Details for: BHLHE22

Gene ID: 27319

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: BHLHE22

Ensembl ID: ENSG00000180828

Description: basic helix-loop-helix family member e22

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • interneuron CL0000099
    CSI 7.35
    rCSI 14.77%
    PRS 97.57
  • progenitor cell CL0011026
    CSI 5.89
    rCSI 12.52%
    PRS 96.96
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 5.25
    rCSI 6.73%
    PRS 97.96
  • OFF-bipolar cell CL0000750
    CSI 3.42
    rCSI 4.68%
    PRS 97.86
  • retinal bipolar neuron CL0000748
    CSI 2.5
    rCSI 4.68%
    PRS 96.63
  • neural progenitor cell CL0011020
    CSI 2.49
    rCSI 10.94%
    PRS 94.29
  • glutamatergic neuron CL0000679
    CSI 2.1
    rCSI 4.32%
    PRS 94.17
  • GABAergic amacrine cell CL4030027
    CSI 1.27
    rCSI 4.36%
    PRS 94.03

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 [BHLHE22](/details-gene/27319), or basic helix-loop-helix family member e22, is a protein-coding gene located on chromosome 8q12.3. It encodes a class E basic helix-loop-helix (bHLH) transcription factor, a class of proteins known for their critical roles in cell fate determination and differentiation ([Link](https://doi.org/10.1006/geno.2002.6833)). The primary function of [BHLHE22](/details-gene/27319) is to regulate gene expression by binding to specific DNA sequences known as E-boxes. **Overall**, its expression profile is highly specific to the nervous system, showing pronounced significance in developing and mature neuronal populations such as [interneuron](/details-cell/CL0000099)s, [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s, and [retinal bipolar neuron](/details-cell/CL0000748)s, highlighting its essential role in neurogenesis and sensory organ development. ## Cellular Roles and Expression Landscape The expression pattern of [BHLHE22](/details-gene/27319) firmly establishes it as a key regulator within the nervous system. The gene exhibits its highest significance in [interneuron](/details-cell/CL0000099)s (CSI: 7.35), a diverse class of inhibitory neurons crucial for regulating neural circuitry. Its high significance is also observed in various progenitor and developing neural cells, including [progenitor cell](/details-cell/CL0011026)s (CSI: 5.89), [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s (CSI: 5.25), and [neural progenitor cell](/details-cell/CL0011020)s (CSI: 2.49). This pattern suggests a fundamental role for [BHLHE22](/details-gene/27319) in the commitment and differentiation of neuronal lineages. Furthermore, [BHLHE22](/details-gene/27319) is a significant marker in specialized sensory neurons of the retina, such as the [OFF-bipolar cell](/details-cell/CL0000750) (CSI: 3.42) and the broader [retinal bipolar neuron](/details-cell/CL0000748) category (CSI: 2.50), underscoring its involvement in the development of the visual system. Its expression in mature neuron types, including [glutamatergic neuron](/details-cell/CL0000679)s and [GABAergic amacrine cell](/details-cell/CL4030027)s, indicates that its function may extend beyond development to include the maintenance of neuronal identity and function. ## Pathways and Molecular Function Functionally, [BHLHE22](/details-gene/27319) acts as a sequence-specific transcription factor. Its molecular activities, as defined by Gene Ontology, include [DNA-binding transcription factor activity](/details-go/GO:0003700), specific recognition of [E-box binding](/details-go/GO:0070888) sites, and [protein dimerization activity](/details-go/GO:0046983), which are characteristic of bHLH proteins ([Link](https://doi.org/10.1016/s0925-4773(03)00130-8)). These activities are localized to the [nucleus](/details-go/GO:0005634), where it acts on [chromatin](/details-go/GO:0000785) to regulate target gene transcription. The biological processes governed by [BHLHE22](/details-gene/27319) are consistent with its cellular expression profile. It is centrally involved in [neuron fate commitment](/details-go/GO:0048663), [axon development](/details-go/GO:0061564), and [sensory organ development](/details-go/GO:0007423). Reactome pathway analysis further implicates [BHLHE22](/details-gene/27319) in processes governing tissue architecture, including [cell-cell communication](/details-pathway/R-HSA-1500931) and [cell junction organization](/details-pathway/R-HSA-446728). Specifically, it is annotated as a regulator of cadherin expression, such as in the [Regulation of cdh11 expression and function](/details-pathway/R-HSA-9759475) pathway. This suggests that [BHLHE22](/details-gene/27319) not only specifies neuronal identity but also orchestrates the expression of cell adhesion molecules necessary for building and maintaining neural circuits. ## Research Directions The highly specific expression of [BHLHE22](/details-gene/27319) in neuronal progenitors and distinct mature neuron subtypes points to its potential role as a master regulator in neurogenesis. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis on Cell Fate Specification:** Given its high significance in both [neural progenitor cell](/details-cell/CL0011020)s and [interneuron](/details-cell/CL0000099)s, [BHLHE22](/details-gene/27319) may function as a terminal selector gene that drives the differentiation of progenitors specifically toward an [interneuron](/details-cell/CL0000099) fate, potentially by activating a downstream cascade of interneuron-specific genes while repressing alternative lineage programs. 2. **Hypothesis on Axonal Guidance and Synaptogenesis:** Its annotated role in [axon development](/details-go/GO:0061564) and regulation of cadherin expression suggests that [BHLHE22](/details-gene/27319) directly controls the expression of cell adhesion molecules essential for proper axon pathfinding and the formation of synaptic connections in the developing retina, particularly in [retinal bipolar neuron](/details-cell/CL0000748)s. A key experiment to test the first hypothesis would be to investigate the role of [BHLHE22](/details-gene/27319) in [interneuron](/details-cell/CL0000099) fate specification. One could utilize a CRISPRi (interference) system to knockdown [BHLHE22](/details-gene/27319) in human pluripotent stem cell-derived [neural progenitor cell](/details-cell/CL0011020)s undergoing directed differentiation towards cortical interneurons. The resulting cell populations could be analyzed by single-cell RNA-sequencing (scRNA-seq) to quantify the efficiency of [interneuron](/details-cell/CL0000099) generation and identify shifts in cell fate trajectories. As an intracellular transcription factor, [BHLHE22](/details-gene/27319) represents a challenging therapeutic target for direct modulation with small molecules. However, its specific expression pattern and critical role in development suggest that its dysregulation could be implicated in neurodevelopmental disorders or in the context of neuronal regeneration following injury. Therapeutic strategies are more likely to be indirect, potentially focusing on modulating its downstream targets or leveraging knowledge of its function to improve protocols for cell replacement therapies.

Genular Protein ID: 913671577

Symbol: BHE22_HUMAN

Name: Class E basic helix-loop-helix protein 22

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 12213201

Title: Functional and structural characterization of the human gene BHLHB5, encoding a basic helix-loop-helix transcription factor.

PubMed ID: 12213201

DOI: 10.1006/geno.2002.6833

PubMed ID: 14516699

Title: Exhaustive identification of human class II basic helix-loop-helix proteins by virtual library screening.

PubMed ID: 14516699

DOI: 10.1016/s0925-4773(03)00130-8

Sequence Information:

  • Length: 381
  • Mass: 36997
  • Checksum: 7B17A9BD5C7F8569
  • Sequence:
  • MERGMHLGAA AAGEDDLFLH KSLSASTSKR LEAAFRSTPP GMDLSLAPPP RERPASSSSS 
    PLGCFEPADP EGAGLLLPPP GGGGGGSAGS GGGGGGGVGV PGLLVGSAGV GGDPSLSSLP 
    AGAALCLKYG ESASRGSVAE SSGGEQSPDD DSDGRCELVL RAGVADPRAS PGAGGGGAKA 
    AEGCSNAHLH GGASVPPGGL GGGGGGGSSS GSSGGGGGSG SGSGGSSSSS SSSSKKSKEQ 
    KALRLNINAR ERRRMHDLND ALDELRAVIP YAHSPSVRKL SKIATLLLAK NYILMQAQAL 
    EEMRRLVAYL NQGQAISAAS LPSSAAAAAA AAALHPALGA YEQAAGYPFS AGLPPAASCP 
    EKCALFNSVS SSLCKQCTEK P

Genular Protein ID: 4261306001

Symbol: B4DF88_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Sequence Information:

  • Length: 384
  • Mass: 37197
  • Checksum: A891DEC8C662C06A
  • Sequence:
  • MERGMHLGAA AAGEDDLFLH KSLSASTAKR LEAAFRSTPP GMDLSLAPPP RERPASSSSS 
    PQGCFEPADP EGAGLLLPPP GGGGGGSAGS GGGGGGGGVG VPGLLVGSAG VGGDPSLSSL 
    PAGAALCLKY GESASRGSVA ESSGGEQSPD DDSDGRCELV LRAGVADPRA SPGAGGGGAK 
    AAEGCSNAHL HGGASVPPGG LGGGGGGGSS SGSSGGGGGS GSGSGSGGSS SSSSSSSKKS 
    KEQKALRLNI NARERRRMHD LNDALDELRA VIPYAHSPSV RKLSKIATLL LAKNYILMQA 
    QALEEMRRLV AYLNQGQAIS AASLPSSAAA AAAAAALHPA LGAYEQAAGY PFSAGLPPAA 
    SCPEKCALFN SVSSSLCKQC TEKP