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): 52 total — 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈5% of expected missense variation)
• GTEx eGene: eQTL in 31 tissues, sQTL in 32 (q < 0.05)
• Cancer dependency (DepMap): dependent in 39.0% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.32 (highly constrained)
• MANE Select transcript: NM_152862
• Interaction hub: 2,051 STRING partners (top 7% of genes corpus-wide)
• Notable: 52 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 55 — 30 protein_coding, 13 nonsense_mediated_decay, 7 protein_coding_CDS_not_defined, 5 retained_intron

MANE Select: ENST00000315717

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 8, TSL 3: 7, TSL 4: 1

ENST00000315717, ENST00000295685, 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, ENST00000978773, ENST00000978774, ENST00000978777, ENST00000978778, ENST00000978779, ENST00000978780, ENST00000978782, ENST00000978783, ENST00001047947, ENST00001047952, ENST00001047957, ENST00001115546, ENST00001119456, ENST00001130969, ENST00001130970, ENST00001130971, ENST00001139306

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.

Highest expression (Bgee): esophagus squamous epithelium, mucosa of sigmoid colon, epithelium of esophagus, granulocyte, pharyngeal mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ARPC2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 32 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 63 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	3.6e-50	-0.33	2:218244190:C:A
Nerve Tibial	eqtl	3.8e-39	+0.30	2:218234030:A:G
Nerve Tibial	sqtl	1.8e-35	+0.37	2:218237609:C:T
Skin Sun Exposed Lower leg	sqtl	8.0e-30	+0.34	2:218207952:G:A
Adipose Subcutaneous	sqtl	9.4e-29	+0.33	2:218240727:T:TA
Adipose Subcutaneous	eqtl	3.3e-26	+0.24	2:218207952:G:A
Lung	eqtl	3.4e-26	+0.21	2:218207952:G:A
Skin Not Sun Exposed Suprapubic	sqtl	1.4e-25	+0.33	2:218240727:T:TA
Artery Tibial	sqtl	2.2e-19	+0.29	2:218237609:C:T
Testis	sqtl	4.9e-18	-0.48	2:218218595:G:T
Spleen	eqtl	1.3e-17	+0.24	2:218209248:G:GT
Lung	sqtl	7.1e-15	+0.21	2:218233050:A:G
Breast Mammary Tissue	sqtl	1.8e-14	+0.27	2:218237609:C:T
Thyroid	eqtl	2.0e-14	+0.16	2:218209248:G:GT
Colon Transverse	sqtl	3.2e-13	+0.28	2:218240727:T:TA
Thyroid	sqtl	6.7e-12	+0.23	2:218207952:G:A
Skin Sun Exposed Lower leg	eqtl	1.8e-11	+0.11	2:218193087:A:C
Artery Aorta	sqtl	2.0e-11	+0.25	2:218245998:G:A
Whole Blood	sqtl	3.8e-11	+0.16	2:218209248:G:GT
Pancreas	eqtl	3.8e-11	+0.25	2:218217607:A:G

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

showing 100 of 303 tissues 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
smooth muscle tissue	UBERON:0001135	99.39	gold quality
placenta	UBERON:0001987	99.38	gold quality
body of tongue	UBERON:0011876	99.38	gold quality
upper arm skin	UBERON:0004263	99.37	gold quality
bone marrow	UBERON:0002371	99.34	gold quality
zone of skin	UBERON:0000014	99.33	gold quality
nipple	UBERON:0002030	99.33	gold quality
right lung	UBERON:0002167	99.33	gold quality
skin of abdomen	UBERON:0001416	99.32	gold quality
skin of leg	UBERON:0001511	99.32	gold quality
lower esophagus mucosa	UBERON:0035834	99.32	gold quality
ascending aorta	UBERON:0001496	99.31	gold quality
thoracic aorta	UBERON:0001515	99.31	gold quality
descending thoracic aorta	UBERON:0002345	99.31	gold quality
gingiva	UBERON:0001828	99.30	gold quality
spleen	UBERON:0002106	99.30	gold quality
upper leg skin	UBERON:0004262	99.30	gold quality
jejunal mucosa	UBERON:0000399	99.28	gold quality
bone element	UBERON:0001474	99.28	gold quality
upper lobe of lung	UBERON:0008948	99.28	gold quality
esophagus	UBERON:0001043	99.27	gold quality
upper lobe of left lung	UBERON:0008952	99.27	gold quality
rectum	UBERON:0001052	99.23	gold quality
gall bladder	UBERON:0002110	99.23	gold quality
cartilage tissue	UBERON:0002418	99.23	gold quality
mucosa of transverse colon	UBERON:0004991	99.23	gold quality
left testis	UBERON:0004533	99.22	gold quality
right testis	UBERON:0004534	99.22	gold quality
right coronary artery	UBERON:0001625	99.21	gold quality
gingival epithelium	UBERON:0001949	99.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.21	gold quality
cardia of stomach	UBERON:0001162	99.20	gold quality
vagina	UBERON:0000996	99.19	gold quality
palpebral conjunctiva	UBERON:0001812	99.19	gold quality
bone marrow cell	CL:0002092	99.18	gold quality
mucosa of urinary bladder	UBERON:0001259	99.18	gold quality
urinary bladder	UBERON:0001255	99.17	gold quality
left coronary artery	UBERON:0001626	99.17	gold quality
cortical plate	UBERON:0005343	99.17	gold quality
sigmoid colon	UBERON:0001159	99.16	gold quality
large intestine	UBERON:0000059	99.15	gold quality
pancreatic ductal cell	CL:0002079	99.14	gold quality
intestine	UBERON:0000160	99.14	gold quality
colon	UBERON:0001155	99.14	gold quality
coronary artery	UBERON:0001621	99.14	gold quality
epithelium of nasopharynx	UBERON:0001951	99.14	gold quality
nasal cavity epithelium	UBERON:0005384	99.13	gold quality
aorta	UBERON:0000947	99.12	gold quality
nasopharynx	UBERON:0001728	99.12	gold quality
small intestine	UBERON:0002108	99.12	gold quality
transverse colon	UBERON:0001157	99.11	gold quality
superficial temporal artery	UBERON:0001614	99.11	gold quality
body of stomach	UBERON:0001161	99.10	gold quality
stromal cell of endometrium	CL:0002255	99.09	gold quality
mucosa of stomach	UBERON:0001199	99.08	gold quality
saphenous vein	UBERON:0007318	99.08	gold quality
fundus of stomach	UBERON:0001160	99.06	gold quality
peritoneum	UBERON:0002358	99.06	gold quality
omental fat pad	UBERON:0010414	99.06	gold quality
lower esophagus	UBERON:0013473	99.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.06	gold quality
lung	UBERON:0002048	99.05	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.05	gold quality
jejunum	UBERON:0002115	99.04	gold quality
endometrium epithelium	UBERON:0004811	99.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.04	gold quality
duodenum	UBERON:0002114	99.03	gold quality
uterine cervix	UBERON:0000002	99.02	gold quality
trigeminal ganglion	UBERON:0001675	99.01	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tonsil	tissue	586.2	high
Bone marrow	tissue	513.6	high
Lymph node	tissue	471.8	high
Esophagus	tissue	402.8	high
Urinary bladder	tissue	375.7	high
Skeletal muscle	tissue	361.1	low
Appendix	tissue	341.1	high
Hippocampal formation	tissue	304.2
Caudate putamen	tissue	296.7
Thymus	tissue	277.9
Spleen	tissue	277.6	high
Skin 1	tissue	277.2	high
Placenta	tissue	277.1	high
Putamen	tissue	276.2
Smooth muscle	tissue	271.9	medium
Frontal cortex	tissue	260.8
Basal ganglia	tissue	258.3	high
Rectum	tissue	258.0	high
Lung	tissue	244.8	high
Vagina	tissue	240.9	medium
Stomach 1	tissue	237.3	high
Colon	tissue	236.9	high
Septum	tissue	236.9
Tongue	tissue	234.3
Ventral forebrain	tissue	220.9
Spinal cord	tissue	215.1
Small intestine	tissue	213.3	high
Pons	tissue	203.9
Substantia nigra	tissue	201.8
Gallbladder	tissue	198.0	high
Hypothalamus	tissue	196.9
Midbrain	tissue	188.8
Duodenum	tissue	188.4	high
Medulla oblongata	tissue	186.0
Cerebral cortex	tissue	185.3	high
Motor cortex	tissue	185.3
Prefrontal cortex	tissue	184.2
Thalamus	tissue	180.2
Adipose tissue	tissue	179.8	medium
Superior colliculi	tissue	177.8
Periaqueductal gray	tissue	173.0
Temporal cortex	tissue	171.6
Occipital cortex	tissue	171.0
Somatosensory cortex	tissue	168.3
Entorhinal cortex	tissue	168.1
Seminal vesicle	tissue	165.8	high
Amygdala	tissue	164.1
Corpus callosum	tissue	163.0
Retrosplenial and cingulate cortex	tissue	157.3
Heart muscle	tissue	156.7	medium
Epididymis	tissue	152.9	high
Retrosplenial cortex	tissue	150.0
Insular cortex	tissue	149.0
Ovary	tissue	146.7	medium
Liver	tissue	142.7	low
Breast	tissue	141.5	medium
Cervix	tissue	139.9	high
Testis	tissue	139.9	high
Olfactory bulb	tissue	138.9
Kidney	tissue	138.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (318.9), Dorsal hippocampus (304.2), Ventral hippocampus (241.6), Dorsal spinal cord (215.1), Ventral spinal cord (214.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ARPC2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 79 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.319, missense Z 2.84 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000315717 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:218,217,471–218,239,458	135 / 214.1	0.63	no
2:218,239,459–218,245,441	2 / 21.0	0.10	yes (p 3.5e-05)
2:218,245,442–218,253,912	92 / 152.3	0.60	no
DepMap (CRISPR cell-line fitness): dependent in 39.0% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): MM127 (-1.195), RERF-GC-1B (-1.19), SK-MEL-2 (-1.163), SNU-16 (-1.115), DAN-G (-1.081), U-2 OS (-1.076), Caov-4 (-1.072), NCI-H1993 (-1.052), A-673 (-1.039), J82 (-1.026), MPP 89 (-1.012), COV413A (-0.994), UM-UC-13 (-0.99), PACADD-165 (-0.984), U-118 MG (-0.977).

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923959) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	1
abnormal coat/hair pigmentation	1
increased mean corpuscular hemoglobin	1
decreased total body fat amount	1
preweaning lethality, complete penetrance	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
Pongo abelii	Q5R5Z5	100.0%	Diamond
Bos taurus	Q3MHR7	99.7%	Diamond
Xenopus laevis	Q0IH88	97.3%	Diamond
Anopheles gambiae	Q7PVX8	84.1%	Diamond
Schizosaccharomyces pombe 972h-	O14241	45.9%	Diamond
Dictyostelium discoideum	O96623	42.0%	Diamond
Saccharomyces cerevisiae S288C	P53731	40.1%	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
AAMP	protein-coding	14
GPBAR1	protein-coding	151306
TRY-ATA1-1	tRNA	100189253
MIR6513	ncRNA	102465256
PNKD	protein-coding	25953
TMBIM1	protein-coding	64114
CXCR1	protein-coding	3577

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): O15144, C9JTV5, 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 (39 total): helix 18, strand 11, turn 5, modified residue 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
9I2B	SPIN90-Arp2/3 nucleated bidirectional actin filaments	ELECTRON MICROSCOPY	3
8P94	Cryo-EM structure of cortactin stabilized Arp2/3-complex nucleated actin branches	ELECTRON MICROSCOPY	3.3
6UHC	CryoEM structure of human Arp2/3 complex with bound NPFs	ELECTRON MICROSCOPY	3.9
6YW6	Cryo-EM structure of the ARP2/3 1B5CL isoform complex.	ELECTRON MICROSCOPY	4.2
6YW7	Cryo-EM structure of the ARP2/3 1A5C isoform complex.	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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)

Type	Positions
N6-acetyllysine	275, 295

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 24; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

24 pathways:

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

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 (7): positive regulation of lamellipodium assembly (GO:0010592), actin filament polymerization (GO:0030041), Arp2/3 complex-mediated actin nucleation (GO:0034314), actin polymerization-dependent cell motility (GO:0070358), positive regulation of cellular component biogenesis (GO:0044089), actin cortical patch organization (GO:0044396), positive regulation of cellular component organization (GO:0051130)

GO Molecular Function (5): actin binding (GO:0003779), structural constituent of cytoskeleton (GO:0005200), protein binding (GO:0005515), actin filament binding (GO:0051015), molecular adaptor activity (GO:0060090)

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

15 top-level categories:

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

44 GO namespaces:

Category	Terms
cellular anatomical structure	6
positive regulation of cellular process	2
cellular component organization	2
cytoskeleton	2
binding	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 nucleation	1
cell motility	1
cellular component biogenesis	1
regulation of cellular component biogenesis	1
cortical actin cytoskeleton organization	1
regulation of cellular component organization	1
cytoskeletal protein binding	1
structural molecule activity	1
cytoskeleton organization	1
actin binding	1
protein-containing complex binding	1
molecular_function	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
synaptic vesicle	1
exocytic vesicle membrane	1
site of DNA damage	1
cell projection membrane	1
muscle cell projection	1
extracellular vesicle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 34 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
Arp2/3 complex-mediated actin nucleation	BP	direct assay
positive regulation of lamellipodium assembly	BP	mutant phenotype
Arp2/3 protein complex	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
lamellipodium	CC	direct assay
nucleoplasm	CC	direct assay
structural constituent of cytoskeleton	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,051 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARPC2	ARPC3	O15145	977
ARPC2	ARPC5	O15511	968
ARPC2	ACTR2	P61160	952
ARPC2	ARPC1B	O15143	951
ARPC2	ACTR3	P32391	938
ARPC2	WAS	P42768	900
ARPC2	ARPC4	P59998	819
ARPC2	ARPC1A	Q92747	800
ARPC2	WASL	O00401	741
ARPC2	ARPC5L	Q9BPX5	678
ARPC2	WASF1	Q92558	631
ARPC2	CTTN	Q14247	590
ARPC2	HCLS1	P14317	587
ARPC2	WASF2	Q9Y6W5	576
ARPC2	BRK1	Q8WUW1	525

IntAct

Human interaction partners of ARPC2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

22 partners by confidence:

Partner	Interaction type	MIscore	Records
ARPC1B	physical association	0.920	14
ARPC1A	association	0.900	13
ACTR3B	association	0.670	3
ACTR3	association	0.640	2
ARPC3	association	0.640	2
NFE2L2	physical association	0.630	5
ARPIN	physical association	0.520	2
CORO1B	association	0.500	2
VCL	direct interaction	0.440	3
PARD3	physical association	0.400	1
WASL	physical association	0.400	1
SHANK3	physical association	0.370	1
PAK4	association	0.350	2
APPL1	association	0.350	1
ARL14EP	association	0.350	1
ARL8B	association	0.350	1
CXCR2	association	0.350	1
DOK2	association	0.350	1
SSH1	association	0.350	1
USP22	association	0.350	1
HLA-B	physical association	0.000	1
TRAF6	physical association	0.000	1

BioGRID (369 interactions; top human partners by supporting records): ARPC1B (Affinity Capture-MS; 20 records), ACTR3 (Co-fractionation; 18 records), ACTR2 (Co-fractionation; 17 records), ARPC3 (Affinity Capture-MS; 15 records), ARPC1A (Affinity Capture-MS; 11 records), ACTR3B (Affinity Capture-MS; 8 records), ARPC4 (Co-fractionation; 8 records), ARPC5 (Co-fractionation; 7 records), ARPC5L (Co-fractionation; 6 records), ACTB (Affinity Capture-MS; 3 records), ANLN (Affinity Capture-MS; 3 records), CTTN (Affinity Capture-MS; 3 records), NFE2L2 (Two-hybrid; 3 records), ACTG1 (Affinity Capture-MS; 2 records), AGR2 (Proximity Label-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
Arp2/3 protein complex	7	ACTR3, ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ACTR2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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
RHO GTPases Activate WASPs and WAVEs	5	105.7×	9e-08
EPHB-mediated forward signaling	5	88.5×	1e-07
FCGR3A-mediated phagocytosis	5	62.4×	4e-07
Regulation of actin dynamics for phagocytic cup formation	5	61.4×	4e-07
Infectious disease	5	8.3×	2e-03

Disease & clinical

Genetic variants

Variant evidence for ARPC2: 52 ClinVar records (1 pathogenic / likely pathogenic); 15 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	19
Likely benign	0
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
493568	GRCh37/hg19 2q35-36.3(chr2:217374144-227643620)x1	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ARPC2’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; 35 predictions of 897):

Position(s)	Effect	Δscore	Sites
2:218217545–218217546	donor_loss	1.0000	4
2:218228736–218228737	acceptor_loss	1.0000	6
2:218238662–218238663	acceptor_loss	1.0000	6
2:218238805	donor_gain	1.0000
2:218238819	donor_gain	1.0000
2:218239485–218239486	donor_loss	1.0000	4
2:218249355	acceptor_gain	1.0000
2:218249362–218249363	acceptor_loss	1.0000	6
2:218249465–218249466	donor_loss	1.0000	5
2:218217545	donor_loss	0.9900

AlphaMissense

1,486 missense substitutions predicted likely pathogenic (of 2,002 scored), across 277 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
M266	9	0.994	1.000
H254	8	1.000	1.000
D37	8	0.999	1.000
D39	8	0.999	1.000
F169	8	0.999	1.000
D174	8	0.999	1.000
H231	8	0.999	1.000
H252	8	0.999	1.000
D159	8	0.998	1.000
F181	8	0.998	1.000
H263	8	0.998	1.000
F225	8	0.997	1.000
F125	8	0.995	0.999
F129	8	0.993	0.999
F165	8	0.993	1.000
F247	8	0.991	0.999
F185	8	0.990	1.000
F273	8	0.989	0.999
F121	8	0.985	0.998
F228	8	0.983	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.42e-05
Breast Invasive Carcinoma (TCGA)	unfavorable	0.000524

Disease associations

OMIM: gene MIM:604224 | disease phenotypes:

GWAS associations

15 associations:

Study	Trait	p-value
GCST90002401_448	Platelet distribution width	1e-74
GCST90002402_558	Platelet count	4e-51
GCST90002395_241	Mean platelet volume	3e-34
GCST004616_140	Platelet distribution width	6e-26
GCST004603_146	Platelet count	7e-19
GCST90002395_242	Mean platelet volume	5e-16
GCST004599_236	Mean platelet volume	4e-15
GCST005974_12	Neutrophil count	4e-13
GCST001725_74	Inflammatory bowel disease	4e-12
GCST005973_41	White blood cell count	3e-11
GCST002556_2	White blood cell count	9e-9
GCST004131_76	Inflammatory bowel disease	2e-7
GCST001762_333	Obesity-related traits	2e-6
GCST001762_878	Obesity-related traits	3e-6
GCST001762_215	Obesity-related traits	7e-6

EFO canonical traits (from GWAS)

5 canonical traits:

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 (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 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 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	affects expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases 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	increases expression, affects cotreatment, decreases reaction	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 localization, increases expression, affects cotreatment	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)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ARPC2 across ~30M SureChEMBL compounds — explore on Sugi Predict.