Details for: RASAL1

Gene ID: 8437

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: RASAL1

Ensembl ID: ENSG00000111344

Description: RAS protein activator like 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • small pre-B-II cell CL0000954
    CSI 3.74
    rCSI 3.59%
    PRS 98.84
  • renal principal cell CL0005009
    CSI 3.24
    rCSI 8.43%
    PRS 96.65
  • Langerhans cell CL0000453
    CSI 2.22
    rCSI 3.4%
    PRS 98.98
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.74
    rCSI 4.41%
    PRS 94.55
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.67
    rCSI 4.32%
    PRS 95.97
  • parietal epithelial cell CL1000452
    CSI 1.57
    rCSI 4.2%
    PRS 95.03
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.9
    rCSI 3.41%
    PRS 91.41
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.89
    rCSI 2.18%
    PRS 89.98
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.83
    rCSI 2.59%
    PRS 92.08
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.71
    rCSI 2.56%
    PRS 90.21
  • direct pathway medium spiny neuron CL4023026
    CSI 0.47
    rCSI 11.23%
    PRS 89.31
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.42
    rCSI 2.47%
    PRS 91.59

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.

Comma-separated if multiple.
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)

Loading network (please wait)...

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 [RASAL1](/details-gene/8437) (RAS protein activator like 1) is a protein-coding gene that functions as a GTPase-activating protein (GAP). Its primary role is to act as a negative regulator of Ras protein signaling by accelerating the conversion of active GTP-bound Ras to its inactive GDP-bound state. This positions [RASAL1](/details-gene/8437) as a key modulator of the MAPK signaling cascade, which is fundamental to cell proliferation, differentiation, and survival. Expression data indicates that [RASAL1](/details-gene/8437) has a highly specific cellular footprint, with its most significant expression observed in hematopoietic precursors, specifically `[small pre-B-II cell](/details-cell/CL0000954)`, and in various specialized epithelial cells of the kidney, including `[renal principal cell](/details-cell/CL0005009)`. It also shows moderate significance in several types of glutamatergic neurons. ## Cellular Roles and Expression Landscape Analysis of the **Overall** expression landscape reveals that [RASAL1](/details-gene/8437) has a restricted and highly specific expression pattern, suggesting specialized functions in distinct cellular contexts, a finding consistent with early characterization studies ([Link](https://doi.org/10.1016/s0378-1119(98)00394-1)). The gene's highest significance is observed in the immune and renal systems. In the hematopoietic lineage, its prominent expression in `[small pre-B-II cell](/details-cell/CL0000954)` (CSI: 3.74) suggests a critical role in regulating Ras-dependent signaling checkpoints during B-lymphocyte development. Additionally, its notable expression in `[Langerhans cell](/details-cell/CL0000453)` (CSI: 2.22), a type of tissue-resident dendritic cell, implies a potential function in modulating immune surveillance and antigen presentation. In the renal system, [RASAL1](/details-gene/8437) is a key marker for multiple epithelial cell types. It shows very high significance in `[renal principal cell](/details-cell/CL0005009)` (CSI: 3.24) and `[kidney connecting tubule epithelial cell](/details-cell/CL1000768)` (CSI: 1.74), among others. This strong, localized expression suggests that [RASAL1](/details-gene/8437) is crucial for maintaining the differentiated state and function of the kidney tubule, potentially by constraining proliferative signals. A secondary but distinct role is indicated in the nervous system. [RASAL1](/details-gene/8437) is expressed across several glutamatergic neuron subtypes, such as `[near-projecting glutamatergic cortical neuron](/details-cell/CL4023012)` (CSI: 0.90), although at lower significance levels than in immune or renal cells. This expression is consistent with its annotated function in the positive regulation of dendrite extension. ## Pathways and Molecular Function [RASAL1](/details-gene/8437) functions primarily as a GTPase activator ([GO:0005096](https://www.ebi.ac.uk/QuickGO/term/GO:0005096)), localizing to the `[cytosol](/details-cell/GO0005829)` and the `[plasma membrane](/details-cell/GO0005886)` where Ras signaling is initiated. Its core molecular action is the `negative regulation of ras protein signal transduction` ([GO:0046580](https://www.ebi.ac.uk/QuickGO/term/GO:0046580)). By inactivating Ras, [RASAL1](/details-gene/8437) serves as a brake on downstream signaling pathways. According to Reactome, this places it as a direct participant in the `[Regulation of RAS by GAPs](/details-pathway/R-HSA-5658442)` pathway, which in turn modulates the `[Raf/map kinase cascade](/details-pathway/R-HSA-5673001)` and broader `[Mapk family signaling cascades](/details-pathway/R-HSA-5683057)`. The involvement in these central signaling hubs aligns with its significant expression in cells undergoing tightly regulated differentiation, such as `[small pre-B-II cell](/details-cell/CL0000954)`, and in terminally differentiated cells like neurons, where it may contribute to processes like dendrite morphogenesis ([GO:1903861](https://www.ebi.ac.uk/QuickGO/term/GO:1903861)). ## Research Directions The specific expression pattern of [RASAL1](/details-gene/8437) and its function as a negative regulator of the frequently oncogenic Ras pathway provide clear directions for future research. **Proposed Hypotheses:** 1. Given its role as a Ras inhibitor and high expression in B-cell precursors, it is hypothesized that the loss or epigenetic silencing of [RASAL1](/details-gene/8437) in `[small pre-B-II cell](/details-cell/CL0000954)` progenitors is a contributing event in the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL) by permitting uncontrolled Ras-driven proliferation. 2. The high and specific expression of [RASAL1](/details-gene/8437) in `[renal principal cell](/details-cell/CL0005009)` suggests a role in maintaining tubular homeostasis. We hypothesize that dysregulation of [RASAL1](/details-gene/8437) is implicated in kidney diseases characterized by abnormal cell proliferation or dedifferentiation, such as in the development of renal cysts or clear cell renal cell carcinoma. **Suggested Experimental Approach:** To test the hypothesis that [RASAL1](/details-gene/8437) functions as a tumor suppressor in B-cell development (Hypothesis 1), a robust approach would be to use a CRISPR-Cas9 system to mediate its knockout in primary human hematopoietic stem and progenitor cells (HSPCs). These edited cells, alongside unedited controls, would be cultured *in vitro* under B-cell differentiating conditions. The impact of [RASAL1](/details-gene/8437) loss on cell proliferation, survival, and differentiation fidelity could be quantified using techniques such as flow cytometry to track immunophenotypic changes and RNA-sequencing to analyze downstream gene expression signatures related to the Ras-MAPK pathway. **Therapeutic Potential:** As a negative regulator of an oncogenic pathway, [RASAL1](/details-gene/8437) is a candidate tumor suppressor. Consequently, therapeutic strategies would not involve inhibition but rather **activation** or restoration of its function in disease contexts. In malignancies such as leukemias or renal carcinomas where [RASAL1](/details-gene/8437) expression is lost, re-introducing its function via gene therapy or identifying small-molecule activators that enhance its GAP activity could represent a targeted therapeutic strategy to suppress tumor growth.

Genular Protein ID: 2102281162

Symbol: RASL1_HUMAN

Name: N/A

UniProtKB Accession Codes:

O95294 B7ZKM4 C9JFK5 F8VQX1 Q52M03 Q59H24 Q96CC7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CDD 1 CTD 1 ChEBI 21 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 4 GO 10 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 10 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 5 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 9 SMART 4 SMR 1 STRING 1 SUPFAM 3 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9751798

Title: Restricted tissue expression pattern of a novel human rasGAP-related gene and its murine ortholog.

PubMed ID: 9751798

DOI: 10.1016/s0378-1119(98)00394-1

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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: 11230166

Title: Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

PubMed ID: 11230166

DOI: 10.1101/gr.gr1547r

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23999003

Title: SYT14L, especially its C2 domain, is involved in regulating melanocyte differentiation.

PubMed ID: 23999003

DOI: 10.1016/j.jdermsci.2013.07.010

Sequence Information:

  • Length: 804
  • Mass: 90016
  • Checksum: 5D0065A093487FD0
  • Sequence:
    • MAKSSSLNVR VVEGRALPAK DVSGSSDPYC LVKVDDEVVA RTATVWRSLG PFWGEEYTVH 
LPLDFHQLAF YVLDEDTVGH DDIIGKISLS REAITADPRG IDSWINLSRV DPDAEVQGEI 
CLSVQMLEDG QGRCLRCHVL QARDLAPRDI SGTSDPFARV FWGSQSLETS TIKKTRFPHW 
DEVLELREMP GAPSPLRVEL WDWDMVGKND FLGMVEFSPK TLQQKPPKGW FRLLPFPRAE 
EDSGGNLGAL RVKVRLIEDR VLPSQCYQPL MELLMESVQG PAEEDTASPL ALLEELTLGD 
CRQDLATKLV KLFLGRGLAG RFLDYLTRRE VARTMDPNTL FRSNSLASKS MEQFMKLVGM 
PYLHEVLKPV ISRVFEEKKY MELDPCKMDL GRTRRISFKG ALSEEQMRET SLGLLTGYLG 
PIVDAIVGSV GRCPPAMRLA FKQLHRRVEE RFPQAEHQDV KYLAISGFLF LRFFAPAILT 
PKLFDLRDQH ADPQTSRSLL LLAKAVQSIG NLGQQLGQGK ELWMAPLHPF LLQCVSRVRD 
FLDRLVDVDG DEAGVPARAL FPPSAIVREG YLLKRKEEPA GLATRFAFKK RYVWLSGETL 
SFSKSPEWQM CHSIPVSHIR AVERVDEGAF QLPHVMQVVT QDGTGALHTT YLQCKNVNEL 
NQWLSALRKA SAPNPNKLAA CHPGAFRSAR WTCCLQAERS AAGCSRTHSA VTLGDWSDPL 
DPDAEAQTVY RQLLLGRDQL RLKLLEDSNM DTTLEADTGA CPEVLARQRA ATARLLEVLA 
DLDRAHEEFQ QQERGKAALG PLGP