Details for: PIGQ

Gene ID: 9091

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: PIGQ

Ensembl ID: ENSG00000007541

Description: phosphatidylinositol glycan anchor biosynthesis class Q

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • mature astrocyte CL0002627
    CSI 4.13
    rCSI 17.53%
    PRS 90.32
  • renal principal cell CL0005009
    CSI 3.85
    rCSI 10.01%
    PRS 94.52
  • epithelial cell of lung CL0000082
    CSI 3.49
    rCSI 2.89%
    PRS 95.93
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 3
    rCSI 7.82%
    PRS 96.32
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.97
    rCSI 4.21%
    PRS 93.8
  • neural progenitor cell CL0011020
    CSI 2.93
    rCSI 12.88%
    PRS 86.63
  • erythrocyte CL0000232
    CSI 2.88
    rCSI 6.53%
    PRS 93.28
  • renal alpha-intercalated cell CL0005011
    CSI 2.76
    rCSI 3.69%
    PRS 96.57
  • lung ciliated cell CL1000271
    CSI 2.7
    rCSI 3.12%
    PRS 91.17
  • choroid plexus epithelial cell CL0000706
    CSI 2.66
    rCSI 4.36%
    PRS 90.53
  • ciliated epithelial cell CL0000067
    CSI 2.62
    rCSI 2.3%
    PRS 88.7
  • ionocyte CL0005006
    CSI 2.51
    rCSI 2.69%
    PRS 95.79
  • renal beta-intercalated cell CL0002201
    CSI 2.27
    rCSI 5.41%
    PRS 95.18
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.21
    rCSI 5.72%
    PRS 93.52
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.19
    rCSI 1.89%
    PRS 96.13
  • erythroblast CL0000765
    CSI 2.17
    rCSI 5.75%
    PRS 94.92
  • ciliated cell CL0000064
    CSI 2.11
    rCSI 3.42%
    PRS 89.97
  • epithelial cell of proximal tubule CL0002306
    CSI 2.08
    rCSI 5.09%
    PRS 90.47
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.08
    rCSI 2.68%
    PRS 87.83
  • multi-ciliated epithelial cell CL0005012
    CSI 2.06
    rCSI 2.05%
    PRS 90.86
  • mesenchymal cell CL0008019
    CSI 2.03
    rCSI 5.15%
    PRS 92.2
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.03
    rCSI 2.52%
    PRS 84.95
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.99
    rCSI 6.22%
    PRS 87.85
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.88
    rCSI 3.32%
    PRS 86.4
  • peripheral nervous system neuron CL2000032
    CSI 1.83
    rCSI 2.5%
    PRS 90.74
  • primitive red blood cell CL0002355
    CSI 1.78
    rCSI 9.58%
    PRS 95.5
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.68
    rCSI 3.78%
    PRS 87.1
  • retinal cone cell CL0000573
    CSI 1.5
    rCSI 2.41%
    PRS 89.33
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.39
    rCSI 3.34%
    PRS 87.8
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.34
    rCSI 3.39%
    PRS 91.61
  • amacrine cell CL0000561
    CSI 1.31
    rCSI 3.79%
    PRS 89.28
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.16
    rCSI 2.83%
    PRS 85.05
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.16
    rCSI 6.85%
    PRS 87.31
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.13
    rCSI 2.57%
    PRS 89.28
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.8
    rCSI 2.88%
    PRS 85.36

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 [PIGQ](/details-gene/9091) (Phosphatidylinositol Glycan Anchor Biosynthesis Class Q) is a protein-coding gene located on chromosome 16p13.3. It encodes a crucial component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex, which catalyzes the first step in the biosynthesis of GPI anchors. These anchors are essential for tethering a wide array of proteins to the cell surface. Consistent with this fundamental "housekeeping" role, [PIGQ](/details-gene/9091) shows significant expression across a diverse range of cell types, including [mature astrocyte](/details-cell/CL0002627), various epithelial cells such as [renal principal cell](/details-cell/CL0005009), and hematopoietic cells like [erythrocyte](/details-cell/CL0000232). Mutations in [PIGQ](/details-gene/9091) are associated with inherited GPI deficiencies, a class of congenital disorders often characterized by severe neurological symptoms, including epilepsy and developmental delay [Link](https://doi.org/10.1002/ajmg.a.61185). ## Cellular Roles and Expression Landscape The expression profile of [PIGQ](/details-gene/9091) highlights its essential role in a broad spectrum of cell lineages, rather than being a marker for a specific cell type. * **Broad Functional Importance:** **Overall**, the gene exhibits high significance in functionally diverse and metabolically active cells. This includes glial cells of the central nervous system ([mature astrocyte](/details-cell/CL0002627), CSI: 4.13; [neural progenitor cell](/details-cell/CL0011020), CSI: 2.93), specialized epithelial cells responsible for transport and barrier functions in the kidney ([renal principal cell](/details-cell/CL0005009), CSI: 3.85) and lung ([epithelial cell of lung](/details-cell/CL0000082), CSI: 3.49), and hematopoietic lineages ([erythrocyte](/details-cell/CL0000232), CSI: 2.88; [granulocyte monocyte progenitor cell](/details-cell/CL0000557), CSI: 2.19). * **Widespread Housekeeping Function:** The high significance scores across these varied cell types suggest that the GPI anchor biosynthesis pathway, and [PIGQ](/details-gene/9091)'s role within it, is a fundamental requirement for normal cellular function. Its presence in both progenitor cells and terminally differentiated cells underscores its importance throughout cellular development and maintenance. The diversity of top-ranked cells, from immune to neural to epithelial, points towards a core role in post-translational protein modification that is broadly utilized by many cellular systems. ## Pathways and Molecular Function [PIGQ](/details-gene/9091)'s molecular function is well-defined and centers on the initial stages of protein modification in the endoplasmic reticulum. * **GPI-GnT Complex Component:** [PIGQ](/details-gene/9091) (also known as GPI1) is an integral subunit of the multi-protein GPI-GnT complex ([GO:0000506](https://www.ebi.ac.uk/QuickGO/term/GO:0000506)), which resides in the [endoplasmic reticulum membrane](/details-cell/GO:0005789). This complex initiates the [Gpi anchor biosynthetic process](/details-cell/GO:0006506) by transferring N-acetylglucosamine (GlcNAc) to phosphatidylinositol (PI). Research has established that this first step is mediated by a core complex including PIG-A, PIG-H, PIG-C, and [PIGQ](/details-gene/9091) (GPI1) [Link](https://doi.org/10.1093/emboj/17.4.877). * **Role in Post-Translational Modification:** This activity is the committing step in the [Synthesis of glycosylphosphatidylinositol (gpi)](https://reactome.org/content/detail/R-HSA-162710) pathway. The completed GPI anchor is subsequently attached to the C-terminus of select proteins, a critical form of [Post-translational protein modification](/details-cell/R-HSA-597592). This process is vital for the correct localization and function of numerous cell surface proteins, including enzymes, adhesion molecules, and receptors. ## Research Directions The ubiquitous nature of [PIGQ](/details-gene/9091) and the severe consequences of its dysfunction present several avenues for future investigation. **Proposed Hypotheses:** 1. Given the high significance of [PIGQ](/details-gene/9091) in [mature astrocyte](/details-cell/CL0002627) and the strong association of its deficiency with epilepsy [Link](https://doi.org/10.1093/hmg/ddu030), we hypothesize that an astrocyte-specific defect in GPI-anchor synthesis disrupts the surface localization of key proteins involved in neurotransmitter homeostasis (e.g., glutamate transporters) or ion buffering, leading to network hyperexcitability and seizure generation. 2. The high expression in renal epithelial cells ([renal principal cell](/details-cell/CL0005009), [ionocyte](/details-cell/CL0005006)) suggests that subclinical renal dysfunction may be an underappreciated aspect of [PIGQ](/details-gene/9091)-related disorders. We hypothesize that impaired expression of GPI-anchored proteins in the kidney, such as specific water channels or cell adhesion molecules, compromises renal tubular function and contributes to the systemic pathology observed in patients. **Suggested Experimental Approach:** To test the first hypothesis regarding the role of [PIGQ](/details-gene/9091) in astrocytes, a conditional knockout mouse model could be generated using the Cre-lox system with an astrocyte-specific promoter (e.g., GFAP-Cre) to delete [PIGQ](/details-gene/9091) specifically in this cell type. The resulting mice could be monitored via continuous electroencephalography (EEG) to assess for spontaneous seizure activity. Furthermore, primary astrocytes could be cultured from these mice and subjected to cell surface proteomics to identify which specific GPI-anchored proteins fail to localize to the plasma membrane, followed by functional assays to measure glutamate uptake or potassium buffering capacity. **Therapeutic Potential:** As [PIGQ](/details-gene/9091) is a critical component of a fundamental biosynthetic pathway, its associated diseases are loss-of-function disorders. Therefore, therapeutic strategies would not involve inhibition. Instead, the gene represents a potential candidate for **activation** or replacement strategies. For monogenic PIGQ-deficiency disorders, gene therapy aiming to restore a functional copy of the gene in affected cell types, particularly in the central nervous system, presents a potential long-term therapeutic avenue. However, the widespread expression of the gene presents significant challenges for systemic delivery and controlling expression levels, making this a complex but potentially high-impact therapeutic goal.

Genular Protein ID: 2449152123

Symbol: PIGQ_HUMAN

Name: N-acetylglucosamyl transferase component GPI1

UniProtKB Accession Codes:

Q9BRB3 A2IDE1 D3DU52 O14927 Q96G00 Q96S22 Q9UJH4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 4 ExpressionAtlas 1 GO 5 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 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 3 RNAct 1 Reactome 1 RefSeq 2 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9729469

Title: Human and mouse Gpi1p homologues restore glycosylphosphatidylinositol membrane anchor biosynthesis in yeast mutants.

PubMed ID: 9729469

DOI: 10.1042/bj3340609

PubMed ID: 9463366

Title: The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1.

PubMed ID: 9463366

DOI: 10.1093/emboj/17.4.877

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

PubMed ID: 10944123

Title: Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2.

PubMed ID: 10944123

DOI: 10.1093/emboj/19.16.4402

PubMed ID: 16162815

Title: The initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-Y, a seventh component.

PubMed ID: 16162815

DOI: 10.1091/mbc.e05-08-0743

PubMed ID: 24463883

Title: Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis.

PubMed ID: 24463883

DOI: 10.1093/hmg/ddu030

PubMed ID: 25558065

Title: Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.

PubMed ID: 25558065

DOI: 10.1016/j.celrep.2014.12.015

PubMed ID: 27513193

Title: Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnosed diseases.

PubMed ID: 27513193

DOI: 10.1038/gim.2016.95

PubMed ID: 29388939

Title:

PubMed ID: 29388939

DOI: 10.1038/gim.2017.263

PubMed ID: 31148362

Title: PIGQ glycosylphosphatidylinositol-anchored protein deficiency: Characterizing the phenotype.

PubMed ID: 31148362

DOI: 10.1002/ajmg.a.61185

Sequence Information:

  • Length: 760
  • Mass: 84082
  • Checksum: DBF900ADCE08DA98
  • Sequence:
    • MVLKAFFPTC CVSTDSGLLV GRWVPEQSSA VVLAVLHFPF IPIQVKQLLA QVRQASQVGV 
AVLGTWCHCR QEPEESLGRF LESLGAVFPH EPWLRLCRER GGTFWSCEAT HRQAPTAPGA 
PGEDQVMLIF YDQRQVLLSQ LHLPTVLPDR QAGATTASTG GLAAVFDTVA RSEVLFRSDR 
FDEGPVRLSH WQSEGVEASI LAELARRASG PICLLLASLL SLVSAVSACR VFKLWPLSFL 
GSKLSTCEQL RHRLEHLTLI FSTRKAENPA QLMRKANTVA SVLLDVALGL MLLSWLHGRS 
RIGHLADALV PVADHVAEEL QHLLQWLMGA PAGLKMNRAL DQVLGRFFLY HIHLWISYIH 
LMSPFVEHIL WHVGLSACLG LTVALSLLSD IIALLTFHIY CFYVYGARLY CLKIHGLSSL 
WRLFRGKKWN VLRQRVDSCS YDLDQLFIGT LLFTILLFLL PTTALYYLVF TLLRLLVVAV 
QGLIHLLVDL INSLPLYSLG LRLCRPYRLA DKPTALQPRG AHLPPPQLWL PPQALLGRPV 
PQAVPWGAHL PLEAERGQAG LRELLARLAP PHGHSQPSAL PGWHQLSWRM SCALWTLLCA 
PEHGRPCYHT LGLEVIGSEQ MWGWPARLAA LHHWHCLPWD PLPTCCGHHG GEHSNPRCPE 
HCPMPTLCTQ VQRVRPPQQP QVEGWSPWGL PSGSALAVGV EGPCQDEPPS PRHPLAPSAE 
QHPASGGLKQ SLTPVPSGPG PSLPEPHGVY LRMFPGEVAL

Genular Protein ID: 3628813947

Symbol: B2RAU6_HUMAN

Name: N/A

UniProtKB Accession Codes:

B2RAU6

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 InterPro 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1

Sequence Information:

  • Length: 581
  • Mass: 65314
  • Checksum: 4315A6E114B16619
  • Sequence:
    • MVLKAFFPTC CVSADSGLLV GRWVPEQSSA VVLAVLHFPF IPIQVKQLLA QVRQASQVGV 
AVLGTWCHCR QEPEESLGRF LESLGAVFPH EPWLRLCRER GGTFWSCEAT HRQAPTAPGA 
PGEDQVMLIF YDQRQVLLSQ LHLPTVLPDR QAGATTASTG GLAAVFDTVA RSEVLFRSDR 
FDEGPVRLSH WQSEGVEASI LAELARRASG PICLLLASLL SLVSAVSACR VFKLWPLSFL 
GSKLSTCEQL RHRLEHLTLI FSTRKAENPA QLMRKANTVA SVLLDVALGL MLLSWLHGRS 
RIGHLADALV PVADHVAEEL QHLLQWLMGA PAGLKMNRAL DQVLGRFFLY HIHLWISYIH 
LMSPFVEHIL WHVGLSACLG LTVALSLLSD IIALLTFHIY CFYVYGARLY CLKIHGLSSL 
WRLFRGKKWN VLRQRVDSCS YDLDQLFIGT LLFTILLFLL PTTALYYLVF TLLRLLVVAV 
QGLIHLLVDL INSLPLYSLG LRLCRPYRLA AGVKFRVLRH EAGRPLRLLM QINPLPYSRV 
VHTYRLPSCG CHPKHSWGAL CRKLFLGELI YPWRQRGDKQ D