Details for: GATC

Gene ID: 283459

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: GATC

Ensembl ID: ENSG00000257218

Description: glutamyl-tRNA amidotransferase subunit C

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 6.75
    rCSI 8.06%
    PRS 84.55
  • multi-ciliated epithelial cell CL0005012
    CSI 6.2
    rCSI 6.19%
    PRS 89.35
  • type B pancreatic cell CL0000169
    CSI 3.78
    rCSI 8.36%
    PRS 93.87
  • mucosal invariant T cell CL0000940
    CSI 3.7
    rCSI 2.99%
    PRS 97.13
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 3.61
    rCSI 4.36%
    PRS 97.17
  • neural crest cell CL0011012
    CSI 3.49
    rCSI 2.76%
    PRS 89.02
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.33
    rCSI 5.89%
    PRS 83.98
  • stem cell CL0000034
    CSI 3.17
    rCSI 3.05%
    PRS 91.29
  • early lymphoid progenitor CL0000936
    CSI 3.12
    rCSI 2.74%
    PRS 96.19
  • ionocyte CL0005006
    CSI 3.04
    rCSI 3.25%
    PRS 94.88
  • perivascular cell CL4033054
    CSI 3.03
    rCSI 4.14%
    PRS 96.2
  • interneuron CL0000099
    CSI 2.98
    rCSI 5.99%
    PRS 89.61
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.93
    rCSI 2.27%
    PRS 95.76
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.81
    rCSI 3.5%
    PRS 82.45
  • common myeloid progenitor CL0000049
    CSI 2.69
    rCSI 2.18%
    PRS 94.76
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.45
    rCSI 1.71%
    PRS 96.23
  • common lymphoid progenitor CL0000051
    CSI 2.41
    rCSI 3.22%
    PRS 98.48
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.1
    rCSI 2.02%
    PRS 92.83
  • pancreatic acinar cell CL0002064
    CSI 2.05
    rCSI 2.73%
    PRS 95.74
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.03
    rCSI 1.84%
    PRS 93.01
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.02
    rCSI 2.6%
    PRS 85.48
  • club cell CL0000158
    CSI 1.89
    rCSI 2.77%
    PRS 90.8
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.73
    rCSI 2.9%
    PRS 84.61
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.68
    rCSI 2.16%
    PRS 90.85
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.53
    rCSI 3.43%
    PRS 84.78
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.96
    rCSI 2.33%
    PRS 82.52
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.71
    rCSI 2.69%
    PRS 84.73
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.57
    rCSI 2.04%
    PRS 82.81
  • erythroid progenitor cell CL0000038
    CSI 0.54
    rCSI 3.1%
    PRS 94.85

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 Analyzed for its expression specificity (CSI Z-SCORE), [GATC](/details-gene/283459) is characterized as a ubiquitously expressed gene essential for mitochondrial function, rather than a specific marker for any particular cell type. Its core role is as a subunit of the glutamyl-tRNA(Gln) amidotransferase complex, which is critical for the correct synthesis of glutaminyl-tRNA and subsequent mitochondrial protein translation. Pathogenic variants in [GATC](/details-gene/283459) are associated with severe mitochondrial disease, highlighting its fundamental importance in cellular homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [GATC](/details-gene/283459), when analyzed for specificity, strongly suggests a role as a housekeeping gene. In the **Overall** context, its CSI (Z-SCORE) is 0.00 across a highly diverse array of cell types. This score, which measures the uniqueness of a gene's expression, indicates that [GATC](/details-gene/283459) expression does not distinguish any one cell type from others. This is further supported by a maximal Effect Size of 1.00, signifying its consistent presence across the cellular landscape. Its ubiquitous expression is evident in functionally and developmentally distinct lineages, including: * **Nervous System:** [VIP GABAergic cortical interneuron](/details-cell/CL4023016) and [interneuron](/details-cell/CL0000099). * **Epithelial Tissues:** [multi-ciliated epithelial cell](/details-cell/CL0005012) and [epithelial cell of lower respiratory tract](/details-cell/CL0002632). * **Endocrine System:** [type B pancreatic cell](/details-cell/CL0000169). * **Immune System:** [mucosal invariant T cell](/details-cell/CL0000940) and [CD1c-positive myeloid dendritic cell](/details-cell/CL0002399). * **Progenitor Cells:** [stem cell](/details-cell/CL0000034) and [common myeloid progenitor](/details-cell/CL0000049). This broad expression pattern is entirely consistent with its fundamental role in a core cellular process required by nearly all human cells: mitochondrial protein synthesis. ## Pathways and Molecular Function The ubiquitous expression of [GATC](/details-gene/283459) is directly explained by its critical function in mitochondrial biology. [GATC](/details-gene/283459) is an essential component of the [glutamyl-tRNA(Gln) amidotransferase complex](/details-go/GO:0030956), which resides in the [mitochondrion](/details-go/GO:0005739). This complex is responsible for a crucial step in protein synthesis: the conversion of misacylated Glu-tRNA(Gln) to the correct Gln-tRNA(Gln), a process known as [glutaminyl-tRNAGln biosynthesis via transamidation](/details-go/GO:0070681). This transamidation pathway is essential because human mitochondria lack a dedicated glutaminyl-tRNA synthetase. Therefore, the function of the [GATC](/details-gene/283459)-containing complex is indispensable for incorporating glutamine into nascent mitochondrial-encoded polypeptides, a key part of [mitochondrial translation](/details-go/GO:0032543) (Nagao et al., [PubMed: 19805282](https://pubmed.ncbi.nlm.nih.gov/19805282/)). The failure of this process due to mutations in [GATC](/details-gene/283459) leads to defects in the assembly of oxidative phosphorylation complexes, resulting in severe mitochondrial dysfunction and disease, as reported by D'Souza et al. ([PubMed: 30283131](https://pubmed.ncbi.nlm.nih.gov/30283131/)). ## Research Directions Given that [GATC](/details-gene/283459) is an essential housekeeping gene, research should focus on understanding the consequences of its dysfunction and the variable cellular dependencies on its function, rather than its role as a cell marker. ### Testable Hypotheses: 1. **Hypothesis of Differential Vulnerability:** Cells with high metabolic and energetic demands, such as cardiomyocytes, neurons, and pancreatic beta cells, are disproportionately vulnerable to partial loss-of-function in [GATC](/details-gene/283459). This vulnerability is due to their higher reliance on mitochondrial respiration and protein synthesis, leading to cell-type-specific pathologies despite the gene's ubiquitous expression. * **Experimental Approach:** Utilize CRISPRi to create a titratable knockdown of [GATC](/details-gene/283459) in iPSC-derived cardiomyocytes, motor neurons, and a control cell type like fibroblasts. Assess cell viability, mitochondrial membrane potential, and oxygen consumption rates using a Seahorse XF Analyzer to quantify the differential functional impact. 2. **Hypothesis of Transcriptional Co-regulation:** The expression level of [GATC](/details-gene/283459), while constitutive, is tightly co-regulated with other nuclear-encoded mitochondrial genes (NUGs) under the control of master regulators of mitochondrial biogenesis, such as PGC-1alpha. Cellular states that demand increased mitochondrial capacity (e.g., endurance exercise, cold exposure) will exhibit coordinated upregulation of [GATC](/details-gene/283459] and other components of the mitochondrial translation machinery. * **Experimental Approach:** Perform single-nucleus RNA-sequencing on skeletal muscle biopsies from human subjects before and after a period of high-intensity interval training. Analyze the data for a coordinated upregulation of [GATC](/details-gene/283459) within a gene module containing other known mitochondrial biogenesis and translation factors. 3. **Hypothesis of Compensatory Stress Response:** Sub-lethal dysfunction of the [GATC](/details-gene/283459)-containing complex triggers a specific mitochondrial stress response pathway, such as the mitochondrial unfolded protein response (UPRmt), as a primary compensatory mechanism. Chronic activation of this pathway in individuals with hypomorphic [GATC](/details-gene/283459) variants may contribute to disease pathology. * **Experimental Approach:** Generate a cell line with a mild loss-of-function mutation in [GATC](/details-gene/283459) using base editing. Perform quantitative proteomics and RNA-seq to profile changes in the expression of key UPRmt components, such as HSP60, CLPP, and ATF5, relative to isogenic control cells. ### Therapeutic Potential: The direct therapeutic targeting of [GATC](/details-gene/283459) via inhibition is not viable due to its essential, ubiquitous function. Instead, its clinical relevance lies in diagnostics and restorative therapies for Mendelian mitochondrial diseases. As demonstrated by D'Souza et al. ([PubMed: 30283131](https://pubmed.ncbi.nlm.nih.gov/30283131/)), biallelic mutations in [GATC](/details-gene/283459) cause lethal mitochondrial cardiomyopathy. Therefore, therapeutic potential is primarily in the realm of gene replacement therapy, using AAV-based vectors to deliver a functional copy of the gene to affected tissues, or in the development of mRNA-based therapies to restore protein function.

Genular Protein ID: 700999876

Symbol: GATC_HUMAN

Name: Protein 15E1.2

UniProtKB Accession Codes:

O43716 B3KSU7 Q3B824 Q3KNR8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChEBI 9 ChiTaRS 1 ComplexPortal 1 DIP 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 7 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HAMAP 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 Rhea 3 STRING 1 SUPFAM 1 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 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: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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: 19805282

Title: Biogenesis of glutaminyl-mt tRNAGln in human mitochondria.

PubMed ID: 19805282

DOI: 10.1073/pnas.0907602106

PubMed ID: 30283131

Title: Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.

PubMed ID: 30283131

DOI: 10.1038/s41467-018-06250-w

Sequence Information:

  • Length: 136
  • Mass: 15086
  • Checksum: 113118E9507234E4
  • Sequence:
    • MWSRLVWLGL RAPLGGRQGF TSKADPQGSG RITAAVIEHL ERLALVDFGS REAVARLEKA 
IAFADRLRAV DTDGVEPMES VLEDRCLYLR SDNVVEGNCA DELLQNSHRV VEEYFVAPPG 
NISLPKLDEQ EPFPHS