Details for: TOR1A

Gene ID: 1861

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: TOR1A

Ensembl ID: ENSG00000136827

Description: torsin family 1 member A

Cell Significance Landscape

Associated with

Significant Cells

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

  • goblet cell CL0000160
    CSI 11.18
    rCSI 10.57%
    PRS 89.43
  • neural progenitor cell CL0011020
    CSI 4.65
    rCSI 20.48%
    PRS 81.49
  • common myeloid progenitor CL0000049
    CSI 4.36
    rCSI 3.53%
    PRS 92.49
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 4.34
    rCSI 3.3%
    PRS 98.24
  • placental villous trophoblast CL2000060
    CSI 3.38
    rCSI 5.22%
    PRS 89.75
  • CD4-positive helper T cell CL0000492
    CSI 3.26
    rCSI 2.47%
    PRS 97.26
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 3.23
    rCSI 3.17%
    PRS 97.93
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.96
    rCSI 2.56%
    PRS 93.45
  • pro-B cell CL0000826
    CSI 2.93
    rCSI 2.42%
    PRS 92.58
  • alternatively activated macrophage CL0000890
    CSI 2.86
    rCSI 3.59%
    PRS 95.94
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.73
    rCSI 2.46%
    PRS 90.23
  • neural crest cell CL0011012
    CSI 2.68
    rCSI 2.12%
    PRS 85.06
  • plasmablast CL0000980
    CSI 2.45
    rCSI 1.93%
    PRS 93.51
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.44
    rCSI 1.7%
    PRS 94.33
  • erythrocyte CL0000232
    CSI 2.42
    rCSI 5.49%
    PRS 89.62
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.34
    rCSI 3.06%
    PRS 96.57
  • activated type II NK T cell CL0000931
    CSI 2.3
    rCSI 2.59%
    PRS 97.24
  • mesodermal cell CL0000222
    CSI 2.3
    rCSI 2.75%
    PRS 90.41
  • hematopoietic stem cell CL0000037
    CSI 2.29
    rCSI 1.52%
    PRS 92.83
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.28
    rCSI 1.75%
    PRS 94.15
  • extravillous trophoblast CL0008036
    CSI 2.23
    rCSI 2.76%
    PRS 89.94
  • epithelial cell of lung CL0000082
    CSI 2.2
    rCSI 1.83%
    PRS 92.24
  • early lymphoid progenitor CL0000936
    CSI 2.2
    rCSI 1.93%
    PRS 94.25
  • group 3 innate lymphoid cell CL0001071
    CSI 2.14
    rCSI 1.61%
    PRS 94.28
  • retina horizontal cell CL0000745
    CSI 2.12
    rCSI 3.23%
    PRS 88.47
  • club cell CL0000158
    CSI 2.09
    rCSI 3.05%
    PRS 87.54
  • alveolar adventitial fibroblast CL4028006
    CSI 1.98
    rCSI 3.13%
    PRS 92.27
  • stem cell CL0000034
    CSI 1.88
    rCSI 1.81%
    PRS 87.64
  • granulocyte CL0000094
    CSI 1.78
    rCSI 2.72%
    PRS 94.93
  • mesenchymal cell CL0008019
    CSI 1.72
    rCSI 4.38%
    PRS 86.89
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.7
    rCSI 2.18%
    PRS 87.93
  • type B pancreatic cell CL0000169
    CSI 1.62
    rCSI 3.58%
    PRS 91.42
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.62
    rCSI 2.85%
    PRS 78.89
  • promyelocyte CL0000836
    CSI 1.61
    rCSI 2.32%
    PRS 93.31
  • basal cell CL0000646
    CSI 1.58
    rCSI 2.11%
    PRS 88.94
  • peripheral nervous system neuron CL2000032
    CSI 1.52
    rCSI 2.07%
    PRS 85.53
  • lung macrophage CL1001603
    CSI 1.05
    rCSI 2.35%
    PRS 95.24
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.86
    rCSI 4.31%
    PRS 97.36
  • pancreatic stellate cell CL0002410
    CSI 0.64
    rCSI 3.71%
    PRS 92.77
  • erythroid progenitor cell CL0000038
    CSI 0.58
    rCSI 3.31%
    PRS 93.19

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 [TOR1A](/details-gene/1861), also known as Torsin-1A, is a protein-coding gene located on chromosome 9q34.11. It encodes a member of the AAA+ (ATPases Associated with diverse cellular Activities) superfamily of chaperones, which is primarily localized to the lumen of the endoplasmic reticulum and the contiguous nuclear envelope. Functionally, [TOR1A](/details-gene/1861) is involved in a wide range of cellular processes including protein folding and quality control, membrane trafficking, cytoskeletal organization, and nuclear envelope integrity. Mutations in [TOR1A](/details-gene/1861), particularly a GAG deletion (ΔE), are the primary cause of early-onset torsion dystonia (DYT1), a severe inherited movement disorder ([128100](https://omim.org/entry/128100)) ([Link](https://doi.org/10.1038/ng0997-40)). While widely expressed, its significance is particularly pronounced in highly secretory cells like [goblet cell](/details-cell/CL0000160)s, as well as in [neural progenitor cell](/details-cell/CL0011020)s and various hematopoietic lineages, suggesting a fundamental role in managing protein processing and cellular architecture across diverse tissues. ## Cellular Roles and Expression Landscape The expression profile of [TOR1A](/details-gene/1861) reveals its importance across multiple, functionally distinct cell lineages. **Overall**, the gene shows its most profound significance in [goblet cell](/details-cell/CL0000160) (CSI: 11.18), a highly specialized secretory epithelial cell. This suggests a critical role for [TOR1A](/details-gene/1861) in managing the immense protein folding and trafficking load associated with mucin production and secretion. Beyond this specialized secretory role, [TOR1A](/details-gene/1861) is a significant gene in the developing nervous system, as indicated by its high CSI in [neural progenitor cell](/details-cell/CL0011020) (CSI: 4.65) and [neural crest cell](/details-cell/CL0011012) (CSI: 2.68). This expression pattern is consistent with its established role in [neuron projection development](/details-cell/GO:0031175) and its clinical association with dystonia, a neurological disorder. Furthermore, [TOR1A](/details-gene/1861) appears to play a key role in hematopoiesis and immunity. It is highly significant in multiple progenitor populations, including [common myeloid progenitor](/details-cell/CL0000049) (CSI: 4.36), [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 2.96), and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 2.73). This pattern continues into mature immune effector cells, such as [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) (CSI: 4.34), [CD4-positive helper T cell](/details-cell/CL0000492) (CSI: 3.26), and [alternatively activated macrophage](/details-cell/CL0000890) (CSI: 2.86). This broad expression across hematopoietic lineages points towards a fundamental function in cellular maintenance, differentiation, and effector functions that involve robust secretory activity, such as cytokine or granule release. ## Pathways and Molecular Function The molecular functions of [TOR1A](/details-gene/1861) are centered on its role as an ATP-dependent chaperone ([GO:0140662](https://www.ebi.ac.uk/QuickGO/term/GO:0140662)) that binds to misfolded or unfolded proteins ([GO:0051787](https://www.ebi.ac.uk/QuickGO/term/GO:0051787), [GO:0051082](https://www.ebi.ac.uk/QuickGO/term/GO:0051082)). This activity is essential for protein quality control within the [endoplasmic reticulum](/details-cell/GO:0005783), where it participates in the ER-associated degradation (ERAD) pathway ([GO:0036503](https://www.ebi.ac.uk/QuickGO/term/GO:0036503)). These chaperone activities likely underpin its high significance in professional secretory cells like [goblet cell](/details-cell/CL0000160)s. [TOR1A](/details-gene/1861) is also integral to cellular mechanics and transport. It contributes to [nuclear envelope organization](/details-cell/GO:0006998) by interacting with nesprin proteins to link the nuclear membrane to the cytoskeleton ([Link](https://doi.org/10.1242/jcs.029454)). This structural role extends to its involvement in [intermediate filament cytoskeleton organization](/details-cell/GO:0045104). The gene's function in membrane dynamics is highlighted by its participation in vesicle-mediated transport pathways, including [clathrin-mediated endocytosis](/details-cell/R-HSA-8856828) ([R-HSA-8856825](https://reactome.org/content/detail/R-HSA-8856825)). This function is particularly relevant to its neurological roles, where it modulates [synaptic vesicle recycling](/details-cell/GO:0008021) and transport ([GO:0048489](https://www.ebi.ac.uk/QuickGO/term/GO:0048489)), a process that is disrupted by disease-causing mutations ([Link](https://doi.org/10.1074/jbc.m704097200)). ## Research Directions The diverse expression pattern of [TOR1A](/details-gene/1861) opens several avenues for future investigation beyond its well-established role in dystonia. The striking finding of its top significance in [goblet cell](/details-cell/CL0000160)s warrants further exploration into its role in mucosal biology. ### Proposed Hypotheses: 1. **[TOR1A](/details-gene/1861) is a critical regulator of mucin biosynthesis and secretion.** Given its exceptionally high CSI in [goblet cell](/details-cell/CL0000160)s, it is hypothesized that [TOR1A](/details-gene/1861) functions as a key chaperone for the proper folding and processing of highly complex glycoproteins like mucins. Dysfunction of [TOR1A](/details-gene/1861) in the gut epithelium could lead to ER stress, impaired mucosal barrier integrity, and susceptibility to inflammatory bowel diseases. 2. **[TOR1A](/details-gene/1861) modulates the effector function of cytotoxic T lymphocytes.** The high significance of [TOR1A](/details-gene/1861) in [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050)s suggests a role in regulating the trafficking and release of cytotoxic granules. It may act as a chaperone for key effector proteins like perforin and granzymes or facilitate the cytoskeletal rearrangements necessary for forming a functional immunological synapse. ### Key Experimental Approach: To test the hypothesis regarding its role in goblet cells, a compelling experiment would be to use CRISPR-Cas9 to knock out [TOR1A](/details-gene/1861) in human intestinal organoids. Following knockout, organoids would be cultured in differentiation media to promote [goblet cell](/details-cell/CL0000160) maturation. The effects would be assessed by quantifying MUC2 production via immunohistochemistry and Western blot, measuring ER stress markers (e.g., XBP1 splicing, CHOP expression) via qPCR, and evaluating mucosal barrier function using permeability assays (e.g., FITC-dextran). ### Therapeutic Potential: As DYT1 dystonia is typically caused by a dominant-negative or loss-of-function mutation ([Link](https://doi.org/10.1073/pnas.0308088101)), therapeutic strategies for this disorder would focus on functional restoration rather than inhibition. Potential approaches could include gene replacement therapy delivered via AAV vectors to affected neurons or the development of small molecule pharmacological chaperones designed to stabilize the mutant protein and restore its function. The widespread expression of [TOR1A](/details-gene/1861) makes systemic inhibition an undesirable strategy due to the high risk of on-target toxicity in numerous healthy tissues.

Genular Protein ID: 2143528982

Symbol: TOR1A_HUMAN

Name: Torsin-1A

UniProtKB Accession Codes:

O14656 B2RB58 Q53Y64 Q96CA0

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChEBI 6 ChiTaRS 1 DIP 1 DNASU 1 DisGeNET 1 EC 1 EMBL 6 EMDB 1 Ensembl 1 ExpressionAtlas 1 GO 40 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9288096

Title: The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein.

PubMed ID: 9288096

DOI: 10.1038/ng0997-40

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

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: 10871631

Title: Torsin A and its torsion dystonia-associated mutant forms are lumenal glycoproteins that exhibit distinct subcellular localizations.

PubMed ID: 10871631

DOI: 10.1074/jbc.m910025199

PubMed ID: 10640617

Title: Immunohistochemical localization and distribution of torsinA in normal human and rat brain.

PubMed ID: 10640617

DOI: 10.1016/s0006-8993(99)02232-5

PubMed ID: 15147511

Title: TorsinB--perinuclear location and association with torsinA.

PubMed ID: 15147511

DOI: 10.1111/j.1471-4159.2004.02404.x

PubMed ID: 14970196

Title: The early onset dystonia protein torsinA interacts with kinesin light chain 1.

PubMed ID: 14970196

DOI: 10.1074/jbc.m401332200

PubMed ID: 15505207

Title: Effect of torsinA on membrane proteins reveals a loss of function and a dominant-negative phenotype of the dystonia-associated DeltaE-torsinA mutant.

PubMed ID: 15505207

DOI: 10.1073/pnas.0308088101

PubMed ID: 15767459

Title: The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein.

PubMed ID: 15767459

DOI: 10.1083/jcb.200411026

PubMed ID: 16361107

Title: Dystonia-causing mutant torsinA inhibits cell adhesion and neurite extension through interference with cytoskeletal dynamics.

PubMed ID: 16361107

DOI: 10.1016/j.nbd.2005.10.012

PubMed ID: 17037984

Title: Biosynthesis of the dystonia-associated AAA+ ATPase torsinA at the endoplasmic reticulum.

PubMed ID: 17037984

DOI: 10.1042/bj20061313

PubMed ID: 17428918

Title: Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells.

PubMed ID: 17428918

DOI: 10.1073/pnas.0701185104

PubMed ID: 18167355

Title: The dystonia-associated protein torsinA modulates synaptic vesicle recycling.

PubMed ID: 18167355

DOI: 10.1074/jbc.m704097200

PubMed ID: 18827015

Title: TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton.

PubMed ID: 18827015

DOI: 10.1242/jcs.029454

PubMed ID: 19535332

Title: Printor, a novel torsinA-interacting protein implicated in dystonia pathogenesis.

PubMed ID: 19535332

DOI: 10.1074/jbc.m109.004838

PubMed ID: 19339278

Title: LULL1 retargets TorsinA to the nuclear envelope revealing an activity that is impaired by the DYT1 dystonia mutation.

PubMed ID: 19339278

DOI: 10.1091/mbc.e09-01-0094

PubMed ID: 20169475

Title: The early-onset torsion dystonia-associated protein, torsinA, displays molecular chaperone activity in vitro.

PubMed ID: 20169475

DOI: 10.1007/s12192-010-0173-2

PubMed ID: 20015956

Title: Relative tissue expression of homologous torsinB correlates with the neuronal specific importance of DYT1 dystonia-associated torsinA.

PubMed ID: 20015956

DOI: 10.1093/hmg/ddp557

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21102408

Title: CSN complex controls the stability of selected synaptic proteins via a torsinA-dependent process.

PubMed ID: 21102408

DOI: 10.1038/emboj.2010.285

PubMed ID: 23569223

Title: Regulation of Torsin ATPases by LAP1 and LULL1.

PubMed ID: 23569223

DOI: 10.1073/pnas.1300676110

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 29053766

Title: TOR1A variants cause a severe arthrogryposis with developmental delay, strabismus and tremor.

PubMed ID: 29053766

DOI: 10.1093/brain/awx230

PubMed ID: 27490483

Title: Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia.

PubMed ID: 27490483

DOI: 10.7554/elife.17983

PubMed ID: 11523564

Title: Novel mutation in the TOR1A (DYT1) gene in atypical early onset dystonia and polymorphisms in dystonia and early onset parkinsonism.

PubMed ID: 11523564

DOI: 10.1007/s100480100111

PubMed ID: 18477710

Title: Novel TOR1A mutation p.Arg288Gln in early-onset dystonia (DYT1).

PubMed ID: 18477710

DOI: 10.1136/jnnp.2008.148270

PubMed ID: 19955557

Title: Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia.

PubMed ID: 19955557

DOI: 10.1136/jmg.2009.072082

PubMed ID: 24930953

Title: Biochemical and cellular analysis of human variants of the DYT1 dystonia protein, TorsinA/TOR1A.

PubMed ID: 24930953

DOI: 10.1002/humu.22602

PubMed ID: 26940431

Title: New THAP1 mutation and role of putative modifier in TOR1A.

PubMed ID: 26940431

DOI: 10.1111/ane.12579

PubMed ID: 28516161

Title: Biallelic TOR1A variants in an infant with severe arthrogryposis.

PubMed ID: 28516161

DOI: 10.1212/nxg.0000000000000154

PubMed ID: 30244176

Title: Biallelic TOR1A mutations cause severe arthrogryposis: A case requiring reverse phenotyping.

PubMed ID: 30244176

DOI: 10.1016/j.ejmg.2018.09.011

Sequence Information:

  • Length: 332
  • Mass: 37809
  • Checksum: B69B28D0B4112080
  • Sequence:
    • MKLGRAVLGL LLLAPSVVQA VEPISLGLAL AGVLTGYIYP RLYCLFAECC GQKRSLSREA 
LQKDLDDNLF GQHLAKKIIL NAVFGFINNP KPKKPLTLSL HGWTGTGKNF VSKIIAENIY 
EGGLNSDYVH LFVATLHFPH ASNITLYKDQ LQLWIRGNVS ACARSIFIFD EMDKMHAGLI 
DAIKPFLDYY DLVDGVSYQK AMFIFLSNAG AERITDVALD FWRSGKQRED IKLKDIEHAL 
SVSVFNNKNS GFWHSSLIDR NLIDYFVPFL PLEYKHLKMC IRVEMQSRGY EIDEDIVSRV 
AEEMTFFPKE ERVFSDKGCK TVFTKLDYYY DD

Genular Protein ID: 1282251968

Symbol: B3KPA1_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KPA1

Database IDs:

ARBA 15 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 5 DNASU 1 DisGeNET 1 EMBL 2 GO 10 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSF 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 RefSeq 1 Rhea 1 SAM 1 SUPFAM 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 301
  • Mass: 34376
  • Checksum: 7536B805D09CB31A
  • Sequence:
    • MKLGRAVLGL LLLAPSVVQA VEPISLGLAL AGVLTGYIYP RLYCLFAECC GQKRSLSREA 
LQKDLDDNLF GQHLAKKIIL NAVFGFINNP KPKKPLTLSL FVATLHFPHA SNITLYKDQL 
QLWIRGNVSA CARSIFIFDE MDKMHAGLID AIKPFLDYYD LVDGVSYQKA MFIFLSNAGA 
ERITDVALDF WRSGKQREDI KLKDIEHALS VSVFNNKNSG FWHSSLIDRN LIDYFVPFLP 
LEYKHLKMCI RVEMQSRGYE IDEDIVSRVA EEMTFFPKEV RVFSDKGCKT VFTKLDYYYD 
D