ARPC4
actin related protein 2/3 complex subunit 4, the group of Actin related protein 2/3 complex subunits
Basic information
Region (hg38): 3:9792495-9807101
Links
Phenotypes
GenCC
Source:
- developmental delay, language impairment, and ocular abnormalities (Moderate), mode of inheritance: AD
- developmental delay, language impairment, and ocular abnormalities (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Developmental delay, language impairment, and ocular abnormalities | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Neurologic; Ophthalmologic | 35047857 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARPC4 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 | 0 | |||||
| missense | 2 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 2 | |||||
| Total | 0 | 0 | 4 | 0 | 0 |
Variants in ARPC4
This is a list of pathogenic ClinVar variants found in the ARPC4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-9793135-C-G | Inborn genetic diseases | Uncertain significance (Oct 24, 2024) | ||
| 3-9793135-C-T | Inborn genetic diseases | Uncertain significance (Apr 23, 2024) | ||
| 3-9793138-G-C | Uncertain significance (May 08, 2024) | |||
| 3-9793140-C-T | Inborn genetic diseases | Uncertain significance (Sep 29, 2023) | ||
| 3-9793162-G-A | Inborn genetic diseases | Uncertain significance (Oct 26, 2022) | ||
| 3-9797730-C-G | not specified | Uncertain significance (Oct 09, 2024) | ||
| 3-9801666-T-G | Inborn genetic diseases | Uncertain significance (Oct 03, 2023) | ||
| 3-9803849-G-A | Inborn genetic diseases | Uncertain significance (Aug 13, 2021) | ||
| 3-9803984-C-T | Developmental delay, language impairment, and ocular abnormalities • Inborn genetic diseases | Conflicting classifications of pathogenicity (Mar 03, 2024) | ||
| 3-9803987-A-G | Uncertain significance (Oct 11, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ARPC4 | protein_coding | protein_coding | ENST00000433034 | 6 | 15232 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.975 | 0.0254 | 124728 | 0 | 1 | 124729 | 0.00000401 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.21 | 42 | 106 | 0.396 | 0.00000589 | 1239 |
| Missense in Polyphen | 8 | 51.441 | 0.15552 | 589 | ||
| Synonymous | 0.859 | 31 | 37.7 | 0.822 | 0.00000188 | 341 |
| Loss of Function | 3.11 | 0 | 11.3 | 0.00 | 7.19e-7 | 120 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000646 | 0.0000646 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Actin-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (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:29925947, ECO:0000269|PubMed:9230079}.;
- 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;Developmental Biology;Signal Transduction;Vesicle-mediated transport;role of pi3k subunit p85 in regulation of actin organization and cell migration;how does salmonella hijack a cell;Membrane Trafficking;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;Clathrin-mediated endocytosis;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
- 0.0989
Intolerance Scores
- loftool
- rvis_EVS
- 0.15
- rvis_percentile_EVS
- 63.81
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.539
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.824
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Arpc4
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; immune system phenotype;
Gene ontology
- Biological process
- actin filament polymerization;Arp2/3 complex-mediated actin nucleation;Fc-gamma receptor signaling pathway involved in phagocytosis;actin nucleation;ephrin receptor signaling pathway;membrane organization
- Cellular component
- nucleus;cytosol;Arp2/3 protein complex;site of double-strand break;cell projection;extracellular exosome
- Molecular function
- structural constituent of cytoskeleton;protein binding;enzyme binding;protein binding, bridging;actin filament binding