ARPC1B

Summary

ARPC1B (actin related protein 2/3 complex subunit 1B, HGNC:704) is a protein-coding gene on chromosome 7q22.1, encoding Actin-related protein 2/3 complex subunit 1B (O15143). 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. This subunit is a member of the SOP2 family of proteins and is most similar to the protein encoded by gene ARPC1A. The similarity between these two proteins suggests that they both may function as p41 subunit of the human Arp2/3 complex that has been implicated in the control of actin polymerization in cells. It is possible that the p41 subunit is involved in assembling and maintaining the structure of the Arp2/3 complex. Multiple versions of the p41 subunit may adapt the functions of the complex to different cell types or developmental stages. This protein also has a role in centrosomal homeostasis by being an activator and substrate of the Aurora A kinase.

Source: NCBI Gene 10095 — RefSeq curated summary.

At a glance

• Gene–disease (curated): platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (Definitive, ClinGen)
• GWAS associations: 8
• Clinical variants (ClinVar): 392 total — 19 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 25
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005720

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:704
Approved symbol	ARPC1B
Name	actin related protein 2/3 complex subunit 1B
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	ARC41, p40-ARC, p41-ARC
Ensembl gene	ENSG00000130429
Ensembl biotype	protein_coding
OMIM	604223
Entrez	10095

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 40 protein_coding, 10 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000414376, ENST00000417330, ENST00000418347, ENST00000427217, ENST00000429246, ENST00000431816, ENST00000432343, ENST00000443222, ENST00000445924, ENST00000451682, ENST00000455009, ENST00000458033, ENST00000463078, ENST00000468337, ENST00000474880, ENST00000481997, ENST00000484375, ENST00000484600, ENST00000491294, ENST00000493403, ENST00000645391, ENST00000646101, ENST00000695607, ENST00000695608, ENST00000695609, ENST00000897879, ENST00000897880, ENST00000897881, ENST00000897882, ENST00000897883, ENST00000897884, ENST00000897885, ENST00000897886, ENST00000897887, ENST00000897888, ENST00000897889, ENST00000897890, ENST00000932831, ENST00000932832, ENST00000932833, ENST00000970469, ENST00000970470, ENST00000970471, ENST00000970472, ENST00000970473, ENST00000970474, ENST00000970475, ENST00000970476, ENST00000970477, ENST00000970478, ENST00000970479, ENST00000970480, ENST00000970481

RefSeq mRNA: 1 — MANE Select: NM_005720 NM_005720

CCDS: CCDS5661

Canonical transcript exons

ENST00000646101 — 10 exons

Exon	Start	End
ENSE00002237677	99390893	99391099
ENSE00003482059	99391178	99391253
ENSE00003548311	99389905	99390012
ENSE00003598946	99385702	99385778
ENSE00003666646	99392671	99392876
ENSE00003702672	99386685	99386789
ENSE00003791697	99388039	99388261
ENSE00003964444	99394029	99394119
ENSE00003964446	99394451	99394816
ENSE00003964450	99374730	99374781

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 157.4546 / max 1329.6891, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79865	98.8151	1824
79863	39.5640	1822
79864	12.7284	1733
79861	5.2244	1588
79866	1.0070	645
79862	0.1156	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.60	gold quality
leukocyte	CL:0000738	99.59	gold quality
granulocyte	CL:0000094	99.56	gold quality
blood	UBERON:0000178	99.43	gold quality
spleen	UBERON:0002106	99.27	gold quality
lymph node	UBERON:0000029	99.20	gold quality
vermiform appendix	UBERON:0001154	99.15	gold quality
upper lobe of left lung	UBERON:0008952	98.58	gold quality
mucosa of transverse colon	UBERON:0004991	98.48	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.36	gold quality
right lung	UBERON:0002167	98.35	gold quality
duodenum	UBERON:0002114	98.30	gold quality
small intestine	UBERON:0002108	98.26	gold quality
descending thoracic aorta	UBERON:0002345	98.24	gold quality
bone marrow	UBERON:0002371	98.24	gold quality
thoracic aorta	UBERON:0001515	98.18	gold quality
placenta	UBERON:0001987	98.18	gold quality
metanephros cortex	UBERON:0010533	98.18	gold quality
ascending aorta	UBERON:0001496	98.17	gold quality
bone marrow cell	CL:0002092	98.14	gold quality
right coronary artery	UBERON:0001625	98.07	gold quality
tibial nerve	UBERON:0001323	98.03	gold quality
left coronary artery	UBERON:0001626	98.01	gold quality
omental fat pad	UBERON:0010414	97.96	gold quality
right lobe of thyroid gland	UBERON:0001119	97.95	gold quality
stromal cell of endometrium	CL:0002255	97.87	gold quality
adipose tissue	UBERON:0001013	97.73	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.54	gold quality
transverse colon	UBERON:0001157	97.46	gold quality
left lobe of thyroid gland	UBERON:0001120	97.35	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	1020.60
E-MTAB-8271	yes	580.39
E-HCAD-56	yes	296.74
E-MTAB-8142	yes	120.73
E-HCAD-4	yes	81.73
E-CURD-122	yes	69.05
E-HCAD-1	yes	62.00
E-MTAB-10287	yes	61.66
E-HCAD-10	yes	45.45
E-HCAD-6	yes	44.66
E-GEOD-135922	yes	43.31
E-HCAD-11	yes	41.22
E-MTAB-10553	yes	39.21
E-CURD-46	yes	32.79
E-MTAB-6701	yes	31.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting ARPC1B, 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-3658	99.96	73.87	4379
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-7843-3P	98.31	67.94	803
HSA-MIR-5585-3P	98.25	67.41	941
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-127-5P	97.78	67.64	869
HSA-MIR-634	97.74	67.11	818
HSA-MIR-6769A-3P	94.91	61.36	412

Literature-anchored findings (GeneRIF, showing 19)

• INSIG1 and p41 Arp2/3 complex (p41-Arc)reduced expression might be involved in gastric cancer development or progression (PMID:12115587)
• Phosphorylation of p41-ARC by p21-activated kinase 1. (PMID:14749719)
• From the analysis of the different radio-sensitivity cancer cell lines, the Arpc1b gene was selected as a prediction marker gene for sensitivity of CMM to radiotherapy. (PMID:16723437)
• Arpc1b is both a physiological activator and substrate of Aurora A kinase and these interactions help to maintain mitotic integrity in mammalian cells. (PMID:20603326)
• p41-Arc activates a senescence program in p53- and Rb-independent ways. (PMID:21628992)
• low-expression of ARPC1B is significantly associated with LNM and advanced tumor staging whereas high expression of Cav-1 can be a prognostic indicator for poor prognosis in OSCC patients. (PMID:26138391)
• This study identified two low-frequency nonsynonymous variants at FKBPL (rs200847762, OR = 0.34, 95% CI = 0.20-0.57, P = 4.31 x 10-5) and ARPC1B (rs1045012, OR = 0.56, 95% CI = 0.43-0.74, P = 4.30 x 10-5) associated with breast cancer risk. (PMID:27479355)
• A homozygous frameshift mutation in ARPC1B (p.Val91Trpfs*30) was identified in a child with microthrombocytopenia, eosinophilia and inflammatory disease. Platelet lysates contained no ARPC1B protein and reduced Arp2/3 complex. Missense ARPC1B mutations were identified in an unrelated patient with similar symptoms and ARPC1B deficiency. ARPC1B-deficient platelets are microthrombocytes with abnormal spreading behavior. (PMID:28368018)
• A homozygous 2 bp deletion, n.c.G623DEL-TC (p.V208VfsX20), in Arp2/3 complex component ARPC1B that causes a frame shift resulting in premature termination was found in 2 brothers with hematopoietic and immunologic symptoms reminiscent of Wiskott-Aldrich syndrome. Wild-type ARPC1B but not mutant was able to rescue a deficiency in a zebrafish model. ARPC1B expression is restricted to hematopoietic cells. (PMID:29127144)
• Inherited ARPC1B deficiency alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of combined immunodeficiency. (PMID:30254128)
• Flow Cytometric Determination of Actin Polymerization in Peripheral Blood Leukocytes Effectively Discriminate Patients With Homozygous Mutation in ARPC1B From Asymptomatic Carriers and Normal Controls. (PMID:31379835)
• mutations in ARPC1B will trigger progressive CTL activation-induced immunodeficiency and provides mechanistic insights into the immune dysregulation observed in this disease. (PMID:31710310)
• DHX36, BAX, and ARPC1B May Be Critical for the Diagnosis and Treatment of Tuberculosis. (PMID:32774561)
• Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma. (PMID:35111386)
• ARPC1B Is Associated with Lethal Prostate Cancer and Its Inhibition Decreases Cell Invasion and Migration In Vitro. (PMID:35163398)
• Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait? (PMID:35967303)
• ARPC1B promotes mesenchymal phenotype maintenance and radiotherapy resistance by blocking TRIM21-mediated degradation of IFI16 and HuR in glioma stem cells. (PMID:36380368)
• Neutrophil motility is regulated by both cell intrinsic and endothelial cell ARPC1B. (PMID:38224139)
• Description of a Novel Pathogenic Variant in the ARPC1B and a Severe Allergy in Two Infants. (PMID:38485907)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arpc1b	ENSDARG00000027063
mus_musculus	Arpc1b	ENSMUSG00000029622
mus_musculus	Gm62072	ENSMUSG00000142832
rattus_norvegicus	Arpc1b	ENSRNOG00000000991
drosophila_melanogaster	Arpc1	FBGN0001961
caenorhabditis_elegans		WBGENE00000201

Paralogs (1): ARPC1A (ENSG00000241685)

Protein

Protein identifiers

Actin-related protein 2/3 complex subunit 1B — O15143 (reviewed: O15143)

Alternative names: Arp2/3 complex 41 kDa subunit, p41-ARC

All UniProt accessions (8): O15143, A4D275, C9JBJ7, C9JEY1, C9JM51, C9JTT6, C9K057, F8VXW2

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. Nucleus.

Disease relevance. Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia (IMD71) [MIM:617718] An autosomal recessive disorder characterized by platelet abnormalities, vasculitis, eosinophilia, and predisposition to inflammatory diseases. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat ARPC1 family.

RefSeq proteins (1): NP_005711* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR017383	ARPC1	Family
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400

UniProt features (11 total): repeat 6, sequence variant 3, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

4 structures.

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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15143-F1	92.81	0.86

Function

Pathways and Gene Ontology

Reactome pathways

21 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-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-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-422475	Axon guidance
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: 300 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, GOBP_RESPONSE_TO_ESTRADIOL, MODULE_151, ZHAN_MULTIPLE_MYELOMA_MF_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, KYNG_DNA_DAMAGE_DN, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_NOT_BY_GAMMA_IN_WS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_RESPONSE_TO_ESTROGEN, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (3): response to estradiol (GO:0032355), Arp2/3 complex-mediated actin nucleation (GO:0034314), response to estrogen (GO:0043627)

GO Molecular Function (5): actin binding (GO:0003779), structural constituent of cytoskeleton (GO:0005200), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), actin filament binding (GO:0051015)

GO Cellular Component (9): nucleus (GO:0005634), cytosol (GO:0005829), Arp2/3 protein complex (GO:0005885), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), tubulobulbar complex (GO:0036284), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-16 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton	2
binding	2
cellular anatomical structure	2
protein-containing complex	2
response to lipid	1
response to oxygen-containing compound	1
actin nucleation	1
response to hormone	1
cytoskeletal protein binding	1
structural molecule activity	1
cytoskeleton organization	1
actin binding	1
protein-containing complex binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
actin cytoskeleton	1
cell-substrate junction	1
extracellular vesicle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1997 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARPC1B	ARPC3	O15145	999
ARPC1B	ARPC5	O15511	998
ARPC1B	ARPC2	O15144	998
ARPC1B	ACTR2	P61160	991
ARPC1B	ACTR3	P32391	990
ARPC1B	ARPC5L	Q9BPX5	909
ARPC1B	WAS	P42768	859
ARPC1B	ARPC1A	Q92747	817
ARPC1B	ARPC4	P59998	796
ARPC1B	WASL	O00401	716
ARPC1B	PAK1	Q13153	578
ARPC1B	TP53RK	Q96S44	563
ARPC1B	LIMK1	P53667	553
ARPC1B	EXOC7	Q9UPT5	542
ARPC1B	OSGEP	Q9NPF4	536

IntAct

137 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
ARPC5	ARPC1B	psi-mi:“MI:0914”(association)	0.890
ACTR3	ARPC1B	psi-mi:“MI:0914”(association)	0.890
ARPC1B	ARPC3	psi-mi:“MI:2364”(proximity)	0.880
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
WAS	ARPC1B	psi-mi:“MI:0915”(physical association)	0.640
ARPC1B	WAS	psi-mi:“MI:0403”(colocalization)	0.640

BioGRID (392): ARPC1B (Affinity Capture-RNA), ARPC2 (Affinity Capture-MS), ARPC5L (Affinity Capture-MS), ARPC5 (Affinity Capture-MS), ACTR2 (Affinity Capture-MS), ARPC3 (Affinity Capture-MS), ACTR3B (Affinity Capture-MS), ACTR3 (Affinity Capture-MS), ARPC4 (Affinity Capture-MS), POGK (Affinity Capture-MS), NT5C (Affinity Capture-MS), ACTR2 (Co-fractionation), ACTR3 (Co-fractionation), ARPC1B (Co-fractionation), ARPC1B (Co-fractionation)

ESM2 similar proteins: A5DHD9, B6QC56, B8M0Q1, G0SA60, O00423, O15143, O62621, O64740, O80856, O88656, O93277, O94319, O95834, O96622, P53024, P55735, P78774, Q04491, Q05BC3, Q0UNA9, Q15269, Q1DZQ0, Q26613, Q2KJH4, Q38884, Q3ZCC9, Q4V8C3, Q54D08, Q58CQ2, Q5B8Y3, Q5EBD9, Q5IH81, Q5RFQ3, Q5XFW8, Q66HB3, Q6BZX5, Q6CSZ5, Q6GNU1, Q6P6T4, Q7K2X8

Diamond homologs: A0A1L8EXB5, O15143, O80856, O88656, O96622, P38328, P78774, Q1JP79, Q58CQ2, Q6GNU1, Q7ZXD5, Q8AVT9, Q92747, Q99PD4, Q9R0Q6, Q9SJW6, Q9WV32

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PAK1	up-regulates	ARPC1B	phosphorylation
AURKA	“up-regulates activity”	ARPC1B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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	45.5×	1e-12
Leishmania phagocytosis	10	45.5×	1e-12
RHO GTPases Activate WASPs and WAVEs	10	41.7×	2e-12
Fcgamma receptor (FCGR) dependent phagocytosis	10	36.6×	9e-12
EPHB-mediated forward signaling	10	34.9×	1e-11
FCGR3A-mediated phagocytosis	13	32.0×	3e-14
Regulation of actin dynamics for phagocytic cup formation	13	31.5×	3e-14
Sensory processing of sound	6	24.4×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
Arp2/3 complex-mediated actin nucleation	7	78.4×	1e-09
actin polymerization or depolymerization	5	40.7×	3e-05
actin filament polymerization	5	25.6×	2e-04
platelet aggregation	5	17.9×	6e-04
cellular response to type II interferon	7	15.5×	5e-05
actin filament organization	7	8.8×	1e-03
actin cytoskeleton organization	10	8.4×	5e-05
regulation of apoptotic process	7	6.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	7
Uncertain significance	144
Likely benign	183
Benign	11

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1030961	NM_005720.4(ARPC1B):c.783G>A (p.Ala261=)	Pathogenic
1455080	NM_005720.4(ARPC1B):c.231C>A (p.Tyr77Ter)	Pathogenic
2131706	NM_005720.4(ARPC1B):c.863del (p.Pro288fs)	Pathogenic
2418950	NM_005720.4(ARPC1B):c.64+2T>A	Pathogenic
2799445	NM_005720.4(ARPC1B):c.258del (p.Thr85_Trp86insTer)	Pathogenic
2872395	NM_005720.4(ARPC1B):c.323del (p.Glu108fs)	Pathogenic
2907374	NM_005720.4(ARPC1B):c.392+2T>C	Pathogenic
444877	NM_005720.4(ARPC1B):c.268_269dup (p.Val91fs)	Pathogenic
444878	NM_005720.4(ARPC1B):c.314C>T (p.Ala105Val)	Pathogenic
4718162	NC_000007.14:g.99386684GA[3]	Pathogenic
4760331	NM_005720.4(ARPC1B):c.48del (p.Ala15_Trp16insTer)	Pathogenic
802341	NM_005720.4(ARPC1B):c.763_764del (p.Asp255fs)	Pathogenic
827685	NM_005720.4(ARPC1B):c.490_491insCC (p.Phe164fs)	Pathogenic
827687	NM_005720.4(ARPC1B):c.739_743del (p.Leu247fs)	Pathogenic
974765	NM_005720.4(ARPC1B):c.491_495delinsCCTGCCC (p.Phe164fs)	Pathogenic
974766	NM_005720.4(ARPC1B):c.624_625del (p.Cys209fs)	Pathogenic
974767	NM_005720.4(ARPC1B):c.64+1G>C	Pathogenic
974768	NM_005720.4(ARPC1B):c.622G>T (p.Val208Phe)	Pathogenic
974769	NM_005720.4(ARPC1B):c.1087dup (p.Glu363fs)	Pathogenic
1516257	NM_005720.4(ARPC1B):c.990-1G>C	Likely pathogenic
1695198	NM_005720.4(ARPC1B):c.311G>C (p.Trp104Ser)	Likely pathogenic
2036173	NM_005720.4(ARPC1B):c.393-2A>G	Likely pathogenic
3062972	GRCh37/hg19 7q22.1(chr7:98396469-102108193)x1	Likely pathogenic
3651097	NM_005720.4(ARPC1B):c.989+2T>C	Likely pathogenic
4723207	NM_005720.4(ARPC1B):c.501-97_628del	Likely pathogenic
976236	NM_005720.4(ARPC1B):c.708-1G>A	Likely pathogenic

SpliceAI

1525 predictions. Top by Δscore:

Variant	Effect	Δscore
7:99374779:G:GT	donor_gain	1.0000
7:99374779:G:T	donor_gain	1.0000
7:99374780:AG:A	donor_loss	1.0000
7:99374781:GGT:G	donor_loss	1.0000
7:99374783:T:A	donor_loss	1.0000
7:99385693:C:CA	acceptor_gain	1.0000
7:99385694:G:A	acceptor_gain	1.0000
7:99385698:ACAG:A	acceptor_gain	1.0000
7:99385699:C:G	acceptor_gain	1.0000
7:99385699:CA:C	acceptor_loss	1.0000
7:99385700:A:AG	acceptor_gain	1.0000
7:99385700:A:T	acceptor_loss	1.0000
7:99385700:AG:A	acceptor_gain	1.0000
7:99385701:G:GT	acceptor_gain	1.0000
7:99385701:GG:G	acceptor_gain	1.0000
7:99385701:GGA:G	acceptor_gain	1.0000
7:99385701:GGAGC:G	acceptor_gain	1.0000
7:99385774:CACCC:C	donor_gain	1.0000
7:99385775:ACCC:A	donor_gain	1.0000
7:99385776:CCC:C	donor_gain	1.0000
7:99385777:CC:C	donor_gain	1.0000
7:99385778:CG:C	donor_loss	1.0000
7:99385779:G:GG	donor_gain	1.0000
7:99385779:G:T	donor_loss	1.0000
7:99385780:T:G	donor_loss	1.0000
7:99386680:TTCA:T	acceptor_loss	1.0000
7:99386683:A:AG	acceptor_gain	1.0000
7:99386684:G:GT	acceptor_gain	1.0000
7:99386684:GA:G	acceptor_gain	1.0000
7:99386684:GAGA:G	acceptor_gain	1.0000

AlphaMissense

2467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:99385760:T:A	W16R	1.000
7:99385760:T:C	W16R	1.000
7:99386691:C:A	A24D	1.000
7:99388047:T:A	W60R	1.000
7:99388047:T:C	W60R	1.000
7:99388069:T:A	I67N	1.000
7:99388072:T:A	V68E	1.000
7:99388078:G:A	C70Y	1.000
7:99388079:C:G	C70W	1.000
7:99388080:G:C	G71R	1.000
7:99388086:G:C	D73H	1.000
7:99388087:A:C	D73A	1.000
7:99388087:A:T	D73V	1.000
7:99388089:C:A	R74S	1.000
7:99388090:G:C	R74P	1.000
7:99388095:G:C	A76P	1.000
7:99388096:C:A	A76D	1.000
7:99388104:T:A	W79R	1.000
7:99388104:T:C	W79R	1.000
7:99388125:T:A	W86R	1.000
7:99388125:T:C	W86R	1.000
7:99388141:T:A	V91D	1.000
7:99388159:G:C	R97P	1.000
7:99388165:C:A	A99D	1.000
7:99388179:T:A	W104R	1.000
7:99388179:T:C	W104R	1.000
7:99388180:G:C	W104S	1.000
7:99388181:G:C	W104C	1.000
7:99388181:G:T	W104C	1.000
7:99388201:T:C	F111S	1.000

dbSNP variants (sampled 300 via entrez): RS1000067653 (7:99393494 G>A), RS1000078522 (7:99393737 C>G), RS1000195668 (7:99382117 G>A), RS1000240346 (7:99387886 C>T), RS1000317665 (7:99372577 T>C), RS1000649885 (7:99387519 C>T), RS1000863520 (7:99377051 G>A), RS1000909639 (7:99393509 T>C,G), RS1000987017 (7:99377921 C>G,T), RS1000996506 (7:99382611 G>A), RS1001158745 (7:99377388 C>A), RS1001209729 (7:99377583 G>A), RS1001274714 (7:99377310 T>G), RS1001329824 (7:99381323 CTGTG>C,CTG,CTGTGTG), RS1001332886 (7:99389423 G>A)

Disease associations

OMIM: gene MIM:604223 | disease phenotypes: MIM:617718

GenCC curated gene-disease

Disease	Classification	Inheritance
platelet abnormalities with eosinophilia and immune-mediated inflammatory disease	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
platelet abnormalities with eosinophilia and immune-mediated inflammatory disease	Definitive	AR

Mondo (3): platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (MONDO:0060583), combined immunodeficiency (MONDO:0015131), thrombocytopenia (MONDO:0002049)

Orphanet (1): Combined T and B cell immunodeficiency (Orphanet:101972)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000498	Blepharitis
HP:0000988	Skin rash
HP:0001287	Meningitis
HP:0001508	Failure to thrive
HP:0001873	Thrombocytopenia
HP:0002037	Inflammation of the large intestine
HP:0002573	Hematochezia
HP:0002633	Vasculitis
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003593	Infantile onset
HP:0005537	Decreased mean platelet volume
HP:0006532	Recurrent pneumonia
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0011896	Subconjunctival hemorrhage
HP:0025085	Bloody diarrhea
HP:0025289	Cervical lymphadenopathy
HP:0031813	Colonic eosinophilia
HP:0032229	Perinuclear antineutrophil antibody positivity
HP:0100658	Cellulitis
HP:0100827	Increased total lymphocyte count
HP:0200029	Vasculitis in the skin

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004730_2	Facial emotion recognition (sad faces)	3.000000e-06
GCST006249_22	Serum metabolite levels	2.000000e-12
GCST006249_46	Serum metabolite levels	4.000000e-21
GCST008757_50	Alcohol consumption	3.000000e-10
GCST90002385_143	High light scatter reticulocyte count	2.000000e-26
GCST90002386_454	High light scatter reticulocyte percentage of red cells	8.000000e-20
GCST90002405_484	Reticulocyte count	9.000000e-28
GCST90002406_251	Reticulocyte fraction of red cells	4.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008329	facial emotion recognition measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295656 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	Kd	50.6	nM	CHEMBL5653589
7.26	ED50	54.47	nM	CHEMBL5653589
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 11 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	2147889: Binding affinity to human ARPC1B incubated for 45 mins by Kinobead based pull down assay	kd	0.0506	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178538: Inhibition of ARPC1B (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	6
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
cobaltous chloride	decreases expression	2
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cisplatin	affects cotreatment, increases expression	2
Ozone	increases abundance, affects cotreatment, increases oxidation	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
sulindac sulfide	decreases expression	1
monomethylarsonous acid	decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119039	Binding	Binding affinity to ARPC1B in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT