Information on ARPC1B

Basic details

Alt. symbols: ARC41 | p40-ARC | p41-ARC

Approved name: actin related protein 2/3 complex subunit 1B
Alt. names: actin related protein 2/3 complex, subunit 1B (41 kD), actin related protein 2/3 complex subunit 1B, 41kDa | ARP2/3 protein complex subunit p41, actin related protein 2/3 complex, subunit 1A (41 kD)

Location: 7q22.1: 99374249 - 99394816 (+)
Gene type: protein_coding, 25 transcripts.

Scores: LoFtool: 0.549000 | pLI: 0.15607050 | LOEUF: 0.645

HGNC: 704

NCBI: 10095, RefSeq: NG_055676.1

Ensembl: ENSG00000130429.16

LRG_1188 | Status: public

OMIM: 604223

Expression | ProteinAtlas

Normal function

ARPC1B encodes one isoform of one subunit of the actin-related protein-2/3 (Arp2/3). The complex consists of seven polypeptides, two actin-related proteins (Arp2 and Arp3) and five regulatory subunits (ARPC1-5). In mammals Arp3, ARPC1 and ARPC5 are each encoded by two genes: Arp3/Arp3B, ARPC1A/ARPC1B and ARPC5/ARPC5L that share 91, 67, and 67% sequence identity, respectively. After ATP binds to the ARP2/3-complex, it changes its conformation to an active state and imitates an actin dimer or trimer working as a template for actin monomers. Subsequent engagement with a nucleation-promoting factor (NFP) initiates the formation of branched actin filaments. Due to the crucial role of branched actin polymerization and reorganization inside the cell, the Arp2/3-complex is essential in a wide variety of cellular processes including cell migration, adhesion, phagocytosis, vesicle trafficking, DNA break repair and many more.

Dysfunction and disease

Biallelic mutations in ARPC1B cause an autosomal recessive disorder known as ARPC1B-deficiency. It manifests early in life and patients present with thrombocytopenia, combined immunodeficiency, severe inflammation and allergy. To this date, a total of 29 patients from 23 different families have been identified. In addition to platelet abnormalities, defects in T-cell development, migration and proliferation, as well as impaired natural killer (NK)-cell degranulation have been described as a resu lt of biallelic ARPC1B mutations. [Load More]

[Reviewed by Elena Sindram on 2022-05-24 13:01:54]

Associated conditions

Acronym Condition's_name MOI Mode_of_actionwww icon OMIM_ID No.cases
IMD71 ARPC1B deficiency ARdict. icon Loss of Function 617718www icon 39 (31 fams)

Transcripts of ARPC1B

Name ENSEMBL_ID LRG_ID CCDS_ID MANE Transcript.type Exons Canonical CDS_length REFSEQ_ID
201 ENST00000414376.6 protein_coding 10 No 572 XM_024446628
222 ENST00000646101.2 1 CCDS5661 Select protein_coding 10 Yes 1511 NM_005720
210 ENST00000451682.5 CCDS5661 protein_coding 12 No 1715 XM_054356979
221 ENST00000645391.1 CCDS5661 protein_coding 11 No 1669 XM_054356982

Published variants

Found 27 variants

Var.name Exon/Intron cDNA_pos. CDS_change Prot.change Var.type Var.class. Patients
9.1Kb-(5'UTR)-DEL EX1 1-52 c.-14_-65del p.? exon_loss_variant Pathogenic 1
Q22* EX2 129 c.64C>T p.Gln22Ter stop_gained Pathogenic 1
EX4+1G>A In4 c.64+1G>A ALTERS SPLICING! Pathogenic 2
EX4+1G>C In4 c.64+1G>C p.T21insPECLLGA ALTERS SPLICING! Pathogenic 1
EX4+2T>A In4 c.64+2T>A ALTERS SPLICING! Pathogenic 3
V32M EX3 159 c.94G>A p.Val32Met missense_variant Uncertain significance 1
K37N EX3 176 c.111G>C p.Lys37Asn missense_variant Likely Benign 1
G71_N75del EX4 275-289 c.212_226del p.Gly71_Asn75del inframe_deletion Pathogenic 1
W86* EX6 567 c.258G>A p.Trp86Ter stop_gained Pathogenic 1
T89P EX4 330 c.265A>C p.Thr89Pro missense_variant Pathogenic 4
V91Wfs*30 EX6 578-579 c.268_269dup p.Val91TrpfsTer30 frameshift_variant Pathogenic 1
W104S EX6 620 c.311G>C p.Trp104Ser missense_variant Likely Pathogenic 1
A107Tfs*13 EX6 623 c.318del p.Asn107ThrfsTer13 frameshift_variant Pathogenic 1
A105V EX6 623 c.314C>T p.Ala105Val missense_variant Pathogenic 2
EX6+2T>C In6 c.392+2T>C splice_donor_variant Pathogenic 1
A158D EX5 538 c.473C>A p.Ala158Asp missense_variant Pathogenic 1
F164Sfs*32 EX7 800-804 c.491_495delins7 p.Phe164SerfsTer32 frameshift_variant Pathogenic 2
V208F EX8 931 c.622G>T p.Val208Phe missense_variant Pathogenic 1
C209Ffs*21 EX8 932-933 c.624_625del p.Cys209PhefsTer21 frameshift_variant Pathogenic 2
EX9-1G>A In8 c.708-1G>A ALTERS SPLICING! Pathogenic 1
A238T EX9 1021 c.712G>A p.Ala238Thr missense_variant Likely Benign 0
L247Gfs*25 EX9 1048-1052 c.739_743del p.Leu247GlyfsTer25 frameshift_variant Pathogenic 1
D255Qfs*18 EX9 1071-1072 c.763_764del p.Asp255GlnfsTer18 frameshift_variant Pathogenic 1
A261A EX9 1092 c.783G>A p.Ala261= ALTERS SPLICING! Pathogenic 3
E300Pfs*153 EX10 1206-1219 c.897_910del p.Glu300ProfsTer153 frameshift_variant Pathogenic 2
E300Gfs*7 EX8 964-1009 c.899_944del p.Glu300GlyfsTer7 frameshift_variant Pathogenic 4
E363Gfs*95 EX12 1394-1395 c.1087dup p.Glu363GlyfsTer95 frameshift_variant Pathogenic 1

Diagnostic pitfalls & paradigms

Considerations to take into account when analyzing this gene

Year Paradigm ⓘ PMID Notes
- Regions of Homology -
2018Somatic reversion30254128In vivo somatic reversion restored ARPC1B expression in CD8+ T-cells in 2 of the 6 studied cases (P1, P6) and in NK cells in P6, and was linked to a skewed TCR repertoire. In P1, memory CD8+ T-cells with normal ARPC1B levels displayed normal TCR-driven proliferation and improved T cell migration. Somatic reversion likely occurred in a lymphoid T cell progenitor prior to TCR rearrangement or because of + clonal selection after infection.
-Cryptic splicing-Unreported or not recorded in our DB.
-Uniparental disomy-Unreported or not recorded in our DB.
-Mosaicism-Unreported or not recorded in our DB.
-Incomplete penetrance-Unreported or not recorded in our DB.
-Di-/oligo-genic inheritance-Unreported or not recorded in our DB.

References linked to variants in ARPC1B

ID Year Title Journal PMID Variants
67 2017 Loss of the Arp2/3 complex component ARPC1B causes platelet ... Nat. Commun. 28368018 3
69 2017 Combined immunodeficiency with severe inflammation and aller... JACI 27965109 1
70 2017 Disruption of thrombocyte and T lymphocyte development by a ... jimmunol 29127144 1
71 2018 T-cell defects in patients with ARPC1B germline mutations ac... Blood 30254128 6
74 2019 A combined immunodeficiency with severe infections, inflamma... JACI 30771411 10
598 2021 Case Report: A Novel Synonymous ARPC1B Gene Mutation Causes ... Front. Immunol. 33679784 1
599 2019 Loss of ARPC1B impairs cytotoxic T lymphocyte maintenance an... J. Clin. Investig. 31710310 2
600 2021 ARPC1B binds WASP to control actin polymerization and curtai... J. Clin. Investig. 34673575 2
601 2020 Whole-genome sequencing of a sporadic primary immunodeficien... Nature 32499645 3
602 2021 A male infant with COVID-19 in the context of ARPC1B deficie... Clin. Case Rep. 32683750 1
603 2020 Cryo-EM of human Arp2/3 complexes provides structural insigh... Biol. Open 32661131 4
604 2020 Sindrome de Wiskott-Aldrich e PLTEID: fenotipos semelhantes,... ASBAI 2
748 2021 Defective Neutrophil Transendothelial Migration and Lateral ... Front. Immunol. 34135903 1
749 2022 Radiosensitivity in patients affected by ARPC1B deficiency: ... Front. Immunol. 35967303 1
750 2022 Hematopoietic Stem Cell Transplantation in ARPC1B Deficiency... JoCI 35767111 7
788 2019 Flow Cytometric Determination of Actin Polymerization in Per... Front. Immunol. 31379835 1
789 2023 Is your kid actin out? A series of six patients with inherit... J. Allergy Clin. Immunol. Pract. 36708766 4
848 2023 Inherited ARPC5 mutations cause an actinopathy impairing cel... Nat. Commun. 37349293 3

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