Details for: GINS3

Gene ID: 64785

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: GINS3

Ensembl ID: ENSG00000181938

Description: GINS complex subunit 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • conventional dendritic cell CL0000990
    CSI 31.89
    rCSI 26.62%
    PRS 98.22
  • regulatory T cell CL0000815
    CSI 26.54
    rCSI 30.76%
    PRS 98.21
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 22.53
    rCSI 27.3%
    PRS 96.04
  • helper T cell CL0000912
    CSI 21.01
    rCSI 29.71%
    PRS 98.7
  • mast cell CL0000097
    CSI 17.23
    rCSI 37.21%
    PRS 97.7
  • innate lymphoid cell CL0001065
    CSI 17.15
    rCSI 35.41%
    PRS 98.7
  • chondrocyte CL0000138
    CSI 16.8
    rCSI 26.72%
    PRS 99.1
  • Schwann cell CL0002573
    CSI 15.83
    rCSI 45.01%
    PRS 99.75
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 10.02
    rCSI 11.57%
    PRS 99.58
  • cardiac neuron CL0010022
    CSI 9.86
    rCSI 31.54%
    PRS 99.81
  • basal cell of epidermis CL0002187
    CSI 9.28
    rCSI 16.44%
    PRS 94.67
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 6.62
    rCSI 12.04%
    PRS 99.76
  • large pre-B-II cell CL0000957
    CSI 5.29
    rCSI 15.1%
    PRS 99.7
  • melanocyte of skin CL1000458
    CSI 5.12
    rCSI 6.98%
    PRS 95.97
  • cytotoxic T cell CL0000910
    CSI 4.17
    rCSI 23.9%
    PRS 98.85
  • enteroglial cell CL4040002
    CSI 4.07
    rCSI 21.39%
    PRS 99.69
  • suprabasal keratinocyte CL4033013
    CSI 3.25
    rCSI 5.31%
    PRS 96.23

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)

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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 [GINS3](/details-gene/64785) (GINS complex subunit 3), also known as PSF3, is a protein-coding gene located on chromosome 16q21. It is an essential component of the GINS complex, which, together with CDC45 and the Mcm2-7 helicase, forms the active replicative helicase CMG (CDC45-Mcm2-7-GINS) ([Link](https://doi.org/10.1038/sj.embor.7401002)). This complex is fundamental for the initiation and elongation phases of DNA replication during the S phase of the cell cycle ([Link](https://doi.org/10.1038/sj.embor.7400870)). Consistent with its core role in cell proliferation, [GINS3](/details-gene/64785) shows significant expression in highly proliferative cell types, particularly within the immune system, such as [conventional dendritic cell](/details-cell/CL0000990) and [regulatory T cell](/details-cell/CL0000815), as well as in other dividing populations like [chondrocyte](/details-cell/CL0000138) and [basal cell of epidermis](/details-cell/CL0002187). ## Cellular Roles and Expression Landscape The expression profile of [GINS3](/details-gene/64785) underscores its universal importance in cell division across diverse lineages. **Overall**, the gene exhibits its highest significance in cell types characterized by high rates of proliferation. This is particularly evident in the immune system, with top-ranking cells including [conventional dendritic cell](/details-cell/CL0000990) (CSI: 31.89), [regulatory T cell](/details-cell/CL0000815) (CSI: 26.54), [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 22.53), [helper T cell](/details-cell/CL0000912) (CSI: 21.01), and [mast cell](/details-cell/CL0000097) (CSI: 17.23). This pattern suggests that [GINS3](/details-gene/64785) is a critical facilitator of clonal expansion and immune surveillance. Beyond the immune compartment, [GINS3](/details-gene/64785) is also a significant marker in other proliferative populations. Its high CSI in [chondrocyte](/details-cell/CL0000138) (CSI: 16.80), [Schwann cell](/details-cell/CL0002573) (CSI: 15.83), [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) (CSI: 10.02), and [basal cell of epidermis](/details-cell/CL0002187) (CSI: 9.28) highlights its general role as a core component of the replication machinery required for tissue development, maintenance, and repair. The broad expression in these varied progenitor and actively cycling cells, as opposed to terminally differentiated, non-dividing cells, reinforces its specialized function in DNA synthesis rather than cell-type-specific identity. ## Pathways and Molecular Function The functional annotations for [GINS3](/details-gene/64785) align precisely with its role as a core component of the DNA replisome. It is a key player in the Reactome pathway [Dna replication (R-HSA-69306)](https://reactome.org/content/detail/R-HSA-69306), participating in critical sub-processes such as [Unwinding of dna (R-HSA-176974)](https://reactome.org/content/detail/R-HSA-176974) and [Dna strand elongation (R-HSA-69190)](https://reactome.org/content/detail/R-HSA-69190). These activities are central to the [S phase (R-HSA-69242)](https://reactome.org/content/detail/R-HSA-69242) of the mitotic cell cycle. Gene Ontology annotations further specify its molecular activities. [GINS3](/details-gene/64785) is integral to the [Gins complex (GO:0000811)](https://www.ebi.ac.uk/QuickGO/term/GO:0000811) and the larger [Cmg complex (GO:0071162)](https://www.ebi.ac.uk/QuickGO/term/GO:0071162), both localized to the [Nucleus (GO:0005634)](https://www.ebi.ac.uk/QuickGO/term/GO:0005634). Its primary biological process is annotated as [Dna unwinding involved in dna replication (GO:0006268)](https://www.ebi.ac.uk/QuickGO/term/GO:0006268). Multiple structural and functional studies have confirmed that the GINS complex is essential for the assembly and function of the CMG helicase, which unwinds the DNA duplex ahead of the replication fork ([Link](https://doi.org/10.1073/pnas.0705558104), [Link](https://doi.org/10.1038/nsmb1231)). Deficiencies in other GINS subunits have been linked to severe human diseases, including growth retardation and immunodeficiency, highlighting the critical, non-redundant role of the complex ([Link](https://doi.org/10.1172/jci90727)). ## Research Directions The essential and ubiquitous role of [GINS3](/details-gene/64785) in cell proliferation opens several avenues for future investigation, particularly concerning its regulation in health and disease. **Proposed Hypotheses:** 1. The high significance of [GINS3](/details-gene/64785) in diverse lymphocyte populations, including [regulatory T cell](/details-cell/CL0000815) and memory T cells, suggests that its transcriptional or post-translational regulation is a critical checkpoint for controlling the magnitude and duration of an adaptive immune response. Fine-tuning [GINS3](/details-gene/64785) levels may be a mechanism to balance effective immunity with the prevention of autoimmunity. 2. Given that many cancers exhibit replicative stress and dependency on DNA replication and repair pathways, tumor cells may be exceptionally sensitive to partial inhibition of [GINS3](/details-gene/64785) function. This dependency could create a therapeutic window where cancer cells are selectively targeted over healthy, proliferating cells. **Experimental Approach:** To test the first hypothesis regarding immune regulation, a conditional knockout mouse model could be generated. Specifically, crossing a `GINS3-fl/fl` mouse with a strain expressing Cre recombinase under a cell-type-specific promoter (e.g., `CD4-Cre` for helper T cells or `Foxp3-Cre` for regulatory T cells) would allow for targeted deletion of [GINS3](/details-gene/64785). The subsequent impact on T cell development, proliferation following antigen stimulation, and effector or suppressor function could be assessed using flow cytometry, in vitro proliferation assays (e.g., CFSE dilution), and in vivo models of infection or autoimmunity. **Therapeutic Potential:** As a core component of the DNA replication machinery, [GINS3](/details-gene/64785) represents a compelling target for anti-proliferative therapies, particularly in oncology. **Inhibition** of its function would theoretically halt cell division, making it a powerful strategy against rapidly dividing cancer cells. However, its essential role in all proliferating cells (e.g., hematopoietic stem cells, gut epithelium) poses a significant risk of on-target toxicity. The development of a successful therapeutic would likely require either a highly specific small molecule inhibitor with a favorable therapeutic index or a sophisticated delivery system (e.g., antibody-drug conjugate) to target the inhibitor specifically to tumor cells.

Genular Protein ID: 3376924009

Symbol: PSF3_HUMAN

Name: DNA replication complex GINS protein PSF3

UniProtKB Accession Codes:

Q9BRX5 B2RDP3 E9PB21 Q9H870

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 2 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 EMDB 5 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 9 PDBsum 9 PRO 1 PathwayCommons 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 1 RefSeq 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 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: 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

PubMed ID: 17170760

Title: The human GINS complex binds to and specifically stimulates human DNA polymerase alpha-primase.

PubMed ID: 17170760

DOI: 10.1038/sj.embor.7400870

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 28414293

Title: Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency.

PubMed ID: 28414293

DOI: 10.1172/jci90727

PubMed ID: 35585232

Title: Fast and efficient DNA replication with purified human proteins.

PubMed ID: 35585232

DOI: 10.1038/s41586-022-04759-1

PubMed ID: 17557111

Title: Molecular architecture of the human GINS complex.

PubMed ID: 17557111

DOI: 10.1038/sj.embor.7401002

PubMed ID: 17545466

Title: Crystal structure of the human GINS complex.

PubMed ID: 17545466

DOI: 10.1101/gad.1548107

PubMed ID: 17417653

Title: Structure of the human GINS complex and its assembly and functional interface in replication initiation.

PubMed ID: 17417653

DOI: 10.1038/nsmb1231

PubMed ID: 17652513

Title: Crystal structure of the GINS complex and functional insights into its role in DNA replication.

PubMed ID: 17652513

DOI: 10.1073/pnas.0705558104

PubMed ID: 32453425

Title: CryoEM structures of human CMG-ATPgammaS-DNA and CMG-AND-1 complexes.

PubMed ID: 32453425

DOI: 10.1093/nar/gkaa429

PubMed ID: 34700328

Title: A conserved mechanism for regulating replisome disassembly in eukaryotes.

PubMed ID: 34700328

DOI: 10.1038/s41586-021-04145-3

PubMed ID: 34694004

Title: Structure of a human replisome shows the organisation and interactions of a DNA replication machine.

PubMed ID: 34694004

DOI: 10.15252/embj.2021108819

Sequence Information:

  • Length: 216
  • Mass: 24535
  • Checksum: A1B264A72371C551
  • Sequence:
    • MSEAYFRVES GALGPEENFL SLDDILMSHE KLPVRTETAM PRLGAFFLER SAGAETDNAV 
PQGSKLELPL WLAKGLFDNK RRILSVELPK IYQEGWRTVF SADPNVVDLH KMGPHFYGFG 
SQLLHFDSPE NADISQSLLQ TFIGRFRRIM DSSQNAYNED TSALVARLDE MERGLFQTGQ 
KGLNDFQCWE KGQASQITAS NLVQNYKKRK FTDMED

Genular Protein ID: 3295555172

Symbol: A0A0S2Z5P2_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0S2Z5P2

Database IDs:

ARBA 5 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CDD 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 GO 3 Gene3D 1 InterPro 4 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 Pfam 2 PhylomeDB 1 RefSeq 1 RuleBase 1 SMR 1 SUPFAM 2 VEuPathDB 1

Citations:

PubMed ID: 26871637

Title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

PubMed ID: 26871637

DOI: 10.1016/j.cell.2016.01.029

Sequence Information:

  • Length: 255
  • Mass: 28775
  • Checksum: 99614F114B6B6CF1
  • Sequence:
    • MSEAYFRVES GALGPEENFL SLDDILMSHE KLPVRTETAM PRLGAFFLER SAGAETDNAV 
PQGFALLPRL ECSGVIWLTA ALTSQAPEIL PPQPPMWLVL QGSKLELPLW LAKGLFDNKR 
RILSVELPKI YQEGWRTVFS ADPNVVDLHK MGPHFYGFGS QLLHFDSPEN ADISQSLLQT 
FIGRFRRIMD SSQNAYNEDT SALVARLDEM ERGLFQTGQK GLNDFQCWEK GQASQITASN 
LVQNYKKRKF TDMED

Genular Protein ID: 925861789

Symbol: A0A0S2Z5L4_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0S2Z5L4

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 GO 3 Gene3D 1 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 RefSeq 1 RuleBase 1 SMR 1 SUPFAM 2 VEuPathDB 1

Citations:

PubMed ID: 26871637

Title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

PubMed ID: 26871637

DOI: 10.1016/j.cell.2016.01.029

Sequence Information:

  • Length: 138
  • Mass: 15655
  • Checksum: 50D249B01A5F66EE
  • Sequence:
    • MSEAYFRVES GALGPEENFL SLDDILMSHE KLPVRTETAM PRLGAFFLER SAGAETDNAV 
PQTFIGRFRR IMDSSQNAYN EDTSALVARL DEMERGLFQT GQKGLNDFQC WEKGQASQIT 
ASNLVQNYKK RKFTDMED