Details for: ARHGAP11A

Gene ID: 9824

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: ARHGAP11A

Ensembl ID: ENSG00000198826

Description: Rho GTPase activating protein 11A

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • neural crest cell CL0011012
    CSI 4.43
    rCSI 3.5%
    PRS 95.98
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.79
    rCSI 2.42%
    PRS 98.58
  • stem cell CL0000034
    CSI 2.78
    rCSI 2.68%
    PRS 96.8
  • common myeloid progenitor CL0000049
    CSI 2.78
    rCSI 2.24%
    PRS 98.64
  • mesodermal cell CL0000222
    CSI 2.68
    rCSI 3.22%
    PRS 98.16
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.6
    rCSI 3%
    PRS 94.55
  • erythrocyte CL0000232
    CSI 2.44
    rCSI 5.54%
    PRS 96.39
  • common dendritic progenitor CL0001029
    CSI 2.43
    rCSI 3.05%
    PRS 99.18
  • placental villous trophoblast CL2000060
    CSI 2.4
    rCSI 3.71%
    PRS 96.9
  • transit amplifying cell of small intestine CL0009012
    CSI 1.85
    rCSI 8.11%
    PRS 98.49
  • promonocyte CL0000559
    CSI 1.77
    rCSI 3.04%
    PRS 98.5
  • large pre-B-II cell CL0000957
    CSI 1.31
    rCSI 3.74%
    PRS 97.07
  • erythroid progenitor cell CL0000038
    CSI 0.5
    rCSI 2.87%
    PRS 98.24

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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  • 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 [ARHGAP11A](/details-gene/9824) (Rho GTPase activating protein 11A) is a protein-coding gene located on chromosome 15q13.3. It functions as a GTPase-activating protein (GAP), specifically targeting Rho-family GTPases to negatively regulate their activity. This function places it as a key component in the [Rho gtpase cycle](/details-gene/R-HSA-9012999) and broader [signal transduction](/details-gene/R-HSA-162582) pathways. **Overall**, expression data reveals that [ARHGAP11A](/details-gene/9824) is a significant marker for various progenitor and developmental cell populations, with particularly high significance in [neural crest cell](/details-cell/CL0011012), as well as hematopoietic progenitors like the [granulocyte monocyte progenitor cell](/details-cell/CL0000557) and [common myeloid progenitor](/details-cell/CL0000049). This expression pattern, combined with its molecular function, suggests a critical role in controlling cell fate, migration, and differentiation during embryogenesis and hematopoiesis. ## Cellular Roles and Expression Landscape The expression profile of [ARHGAP11A](/details-gene/9824) strongly indicates a primary role in undifferentiated and developing cell lineages. Its highest significance is observed in two major developmental systems: neurogenesis and hematopoiesis. In the context of neurodevelopment, it is a top marker for [neural crest cell](/details-cell/CL0011012) (CSI: 4.43) and [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338), suggesting involvement in the migration and differentiation of these crucial embryonic populations that give rise to the peripheral nervous system and other structures. Concurrently, [ARHGAP11A](/details-gene/9824) demonstrates high significance across the myeloid hematopoietic lineage. It is a defining gene for [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 2.79), [common myeloid progenitor](/details-cell/CL0000049) (CSI: 2.78), and [common dendritic progenitor](/details-cell/CL0001029) (CSI: 2.43). This pattern suggests it plays a key regulatory role during the early stages of myelopoiesis, potentially governing the cytoskeletal changes required for cell division and lineage commitment. More broadly, its high significance in generic [stem cell](/details-cell/CL0000034) (CSI: 2.78) and [mesodermal cell](/details-cell/CL0000222) (CSI: 2.68) populations underscores its fundamental role in progenitor cell biology, likely contributing to processes that are common across multiple developmental pathways. ## Pathways and Molecular Function Functionally, [ARHGAP11A](/details-gene/9824) is annotated with [Gtpase activator activity](/details-gene/GO:0005096), localizing primarily to the [cytosol](/details-gene/GO:0005829) and [nucleus](/details-gene/GO:0005634). Its primary role is to accelerate the hydrolysis of GTP bound to Rho GTPases, converting them from an active to an inactive state. This is reflected in its association with the [positive regulation of gtpase activity](/details-gene/GO:0043547) and its central position in Reactome pathways such as the [Rho gtpase cycle](/details-gene/R-HSA-9012999) and [Signaling by rho gtpases](/details-gene/R-HSA-194315). The regulation of Rho GTPases is fundamental for controlling the actin cytoskeleton, which in turn governs cell morphology, adhesion, migration, and cytokinesis. This molecular function is highly consistent with the cellular contexts where [ARHGAP11A](/details-gene/9824) is most significant. For example, the extensive migration of [neural crest cell](/details-cell/CL0011012) during development is critically dependent on precise spatiotemporal regulation of the cytoskeleton, a process directly modulated by RhoGAPs like [ARHGAP11A](/details-gene/9824). Similarly, the cell division and differentiation of hematopoietic progenitors require tight control over cytoskeletal dynamics. ## Research Directions While its human-specific paralog, ARHGAP11B, has been linked to neocortical expansion during human evolution [Link](https://doi.org/10.1126/sciadv.1601941) [Link](https://doi.org/10.1016/j.neuron.2019.11.027), the specific roles of [ARHGAP11A](/details-gene/9824) remain less defined. The expression data provides a strong basis for formulating new hypotheses. **Proposed Hypotheses:** 1. Given its top significance in [neural crest cell](/details-cell/CL0011012), [ARHGAP11A](/details-gene/9824) is a critical regulator of neural crest specification and migration. Its downregulation may be required to permit the RhoA-mediated cytoskeletal activity necessary for delamination and long-range migration from the neural tube. 2. Based on its high significance in a cascade of myeloid progenitors ([common myeloid progenitor](/details-cell/CL0000049), [granulocyte monocyte progenitor cell](/details-cell/CL0000557)), [ARHGAP11A](/details-gene/9824) functions as a checkpoint regulator in myelopoiesis, where its activity dictates the balance between self-renewal and commitment to the granulocyte-monocyte lineage. Dysregulation of [ARHGAP11A](/details-gene/9824) could therefore contribute to lineage bias or the development of myeloproliferative neoplasms. **Key Experimental Approach:** To test the hypothesis regarding its role in neural crest development, a robust *in vitro* differentiation model could be employed. Specifically, one could generate an [ARHGAP11A](/details-gene/9824) knockout line in human pluripotent stem cells (hPSCs) using CRISPR-Cas9 genome editing. These knockout hPSCs, alongside isogenic wild-type controls, would be differentiated towards the [neural crest cell](/details-cell/CL0011012) lineage. The functional consequences would be assessed using a scratch-wound or transwell migration assay to quantify migratory potential. Furthermore, single-cell RNA sequencing at different time points of the differentiation protocol would reveal defects in lineage specification and identify downstream transcriptional targets affected by the loss of [ARHGAP11A](/details-gene/9824). **Therapeutic Potential:** The therapeutic potential of targeting [ARHGAP11A](/details-gene/9824) is complex. As a regulator of fundamental cellular processes in progenitor cells, systemic inhibition or activation would likely lead to significant off-target effects, particularly within the hematopoietic system. However, if specific cancers exhibit a dependency on either the overexpression or functional loss of [ARHGAP11A](/details-gene/9824) to control their metastatic or proliferative potential, it could become a candidate for targeted therapy. Because it is an intracellular enzyme, the most likely therapeutic modality would be a small molecule inhibitor or activator designed to modulate its GAP activity. Such a strategy would require high specificity to avoid cross-reactivity with other RhoGAPs and would be most viable in contexts where a clear therapeutic window exists between cancerous and healthy tissues.

Genular Protein ID: 3348913266

Symbol: RHGBA_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6P4F7 B4DZN9 Q6PI96 Q9Y3S6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 7 EvolutionaryTrace 1 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 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 Reactome 1 RefSeq 4 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7584026

Title: Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1.

PubMed ID: 7584026

DOI: 10.1093/dnares/1.1.27

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18220336

Title: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.

PubMed ID: 18220336

DOI: 10.1021/pr0705441

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

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: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 27957544

Title: A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification.

PubMed ID: 27957544

DOI: 10.1126/sciadv.1601941

PubMed ID: 31883789

Title: Human-specific ARHGAP11B acts in mitochondria to expand neocortical progenitors by glutaminolysis.

PubMed ID: 31883789

DOI: 10.1016/j.neuron.2019.11.027

Sequence Information:

  • Length: 1023
  • Mass: 113866
  • Checksum: 053C89371B5F614F
  • Sequence:
    • MWDQRLVRLA LLQHLRAFYG IKVKGVRGQC DRRRHETAAT EIGGKIFGVP FNALPHSAVP 
EYGHIPSFLV DACTSLEDHI HTEGLFRKSG SVIRLKALKN KVDHGEGCLS SAPPCDIAGL 
LKQFFRELPE PILPADLHEA LLKAQQLGTE EKNKATLLLS CLLADHTVHV LRYFFNFLRN 
VSLRSSENKM DSSNLAVIFA PNLLQTSEGH EKMSSNTEKK LRLQAAVVQT LIDYASDIGR 
VPDFILEKIP AMLGIDGLCA TPSLEGFEEG EYETPGEYKR KRRQSVGDFV SGALNKFKPN 
RTPSITPQEE RIAQLSESPV ILTPNAKRTL PVDSSHGFSS KKRKSIKHNF NFELLPSNLF 
NSSSTPVSVH IDTSSEGSSQ SSLSPVLIGG NHLITAGVPR RSKRIAGKKV CRVESGKAGC 
FSPKISHKEK VRRSLRLKFN LGKNGREVNG CSGVNRYESV GWRLANQQSL KNRIESVKTG 
LLFSPDVDEK LPKKGSEKIS KSEETLLTPE RLVGTNYRMS WTGPNNSSFQ EVDANEASSM 
VENLEVENSL EPDIMVEKSP ATSCELTPSN LNNKHNSNIT SSPLSGDENN MTKETLVKVQ 
KAFSESGSNL HALMNQRQSS VTNVGKVKLT EPSYLEDSPE ENLFETNDLT IVESKEKYEH 
HTGKGEKCFS ERDFSPLQTQ TFNRETTIKC YSTQMKMEHE KDIHSNMPKD YLSKQEFSSD 
EEIKKQQSPK DKLNNKLKEN ENMMEGNLPK CAAHSKDEAR SSFSQQSTCV VTNLSKPRPM 
RIAKQQSLET CEKTVSESSQ MTEHRKVSDH IQWFNKLSLN EPNRIKVKSP LKFQRTPVRQ 
SVRRINSLLE YSRQPTGHKL ASLGDTASPL VKSVSCDGAL SSCIESASKD SSVSCIKSGP 
KEQKSMSCEE SNIGAISKSS MELPSKSFLK MRKHPDSVNA SLRSTTVYKQ KILSDGQVKV 
PLDDLTNHDI VKPVVNNNMG ISSGINNRVL RRPSERGRAW YKGSPKHPIG KTQLLPTSKP 
VDL