ARPC5

Summary

ARPC5 (actin related protein 2/3 complex subunit 5, HGNC:708) is a protein-coding gene on chromosome 1q25.3, encoding Actin-related protein 2/3 complex subunit 5 (O15511). Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF).

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 p16 subunit, has yet to be determined. Alternatively spliced transcript variants encoding different isoforms have been observed for this gene.

Source: NCBI Gene 10092 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 113 with autoimmunity and autoinflammation (Strong, GenCC)
• Clinical variants (ClinVar): 19 total — 1 pathogenic
• Phenotypes (HPO): 35
• Druggable target: yes
• MANE Select transcript: NM_005717

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:708
Approved symbol	ARPC5
Name	actin related protein 2/3 complex subunit 5
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Aliases	p16-Arc, ARC16, dJ127C7.3
Ensembl gene	ENSG00000162704
Ensembl biotype	protein_coding
OMIM	604227
Entrez	10092

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000294742, ENST00000359856, ENST00000367534, ENST00000462965, ENST00000602490

RefSeq mRNA: 2 — MANE Select: NM_005717 NM_001270439, NM_005717

CCDS: CCDS1357, CCDS58050

Canonical transcript exons

ENST00000359856 — 4 exons

Exon	Start	End
ENSE00001324695	183633082	183633154
ENSE00001822185	183620846	183627594
ENSE00001852442	183635517	183635783
ENSE00003473550	183630461	183630637

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 186.9084 / max 3080.2116, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16233	174.0374	1822
16234	12.8710	1769

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.52	gold quality
mononuclear cell	CL:0000842	99.49	gold quality
leukocyte	CL:0000738	99.47	gold quality
germinal epithelium of ovary	UBERON:0001304	99.45	gold quality
lower lobe of lung	UBERON:0008949	99.02	gold quality
blood	UBERON:0000178	99.01	gold quality
superficial temporal artery	UBERON:0001614	98.99	gold quality
vermiform appendix	UBERON:0001154	98.95	gold quality
trabecular bone tissue	UBERON:0002483	98.93	gold quality
granulocyte	CL:0000094	98.80	gold quality
caecum	UBERON:0001153	98.72	gold quality
lymph node	UBERON:0000029	98.65	gold quality
placenta	UBERON:0001987	98.61	gold quality
visceral pleura	UBERON:0002401	98.57	gold quality
cortical plate	UBERON:0005343	98.56	gold quality
right lung	UBERON:0002167	98.40	gold quality
bone marrow cell	CL:0002092	98.37	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.36	gold quality
colonic mucosa	UBERON:0000317	98.33	gold quality
bone marrow	UBERON:0002371	98.33	gold quality
endometrium epithelium	UBERON:0004811	98.33	gold quality
thymus	UBERON:0002370	98.31	gold quality
ileal mucosa	UBERON:0000331	98.28	gold quality
ganglionic eminence	UBERON:0004023	98.26	gold quality
pleura	UBERON:0000977	98.24	gold quality
stromal cell of endometrium	CL:0002255	98.23	gold quality
parietal pleura	UBERON:0002400	98.22	gold quality
oral cavity	UBERON:0000167	98.19	gold quality
endometrium	UBERON:0001295	98.17	gold quality
lung	UBERON:0002048	98.17	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	41.67
E-HCAD-6	yes	36.80
E-CURD-46	yes	30.67
E-HCAD-11	yes	25.03
E-CURD-122	yes	20.81
E-GEOD-130148	yes	19.31
E-MTAB-10042	yes	16.73
E-MTAB-9388	yes	12.78
E-CURD-88	yes	12.35
E-MTAB-9801	yes	8.44
E-GEOD-125970	yes	4.45
E-MTAB-8498	no	8.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting ARPC5, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3185	99.99	68.12	1959
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-659-3P	99.85	70.69	1620

Literature-anchored findings (GeneRIF, showing 10)

• identified as a substrate of MAPK-activated protein kinase 2(MAPKAPK2); the ability of MAPKAPK2 to phosphorylate one isoform of p16-Arc suggests a possible mechanism by which the p38 MAPK cascade regulates remodeling of the actin cytoskeleton (PMID:12829704)
• Levels of ARPC5 expression were significantly higher in invasive cancer cells and gene expression was directly regulated by miR-133a. (PMID:22378351)
• Quantitative PCR demonstrated that ARPC5 was significantly increased in MM patients. GSEA results indicated that ARPC5 might affect cellular growth of myeloma cells through mammalian target of rapamycin (mTOR)C1 signaling pathway. (PMID:30201948)
• YAP facilitates melanoma migration through regulation of actin-related protein 2/3 complex subunit 5 (ARPC5). (PMID:34468072)
• ARPC5 is transcriptionally activated by KLF4, and promotes cell migration and invasion in prostate cancer via up-regulating ADAM17 : ARPC5 serves as an oncogene in prostate cancer. (PMID:36881291)
• ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells. (PMID:37162507)
• Inherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling. (PMID:37349293)
• ARPC5 deficiency leads to severe early-onset systemic inflammation and mortality. (PMID:37382373)
• ARPC5 acts as a potential prognostic biomarker that is associated with cell proliferation, migration and immune infiltrate in gliomas. (PMID:37789267)
• TAGLN2 targeted control of ARPC5-mediated activation of the MEK/ERK signaling pathway influences the proliferation, invasion, and metastasis of pancreatic cancer cells. (PMID:38744388)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	arpc5b	ENSDARG00000019062
danio_rerio	arpc5a	ENSDARG00000039142
mus_musculus	Arpc5	ENSMUSG00000008475
rattus_norvegicus	Arpc5	ENSRNOG00000028062
drosophila_melanogaster	Arpc5	FBGN0031437
caenorhabditis_elegans	arx-7	WBGENE00000205
caenorhabditis_elegans	C46H11.3	WBGENE00016729

Paralogs (1): ARPC5L (ENSG00000136950)

Protein

Protein identifiers

Actin-related protein 2/3 complex subunit 5 — O15511 (reviewed: O15511)

Alternative names: Arp2/3 complex 16 kDa subunit

All UniProt accessions (2): B1ALC0, O15511

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Post-translational modifications. Polyubiquitinated by RNF128 with ‘Lys-63’-linked chains, leading to proteasomal degradation.

Disease relevance. Immunodeficiency 113 with autoimmunity and autoinflammation (IMD113) [MIM:620565] An autosomal recessive immunologic disorder characterized by recurrent and severe infections, early-onset autoimmunity, inflammation, and facial dysmorphism. Features of autoimmunity and autoinflammation include hemolytic anemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ARPC5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15511-1	1	yes
O15511-2	2

RefSeq proteins (2): NP_001257368, NP_005708* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006789	ARPC5	Family
IPR036743	ARPC5_sf	Homologous_superfamily

Pfam: PF04699

UniProt features (6 total): initiator methionine 1, chain 1, region of interest 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6UHC	ELECTRON MICROSCOPY	3.9
6YW7	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15511-F1	92.42	0.82

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

25 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-6798695	Neutrophil degranulation
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: 418 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_MSN, DORSAM_HOXA9_TARGETS_UP, LU_IL4_SIGNALING, GOCC_SECRETORY_GRANULE, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, EFC_Q6, NFKB_Q6, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, NFKB_C, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, RICKMAN_METASTASIS_DN

GO Biological Process (4): cell migration (GO:0016477), actin cytoskeleton organization (GO:0030036), regulation of actin filament polymerization (GO:0030833), Arp2/3 complex-mediated actin nucleation (GO:0034314)

GO Molecular Function (5): actin binding (GO:0003779), structural constituent of cytoskeleton (GO:0005200), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515), actin filament binding (GO:0051015)

GO Cellular Component (15): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), Arp2/3 protein complex (GO:0005885), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), cortical cytoskeleton (GO:0030863), secretory granule lumen (GO:0034774), site of double-strand break (GO:0035861), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Innate Immune System	2
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
Axon guidance	1
Nervous system development	1
Disease	1
Parasitic Infection Pathways	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoskeleton	3
cytoskeleton organization	2
cell motility	1
actin filament-based process	1
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
actin nucleation	1
cytoskeletal protein binding	1
structural molecule activity	1
protein binding	1
molecular adaptor activity	1
binding	1
actin binding	1
protein-containing complex binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
actin cytoskeleton	1
protein-containing complex	1
cell-substrate junction	1
cell leading edge	1
plasma membrane bounded cell projection	1
cell cortex	1
secretory granule	1
cytoplasmic vesicle lumen	1
site of DNA damage	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARPC5	ARPC3	O15145	999
ARPC5	ARPC2	O15144	999
ARPC5	ARPC1B	O15143	998
ARPC5	ACTR2	P61160	998
ARPC5	ACTR3	P32391	984
ARPC5	WAS	P42768	908
ARPC5	ARPC1A	Q92747	894
ARPC5	ARPC4	P59998	846
ARPC5	ACTR3B	Q9P1U1	737
ARPC5	ACTR3C	Q9C0K3	706
ARPC5	WASL	O00401	577
ARPC5	CTTN	Q14247	531
ARPC5	HCLS1	P14317	527
ARPC5	WASF1	Q92558	518
ARPC5	HIP1R	O75146	509

IntAct

86 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
ACTR3	ARPC1B	psi-mi:“MI:0914”(association)	0.890
ARPC5	ARPC3	psi-mi:“MI:0914”(association)	0.730
ARPC5	EGFR	psi-mi:“MI:0915”(physical association)	0.550
EGFR	ARPC5	psi-mi:“MI:0915”(physical association)	0.550
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
CDC42	BBX	psi-mi:“MI:0914”(association)	0.350
Cdk1	IFT88	psi-mi:“MI:0914”(association)	0.350
ZWINT	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
ANLN	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (233): ARPC5 (Affinity Capture-MS), ARPC5 (Affinity Capture-MS), ARPC5 (Affinity Capture-MS), ARPC5 (Affinity Capture-MS), ACTR3 (Co-fractionation), ARPC1A (Co-fractionation), ARPC2 (Co-fractionation), ARPC4-TTLL3 (Co-fractionation), ARPC4 (Co-fractionation), ARPC5 (Co-fractionation), ARPC5 (Co-fractionation), ARPC5 (Co-fractionation), CAPZB (Co-fractionation), ARPC5 (Affinity Capture-MS), ARPC5 (Affinity Capture-MS)

ESM2 similar proteins: A1C987, A1D9P1, A1L108, A3GGB4, A3LPQ8, A5DMM1, A5DPQ5, A6S043, B0YEH1, B3H6Y2, C4YCB9, G5EES6, O14164, O15511, O74432, O96626, P0CN46, P0CN47, P0CN54, P0CN55, P40518, P91167, Q09722, Q0CVT0, Q10316, Q1DP77, Q2H731, Q2U0Q9, Q3SYX9, Q4KLF8, Q4P0P0, Q4PHN4, Q4W9S8, Q4WDK4, Q5AX75, Q5E963, Q5R4M1, Q5R516, Q641B9, Q68FI4

Diamond homologs: A1L108, B3H6Y2, O15511, O96626, P91167, Q3SYX9, Q4KLF8, Q5E963, Q5R4M1, Q5R516, Q641B9, Q68FI4, Q6DE18, Q9BPX5, Q9CPW4, Q9D898, Q9M117, Q10316, P40518

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ARPC5	“form complex”	ARP2/3	binding
PRKCA	“up-regulates activity”	ARPC5	phosphorylation
MAPKAPK2	unknown	ARPC5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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	10	57.7×	2e-13
Leishmania phagocytosis	10	57.7×	2e-13
RHO GTPases Activate WASPs and WAVEs	10	52.9×	3e-13
Fcgamma receptor (FCGR) dependent phagocytosis	10	46.4×	9e-13
EPHB-mediated forward signaling	10	44.3×	9e-13
FCGR3A-mediated phagocytosis	11	34.3×	9e-13
Regulation of actin dynamics for phagocytic cup formation	11	33.8×	9e-13
EPH-Ephrin signaling	10	27.6×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
Arp2/3 complex-mediated actin nucleation	7	99.6×	2e-10
establishment or maintenance of cell polarity	5	27.1×	2e-04
cellular response to type II interferon	6	16.9×	2e-04
actin filament organization	6	9.6×	2e-03
actin cytoskeleton organization	8	8.6×	5e-04
endocytosis	6	7.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2663870	NM_005717.4(ARPC5):c.23C>A (p.Ser8Ter)	Pathogenic

SpliceAI

776 predictions. Top by Δscore:

Variant	Effect	Δscore
1:183627522:T:TA	donor_gain	1.0000
1:183630456:CTTA:C	donor_loss	1.0000
1:183630457:TTACC:T	donor_loss	1.0000
1:183630458:TACCT:T	donor_loss	1.0000
1:183630459:A:AC	donor_gain	1.0000
1:183630459:A:T	donor_loss	1.0000
1:183630460:C:CA	donor_loss	1.0000
1:183630460:C:CC	donor_gain	1.0000
1:183633236:A:C	acceptor_gain	1.0000
1:183627442:C:CT	donor_gain	0.9900
1:183627443:T:TT	donor_gain	0.9900
1:183627448:A:AC	donor_gain	0.9900
1:183627449:C:CC	donor_gain	0.9900
1:183630459:AC:A	donor_gain	0.9900
1:183630460:CC:C	donor_gain	0.9900
1:183630460:CCT:C	donor_gain	0.9900
1:183630460:CCTT:C	donor_gain	0.9900
1:183630460:CCTTT:C	donor_gain	0.9900
1:183630635:GTCC:G	acceptor_loss	0.9900
1:183630638:C:CA	acceptor_loss	0.9900
1:183633232:T:C	acceptor_gain	0.9900
1:183633232:T:TC	acceptor_gain	0.9900
1:183633238:A:C	acceptor_gain	0.9900
1:183635541:C:CA	donor_gain	0.9900
1:183635577:T:TA	donor_gain	0.9900
1:183627449:CAGGG:C	donor_gain	0.9800
1:183630638:C:CC	acceptor_gain	0.9800
1:183630648:A:T	acceptor_gain	0.9800
1:183633227:T:C	acceptor_gain	0.9800
1:183633236:A:AC	acceptor_gain	0.9800

AlphaMissense

991 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:183630472:A:G	W128R	1.000
1:183630472:A:T	W128R	1.000
1:183630470:C:A	W128C	0.999
1:183630470:C:G	W128C	0.999
1:183630570:A:T	V95D	0.999
1:183633137:G:T	A54D	0.999
1:183635627:G:C	F11L	0.999
1:183635627:G:T	F11L	0.999
1:183635629:A:G	F11L	0.999
1:183627560:C:G	R143P	0.998
1:183627566:A:T	I141N	0.998
1:183627572:C:T	G139E	0.998
1:183627573:C:A	G139W	0.998
1:183627573:C:G	G139R	0.998
1:183627573:C:T	G139R	0.998
1:183630469:G:C	H129D	0.998
1:183630471:C:G	W128S	0.998
1:183630477:A:G	L126P	0.998
1:183630537:A:G	L106P	0.998
1:183630618:A:T	V79D	0.998
1:183633082:C:A	K72N	0.998
1:183633082:C:G	K72N	0.998
1:183633122:A:G	L59P	0.998
1:183627561:G:T	R143S	0.997
1:183627563:A:T	V142D	0.997
1:183630480:A:G	L125S	0.997
1:183630513:A:G	F114S	0.997
1:183630525:A:T	I110N	0.997
1:183630537:A:T	L106Q	0.997
1:183630594:T:A	K87I	0.997

dbSNP variants (sampled 300 via entrez): RS1000194118 (1:183634762 C>G,T), RS1000264428 (1:183621059 A>T), RS1000349050 (1:183628334 A>AT), RS1000356554 (1:183632926 T>C), RS1000416443 (1:183622399 C>T), RS1000691769 (1:183634980 C>T), RS1000730413 (1:183621319 C>T), RS1000899543 (1:183632072 G>T), RS1001110645 (1:183624996 G>A), RS1001124463 (1:183627641 A>T), RS1001243359 (1:183631785 G>A), RS1001256269 (1:183629614 A>T), RS1001296592 (1:183636083 T>C), RS1001349541 (1:183629886 T>C), RS1001445699 (1:183621415 C>T)

Disease associations

OMIM: gene MIM:604227 | disease phenotypes: MIM:620565

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 113 with autoimmunity and autoinflammation	Strong	Autosomal recessive

Mondo (1): immunodeficiency 113 with autoimmunity and autoinflammation (MONDO:0957920)

Orphanet (0):

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000964	Eczematoid dermatitis
HP:0001058	Poor wound healing
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001511	Intrauterine growth retardation
HP:0001744	Splenomegaly
HP:0001890	Autoimmune hemolytic anemia
HP:0001973	Autoimmune thrombocytopenia
HP:0001974	Increased total leukocyte count
HP:0002105	Hemoptysis
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0002573	Hematochezia
HP:0002590	Paralytic ileus
HP:0002608	Celiac disease
HP:0002650	Scoliosis
HP:0002718	Recurrent bacterial infections
HP:0002721	Immunodeficiency
HP:0002841	Recurrent fungal infections
HP:0003212	Increased circulating IgE concentration
HP:0003261	Increased circulating IgA concentration
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004322	Short stature
HP:0004429	Recurrent viral infections
HP:0006517	Intraalveolar phospholipid accumulation
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0011897	Increased total neutrophil count
HP:0012115	Hepatitis

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295658 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.53	Kd	2927	nM	CHEMBL5653589
5.53	ED50	2927	nM	CHEMBL5653589
5.46	Kd	3487	nM	CHEMBL3752910
5.46	ED50	3487	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 7 total; 2 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	2147893: Binding affinity to human ARPC5 incubated for 45 mins by Kinobead based pull down assay	kd	2.9272	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147893: Binding affinity to human ARPC5 incubated for 45 mins by Kinobead based pull down assay	kd	3.4872	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, decreases expression	3
sodium arsenite	affects binding, increases reaction, decreases expression, increases abundance, increases expression	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
Cisplatin	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment	1
salinomycin	decreases expression	1
decabromobiphenyl ether	decreases expression	1
cobaltous chloride	decreases expression	1
neferine	decreases reaction, increases expression	1
microcystin RR	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
chloropicrin	affects expression	1
monomethylarsonous acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Arsenic	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Furaldehyde	affects cotreatment, increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118690	Binding	Binding affinity to ARPC5 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_SD55	HAP1 ARPC5 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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