively spliced variants have been characterized to date. Additional alternatively spliced variants have been described but their full length nature has not been determined.

Source: NCBI Gene 10109 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 51 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 39.0% of screened cell lines
• MANE Select transcript: NM_152862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:705
Approved symbol	ARPC2
Name	actin related protein 2/3 complex subunit 2
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	p34-Arc, ARC34
Ensembl gene	ENSG00000163466
Ensembl biotype	protein_coding
OMIM	604224
Entrez	10109

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 24 protein_coding, 7 protein_coding_CDS_not_defined, 5 retained_intron, 2 nonsense_mediated_decay

ENST00000295685, ENST00000315717, ENST00000414983, ENST00000420104, ENST00000420201, ENST00000456575, ENST00000462034, ENST00000465395, ENST00000470146, ENST00000471355, ENST00000472753, ENST00000477992, ENST00000478612, ENST00000480062, ENST00000484961, ENST00000487321, ENST00000489598, ENST00000491780, ENST00000856664, ENST00000856665, ENST00000856666, ENST00000856667, ENST00000856668, ENST00000856669, ENST00000856670, ENST00000856671, ENST00000856672, ENST00000856673, ENST00000856674, ENST00000912996, ENST00000912997, ENST00000943695, ENST00000943696, ENST00000943697, ENST00000943698, ENST00000943699, ENST00000943700, ENST00000943701

RefSeq mRNA: 2 — MANE Select: NM_152862 NM_005731, NM_152862

CCDS: CCDS2410

Canonical transcript exons

ENST00000315717 — 11 exons

Exon	Start	End
ENSE00001815327	218217189	218217254
ENSE00001859529	218253891	218254348
ENSE00003476654	218245420	218245546
ENSE00003500803	218238664	218238850
ENSE00003510187	218249364	218249464
ENSE00003537659	218228738	218228850
ENSE00003538579	218225920	218225954
ENSE00003560230	218249821	218249921
ENSE00003596248	218234352	218234397
ENSE00003615022	218239391	218239484
ENSE00003642965	218217463	218217544

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 256.9968 / max 2925.0930, expressed in 1828 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25286	251.5634	1828
25294	1.5702	929
25287	1.0847	623
25293	1.0019	476
25295	0.7810	504
25296	0.5448	298
25291	0.3097	133
25290	0.1411	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	99.70	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.66	gold quality
epithelium of esophagus	UBERON:0001976	99.64	gold quality
granulocyte	CL:0000094	99.62	gold quality
pharyngeal mucosa	UBERON:0000355	99.62	gold quality
colonic mucosa	UBERON:0000317	99.61	gold quality
skin of hip	UBERON:0001554	99.60	gold quality
trabecular bone tissue	UBERON:0002483	99.60	gold quality
oral cavity	UBERON:0000167	99.59	gold quality
squamous epithelium	UBERON:0006914	99.56	gold quality
monocyte	CL:0000576	99.55	gold quality
leukocyte	CL:0000738	99.55	gold quality
mononuclear cell	CL:0000842	99.55	gold quality
cervix squamous epithelium	UBERON:0006922	99.55	gold quality
blood	UBERON:0000178	99.54	gold quality
mammalian vulva	UBERON:0000997	99.51	gold quality
tongue squamous epithelium	UBERON:0006919	99.49	gold quality
esophagus mucosa	UBERON:0002469	99.46	gold quality
vermiform appendix	UBERON:0001154	99.45	gold quality
superior surface of tongue	UBERON:0007371	99.45	gold quality
adult organism	UBERON:0007023	99.43	gold quality
lymph node	UBERON:0000029	99.42	gold quality
penis	UBERON:0000989	99.42	gold quality
pylorus	UBERON:0001166	99.42	gold quality
decidua	UBERON:0002450	99.41	gold quality
cervix epithelium	UBERON:0004801	99.41	gold quality
periodontal ligament	UBERON:0008266	99.41	gold quality
caecum	UBERON:0001153	99.40	gold quality
tongue	UBERON:0001723	99.40	gold quality
lower lobe of lung	UBERON:0008949	99.40	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	1414.79
E-MTAB-5061	yes	1221.08
E-HCAD-4	yes	102.20
E-CURD-122	yes	50.05
E-GEOD-135922	yes	41.66
E-CURD-46	yes	31.83
E-MTAB-10287	yes	31.17
E-HCAD-31	yes	27.90
E-CURD-88	yes	21.65
E-HCAD-11	yes	19.92
E-GEOD-125970	yes	19.41
E-HCAD-9	yes	19.38
E-GEOD-130148	yes	17.51
E-MTAB-10042	yes	17.43
E-MTAB-8410	yes	13.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting ARPC2, 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-5193	100.00	67.26	1744
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-149-3P	99.72	68.22	3963

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 39.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• Arp2/3 complex genes have roles in actin organization and possibly in cancer phenotypes (PMID:15279900)
• The actin-related protein 2 accumulated in punctate structures that formed an extensivenetwork in a region corresponding to the postition of the Golgi complex. (PMID:15793564)
• Compared with controls, actin-related protein 2/3 level was markedly increased in brains of intractable epilepsy patients. (PMID:18708039)
• These findings strongly suggest that defective IL10 function is central to the pathogenesis of the ulcerative colitis subtype of inflammatory bowel disease. (PMID:18836448)
• WASH is a bimodular protein and a component of the BLOC-1 complex in which the C terminus is involved in Arp2/3-mediated actin nucleation, whereas the N-terminal portion is required for its regulation and localization in the cells (PMID:20308062)
• The results identify Arp2/3 complex as a key factor in the generation of the dynamic actin cluster during mitosis. (PMID:20974812)
• Endogenous Nogo-B, which may exert its effects through ARPC 2/3 and MYL-9, is necessary for the migration and contraction of airway smooth muscle cells. (PMID:21251247)
• Filopodia initiation: focus on the Arp2/3 complex and formins (PMID:21975549)
• The Arp2/3 complex is recruited to invading Rickettsia parkeri and is required for efficient invasion. (PMID:22188208)
• Recent reports now demonstrate a novel aspect of the ARP2/3 complex and the nucleating-promoting factors in the maintenance of endothelial barrier function and junction remodeling of established endothelial cell junctions. (PMID:24621569)
• FOXF1 repressed cell growth and expression of collagen-1 and actin-related protein 2/3 complex, subunit 2. (PMID:25260753)
• Downregulation of the ARP2/3 complex signaling pathway, a common final pathway for multiple signaling cascades that regulate the actin cytoskeleton, would compromise the structural stability of spines, leading to their loss. In concert with findings from deletion of the ARP2/3 complex in mice, these findings support the idea that spine deficits in the DLPFC may contribute to subcortical hyperdopaminergia in schizophrenia. (PMID:27523502)
• In the association analysis of 110 gastric cancer tissues, ARPC2 showed significant associations with large tumor size, lymph node invasion, and high tumor stage. In addition, ARPC2-positive patients exhibited lower RFS and OS rates compared with ARPC2-negative patients. We thus identify that ARPC2 plays an aneretic role in human gastric cancer and provided a new target for gastric cancer therapy. (PMID:28694563)
• Study shows that the T-cell-specific deletion of Arpc2 results in compromised peripheral T-cell homeostasis suggesting that ARPC2 is essential for T-cell homeostasis probably by maintaining surface TCR levels via regulating TCR(+) endosome trafficking. (PMID:28827576)
• Results find that ARPC2 expression is upregulated in breast cancer tissues and cell lines. ARPC2 promotes the proliferation and metastasis of human breast cancer cells. ARPC2 is regulated by RBM2 in a posttranscriptional 3’UTRbinding manner. Also, ARPC2 plays an oncogenic role and mediates the promoting role of RBM3 in the proliferation and metastasis of human breast cancer cells. (PMID:30720048)
• These results collectively indicated that ARPC2 promoted the tumorigenesis of breast carcinoma and the initiation of epithelialmesenchymal transition. Therefore, ARPC2 was revealed to be a potential therapeutic target in patients with breast cancer (BrCa) . (PMID:31002363)
• Study provides evidence that the 5’-UTR1 of ARPC2 has internal ribosome entry site activity and regulates translation during stressful cellular conditions such as high cell density. (PMID:31387452)
• Arp2/3 and Mena/VASP Require Profilin 1 for Actin Network Assembly at the Leading Edge. (PMID:32470361)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	arpc2	ENSDARG00000075989
mus_musculus	Arpc2	ENSMUSG00000006304
rattus_norvegicus	Arpc2	ENSRNOG00000014289
drosophila_melanogaster	Arpc2	FBGN0032859
caenorhabditis_elegans		WBGENE00021170

Protein

Protein identifiers

Actin-related protein 2/3 complex subunit 2 — O15144 (reviewed: O15144)

Alternative names: Arp2/3 complex 34 kDa subunit

All UniProt accessions (6): C9JTV5, O15144, G5E9J0, G5E9S7, H7C3F9, Q53R19

UniProt curated annotations — full annotation on UniProt →

Function. Actin-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. Seems to contact the mother actin filament. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).

Subunit / interactions. Component of the Arp2/3 complex composed of ACTR2/ARP2, ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. Interacts with SHANK3; the interaction probably mediates the association of SHANK3 with the Arp2/3 complex. Interacts with DNAI3; this interaction reduces binding of the Arp2/3 complex to the VCA domain of nucleation promoting factors.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Synapse. Synaptosome. Nucleus.

Similarity. Belongs to the ARPC2 family.

RefSeq proteins (2): NP_005722, NP_690601* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007188	ARPC2	Family
IPR034666	ARPC2/4	Homologous_superfamily

Pfam: PF04045

UniProt features (5 total): modified residue 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9I2B	ELECTRON MICROSCOPY	3
8P94	ELECTRON MICROSCOPY	3.3
6UHC	ELECTRON MICROSCOPY	3.9
6YW6	ELECTRON MICROSCOPY	4.2
6YW7	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15144-F1	94.03	0.92

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 (2): 275, 295

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-422475	Axon guidance
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-9658195	Leishmania infection
R-HSA-9664407	Parasite infection
R-HSA-9664417	Leishmania phagocytosis
R-HSA-9675108	Nervous system development
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 334 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, CREL_01, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_MSN, MODULE_151, MORF_SNRP70, MORF_HDAC1, HSIAO_HOUSEKEEPING_GENES, REACTOME_MEMBRANE_TRAFFICKING, GOBP_POSITIVE_REGULATION_OF_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN

GO Biological Process (8): positive regulation of lamellipodium assembly (GO:0010592), actin filament polymerization (GO:0030041), positive regulation of actin filament polymerization (GO:0030838), Arp2/3 complex-mediated actin nucleation (GO:0034314), actin polymerization-dependent cell motility (GO:0070358), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), positive regulation of cellular component biogenesis (GO:0044089), positive regulation of cellular component organization (GO:0051130)

GO Molecular Function (4): actin binding (GO:0003779), structural constituent of cytoskeleton (GO:0005200), protein binding (GO:0005515), actin filament binding (GO:0051015)

GO Cellular Component (22): nucleus (GO:0005634), nucleoplasm (GO:0005654), endosome (GO:0005768), cytosol (GO:0005829), Arp2/3 protein complex (GO:0005885), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), synaptic vesicle membrane (GO:0030672), site of double-strand break (GO:0035861), muscle cell projection membrane (GO:0036195), neuron projection (GO:0043005), extracellular exosome (GO:0070062), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell leading edge (GO:0031252), cell projection (GO:0042995), synapse (GO:0045202), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Fcgamma receptor (FCGR) dependent phagocytosis	1
EPH-Ephrin signaling	1
RHO GTPase Effectors	1
Membrane Trafficking	1
Leishmania phagocytosis	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Vesicle-mediated transport	1
Innate Immune System	1
Axon guidance	1
Nervous system development	1
Disease	1
Parasitic Infection Pathways	1
Leishmania infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
positive regulation of cellular process	2
cytoskeleton	2
plasma membrane bounded cell projection	2
synapse	2
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
actin polymerization or depolymerization	1
protein polymerization	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
actin nucleation	1
cell motility	1
positive regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
cellular component biogenesis	1
regulation of cellular component biogenesis	1
cellular component organization	1
regulation of cellular component organization	1
cytoskeletal protein binding	1
structural molecule activity	1
cytoskeleton organization	1
binding	1
actin binding	1
protein-containing complex binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
endomembrane system	1
cytoplasmic vesicle	1
cytoplasm	1
actin cytoskeleton	1
protein-containing complex	1
cell-substrate junction	1
cell leading edge	1

Protein interactions and networks

STRING

1734 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARPC2	ARPC3	O15145	999
ARPC2	ARPC5	O15511	999
ARPC2	ARPC1B	O15143	998
ARPC2	ACTR2	P61160	997
ARPC2	ACTR3	P32391	986
ARPC2	WAS	P42768	945
ARPC2	ARPC1A	Q92747	935
ARPC2	ARPC4	P59998	885
ARPC2	WASL	O00401	849
ARPC2	ARPC5L	Q9BPX5	800
ARPC2	ACTR3B	Q9P1U1	727
ARPC2	ACTR3C	Q9C0K3	712
ARPC2	WASF1	Q92558	660
ARPC2	VCL	P18206	641
ARPC2	CTTN	Q14247	611

IntAct

175 interactions, top by confidence:

A	B	Type	Score
ARPC1B	ARPC2	psi-mi:“MI:0915”(physical association)	0.920
ARPC1B	ARPC2	psi-mi:“MI:0914”(association)	0.920
ARPC4	ARPC1B	psi-mi:“MI:0914”(association)	0.910
ARPC1A	ARPC2	psi-mi:“MI:0914”(association)	0.900
ARPC1A	ARPC2	psi-mi:“MI:0915”(physical association)	0.900
ARPC5	ARPC1B	psi-mi:“MI:0914”(association)	0.890

BioGRID (362): ARPC2 (Affinity Capture-MS), ARPC2 (Affinity Capture-MS), ARPC2 (Affinity Capture-MS), ARPC2 (Affinity Capture-MS), ARPC2 (Affinity Capture-MS), ARPC2 (Affinity Capture-RNA), ACTR3 (Co-fractionation), ARPC2 (Co-fractionation), ARPC2 (Co-fractionation), ARPC2 (Co-fractionation), ARPC2 (Co-fractionation), ARPC2 (Co-fractionation), ARPC2 (Co-fractionation), ARPC2 (Co-fractionation), ARPC2 (Co-fractionation)

ESM2 similar proteins: A2T3M2, A2T3P0, A3DSK8, A4ZCW3, B2BRG3, B3SRQ6, B3SRR4, B3SRS2, B3SRV4, B3SRX0, B3SRX8, D5LJN4, O15144, O96623, P03537, P09366, P0CAH0, P0CAH1, P0CAH2, P13094, P17381, P33544, P52536, P58213, P85970, Q01051, Q03240, Q03241, Q03242, Q03243, Q03245, Q0IH88, Q31HD6, Q3MHR7, Q3ZK62, Q5R5Z5, Q65180, Q65195, Q65238, Q6FV72

Diamond homologs: O14241, O15144, O96623, P53731, P85970, Q0IH88, Q3MHR7, Q5R5Z5, Q6IRB1, Q7PVX8, Q8WTM6, Q9CVB6, Q9VIM5, F4IVU1, Q8LGI3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ARPC2	“form complex”	ARP2/3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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
Parasite infection	11	43.8×	1e-13
Leishmania phagocytosis	11	43.8×	1e-13
RHO GTPases Activate WASPs and WAVEs	11	40.1×	2e-13
Fcgamma receptor (FCGR) dependent phagocytosis	11	35.2×	7e-13
EPHB-mediated forward signaling	10	30.5×	5e-11
FCGR3A-mediated phagocytosis	13	28.0×	1e-13
Regulation of actin dynamics for phagocytic cup formation	13	27.5×	1e-13
Signaling by RAS mutants	5	24.3×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
Arp2/3 complex-mediated actin nucleation	8	75.9×	4e-11
regulation of synaptic vesicle endocytosis	5	40.0×	3e-05
negative regulation of endothelial cell apoptotic process	5	22.3×	4e-04
establishment or maintenance of cell polarity	6	21.7×	5e-05
platelet aggregation	5	15.2×	2e-03
neuron projection morphogenesis	5	12.4×	3e-03
cellular response to type II interferon	5	9.4×	8e-03
axonogenesis	6	8.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	18
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
493568	GRCh37/hg19 2q35-36.3(chr2:217374144-227643620)x1	Likely pathogenic

SpliceAI

1649 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218217540:GCCGG:G	donor_gain	1.0000
2:218217543:GG:G	donor_gain	1.0000
2:218217544:GG:G	donor_gain	1.0000
2:218217545:G:GC	donor_loss	1.0000
2:218217545:G:GG	donor_gain	1.0000
2:218217546:T:A	donor_loss	1.0000
2:218228732:TCACA:T	acceptor_loss	1.0000
2:218228733:CACA:C	acceptor_loss	1.0000
2:218228734:ACAG:A	acceptor_loss	1.0000
2:218228735:CA:C	acceptor_loss	1.0000
2:218228736:A:AG	acceptor_gain	1.0000
2:218228736:A:T	acceptor_loss	1.0000
2:218228737:G:GG	acceptor_gain	1.0000
2:218230949:C:CA	acceptor_gain	1.0000
2:218238658:CTCCA:C	acceptor_loss	1.0000
2:218238659:TCCA:T	acceptor_loss	1.0000
2:218238660:CCA:C	acceptor_loss	1.0000
2:218238661:CA:C	acceptor_loss	1.0000
2:218238662:A:AC	acceptor_loss	1.0000
2:218238662:A:AG	acceptor_gain	1.0000
2:218238663:G:GG	acceptor_gain	1.0000
2:218238804:G:GT	donor_gain	1.0000
2:218238805:A:T	donor_gain	1.0000
2:218238819:G:T	donor_gain	1.0000
2:218238851:G:GG	donor_gain	1.0000
2:218239480:TGCAG:T	donor_loss	1.0000
2:218239482:CAG:C	donor_loss	1.0000
2:218239483:AG:A	donor_loss	1.0000
2:218239484:GGTAT:G	donor_loss	1.0000
2:218239485:GTAT:G	donor_loss	1.0000

AlphaMissense

2002 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:218217494:C:A	N8K	1.000
2:218217494:C:G	N8K	1.000
2:218225954:G:C	D37H	1.000
2:218228738:A:T	D37V	1.000
2:218228740:T:A	F38I	1.000
2:218228740:T:C	F38L	1.000
2:218228741:T:G	F38C	1.000
2:218228742:C:A	F38L	1.000
2:218228742:C:G	F38L	1.000
2:218228743:G:C	D39H	1.000
2:218228744:A:T	D39V	1.000
2:218228798:T:A	V57D	1.000
2:218228800:A:C	S58R	1.000
2:218228802:T:A	S58R	1.000
2:218228802:T:G	S58R	1.000
2:218228815:T:C	F63L	1.000
2:218228817:C:A	F63L	1.000
2:218228817:C:G	F63L	1.000
2:218228828:T:A	L67H	1.000
2:218228828:T:C	L67P	1.000
2:218238742:T:C	L116S	1.000
2:218238746:G:C	K117N	1.000
2:218238746:G:T	K117N	1.000
2:218238748:G:C	R118P	1.000
2:218238753:T:C	C120R	1.000
2:218238754:G:A	C120Y	1.000
2:218238755:T:G	C120W	1.000
2:218238759:G:C	A122P	1.000
2:218238760:C:A	A122D	1.000
2:218238766:T:A	V124D	1.000

dbSNP variants (sampled 300 via entrez): RS1000014083 (2:218243634 G>A), RS1000017988 (2:218243386 G>A), RS1000064686 (2:218243283 A>G), RS1000081647 (2:218241977 C>T), RS1000375874 (2:218230622 T>A), RS1000380362 (2:218230863 A>G), RS1000438952 (2:218225007 C>A,T), RS1000473053 (2:218243079 C>T), RS1000491197 (2:218224683 C>G,T), RS1000598795 (2:218226356 G>A), RS1000611799 (2:218220316 C>T), RS1000680210 (2:218219121 G>A), RS1000706080 (2:218232523 A>C), RS1000764317 (2:218226425 C>T), RS1000786010 (2:218217022 A>G)

Disease associations

OMIM: gene MIM:604224 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001725_74	Inflammatory bowel disease	4.000000e-12
GCST001762_240	Obesity-related traits	7.000000e-06
GCST001762_358	Obesity-related traits	2.000000e-06
GCST001762_778	Obesity-related traits	3.000000e-06
GCST002556_2	White blood cell count	9.000000e-09
GCST004131_76	Inflammatory bowel disease	2.000000e-07
GCST004599_286	Mean platelet volume	4.000000e-15
GCST004603_217	Platelet count	7.000000e-19
GCST004616_132	Platelet distribution width	6.000000e-26
GCST005973_24	White blood cell count	3.000000e-11
GCST005974_12	Neutrophil count	4.000000e-13
GCST90002395_356	Mean platelet volume	3.000000e-34
GCST90002395_357	Mean platelet volume	5.000000e-16
GCST90002401_423	Platelet distribution width	1.000000e-74
GCST90002402_288	Platelet count	4.000000e-51

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0005115	metabolic rate measurement
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295657 (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
7.32	Kd	47.93	nM	CHEMBL5653589
7.29	ED50	50.95	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	2147890: Binding affinity to human ARPC2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0479	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	4
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
terbufos	decreases methylation	1
methylparaben	increases expression	1
cobaltous chloride	decreases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases reaction, increases expression	1
nickel sulfate	increases expression	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bromovanin	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases methylation	1
Benzo(a)pyrene	increases expression	1
Carmustine	decreases expression	1
Cisplatin	increases expression	1
Dinitrochlorobenzene	affects binding	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	decreases methylation	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118583	Binding	Binding affinity to ARPC2 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7KE	Ubigene A-549 ARPC2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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