Details for: PRRG1

Gene ID: 5638

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: PRRG1

Ensembl ID: ENSG00000130962

Description: proline rich and Gla domain 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 10.64
    rCSI 27.52%
    PRS 86.83
  • extravillous trophoblast CL0008036
    CSI 9.41
    rCSI 11.64%
    PRS 88.42
  • epithelial cell CL0000066
    CSI 7.06
    rCSI 10.85%
    PRS 78.41
  • retinal blood vessel endothelial cell CL0002585
    CSI 5.92
    rCSI 9.45%
    PRS 92.19
  • cardiac muscle cell CL0000746
    CSI 5.76
    rCSI 8.27%
    PRS 82.01
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 5.52
    rCSI 7.82%
    PRS 87.52
  • cerebral cortex endothelial cell CL1001602
    CSI 4.98
    rCSI 8.61%
    PRS 84.39
  • neural crest cell CL0011012
    CSI 3.82
    rCSI 3.02%
    PRS 82.67
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.79
    rCSI 6.7%
    PRS 76.02
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.7
    rCSI 4.05%
    PRS 91.33
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 3.67
    rCSI 11.47%
    PRS 79.61
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 3.6
    rCSI 12.96%
    PRS 74.49
  • stem cell CL0000034
    CSI 3.35
    rCSI 3.23%
    PRS 85.77
  • placental villous trophoblast CL2000060
    CSI 3.19
    rCSI 4.92%
    PRS 88.13
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.51
    rCSI 5.62%
    PRS 77
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.36
    rCSI 5.99%
    PRS 83.44
  • endocardial cell CL0002350
    CSI 2.35
    rCSI 11.26%
    PRS 86.2
  • renal interstitial pericyte CL1001318
    CSI 2.28
    rCSI 6.29%
    PRS 87.03
  • parietal epithelial cell CL1000452
    CSI 1.91
    rCSI 5.11%
    PRS 84.28
  • epithelial cell of proximal tubule CL0002306
    CSI 1.83
    rCSI 4.48%
    PRS 83.22
  • retina horizontal cell CL0000745
    CSI 1.45
    rCSI 2.21%
    PRS 86.71
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.42
    rCSI 5.37%
    PRS 76.8
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.42
    rCSI 2.28%
    PRS 77.59
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.34
    rCSI 4.18%
    PRS 77.97
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.33
    rCSI 3.18%
    PRS 79.22
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.31
    rCSI 3.19%
    PRS 74.37
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.19
    rCSI 3.9%
    PRS 78.16
  • direct pathway medium spiny neuron CL4023026
    CSI 1.13
    rCSI 26.94%
    PRS 74.18
  • indirect pathway medium spiny neuron CL4023029
    CSI 1
    rCSI 24.07%
    PRS 74.38
  • retinal ganglion cell CL0000740
    CSI 0.93
    rCSI 2.06%
    PRS 79.1
  • H2 horizontal cell CL0004218
    CSI 0.86
    rCSI 4.28%
    PRS 84.38
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.77
    rCSI 4.56%
    PRS 77.03

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 [PRRG1](/details-gene/5638), or Proline Rich and Gla Domain 1, encodes a transmembrane protein characterized by a gamma-carboxyglutamic acid (Gla) domain, which is crucial for calcium-dependent functions. Functional annotations strongly suggest its involvement in biological processes such as `[Blood coagulation](/details-go/GO:0007596)` and molecular activities including `[Calcium ion binding](/details-go/GO:0005509)`. Gene expression analysis reveals that **Overall**, [PRRG1](/details-gene/5638) is most significantly expressed in specialized epithelial and endothelial cells, particularly in the `[kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107)`, `[extravillous trophoblast](/details-cell/CL0008036)`, and various vascular endothelial cells. This expression pattern, combined with its molecular function, points toward a specialized role in tissues requiring active transport, barrier integrity, and vascular homeostasis. The initial discovery and characterization of this gene highlighted it as a novel proline-rich, Gla-containing protein [Link](https://doi.org/10.1073/pnas.94.17.9058). ## Cellular Roles and Expression Landscape The expression profile of [PRRG1](/details-gene/5638) indicates a highly specific set of cellular roles primarily outside the hematopoietic system. **Overall**, its most significant expression is observed in distinct epithelial lineages. It is a top marker for `[kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107)` (CSI: 10.64) and `[kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111)`, suggesting a fundamental role in renal physiology. Furthermore, its high significance in placental cells like `[extravillous trophoblast](/details-cell/CL0008036)` (CSI: 9.41) points to a function in fetal-maternal interface development and maintenance. A secondary but prominent site of [PRRG1](/details-gene/5638) expression is the vasculature, with high significance in `[retinal blood vessel endothelial cell](/details-cell/CL0002585)` (CSI: 5.92) and `[cerebral cortex endothelial cell](/details-cell/CL1001602)`. This, along with its high expression in `[cardiac muscle cell](/details-cell/CL0000746)` (CSI: 5.76), suggests a role in cardiovascular function and integrity. While also expressed in various neuronal subtypes and glial cells, such as `[caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064)` and `[astrocyte of the cerebral cortex](/details-cell/CL0002605)`, its significance scores are comparatively lower, indicating that its primary functions are likely concentrated in epithelial and endothelial tissues. ## Pathways and Molecular Function The functional annotations for [PRRG1](/details-gene/5638) are highly consistent with its structure as a Gla-domain containing protein. Its involvement in the `[Blood coagulation](/details-go/GO:0007596)` biological process is a key feature, as many vitamin K-dependent coagulation factors rely on their Gla domains for function. This is supported by its annotated molecular functions, which include `[Calcium ion binding](/details-go/GO:0005509)` and potential `[Serine-type endopeptidase activity](/details-go/GO:0004252)`, both of which are hallmarks of proteins in the coagulation cascade. Located at the `[Plasma membrane](/details-go/GO:0005886)` and in the `[Extracellular space](/details-go/GO:0005615)`, [PRRG1](/details-gene/5638) is positioned to interact with extracellular signaling molecules or components of the coagulation system. Its high expression in endothelial cells lining blood vessels is particularly relevant, suggesting it may act as a membrane-anchored factor that modulates local thrombotic events. In tissues like the kidney and heart, its `[Calcium ion binding](/details-go/GO:0005509)` capability may be more related to ion transport or cellular signaling processes critical for the function of those organs. ## Research Directions The specific expression patterns and functional annotations of [PRRG1](/details-gene/5638) raise several testable hypotheses regarding its precise physiological roles. 1. **Hypothesis 1 (Vascular Homeostasis):** Given its structural similarity to coagulation factors (Gla domain) and high expression in endothelial cells like `[retinal blood vessel endothelial cell](/details-cell/CL0002585)`, [PRRG1](/details-gene/5638) may function as a localized, membrane-bound modulator of the coagulation cascade, acting to promote or inhibit thrombosis at the endothelial surface under specific physiological or pathological conditions. 2. **Hypothesis 2 (Renal Function):** The exceptionally high and specific expression of [PRRG1](/details-gene/5638) in the `[kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107)` suggests it plays a critical, calcium-dependent role in ion transport or signaling, contributing to the maintenance of the renal concentration gradient necessary for water reabsorption. 3. **Hypothesis 3 (Placental Development):** The high significance of [PRRG1](/details-gene/5638) in `[extravillous trophoblast](/details-cell/CL0008036)` indicates it could be essential for proper placental implantation and uterine remodeling, possibly by mediating calcium-dependent cell-matrix interactions during trophoblast invasion. To investigate the role of [PRRG1](/details-gene/5638) in endothelial-mediated coagulation (Hypothesis 1), a targeted experiment could be designed. CRISPR-Cas9-mediated knockout of [PRRG1](/details-gene/5638) in a human endothelial cell line (e.g., HUVECs) would be a primary step. The functional consequences could then be assessed by measuring the kinetics of thrombin generation and fibrin clot formation on the surface of these cells in response to tissue factor stimulation. Co-immunoprecipitation followed by mass spectrometry could further identify its interacting partners at the plasma membrane, clarifying its position within the coagulation pathway. As a therapeutic target, [PRRG1](/details-gene/5638) presents a complex profile. Its nature as a transmembrane protein makes it accessible to antibody-based therapies, and its potential role in coagulation suggests it could be a target for managing thrombotic disorders. However, its significant expression in vital organs such as the kidney and heart raises concerns about potential on-target, off-tissue toxicities with systemic inhibition. Therefore, therapeutic strategies would likely require highly targeted approaches. Its clinical association with an X-linked syndromic disorder ([300935](https://omim.org/entry/300935)) further underscores the need to elucidate its fundamental developmental and physiological functions.

Genular Protein ID: 736371549

Symbol: TMG1_HUMAN

Name: Transmembrane gamma-carboxyglutamic acid protein 1

UniProtKB Accession Codes:

O14668 B2R7A3 C9JXL7 D3DWA9 Q5JT66

Database IDs:

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

Citations:

PubMed ID: 9256434

Title: Primary structure and tissue distribution of two novel proline-rich gamma-carboxyglutamic acid proteins.

PubMed ID: 9256434

DOI: 10.1073/pnas.94.17.9058

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 218
  • Mass: 24947
  • Checksum: 26538A61AB0AEB98
  • Sequence:
    • MGRVFLTGEK ANSILKRYPR ANGFFEEIRQ GNIERECKEE FCTFEEAREA FENNEKTKEF 
WSTYTKAQQG ESNRGSDWFQ FYLTFPLIFG LFIILLVIFL IWRCFLRNKT RRQTVTEGHI 
PFPQHLNIIT PPPPPDEVFD SSGLSPGFLG YVVGRSDSVS TRLSNCDPPP TYEEATGQVN 
LQRSETEPHL DPPPEYEDIV NSNSASAIPM VPVVTTIK

Genular Protein ID: 4163078259

Symbol: Q8NEK6_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8NEK6

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 3 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 2 SAM 2 SMART 1 SUPFAM 1

Citations:

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: 266
  • Mass: 30151
  • Checksum: 175768D24D635351
  • Sequence:
    • VRSRFLAPAR LGRNRSAQAR RAARRTASSG AGPAGIIIQG RARNHKKTWG RVFLTGEKAN 
SILKRYPRAN GFFEEIRQGN IERECKEEFC TFEEAREAFE NNEKTKEFWS TYTKAQQGES 
NRGSDWFQFY LTFPLIFGLF IILLVIFLIW RCFLRNKTRR QTVTEGHIPF PQHLNIITPP 
PPPDEVFDSS GLSPGFLGYV VGRSDSVSTR LSNCDPPPTY EEATGQVNLQ RSETEPHLDP 
PPEYEDIVNS NSASAIPMVP VVTTIK