Details for: HAND1

Gene ID: 9421

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: HAND1

Ensembl ID: ENSG00000113196

Description: heart and neural crest derivatives expressed 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • enteric smooth muscle cell CL0002504
    CSI 31.17
    rCSI 44.49%
    PRS 99.47
  • mesodermal cell CL0000222
    CSI 26.22
    rCSI 31.47%
    PRS 99.65
  • interstitial cell of Cajal CL0002088
    CSI 14.38
    rCSI 18.31%
    PRS 99.75
  • myofibroblast cell CL0000186
    CSI 10.27
    rCSI 14.22%
    PRS 99.04
  • basal cell of epidermis CL0002187
    CSI 6.48
    rCSI 11.48%
    PRS 89.27
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 4.56
    rCSI 5.53%
    PRS 92.08
  • helper T cell CL0000912
    CSI 2.68
    rCSI 3.79%
    PRS 97.14
  • suprabasal keratinocyte CL4033013
    CSI 1.96
    rCSI 3.2%
    PRS 91.05
  • melanocyte of skin CL1000458
    CSI 1.28
    rCSI 1.75%
    PRS 90.79

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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  • 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 [HAND1](/details-gene/9421) (Heart and Neural Crest Derivatives Expressed 1) is a protein-coding gene that encodes a basic helix-loop-helix (bHLH) transcription factor. This protein is a critical regulator of embryonic development, particularly in the formation of the heart and derivatives of the neural crest. Its function is primarily associated with cardiovascular morphogenesis, mesoderm differentiation, and trophectodermal cell lineage commitment. **Overall**, expression data reveals that [HAND1](/details-gene/9421) is most significantly expressed in cells of mesenchymal origin, with the highest significance observed in [enteric smooth muscle cell](/details-cell/CL0002504) and [mesodermal cell](/details-cell/CL0000222), underscoring its role in the development and identity of these lineages. Early research established its tissue-restricted expression in cytotrophoblastic cells and the developing heart ([Link](https://doi.org/10.1016/s0378-1119(98)00511-3)). ## Cellular Roles and Expression Landscape The expression profile of [HAND1](/details-gene/9421) highlights its fundamental role in establishing and maintaining the identity of specific mesenchymal and smooth muscle cell populations. **Overall**, the gene shows the highest significance in [enteric smooth muscle cell](/details-cell/CL0002504) (CSI: 31.17) and its developmental precursors, [mesodermal cell](/details-cell/CL0000222)s (CSI: 26.22), suggesting it is a key determinant of the visceral smooth muscle lineage. This is further supported by its high significance in related cell types such as [interstitial cell of Cajal](/details-cell/CL0002088) and [myofibroblast cell](/details-cell/CL0000186), which are involved in gut motility and tissue remodeling, respectively. Beyond the gastrointestinal system, [HAND1](/details-gene/9421) also shows notable significance in epidermal lineages, including [basal cell of epidermis](/details-cell/CL0002187) and [suprabasal keratinocyte](/details-cell/CL4033013), which may relate to its broader function in ectodermal and mesodermal development. Lower but still significant expression is observed in some immune cell subsets like [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) and [helper T cell](/details-cell/CL0000912), though its function in these mature hematopoietic cells remains less defined compared to its well-established developmental roles. ## Pathways and Molecular Function [HAND1](/details-gene/9421) functions as a sequence-specific DNA-binding protein located in the [nucleus](/details-cell/GO:0005634), where it can act as both a transcriptional activator ([GO:0001228](https://www.ebi.ac.uk/QuickGO/term/GO:0001228)) and repressor ([GO:0001227](https://www.ebi.ac.uk/QuickGO/term/GO:0001227)), indicating a context-dependent regulatory role. Its molecular activities include forming homodimers ([GO:0042803](https://www.ebi.ac.uk/QuickGO/term/GO:0042803)) and binding to other bHLH transcription factors ([GO:0043425](https://www.ebi.ac.uk/QuickGO/term/GO:0043425)) to modulate gene expression programs. The biological processes associated with [HAND1](/details-gene/9421) are predominantly developmental. It is a central component of the [Cardiogenesis](/details-pathway/R-HSA-9733709) pathway and is involved in multiple facets of heart formation, including [Heart looping](/details-cell/GO:0001947), [Cardiac septum morphogenesis](/details-cell/GO:0060411), and the formation of both the left ([GO:0003218](https://www.ebi.ac.uk/QuickGO/term/GO:0003218)) and right ([GO:0003219](https://www.ebi.ac.uk/QuickGO/term/GO:0003219)) ventricles. Its high expression in [mesodermal cell](/details-cell/CL0000222)s is consistent with its involvement in [Mesenchyme development](/details-cell/GO:0060485) and [Mesoderm formation](/details-cell/GO:0001707). Furthermore, its role extends to early embryogenesis, impacting [Trophectodermal cell differentiation](/details-cell/GO:0001829) and [Blastocyst development](/details-cell/GO:0001824). ## Research Directions While the developmental role of [HAND1](/details-gene/9421) is well-documented, its high significance in mature cell types like [enteric smooth muscle cell](/details-cell/CL0002504) and [myofibroblast cell](/details-cell/CL0000186) suggests ongoing functions in tissue homeostasis and pathology. The following hypotheses could guide future research: 1. **[HAND1](/details-gene/9421) is essential for maintaining the differentiated phenotype and contractile function of mature enteric smooth muscle cells.** Its exceptionally high significance in this cell type suggests a role beyond development, possibly in regulating the expression of contractile proteins and ion channels necessary for gut peristalsis. 2. **Dysregulation of [HAND1](/details-gene/9421) in myofibroblasts is a key driver of pathological fibrosis.** Given its high significance in [myofibroblast cell](/details-cell/CL0000186)s and its developmental role in mesenchymal tissues, it is plausible that its re-activation or altered function contributes to fibrotic diseases in organs such as the heart, lung, or liver by promoting excessive extracellular matrix deposition. A compelling experimental approach to test the second hypothesis would be to investigate its role in cardiac fibrosis. Using a mouse model of cardiac injury (e.g., myocardial infarction or pressure overload), one could employ a conditional knockout or AAV-mediated shRNA knockdown of [HAND1](/details-gene/9421) specifically in cardiac fibroblasts. The impact on myofibroblast activation (e.g., α-SMA expression), collagen production, and overall cardiac function (assessed by echocardiography) could then be quantified to determine if targeting [HAND1](/details-gene/9421) mitigates the fibrotic response. From a therapeutic standpoint, [HAND1](/details-gene/9421) presents a potential target for anti-fibrotic therapies. As fibrosis involves the over-activity of myofibroblasts, **inhibition** of [HAND1](/details-gene/9421) function would be the likely therapeutic strategy. However, as a nuclear transcription factor, it represents a challenging drug target for small molecules. Novel therapeutic modalities, such as antisense oligonucleotides or siRNAs designed to reduce its expression in affected tissues, could offer a more viable path forward. The relatively restricted expression profile of [HAND1](/details-gene/9421) to specific mesenchymal lineages may help minimize off-target effects.

Genular Protein ID: 2093522430

Symbol: HAND1_HUMAN

Name: Heart- and neural crest derivatives-expressed protein 1

UniProtKB Accession Codes:

O96004

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 GO 39 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 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 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9931445

Title: Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted expression in cytotrophoblastic cells and heart.

PubMed ID: 9931445

DOI: 10.1016/s0378-1119(98)00511-3

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: 215
  • Mass: 23627
  • Checksum: 7ED98EA081A8D6BA
  • Sequence:
    • MNLVGSYAHH HHHHHPHPAH PMLHEPFLFG PASRCHQERP YFQSWLLSPA DAAPDFPAGG 
PPPAAAAAAT AYGPDARPGQ SPGRLEALGG RLGRRKGSGP KKERRRTESI NSAFAELREC 
IPNVPADTKL SKIKTLRLAT SYIAYLMDVL AKDAQSGDPE AFKAELKKAD GGRESKRKRE 
LQQHEGFPPA LGPVEKRIKG RTGWPQQVWA LELNQ