ARPC5L

Summary

ARPC5L (actin related protein 2/3 complex subunit 5 like, HGNC:23366) is a protein-coding gene on chromosome 9q33.3, encoding Actin-related protein 2/3 complex subunit 5-like protein (Q9BPX5). May function as component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks.

Predicted to enable actin filament binding activity. Predicted to be involved in Arp2/3 complex-mediated actin nucleation and cell migration. Located in extracellular exosome and focal adhesion.

Source: NCBI Gene 81873 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• Druggable target: yes
• MANE Select transcript: NM_030978

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23366
Approved symbol	ARPC5L
Name	actin related protein 2/3 complex subunit 5 like
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC3038, ARC16-2
Ensembl gene	ENSG00000136950
Ensembl biotype	protein_coding
Entrez	81873

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000259477, ENST00000353214, ENST00000465124, ENST00000866775, ENST00000911390, ENST00000964188

RefSeq mRNA: 1 — MANE Select: NM_030978 NM_030978

CCDS: CCDS6859

Canonical transcript exons

ENST00000353214 — 6 exons

Exon	Start	End
ENSE00000806655	124873692	124873764
ENSE00001379505	124868428	124869439
ENSE00001397399	124876878	124877733
ENSE00001404537	124862130	124862398
ENSE00001432409	124863988	124864107
ENSE00003693470	124874975	124875151

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.6947 / max 431.3695, expressed in 1827 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98491	44.6854	1826
98489	1.9801	921
98492	0.0214	7
98490	0.0078	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.35	gold quality
middle temporal gyrus	UBERON:0002771	98.22	gold quality
adult organism	UBERON:0007023	97.33	gold quality
gingival epithelium	UBERON:0001949	97.25	gold quality
esophagus squamous epithelium	UBERON:0006920	97.18	gold quality
right testis	UBERON:0004534	97.07	gold quality
gingiva	UBERON:0001828	97.04	gold quality
endothelial cell	CL:0000115	97.03	gold quality
left testis	UBERON:0004533	97.03	gold quality
lower esophagus mucosa	UBERON:0035834	97.01	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.00	gold quality
epithelium of esophagus	UBERON:0001976	96.94	gold quality
squamous epithelium	UBERON:0006914	96.77	gold quality
pharyngeal mucosa	UBERON:0000355	96.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.62	gold quality
right frontal lobe	UBERON:0002810	96.56	gold quality
oocyte	CL:0000023	96.49	gold quality
esophagus mucosa	UBERON:0002469	96.45	gold quality
tendon of biceps brachii	UBERON:0008188	96.38	gold quality
cingulate cortex	UBERON:0003027	96.37	gold quality
anterior cingulate cortex	UBERON:0009835	96.37	gold quality
mammalian vulva	UBERON:0000997	96.25	gold quality
frontal cortex	UBERON:0001870	96.25	gold quality
frontal lobe	UBERON:0016525	96.25	gold quality
prefrontal cortex	UBERON:0000451	96.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.23	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.21	gold quality
primary visual cortex	UBERON:0002436	96.10	gold quality
mucosa of transverse colon	UBERON:0004991	96.08	gold quality
pons	UBERON:0000988	96.05	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	33.64
E-MTAB-10287	yes	28.29
E-MTAB-10042	yes	12.00
E-MTAB-10553	yes	7.44
E-MTAB-6379	no	1051.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting ARPC5L, 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-126-5P	100.00	72.71	3180
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-361-3P	99.19	66.45	1381

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	arpc5lb	ENSDARG00000035433
danio_rerio	arpc5la	ENSDARG00000041720
mus_musculus	Arpc5l	ENSMUSG00000026755
rattus_norvegicus	Arpc5l	ENSRNOG00000014317
rattus_norvegicus	Arpc5l-ps1	ENSRNOG00000067388
drosophila_melanogaster	Arpc5	FBGN0031437
caenorhabditis_elegans	arx-7	WBGENE00000205
caenorhabditis_elegans	C46H11.3	WBGENE00016729

Paralogs (1): ARPC5 (ENSG00000162704)

Protein

Protein identifiers

Actin-related protein 2/3 complex subunit 5-like protein — Q9BPX5 (reviewed: Q9BPX5)

Alternative names: Arp2/3 complex 16 kDa subunit 2

All UniProt accessions (2): A0A024R897, Q9BPX5

UniProt curated annotations — full annotation on UniProt →

Function. May function as component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks.

Subunit / interactions. May be a component of the Arp2/3 complex in which it may replace ARPC5.

Subcellular location. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the ARPC5 family.

RefSeq proteins (1): NP_112240* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006789	ARPC5	Family
IPR036743	ARPC5_sf	Homologous_superfamily

Pfam: PF04699

UniProt features (4 total): sequence conflict 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BPX5-F1	89.33	0.65

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): 64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 235 (showing top): RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, TGANTCA_AP1_C, RYTTCCTG_ETS2_B, GOMF_ACTIN_BINDING, BASAKI_YBX1_TARGETS_UP, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN

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

GO Molecular Function (3): actin binding (GO:0003779), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (9): Arp2/3 protein complex (GO:0005885), focal adhesion (GO:0005925), cortical cytoskeleton (GO:0030863), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), actin cytoskeleton (GO:0015629), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton	2
cell motility	1
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
actin nucleation	1
cytoskeletal protein binding	1
protein binding	1
molecular adaptor activity	1
binding	1
actin cytoskeleton	1
protein-containing complex	1
cell-substrate junction	1
cell cortex	1
extracellular vesicle	1
synapse	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

1250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARPC5L	ARPC1B	O15143	909
ARPC5L	ARPC1A	Q92747	865
ARPC5L	ARPC3	O15145	816
ARPC5L	ARPC2	O15144	800
ARPC5L	ACTR3B	Q9P1U1	732
ARPC5L	ACTR3	P32391	660
ARPC5L	ACTR2	P61160	647
ARPC5L	ACTG1	P02571	632
ARPC5L	WASL	O00401	481
ARPC5L	SNX27	Q96L92	459
ARPC5L	ACTR3C	Q9C0K3	453
ARPC5L	SPCS2	Q15005	447
ARPC5L	SPCS3	P12280	438
ARPC5L	WAS	P42768	404
ARPC5L	CFTR	P13569	375

IntAct

133 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
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
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GADD45G	ARPC5L	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (184): ARPC5L (Affinity Capture-RNA), ARPC5L (Affinity Capture-RNA), ARPC5L (Affinity Capture-MS), ARPC5L (Affinity Capture-MS), ACTR3 (Co-fractionation), ARPC1A (Co-fractionation), ARPC2 (Co-fractionation), ARPC4-TTLL3 (Co-fractionation), ARPC4 (Co-fractionation), ARPC5L (Co-fractionation), ARPC5L (Co-fractionation), ARPC5L (Co-fractionation), ARPC5L (Co-fractionation), CAPZB (Co-fractionation), ARPC5L (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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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	12	62.0×	4e-17
Leishmania phagocytosis	12	62.0×	4e-17
Fcgamma receptor (FCGR) dependent phagocytosis	12	49.9×	6e-16
RHO GTPases activate PAKs	6	48.7×	5e-08
RHO GTPases Activate WASPs and WAVEs	10	47.4×	3e-13
EPHB-mediated forward signaling	10	39.6×	2e-12
Regulation of actin dynamics for phagocytic cup formation	13	35.7×	2e-15
FCGR3A-mediated phagocytosis	12	33.5×	7e-14

GO biological processes:

GO term	Partners	Fold	FDR
Arp2/3 complex-mediated actin nucleation	7	83.8×	7e-10
platelet aggregation	5	19.1×	8e-04
neuron projection morphogenesis	5	15.7×	2e-03
cellular response to type II interferon	5	11.8×	4e-03
actin cytoskeleton organization	9	8.1×	4e-04
actin filament organization	6	8.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

934 predictions. Top by Δscore:

Variant	Effect	Δscore
9:124863985:C:G	acceptor_gain	1.0000
9:124863986:A:AG	acceptor_gain	1.0000
9:124863987:G:GG	acceptor_gain	1.0000
9:124863987:GCC:G	acceptor_gain	1.0000
9:124863987:GCCA:G	acceptor_gain	1.0000
9:124864104:CAAGG:C	donor_loss	1.0000
9:124864105:AAG:A	donor_loss	1.0000
9:124864106:AGGTG:A	donor_loss	1.0000
9:124864109:T:A	donor_loss	1.0000
9:124874970:TGCAG:T	acceptor_loss	1.0000
9:124874971:GCA:G	acceptor_loss	1.0000
9:124874972:CA:C	acceptor_loss	1.0000
9:124874972:CAGG:C	acceptor_gain	1.0000
9:124874973:A:AG	acceptor_gain	1.0000
9:124874973:AG:A	acceptor_gain	1.0000
9:124874973:AGG:A	acceptor_loss	1.0000
9:124874973:AGGA:A	acceptor_gain	1.0000
9:124874974:G:A	acceptor_loss	1.0000
9:124874974:G:GG	acceptor_gain	1.0000
9:124874974:GG:G	acceptor_gain	1.0000
9:124874974:GGA:G	acceptor_gain	1.0000
9:124874974:GGAG:G	acceptor_gain	1.0000
9:124874974:GGAGC:G	acceptor_gain	1.0000
9:124875079:G:GT	donor_gain	1.0000
9:124862231:G:GT	donor_gain	0.9900
9:124862234:G:GT	donor_gain	0.9900
9:124862254:G:GG	donor_gain	0.9900
9:124862399:G:GT	donor_gain	0.9900
9:124863983:CACA:C	acceptor_loss	0.9900
9:124863985:CA:C	acceptor_loss	0.9900

AlphaMissense

994 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:124869318:T:C	F10L	1.000
9:124869320:C:A	F10L	1.000
9:124869320:C:G	F10L	1.000
9:124875140:T:A	W130R	1.000
9:124875140:T:C	W130R	1.000
9:124869321:C:A	R11S	0.999
9:124875075:T:C	L108S	0.999
9:124875089:T:G	Y113D	0.999
9:124875095:G:C	G115R	0.999
9:124875135:T:C	L128P	0.999
9:124875141:G:C	W130S	0.999
9:124875142:G:C	W130C	0.999
9:124875142:G:T	W130C	0.999
9:124875143:C:G	H131D	0.999
9:124876899:G:C	G141R	0.999
9:124876900:G:A	G141D	0.999
9:124876912:G:C	R145T	0.999
9:124876912:G:T	R145I	0.999
9:124876936:T:A	V153D	0.999
9:124869319:T:C	F10S	0.998
9:124873764:G:C	K74N	0.998
9:124873764:G:T	K74N	0.998
9:124875006:T:A	L85H	0.998
9:124875006:T:C	L85P	0.998
9:124875042:T:A	V97E	0.998
9:124875087:T:A	I112N	0.998
9:124875099:T:C	F116S	0.998
9:124875132:T:C	L127S	0.998
9:124875135:T:A	L128H	0.998
9:124875144:A:C	H131P	0.998

dbSNP variants (sampled 300 via entrez): RS1000070012 (9:124876698 C>T), RS1000199376 (9:124874615 G>A), RS1000368212 (9:124868841 C>T), RS1000408117 (9:124873867 G>C), RS1000527160 (9:124871304 G>A), RS1000693726 (9:124875464 A>G), RS1000820478 (9:124869933 G>A), RS1000933793 (9:124864470 T>A), RS1001238372 (9:124877709 A>AAAG), RS1001267089 (9:124868167 G>C), RS1001360537 (9:124873015 C>T), RS1001371271 (9:124862510 T>A), RS1001386188 (9:124864129 T>C), RS1001506741 (9:124862844 T>A), RS1001824326 (9:124869071 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066486 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.58	Kd	26.29	nM	CHEMBL5653589
7.46	ED50	34.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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	2147894: Binding affinity to human ARPC5L incubated for 45 mins by Kinobead based pull down assay	kd	0.0263	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Particulate Matter	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
decabromobiphenyl ether	increases expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	affects expression	1
PCI 5002	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Diethylstilbestrol	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650936	Binding	Binding affinity to human ARPC5L 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 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2S7	Abcam HEK293T ARPC5L KO	Transformed cell line	Female

Clinical trials (associated diseases)

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