Details for: ARHGAP36

Gene ID: 158763

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: ARHGAP36

Ensembl ID: ENSG00000147256

Description: Rho GTPase activating protein 36

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.36
    rCSI 5.41%
    PRS 99.92

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

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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 [ARHGAP36](/details-gene/158763) is a protein-coding gene located on the X chromosome that encodes Rho GTPase activating protein 36. Functionally, the protein is involved in [signal transduction](/details-go/GO:0007165) and exhibits [GTPase activator activity](/details-go/GO:0005096), a critical role in regulating cellular processes mediated by Rho family GTPases. Expression data indicates that [ARHGAP36](/details-gene/158763) is a significant marker for [sncg GABAergic cortical interneuron](/details-cell/CL4023015), suggesting a specialized function within the central nervous system. Clinically, duplications in the genomic region containing this gene are associated with Bazex-Dupre-Christol syndrome ([153245](https://omim.org/entry/300937)), a genetic disorder that confers susceptibility to basal cell carcinomas ([Link](https://doi.org/10.1111/bjd.21842)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [ARHGAP36](/details-gene/158763) points towards a highly specialized role. The gene shows its most significant expression in [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 3.36). This strong and specific expression signature suggests that [ARHGAP36](/details-gene/158763) may be integral to the identity, development, or function of this particular subset of inhibitory neurons within the cerebral cortex. The current data does not highlight significant expression in other cell lineages, pointing towards a specific function in the nervous system rather than a ubiquitous housekeeping role. ## Pathways and Molecular Function [ARHGAP36](/details-gene/158763) is functionally annotated as a GTPase activator, a class of proteins that negatively regulate Rho GTPases by accelerating the hydrolysis of GTP to GDP. This activity is a key control point in a wide array of cellular signaling pathways. Consistent with this, the gene is implicated in the broad biological process of [signal transduction](/details-go/GO:0007165). Research has more specifically linked [ARHGAP36](/details-gene/158763) to the regulation of the Hedgehog (Hh) signaling pathway, a fundamental pathway in embryonic development and tissue maintenance ([Link](https://doi.org/10.1111/bjd.21842)). Dysregulation of Hh signaling is a known driver of certain cancers, including basal cell carcinoma. This functional role is consistent with its potential involvement in both complex neuronal processes and oncogenesis. ## Research Directions The association of [ARHGAP36](/details-gene/158763) with both a specific neuronal cell type and a cancer predisposition syndrome presents intriguing avenues for future research. The key challenge is to reconcile its prominent neuronal expression with its implication in a skin-related malignancy. Based on the available data, several testable hypotheses can be proposed: 1. Genomic duplication leading to overexpression of [ARHGAP36](/details-gene/158763) in skin progenitor cells dysregulates Hedgehog signaling, thereby promoting the development of basal cell carcinomas in individuals with Bazex-Dupre-Christol syndrome. 2. [ARHGAP36](/details-gene/158763) is essential for the proper differentiation, migration, or synaptic function of [sncg GABAergic cortical interneuron](/details-cell/CL4023015)s, and its loss-of-function or misexpression could contribute to neurological disorders characterized by imbalances in cortical inhibition. A key experiment to investigate the first hypothesis would be to test the direct oncogenic potential of [ARHGAP36](/details-gene/158763) in a relevant cell type. To test this role, one could use a lentiviral system to induce stable overexpression of [ARHGAP36](/details-gene/158763) in human keratinocytes. The impact on cell proliferation, colony formation, and Hedgehog pathway activation (e.g., measuring GLI1 and PTCH1 expression) could then be assessed via quantitative PCR and western blotting. As a therapeutic target, [ARHGAP36](/details-gene/158763) is a compelling candidate for inhibition, particularly in the context of cancers driven by its overexpression. Its enzymatic function as a RhoGAP suggests that developing small molecule inhibitors to block its catalytic site could be a viable strategy to counteract its pro-tumorigenic effects by normalizing Rho GTPase and Hedgehog pathway signaling.

Genular Protein ID: 2390969537

Symbol: RHG36_HUMAN

Name: Rho GTPase-activating protein 36

UniProtKB Accession Codes:

Q6ZRI8 B7Z234 B7Z439 Q5JRL9 Q5JRM0 Q5JRM1 Q96NU6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 5 ExpressionAtlas 1 GO 2 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 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 5 RNAct 1 RefSeq 4 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 35986704

Title: Germline intergenic duplications at Xq26.1 underlie Bazex-Dupre-Christol basal cell carcinoma susceptibility syndrome.

PubMed ID: 35986704

DOI: 10.1111/bjd.21842

Sequence Information:

  • Length: 547
  • Mass: 61664
  • Checksum: 28EB8168F3928DF9
  • Sequence:
    • MGGCIPFLKA ARALCPRIMP PLLLLSAFIF LVSVLGGAPG HNPDRRTKMV SIHSLSELER 
LKLQETAYHE LVARHFLSEF KPDRALPIDR PNTLDKWFLI LRGQQRAVSH KTFGISLEEV 
LVNEFTRRKH LELTATMQVE EATGQAAGRR RGNVVRRVFG RIRRFFSRRR NEPTLPREFT 
RRGRRGAVSV DSLAELEDGA LLLQTLQLSK ISFPIGQRLL GSKRKMSLNP IAKQIPQVVE 
ACCQFIEKHG LSAVGIFTLE YSVQRVRQLR EEFDQGLDVV LDDNQNVHDV AALLKEFFRD 
MKDSLLPDDL YMSFLLTATL KPQDQLSALQ LLVYLMPPCH SDTLERLLKA LHKITENCED 
SIGIDGQLVP GNRMTSTNLA LVFGSALLKK GKFGKRESRK TKLGIDHYVA SVNVVRAMID 
NWDVLFQVPP HIQRQVAKRV WKSSPEALDF IRRRNLRKIQ SARIKMEEDA LLSDPVETSA 
EARAAVLAQS KPSDEGSSEE PAVPSGTARS HDDEEGAGNP PIPEQDRPLL RVPREKEAKT 
GVSYFFP