ARPC1B

actin related protein 2/3 complex subunit 1B, the group of WD repeat domain containing|Actin related protein 2/3 complex subunits

Basic information

Region (hg38): 7:99374249-99394816

Links

ENSG00000130429 ∙ NCBI:10095 ∙ OMIM:604223 ∙ HGNC:704 ∙ Uniprot:O15143 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (Strong), mode of inheritance: AR
• platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia	AR	Allergy/Immunology/Infectious	The condition can involve immunologic abnormalities, including immunodeficiency and vasculitis, and diagnosis may allow preventative measures and early and prompt treatment of infections (for example, with IVIG, immunosuppression, and prophylactic antibiotics); HSCT has been described	Allergy/Immunology/Infectious; Hematologic	27965109; 28368018; 29127144; 30254128; 32499645

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARPC1B gene.

• not provided (8 variants)
• Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (4 variants)
• Combined immunodeficiency (2 variants)
• Inherited Immunodeficiency Diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARPC1B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	73	7	83
missense		1	98	3	3	105
nonsense	1		1			2
start loss						0
frameshift	6	1				7
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	3	1			6
splice region	2		8	19		29
non coding				42	3	45
Total	9	5	106	118	13

Highest pathogenic variant AF is 0.00000657

Variants in ARPC1B

This is a list of pathogenic ClinVar variants found in the ARPC1B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-99385726-C-T			Likely benign (Feb 15, 2023)
7-99385747-C-T			Likely benign (Jun 01, 2022)
7-99385753-C-G		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
7-99385756-C-T		ARPC1B-related disorder	Likely benign (Oct 05, 2023)
7-99385765-C-G		not specified	Uncertain significance (Jan 22, 2024)
7-99385766-A-C		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
7-99385772-C-T			Uncertain significance (Sep 29, 2022)
7-99385773-G-A			Uncertain significance (Aug 19, 2022)
7-99385775-A-G			Uncertain significance (Jul 06, 2022)
7-99385778-CGTGAGTGCTTGCTGGGGGCCG-C			Uncertain significance (Dec 25, 2021)
7-99385779-G-A		-	no classification for the single variant (-)
7-99385779-G-C		Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease	Pathogenic (Aug 03, 2020)
7-99385780-T-A			Pathogenic (Jul 15, 2022)
7-99385798-C-T			Benign (Jan 25, 2024)
7-99386670-C-T			Likely benign (Nov 03, 2022)
7-99386676-C-T			Likely benign (Jan 01, 2021)
7-99386678-C-T			Likely benign (Jun 08, 2022)
7-99386686-G-T			Uncertain significance (Feb 08, 2022)
7-99386697-G-C			Uncertain significance (Aug 22, 2022)
7-99386714-G-A		Inborn genetic diseases	Uncertain significance (Mar 24, 2023)
7-99386716-G-A			Likely benign (Jan 14, 2022)
7-99386718-A-G			Benign (Jan 22, 2024)
7-99386731-G-C		ARPC1B-related disorder	Benign (Jan 31, 2024)
7-99386734-C-T			Likely benign (Nov 03, 2023)
7-99386735-G-A		Inborn genetic diseases	Uncertain significance (Jun 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARPC1B	protein_coding	protein_coding	ENST00000451682	9	20553

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0110	0.987	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.18	200	253	0.791	0.0000164	2444
Missense in Polyphen		50	67.451	0.74128		761
Synonymous	0.149	105	107	0.982	0.00000769	710
Loss of Function	2.75	7	20.4	0.343	0.00000107	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000307	0.000301
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000493	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation- promoting factor (NPF) (PubMed:11741539, PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:11741539, PubMed:9230079). 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 (PubMed:29925947). 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) (PubMed:29925947). {ECO:0000269|PubMed:11741539, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9230079}.
• Disease: DISEASE: Platelet abnormalities with eosinophilia and immune- mediated inflammatory disease (PLTEID) [MIM:617718]: An autosomal recessive disorder characterized by platelet abnormalities, vasculitis, eosinophilia, and predisposition to inflammatory diseases. {ECO:0000269|PubMed:28368018}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Endocytosis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Pathogenic Escherichia coli infection;Microglia Pathogen Phagocytosis Pathway;Developmental Biology;Signal Transduction;role of pi3k subunit p85 in regulation of actin organization and cell migration;how does salmonella hijack a cell;y branching of actin filaments;Fcgamma receptor (FCGR) dependent phagocytosis;EPH-Ephrin signaling;Innate Immune System;Immune System;EPHB-mediated forward signaling;RHO GTPases Activate WASPs and WAVEs;RHO GTPase Effectors;Signaling by Rho GTPases;ErbB1 downstream signaling;Regulation of actin dynamics for phagocytic cup formation;Axon guidance;RAC1 signaling pathway;CDC42 signaling events;PDGFR-beta signaling pathway (Consensus)

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.549
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.56

Haploinsufficiency Scores

• pHI: 0.413
• hipred: Y
• hipred_score: 0.736
• ghis: 0.584

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.822

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Arpc1b
• Phenotype: homeostasis/metabolism phenotype; skeleton phenotype; hematopoietic system phenotype

Zebrafish Information Network

• Gene name: arpc1b
• Affected structure: pro-T cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: response to estradiol;Arp2/3 complex-mediated actin nucleation;Fc-gamma receptor signaling pathway involved in phagocytosis;response to estrogen;ephrin receptor signaling pathway
• Cellular component: nucleus;cytosol;Arp2/3 protein complex;focal adhesion;actin cytoskeleton;tubulobulbar complex;extracellular exosome
• Molecular function: structural constituent of cytoskeleton;protein binding;actin filament binding