ARPC4

Summary

ARPC4 (actin related protein 2/3 complex subunit 4, HGNC:707) is a protein-coding gene on chromosome 3p25.3, encoding Actin-related protein 2/3 complex subunit 4 (P59998). 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: 74.3% of cell lines).

This gene encodes one of seven subunits of the human Arp2/3 protein complex. This complex controls actin polymerization in cells and has been conserved throughout eukaryotic evolution. This gene encodes the p20 subunit, which is necessary for actin nucleation and high-affinity binding to F-actin. Alternative splicing results in multiple transcript variants. Naturally occurring read-through transcription exists between this gene and the downstream tubulin tyrosine ligase-like family, member 3 (TTLL3), which results in the production of a fusion protein.

Source: NCBI Gene 10093 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental delay, language impairment, and ocular abnormalities (Strong, GenCC)
• Clinical variants (ClinVar): 54 total — 7 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 28
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 74.3% of screened cell lines
• MANE Select transcript: NM_005718

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:707
Approved symbol	ARPC4
Name	actin related protein 2/3 complex subunit 4
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	p20-Arc, ARC20
Ensembl gene	ENSG00000241553
Ensembl biotype	protein_coding
OMIM	604226
Entrez	10093

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000397261, ENST00000417500, ENST00000433034, ENST00000440787, ENST00000467289, ENST00000479956, ENST00000485273, ENST00000498623, ENST00000905840, ENST00000905841, ENST00000929598, ENST00000929599, ENST00000957522

RefSeq mRNA: 4 — MANE Select: NM_005718 NM_001024959, NM_001024960, NM_001198780, NM_005718

CCDS: CCDS43047, CCDS46743, CCDS56238

Canonical transcript exons

ENST00000397261 — 6 exons

Exon	Start	End
ENSE00003419950	9806210	9807101
ENSE00003703417	9797659	9797777
ENSE00003709822	9801661	9801756
ENSE00003710333	9793082	9793124
ENSE00003711155	9800185	9800296
ENSE00003789499	9803843	9804013

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6869 / max 54.1666, expressed in 1623 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35232	127.2627	1828
35231	3.6869	1623
35230	2.1593	1376
35233	1.0040	526
35234	0.7871	458

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.20	gold quality
granulocyte	CL:0000094	98.97	gold quality
leukocyte	CL:0000738	98.94	gold quality
mononuclear cell	CL:0000842	98.92	gold quality
rectum	UBERON:0001052	98.36	gold quality
smooth muscle tissue	UBERON:0001135	98.31	gold quality
mucosa of transverse colon	UBERON:0004991	98.26	gold quality
right coronary artery	UBERON:0001625	98.06	gold quality
descending thoracic aorta	UBERON:0002345	97.97	gold quality
gall bladder	UBERON:0002110	97.96	gold quality
lower esophagus mucosa	UBERON:0035834	97.96	gold quality
popliteal artery	UBERON:0002250	97.93	gold quality
tibial artery	UBERON:0007610	97.93	gold quality
islet of Langerhans	UBERON:0000006	97.92	gold quality
thoracic aorta	UBERON:0001515	97.92	gold quality
ascending aorta	UBERON:0001496	97.90	gold quality
aorta	UBERON:0000947	97.84	gold quality
cortical plate	UBERON:0005343	97.80	gold quality
left coronary artery	UBERON:0001626	97.79	gold quality
blood	UBERON:0000178	97.65	gold quality
transverse colon	UBERON:0001157	97.63	gold quality
esophagus mucosa	UBERON:0002469	97.51	gold quality
stromal cell of endometrium	CL:0002255	97.49	gold quality
skin of leg	UBERON:0001511	97.47	gold quality
mucosa of stomach	UBERON:0001199	97.39	gold quality
coronary artery	UBERON:0001621	97.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.39	gold quality
upper lobe of left lung	UBERON:0008952	97.37	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.36	gold quality
ectocervix	UBERON:0012249	97.33	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	20.39
E-ANND-3	yes	10.68
E-MTAB-6379	no	344.85
E-MTAB-5061	no	3.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting ARPC4, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-7108-5P	96.42	66.17	598
HSA-MIR-6880-3P	85.95	63.83	83

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 74.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• We show that coronin 3 similar to other coronins interacts with the Arp2/3-complex and cofilin indicating that this family in general is involved in regulating Arp2/3-mediated events. (PMID:17274980)
• we show cell line-specific differences in ARP2/3 complex subunit dependency on cell migratory potential, and suggest ARPC4 to be one of the key members of the ARP2/3 complex in pancreatic cancer. (PMID:23267127)
• Expression of the ARPC4 severely affects mycobacterium tuberculosis growth and suppresses immunogenic response in murine macrophages (PMID:23894563)
• ARPC4 promotes bladder cancer cell invasion and is associated with lymph node metastasis. (PMID:31190401)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arpc4	ENSDARG00000054063
danio_rerio	arpc4l	ENSDARG00000058225
mus_musculus	Arpc4	ENSMUSG00000079426
rattus_norvegicus	Arpc4	ENSRNOG00000008994
drosophila_melanogaster	Arpc4	FBGN0284255
caenorhabditis_elegans		WBGENE00000204

Protein

Protein identifiers

Actin-related protein 2/3 complex subunit 4 — P59998 (reviewed: P59998)

Alternative names: Arp2/3 complex 20 kDa subunit

All UniProt accessions (4): F8WDD7, F8WDW3, P59998, R4GN08

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. 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.

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

Disease relevance. Developmental delay, language impairment, and ocular abnormalities (DEVLO) [MIM:620141] An autosomal dominant disorder characterized by mild motor delay, mildly impaired intellectual development, and significant speech impairment. Most affected individuals have microcephaly and may have mild dysmorphic features. Variable ocular anomalies include strabismus, cataracts, and cortical visual impairment. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ARPC4 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P59998-1	1	yes
P59998-2	2
P59998-3	3
P59998-4	4

RefSeq proteins (4): NP_001020130, NP_001020131, NP_001185709, NP_005709* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008384	ARPC4	Family
IPR034666	ARPC2/4	Homologous_superfamily

Pfam: PF05856

UniProt features (8 total): splice variant 3, initiator methionine 1, chain 1, modified residue 1, sequence variant 1, sequence conflict 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-P59998-F1	94.20	0.90

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 (1): 2

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: 286 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, ELVIDGE_HYPOXIA_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MODULE_45, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, REACTOME_MEMBRANE_TRAFFICKING, MODULE_16, SP1_Q2_01, SRF_Q5_01, SRF_C, AMIT_EGF_RESPONSE_120_HELA, GOBP_ACTIN_FILAMENT_ORGANIZATION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN

GO Biological Process (3): actin filament polymerization (GO:0030041), Arp2/3 complex-mediated actin nucleation (GO:0034314), actin nucleation (GO:0045010)

GO Molecular Function (6): actin binding (GO:0003779), structural constituent of cytoskeleton (GO:0005200), enzyme binding (GO:0019899), protein binding (GO:0005515), protein-macromolecule adaptor activity (GO:0030674), actin filament binding (GO:0051015)

GO Cellular Component (9): nucleus (GO:0005634), cytosol (GO:0005829), Arp2/3 protein complex (GO:0005885), site of double-strand break (GO:0035861), cell projection (GO:0042995), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), actin cytoskeleton (GO:0015629)

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	3
cytoskeleton	2
protein binding	2
actin polymerization or depolymerization	1
protein polymerization	1
actin nucleation	1
actin filament organization	1
cytoskeletal protein binding	1
structural molecule activity	1
cytoskeleton organization	1
binding	1
molecular adaptor activity	1
actin binding	1
protein-containing complex binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
actin cytoskeleton	1
protein-containing complex	1
site of DNA damage	1
extracellular vesicle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARPC4	ARPC2	O15144	885
ARPC4	ARPC5	O15511	846
ARPC4	ARPC3	O15145	810
ARPC4	ACTR2	P61160	810
ARPC4	ARPC1B	O15143	796
ARPC4	ACTR3	P32391	776
ARPC4	WAS	P42768	591
ARPC4	ACTR3C	Q9C0K3	421
ARPC4	ACTR3B	Q9P1U1	413
ARPC4	LCP1	P13796	393
ARPC4	ARPC5L	Q9BPX5	349
ARPC4	GPBAR1	Q8TDU6	349
ARPC4	BRK1	Q8WUW1	349
ARPC4	ARPC1A	Q92747	337
ARPC4	S100A8	P05109	331

IntAct

171 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
ARPC5L	ARPC4	psi-mi:“MI:0915”(physical association)	0.890
ARPC4	ARPC5L	psi-mi:“MI:0915”(physical association)	0.890
ACTR3	ARPC1B	psi-mi:“MI:0914”(association)	0.890
ARPC3	ARPC1B	psi-mi:“MI:0914”(association)	0.880
ARPC5L	ARPC1B	psi-mi:“MI:0914”(association)	0.830

BioGRID (352): PNMA5 (Two-hybrid), ARPC4 (Affinity Capture-RNA), ARPC4 (Affinity Capture-RNA), ARPC4 (Affinity Capture-RNA), ARPC4-TTLL3 (Affinity Capture-RNA), ARPC4 (Affinity Capture-MS), ARPC4 (Affinity Capture-MS), ARPC4 (Affinity Capture-RNA), ACTR3 (Co-fractionation), ACTR3 (Co-fractionation), ARPC1A (Co-fractionation), ARPC1A (Co-fractionation), ARPC1B (Co-fractionation), ARPC1B (Co-fractionation), ARPC2 (Co-fractionation)

ESM2 similar proteins: A0JN39, A4FUD3, B5DGH9, D2SW95, F4JUL9, O08810, P23514, P53618, P59998, P59999, P60228, P60229, Q05AY2, Q0P5J8, Q148J6, Q15029, Q1LUA8, Q28EN2, Q3B8M3, Q3T102, Q40281, Q4R6G8, Q5F3X4, Q5F428, Q5R6E0, Q5R7S4, Q5R8K9, Q5R8N4, Q5R922, Q5RAK7, Q5VSL9, Q5XI83, Q5ZIA5, Q5ZLA5, Q641G7, Q641X8, Q66HV4, Q6DRI1, Q6P6M7, Q6P7L9

Diamond homologs: F4JUL9, O96625, P33204, P58798, P59998, P59999, Q148J6, Q641G7, Q92352

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ARPC4	“form complex”	ARP2/3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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	11	39.6×	3e-13
Parasite infection	10	39.3×	5e-12
Leishmania phagocytosis	10	39.3×	5e-12
Fcgamma receptor (FCGR) dependent phagocytosis	10	31.6×	4e-11
RHO GTPases activate PAKs	5	30.9×	1e-05
EPHB-mediated forward signaling	10	30.2×	6e-11
FCGR3A-mediated phagocytosis	13	27.7×	3e-13
Regulation of actin dynamics for phagocytic cup formation	13	27.2×	3e-13

GO biological processes:

GO term	Partners	Fold	FDR
Arp2/3 complex-mediated actin nucleation	8	78.8×	3e-11
actin polymerization or depolymerization	5	35.8×	6e-05
regulation of actin filament polymerization	5	27.1×	2e-04
cellular response to type II interferon	7	13.6×	2e-04
actin cytoskeleton organization	11	8.1×	4e-05
actin filament organization	6	6.7×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	3
Uncertain significance	36
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
148359	GRCh38/hg38 3p25.3-25.2(chr3:9394874-11690612)x1	Pathogenic
155699	GRCh38/hg38 3p26.1-25.1(chr3:7356110-14360442)x3	Pathogenic
253614	GRCh37/hg19 3p25.3-25.2(chr3:8922160-12338637)x1	Pathogenic
3062673	GRCh37/hg19 3p26.1-25.3(chr3:6306331-11468530)x1	Pathogenic
3246936	NC_000003.11:g.(?9703931)(11078652_?)del	Pathogenic
395270	GRCh37/hg19 3p25.3(chr3:9666380-10028247)x1	Pathogenic
57741	GRCh38/hg38 3p25.3(chr3:9393349-9956171)x1	Pathogenic
146336	GRCh38/hg38 3p26.1-25.3(chr3:8038727-11240931)x4	Likely pathogenic
148234	GRCh38/hg38 3p26.1-25.2(chr3:7975734-12636917)x3	Likely pathogenic
253334	GRCh37/hg19 3p25.3(chr3:9405337-10168892)x3	Likely pathogenic

SpliceAI

1017 predictions. Top by Δscore:

Variant	Effect	Δscore
3:9797644:T:TA	acceptor_gain	1.0000
3:9797648:A:AG	acceptor_gain	1.0000
3:9797649:T:G	acceptor_gain	1.0000
3:9797653:CTATA:C	acceptor_loss	1.0000
3:9797654:TATA:T	acceptor_loss	1.0000
3:9797654:TATAG:T	acceptor_loss	1.0000
3:9797655:ATAG:A	acceptor_loss	1.0000
3:9797655:ATAGA:A	acceptor_loss	1.0000
3:9797656:T:G	acceptor_gain	1.0000
3:9797656:TA:T	acceptor_loss	1.0000
3:9797656:TAGAC:T	acceptor_loss	1.0000
3:9797657:A:AG	acceptor_gain	1.0000
3:9797657:A:T	acceptor_loss	1.0000
3:9797657:AG:A	acceptor_loss	1.0000
3:9797657:AGACT:A	acceptor_gain	1.0000
3:9797658:G:GC	acceptor_gain	1.0000
3:9797658:GA:G	acceptor_gain	1.0000
3:9797658:GAC:G	acceptor_gain	1.0000
3:9797658:GACT:G	acceptor_gain	1.0000
3:9797658:GACTG:G	acceptor_gain	1.0000
3:9797764:G:GT	donor_gain	1.0000
3:9797770:G:GT	donor_gain	1.0000
3:9797773:GTCAG:G	donor_gain	1.0000
3:9797774:TCAG:T	donor_loss	1.0000
3:9797776:AG:A	donor_loss	1.0000
3:9797777:GG:G	donor_loss	1.0000
3:9797778:G:GA	donor_loss	1.0000
3:9797778:G:GG	donor_gain	1.0000
3:9797779:T:A	donor_loss	1.0000
3:9797779:T:G	donor_loss	1.0000

AlphaMissense

1131 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:9797728:T:C	F25L	1.000
3:9797730:C:A	F25L	1.000
3:9797730:C:G	F25L	1.000
3:9800226:G:C	R55T	1.000
3:9800226:G:T	R55M	1.000
3:9800227:G:C	R55S	1.000
3:9800227:G:T	R55S	1.000
3:9800266:C:A	N68K	1.000
3:9800266:C:G	N68K	1.000
3:9800267:T:C	S69P	1.000
3:9800268:C:T	S69F	1.000
3:9800277:T:A	V72D	1.000
3:9800279:A:C	S73R	1.000
3:9800281:C:A	S73R	1.000
3:9800281:C:G	S73R	1.000
3:9801703:T:C	F93L	1.000
3:9801705:C:A	F93L	1.000
3:9801705:C:G	F93L	1.000
3:9801737:T:A	L104H	1.000
3:9801737:T:C	L104P	1.000
3:9801743:G:C	R106T	1.000
3:9801743:G:T	R106M	1.000
3:9801744:G:C	R106S	1.000
3:9801744:G:T	R106S	1.000
3:9803855:A:C	S115R	1.000
3:9803857:C:A	S115R	1.000
3:9803857:C:G	S115R	1.000
3:9803859:T:C	F116S	1.000
3:9803862:T:C	L117P	1.000
3:9803912:T:C	F134L	1.000

dbSNP variants (sampled 300 via entrez): RS1000147499 (3:9800462 T>A), RS1000304726 (3:9792329 G>A), RS1000375701 (3:9806035 G>T), RS1000664067 (3:9806370 G>A,T), RS1000833333 (3:9792547 G>A,C), RS1000932385 (3:9795715 G>C), RS1001065122 (3:9800032 A>G), RS1001109288 (3:9807557 G>A,C), RS1001193476 (3:9794674 C>T), RS1001259964 (3:9795963 G>T), RS1001365597 (3:9799036 G>A), RS1001523360 (3:9796547 C>T), RS1001544804 (3:9806926 T>TCAGTGC), RS1001756410 (3:9806854 C>T), RS1001804806 (3:9796880 G>A,C)

Disease associations

OMIM: gene MIM:604226 | disease phenotypes: MIM:620141, MIM:606217, MIM:616421

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental delay, language impairment, and ocular abnormalities	Strong	Autosomal dominant

Mondo (4): developmental delay, language impairment, and ocular abnormalities (MONDO:0859324), atrioventricular septal defect, susceptibility to, 2 (MONDO:0011650), epilepsy with myoclonic atonic seizures (MONDO:0014633), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Motor delay-microcephaly-speech impairment-ocular abnormalities syndrome (Orphanet:662762), Epilepsy with myoclonic-atonic seizures (Orphanet:1942)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000126	Hydronephrosis
HP:0000252	Microcephaly
HP:0000486	Strabismus
HP:0000519	Developmental cataract
HP:0000577	Exotropia
HP:0000718	Aggressive behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001256	Mild intellectual disability
HP:0001270	Motor delay
HP:0001642	Pulmonic stenosis
HP:0002144	Tethered cord
HP:0002186	Apraxia
HP:0002475	Myelomeningocele
HP:0002650	Scoliosis
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0007018	Attention deficit hyperactivity disorder
HP:0007380	Facial telangiectasia
HP:0009185	Contracture of the proximal interphalangeal joint of the 5th finger
HP:0020046	Accommodative esotropia
HP:0025161	Frequent temper tantrums
HP:0100704	Cerebral visual impairment
HP:0100710	Impulsivity
HP:0500041	Myopic astigmatism

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C565249	Atrioventricular Septal Defect, Partial, with Heterotaxy Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724754 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Nickel	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
cobaltous chloride	decreases expression	1
nickel sulfate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
AM 251	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	affects response to substance	1
Acetylglucosamine	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	decreases expression	1
Cisplatin	increases expression, decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Diuron	decreases expression	1
Doxorubicin	increases expression	1
Gallic Acid	increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650934	Binding	Binding affinity to human ARPC4 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_D7KF	Ubigene A-549 ARPC4 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT04048213	Not specified	UNKNOWN	The Becoming of Children With Doose Syndrome
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge