Details for: RHBDL1

Gene ID: 9028

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: RHBDL1

Ensembl ID: ENSG00000103269

Description: rhomboid like 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 5.31
    rCSI 6.34%
    PRS 83.07
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 4.83
    rCSI 6.01%
    PRS 80.88
  • cerebellar granule cell CL0001031
    CSI 3.05
    rCSI 4.49%
    PRS 89.27
  • glycinergic amacrine cell CL4030028
    CSI 2.71
    rCSI 7.05%
    PRS 88.23
  • inhibitory interneuron CL0000498
    CSI 2.26
    rCSI 5.22%
    PRS 86.11
  • lung neuroendocrine cell CL1000223
    CSI 2.14
    rCSI 3.16%
    PRS 94.23
  • sst GABAergic cortical interneuron CL4023017
    CSI 2
    rCSI 2.58%
    PRS 84.01
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.83
    rCSI 3.23%
    PRS 82.4
  • amacrine cell CL0000561
    CSI 1.48
    rCSI 4.29%
    PRS 86.33
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.42
    rCSI 3.18%
    PRS 83.33
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.36
    rCSI 2.29%
    PRS 83.09
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.35
    rCSI 2.17%
    PRS 84.03
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.2
    rCSI 3.74%
    PRS 84.08
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.94
    rCSI 2.94%
    PRS 85.83
  • retinal ganglion cell CL0000740
    CSI 0.86
    rCSI 1.91%
    PRS 84.85
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.83
    rCSI 2.03%
    PRS 80.94
  • dopaminergic neuron CL0000700
    CSI 0.74
    rCSI 4.16%
    PRS 84.47
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.66
    rCSI 2.39%
    PRS 81.27
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.62
    rCSI 2.35%
    PRS 83.16
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.5
    rCSI 2.92%
    PRS 83.46

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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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 [RHBDL1](/details-gene/9028) is a protein-coding gene located on chromosome 16p13.3 that encodes Rhomboid-like protein 1, a member of the rhomboid family of intramembrane serine proteases. Functional annotations indicate its involvement in [proteolysis](/details-cell/GO:0006508) and [signal transduction](/details-cell/GO:0007165), with enzymatic activity localized to the [plasma membrane](/details-cell/GO:0005886). The initial characterization of this protein highlighted its similarity to the *Drosophila* Rhomboid protein, a key regulator of developmental signaling pathways ([Link](https://doi.org/10.1016/s0014-5793(98)00622-x)). Expression data reveals that **Overall**, [RHBDL1](/details-gene/9028) is a highly significant gene within the central nervous system, showing prominent expression in various neuronal subtypes, particularly inhibitory GABAergic cortical interneurons, suggesting a specialized role in neural circuit function and maintenance. ## Cellular Roles and Expression Landscape The expression profile of [RHBDL1](/details-gene/9028) strongly points to a specialized function within the nervous system. **Overall**, the gene demonstrates its highest significance in several classes of inhibitory neurons. It is a top marker in [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 5.31) and [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 4.83), which are critical for regulating cortical network activity. Its significance extends to other key neuronal populations, including [cerebellar granule cells](/details-cell/CL0001031), [glycinergic amacrine cells](/details-cell/CL4030028) in the retina, and other cortical interneuron subtypes such as [sst GABAergic cortical interneurons](/details-cell/CL4023017). Beyond its role in inhibitory circuits, [RHBDL1](/details-gene/9028) also shows notable significance in other neural cells like [astrocytes of the cerebral cortex](/details-cell/CL0002605) and [lung neuroendocrine cells](/details-cell/CL1000223), suggesting a broader, albeit less prominent, role in glial support and neuroendocrine signaling. The highly specific enrichment within neuronal and related cell types implies that its function is less critical in other major physiological systems, such as the hematopoietic or epithelial lineages. ## Pathways and Molecular Function [RHBDL1](/details-gene/9028) is functionally annotated as a serine protease that operates within the cell membrane. Its classification as having [serine-type endopeptidase activity](/details-cell/GO:0004252) and its localization to the [membrane](/details-cell/GO:0016020) are characteristic of regulated intramembrane proteolysis (RIP). This process involves the cleavage of membrane-anchored substrate proteins to release active fragments, which can then translocate to other cellular compartments to initiate a [signal transduction](/details-cell/GO:0007165) cascade. Consistent with its high expression in diverse neuronal populations, the proteolytic activity of [RHBDL1](/details-gene/9028) likely plays a crucial role in modulating cell-cell communication, neuronal development, or synaptic plasticity. By cleaving specific membrane-bound substrates, it may regulate the availability of signaling molecules, growth factors, or adhesion proteins essential for maintaining the integrity and function of complex neural circuits. ## Research Directions The specific and high-level expression of [RHBDL1](/details-gene/9028) in inhibitory interneurons presents compelling avenues for future research into the molecular mechanisms governing neural circuit function and dysfunction. **Proposed Hypotheses:** 1. [RHBDL1](/details-gene/9028)-mediated proteolysis is essential for the maturation, synaptic integration, or long-term survival of specific cortical interneuron subtypes. Its substrates are likely to be membrane-tethered proteins that regulate synaptic transmission, cell adhesion, or neurotrophic factor signaling. 2. Dysregulation of [RHBDL1](/details-gene/9028) expression or enzymatic activity contributes to the pathology of neurodevelopmental or psychiatric disorders characterized by an imbalance of excitation and inhibition, such as epilepsy or schizophrenia, through the aberrant processing of its neuronal substrates. **Experimental Approach:** To test the hypothesis that [RHBDL1](/details-gene/9028) is critical for interneuron function, a conditional knockout mouse model could be developed using a Cre-Lox system to specifically delete the gene in GABAergic neurons (e.g., via a *Gad2-Cre* or *Pvalb-Cre* driver line). The resulting phenotype could be assessed through a combination of electrophysiological recordings to measure changes in synaptic inhibition, detailed histological analysis to examine interneuron morphology and density, and behavioral tests relevant to cortical circuit function. Concurrently, an unbiased proteomics approach, such as secretome profiling in primary neuronal cultures with [RHBDL1](/details-gene/9028) knockout, could be used to identify its physiological substrates. **Therapeutic Potential:** As a protease, [RHBDL1](/details-gene/9028) is a potentially druggable enzyme. Its highly restricted expression within the central nervous system suggests that targeted therapies could achieve high specificity with minimal off-target effects in peripheral tissues. If gain-of-function mutations or over-activity are linked to neurological disease, [RHBDL1](/details-gene/9028) could be a target for small molecule inhibitors. The primary challenge would be developing agents that can effectively cross the blood-brain barrier. Therefore, **inhibition** would be the likely therapeutic strategy for conditions driven by aberrant proteolytic activity of this enzyme.

Genular Protein ID: 530664670

Symbol: RHBL1_HUMAN

Name: Rhomboid-related protein 1

UniProtKB Accession Codes:

O75783 A2IDC0 A2IDC1 Q0VAX4 Q9NQ85

Database IDs:

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

Citations:

PubMed ID: 9662444

Title: Characterization of a mammalian cDNA encoding a protein with high sequence similarity to the Drosophila regulatory protein Rhomboid.

PubMed ID: 9662444

DOI: 10.1016/s0014-5793(98)00622-x

PubMed ID: 11157797

Title: Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16.

PubMed ID: 11157797

DOI: 10.1093/hmg/10.4.339

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

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

Sequence Information:

  • Length: 438
  • Mass: 48314
  • Checksum: A7644AD39644A2F6
  • Sequence:
    • MGRVEDGGTT EELEDWDPGT SALPAPGIKQ GPREQTGTGP LSQKCWEPEP DAPSQPGPAL 
WSRGRARTQA LAGGSSLQQL DPENTGFIGA DTFTGLVHSH ELPLDPAKLD MLVALAQSNE 
QGQVCYQELV DLISSKRSSS FKRAIANGQR ALPRDGPLDE PGLGVYKRFV RYVAYEILPC 
EVDRRWYFYR HRSCPPPVFM ASVTLAQIIV FLCYGARLNK WVLQTYHPEY MKSPLVYHPG 
HRARAWRFLT YMFMHVGLEQ LGFNALLQLM IGVPLEMVHG LLRISLLYLA GVLAGSLTVS 
ITDMRAPVVG GSGGVYALCS AHLANVVMNW AGMRCPYKLL RMVLALVCMS SEVGRAVWLR 
FSPPLPASGP QPSFMAHLAG AVVGVSMGLT ILRSYEERLR DQCGWWVVLL AYGTFLLFAV 
FWNVFAYDLL GAHIPPPP