Details for: ARVCF

Gene ID: 421

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ARVCF

Ensembl ID: ENSG00000099889

Description: ARVCF delta catenin family member

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • progenitor cell CL0011026
    CSI 6.31
    rCSI 13.42%
    PRS 88.5
  • fibroblast of lung CL0002553
    CSI 5.39
    rCSI 5.01%
    PRS 95.25
  • cerebral cortex endothelial cell CL1001602
    CSI 3.57
    rCSI 6.17%
    PRS 90.58
  • ionocyte CL0005006
    CSI 3.14
    rCSI 3.36%
    PRS 94.97
  • pancreatic D cell CL0000173
    CSI 2.77
    rCSI 2.73%
    PRS 94.96
  • neural crest cell CL0011012
    CSI 2.56
    rCSI 2.02%
    PRS 89.28
  • cerebellar granule cell CL0001031
    CSI 2.55
    rCSI 3.74%
    PRS 90.36
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.29
    rCSI 2.73%
    PRS 84.89
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.15
    rCSI 2.78%
    PRS 85.85
  • ependymal cell CL0000065
    CSI 2.12
    rCSI 4.3%
    PRS 79.79
  • glioblast CL0000030
    CSI 2.02
    rCSI 3.23%
    PRS 88.17
  • inhibitory interneuron CL0000498
    CSI 1.95
    rCSI 4.51%
    PRS 87.37
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.92
    rCSI 3.39%
    PRS 84.35
  • enteroendocrine cell CL0000164
    CSI 1.86
    rCSI 2.55%
    PRS 92.27
  • peripheral nervous system neuron CL2000032
    CSI 1.71
    rCSI 2.33%
    PRS 89.16
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.7
    rCSI 2.86%
    PRS 84.97
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.67
    rCSI 3.74%
    PRS 85.13
  • type B pancreatic cell CL0000169
    CSI 1.53
    rCSI 3.38%
    PRS 93.98
  • retinal ganglion cell CL0000740
    CSI 1.09
    rCSI 2.41%
    PRS 86.36
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.94
    rCSI 2.72%
    PRS 93.53
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.59
    rCSI 2.13%
    PRS 83.18

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ARVCF](/details-gene/421) (Armadillo Repeat Gene Deleted in Velo-Cardio-Facial Syndrome) is a protein-coding gene located on chromosome 22q11.21, a region frequently deleted in Velo-Cardio-Facial syndrome ([Link](https://doi.org/10.1006/geno.1997.4627)). As a member of the p120-catenin (delta-catenin) family, [ARVCF](/details-gene/421) exhibits a notable dual functionality. It localizes to both the cytoplasm, where it participates in cell-cell adhesion at [adherens junction](/details-cell/GO:0005912) complexes through [cadherin binding](/details-cell/GO:0045296), and to the [nucleus](/details-cell/GO:0005634), where it is involved in [mRNA processing](/details-cell/GO:0006397) and alternative [RNA splicing](/details-cell/GO:0008380) ([Link](https://doi.org/10.1074/jbc.m113.530717)). **Overall**, its expression profile is widespread, with particularly high significance in [progenitor cell](/details-cell/CL0011026), [fibroblast of lung](/details-cell/CL0002553), and a diverse array of neuronal and endothelial cell types, suggesting fundamental roles in tissue development, maintenance, and neuronal function. ## Cellular Roles and Expression Landscape The expression pattern of [ARVCF](/details-gene/421) highlights its importance across multiple fundamental cell types rather than a single lineage. **Overall**, the gene shows its highest significance in [progenitor cell](/details-cell/CL0011026) (CSI: 6.31), which may indicate a role in development and cell fate determination. It is also a highly significant gene in mesenchymal cells such as [fibroblast of lung](/details-cell/CL0002553) (CSI: 5.39), consistent with its well-established function in cell adhesion. A striking feature of its expression landscape is its prominence within the central nervous system and neuro-associated cells. [ARVCF](/details-gene/421) is significantly expressed in [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 3.57), suggesting a role in maintaining the blood-brain barrier. Furthermore, it is a key gene in numerous neuronal subtypes, including [cerebellar granule cell](/details-cell/CL0001031) (CSI: 2.55), various GABAergic cortical interneurons like [VIP GABAergic cortical interneuron](/details-cell/CL4023016) and [sst GABAergic cortical interneuron](/details-cell/CL4023017), and [peripheral nervous system neuron](/details-cell/CL2000032). This broad neuronal expression is consistent with its dual role in maintaining synaptic adhesion and regulating neuronal-specific alternative splicing. Its significance also extends to specialized secretory cells like [pancreatic D cell](/details-cell/CL0000173) and [enteroendocrine cell](/details-cell/CL0000164), further underscoring its broad utility in diverse cellular contexts requiring strong adhesion and regulated gene expression. ## Pathways and Molecular Function The functional annotations for [ARVCF](/details-gene/421) align with its dual localization and diverse cellular expression pattern. Its molecular functions are dominated by roles in cell adhesion and RNA processing. * **Cell Adhesion and Junctional Integrity:** [ARVCF](/details-gene/421) is critically involved in [cell-cell adhesion](/details-cell/GO:0098609). It functions as a component of the [adherens junction](/details-cell/GO:0005912), where it engages in [cadherin binding](/details-cell/GO:0045296). This role is foundational to its high significance in fibroblasts, endothelial cells, and neuronal networks, where it helps maintain tissue architecture and stable cell-cell contacts. Studies have shown that [ARVCF](/details-gene/421) and the related p120(ctn) are often mutually exclusive in E-cadherin complexes, suggesting distinct regulatory roles at the cell membrane ([Link](https://doi.org/10.1242/jcs.113.8.1481)). * **Nuclear Regulation of Gene Expression:** Beyond the plasma membrane, [ARVCF](/details-gene/421) localizes to the [nucleus](/details-cell/GO:0005634) and participates in post-transcriptional gene regulation. It is annotated with functions in [mRNA processing](/details-cell/GO:0006397) and [RNA splicing](/details-cell/GO:0008380). This nuclear function has been demonstrated experimentally, with nuclear [ARVCF](/details-gene/421) binding to splicing factors and contributing to the regulation of alternative splicing events ([Link](https://doi.org/10.1074/jbc.m113.530717)). This activity is likely crucial for generating proteomic diversity in the complex cell types where it is highly expressed, particularly the various neuronal subtypes. ## Research Directions The dual functionality of [ARVCF](/details-gene/421) in cell adhesion and RNA splicing, combined with its specific expression profile, opens several avenues for future investigation. Its location within the 22q11.21 deletion region suggests that its haploinsufficiency may contribute to the neurological and developmental phenotypes seen in Velo-Cardio-Facial syndrome. **Proposed Hypotheses:** 1. Given its high expression across multiple neuronal subtypes and its demonstrated role in RNA processing, it is hypothesized that **[ARVCF](/details-gene/421) orchestrates the alternative splicing of a specific subset of transcripts essential for neuronal subtype identity, synaptic maturation, and function.** 2. The high significance of [ARVCF](/details-gene/421) in [progenitor cell](/details-cell/CL0011026) suggests a key developmental role. It is hypothesized that **the dynamic regulation of [ARVCF](/details-gene/421) localization, shifting from the nucleus to the adherens junction, is a critical molecular switch that governs the transition from progenitor proliferation to terminal differentiation and tissue integration.** **Experimental Approach:** To test the first hypothesis regarding the role of [ARVCF](/details-gene/421) in neuronal splicing, a multi-faceted approach could be employed. A conditional knockout mouse model could be generated to specifically delete [ARVCF](/details-gene/421) in a targeted neuronal population, such as cerebellar granule cells. Bulk and single-cell RNA sequencing of isolated neurons from these mice compared to wild-type controls would reveal global changes in gene expression and, more importantly, differential splicing events. Candidate splicing events in genes related to synaptic function could then be validated using RT-qPCR. Subsequently, electrophysiological and behavioral analyses would be essential to determine if these molecular changes translate into functional deficits in synaptic transmission and circuit-level activity. **Therapeutic Potential:** As [ARVCF](/details-gene/421) loss-of-function (via haploinsufficiency) is associated with developmental pathology, therapeutic strategies would likely focus on **activation or functional compensation** rather than inhibition. However, its broad expression pattern across many essential cell types, including progenitors and neurons, makes it a challenging therapeutic target. Systemic administration of a drug to boost its activity could lead to widespread, unpredictable off-target effects. A more viable long-term strategy might involve gene therapy aimed at restoring normal expression levels in specific affected tissues. Furthermore, understanding the precise splicing events regulated by [ARVCF](/details-gene/421) in pathogenic contexts could reveal downstream targets that are more amenable to specific therapeutic intervention.

Genular Protein ID: 3991344715

Symbol: ARVC_HUMAN

Name: N/A

UniProtKB Accession Codes:

O00192 B7WNV2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 3 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9126485

Title: Identification of a new human catenin gene family member (ARVCF) from the region deleted in velo-cardio-facial syndrome.

PubMed ID: 9126485

DOI: 10.1006/geno.1997.4627

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

PubMed ID: 10725230

Title: ARVCF localizes to the nucleus and adherens junction and is mutually exclusive with p120(ctn) in E-cadherin complexes.

PubMed ID: 10725230

DOI: 10.1242/jcs.113.8.1481

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19706687

Title: PDZ-domain-directed basolateral targeting of the peripheral membrane protein FRMPD2 in epithelial cells.

PubMed ID: 19706687

DOI: 10.1242/jcs.046854

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24644279

Title: Nuclear ARVCF protein binds splicing factors and contributes to the regulation of alternative splicing.

PubMed ID: 24644279

DOI: 10.1074/jbc.m113.530717

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25009281

Title: DIPA-family coiled-coils bind conserved isoform-specific head domain of p120-catenin family: potential roles in hydrocephalus and heterotopia.

PubMed ID: 25009281

DOI: 10.1091/mbc.e13-08-0492

PubMed ID: 29034528

Title: Patients with a new variant of endemic pemphigus foliaceus have autoantibodies against arrector pili muscle, colocalizing with MYZAP, p0071, desmoplakins 1 and 2 and ARVCF.

PubMed ID: 29034528

DOI: 10.1111/ced.13214

PubMed ID: 30479852

Title: Subclinical oral involvement in patients with endemic pemphigus foliaceus.

PubMed ID: 30479852

DOI: 10.5826/dpc.0804a02

Sequence Information:

  • Length: 962
  • Mass: 104642
  • Checksum: 74A1814A022FF2B1
  • Sequence:
    • MEDCNVHSAA SILASVKEQE ARFERLTRAL EQERRHVALQ LERAQQPGMV SGGMGSGQPL 
PMAWQQLVLQ EQSPGSQASL ATMPEAPDVL EETVTVEEDP GTPTSHVSIV TSEDGTTRRT 
ETKVTKTVKT VTTRTVRQVP VGPDGLPLLD GGPPLGPFAD GALDRHFLLR GGGPVATLSR 
AYLSSGGGFP EGPEPRDSPS YGSLSRGLGM RPPRAGPLGP GPGDGCFTLP GHREAFPVGP 
EPGPPGGRSL PERFQAEPYG LEDDTRSLAA DDEGGPELEP DYGTATRRRP ECGRGLHTRA 
YEDTADDGGE LADERPAFPM VTAPLAQPER GSMGSLDRLV RRSPSVDSAR KEPRWRDPEL 
PEVLAMLRHP VDPVKANAAA YLQHLCFENE GVKRRVRQLR GLPLLVALLD HPRAEVRRRA 
CGALRNLSYG RDTDNKAAIR DCGGVPALVR LLRAARDNEV RELVTGTLWN LSSYEPLKMV 
IIDHGLQTLT HEVIVPHSGW EREPNEDSKP RDAEWTTVFK NTSGCLRNVS SDGAEARRRL 
RECEGLVDAL LHALQSAVGR KDTDNKSVEN CVCIMRNLSY HVHKEVPGAD RYQEAEPGPL 
GSAVGSQRRR RDDASCFGGK KAKEEWFHQG KKDGEMDRNF DTLDLPKRTE AAKGFELLYQ 
PEVVRLYLSL LTESRNFNTL EAAAGALQNL SAGNWMWATY IRATVRKERG LPVLVELLQS 
ETDKVVRAVA IALRNLSLDR RNKDLIGSYA MAELVRNVRN AQAPPRPGAC LEEDTVVAVL 
NTIHEIVSDS LDNARSLLQA RGVPALVALV ASSQSVREAK AASHVLQTVW SYKELRGTLQ 
KDGWTKARFQ SAAATAKGPK GALSPGGFDD STLPLVDKSL EGEKTGSRDV IPMDALGPDG 
YSTVDRRERR PRGASSAGEA SEKEPLKLDP SRKAPPPGPS RPAVRLVDAV GDAKPQPVDS 
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