Details for: THAP12

Gene ID: 5612

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: THAP12

Ensembl ID: ENSG00000137492

Description: THAP domain containing 12

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • rod bipolar cell CL0000751
    CSI 8.8
    rCSI 15.81%
    PRS 71.02
  • progenitor cell CL0011026
    CSI 7.57
    rCSI 16.09%
    PRS 72.32
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 4.81
    rCSI 2.84%
    PRS 92.46
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 4.64
    rCSI 3.53%
    PRS 89.71
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 4.26
    rCSI 4.45%
    PRS 91.06
  • retinal blood vessel endothelial cell CL0002585
    CSI 3.73
    rCSI 5.96%
    PRS 81.41
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 3.67
    rCSI 8.82%
    PRS 90.84
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 3.47
    rCSI 2.34%
    PRS 90.08
  • double negative thymocyte CL0002489
    CSI 3.32
    rCSI 2.31%
    PRS 88.67
  • Kupffer cell CL0000091
    CSI 3.14
    rCSI 7.18%
    PRS 78.57
  • mature T cell CL0002419
    CSI 3.08
    rCSI 2.4%
    PRS 91.35
  • hematopoietic precursor cell CL0008001
    CSI 2.99
    rCSI 3.07%
    PRS 89.61
  • mucosal invariant T cell CL0000940
    CSI 2.95
    rCSI 2.39%
    PRS 86.48
  • Mueller cell CL0000636
    CSI 2.95
    rCSI 6.73%
    PRS 69.17
  • interneuron CL0000099
    CSI 2.81
    rCSI 5.65%
    PRS 67.57
  • perivascular cell CL4033054
    CSI 2.75
    rCSI 3.76%
    PRS 82.14
  • colon epithelial cell CL0011108
    CSI 2.63
    rCSI 2.76%
    PRS 75.02
  • goblet cell CL0000160
    CSI 2.59
    rCSI 2.45%
    PRS 76.6
  • ionocyte CL0005006
    CSI 2.52
    rCSI 2.7%
    PRS 78.8
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 2.5
    rCSI 2.28%
    PRS 89.51
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.49
    rCSI 5.58%
    PRS 60.3
  • myeloid leukocyte CL0000766
    CSI 2.45
    rCSI 2.26%
    PRS 79.15
  • CD4-positive helper T cell CL0000492
    CSI 2.38
    rCSI 1.8%
    PRS 89.46
  • club cell CL0000158
    CSI 2.36
    rCSI 3.46%
    PRS 72.19
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.36
    rCSI 1.69%
    PRS 89.96
  • precursor B cell CL0000817
    CSI 2.33
    rCSI 2.04%
    PRS 85.18
  • intestine goblet cell CL0019031
    CSI 2.26
    rCSI 2.01%
    PRS 75.51
  • pro-B cell CL0000826
    CSI 2.22
    rCSI 1.84%
    PRS 80.2
  • mesenchymal cell CL0008019
    CSI 2.17
    rCSI 5.52%
    PRS 71.1
  • mature B cell CL0000785
    CSI 2.16
    rCSI 1.88%
    PRS 87.24
  • neural crest cell CL0011012
    CSI 2.16
    rCSI 1.7%
    PRS 66.04
  • group 3 innate lymphoid cell CL0001071
    CSI 2.09
    rCSI 1.57%
    PRS 83.5
  • retina horizontal cell CL0000745
    CSI 2.09
    rCSI 3.18%
    PRS 74.62
  • respiratory hillock cell CL4030023
    CSI 2.08
    rCSI 3.71%
    PRS 86.67
  • ciliated epithelial cell CL0000067
    CSI 2.04
    rCSI 1.8%
    PRS 66.65
  • retinal bipolar neuron CL0000748
    CSI 2.03
    rCSI 3.81%
    PRS 65.87
  • mononuclear phagocyte CL0000113
    CSI 1.97
    rCSI 4.33%
    PRS 81.5
  • stem cell CL0000034
    CSI 1.96
    rCSI 1.89%
    PRS 70.67
  • type L enteroendocrine cell CL0002279
    CSI 1.94
    rCSI 3.64%
    PRS 85.96
  • bronchus fibroblast of lung CL2000093
    CSI 1.9
    rCSI 1.54%
    PRS 77.13
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.9
    rCSI 1.71%
    PRS 75.91
  • cerebral cortex endothelial cell CL1001602
    CSI 1.9
    rCSI 3.28%
    PRS 68.97
  • extravillous trophoblast CL0008036
    CSI 1.8
    rCSI 2.22%
    PRS 75.56
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.75
    rCSI 2.09%
    PRS 59.5
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 1.74
    rCSI 2.39%
    PRS 92.77
  • vascular associated smooth muscle cell CL0000359
    CSI 1.73
    rCSI 5.62%
    PRS 75.68
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.73
    rCSI 2.9%
    PRS 59.52
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.68
    rCSI 1.94%
    PRS 70.04
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.65
    rCSI 1.59%
    PRS 77.01
  • pancreatic acinar cell CL0002064
    CSI 1.63
    rCSI 2.16%
    PRS 83.47
  • placental villous trophoblast CL2000060
    CSI 1.61
    rCSI 2.49%
    PRS 76.78
  • retinal rod cell CL0000604
    CSI 1.61
    rCSI 2.83%
    PRS 73.62
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.59
    rCSI 4.69%
    PRS 78.86
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.57
    rCSI 1.21%
    PRS 80.38
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.55
    rCSI 1.93%
    PRS 57.38
  • glioblast CL0000030
    CSI 1.53
    rCSI 2.44%
    PRS 69.46
  • paneth cell CL0000510
    CSI 1.49
    rCSI 2.2%
    PRS 88.47
  • BEST4+ enteroycte CL4030026
    CSI 1.47
    rCSI 1.83%
    PRS 79.11
  • basal cell CL0000646
    CSI 1.38
    rCSI 1.85%
    PRS 76.55
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.35
    rCSI 2.38%
    PRS 58.76
  • colon goblet cell CL0009039
    CSI 0.96
    rCSI 2.28%
    PRS 83.64
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.91
    rCSI 4.57%
    PRS 89.12
  • retinal cone cell CL0000573
    CSI 0.81
    rCSI 1.3%
    PRS 67.63
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.76
    rCSI 1.85%
    PRS 57.54
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.64
    rCSI 2.01%
    PRS 61.18
  • podocyte CL0000653
    CSI 0.64
    rCSI 2.84%
    PRS 78.22
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.47
    rCSI 2.76%
    PRS 60.34
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.45
    rCSI 1.61%
    PRS 57.47

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 [THAP12](/details-gene/5612) is a protein-coding gene located on chromosome 11q13.5 that encodes the THAP domain-containing protein 12. This protein is known to function as a nuclear repressor of the interferon-induced protein kinase PKR, as described in early studies ([Link](https://doi.org/10.1128/mcb.18.2.859)). Consistent with this role, functional annotations implicate [THAP12](/details-gene/5612) in the negative regulation of cell proliferation ([GO:0008285](https://www.ebi.ac.uk/QuickGO/term/GO:0008285)) and signal transduction ([GO:0007165](https://www.ebi.ac.uk/QuickGO/term/GO:0007165)). Its expression profile highlights a significant role in highly specialized cell types, showing the highest significance in retinal [rod bipolar cell](/details-cell/CL0000751)s, as well as in various [progenitor cell](/details-cell/CL0011026)s and multiple subsets of T lymphocytes, suggesting a key function in both neuronal signal processing and immune cell homeostasis. ## Cellular Roles and Expression Landscape The **Overall** expression pattern of [THAP12](/details-gene/5612) indicates a highly specialized function across distinct biological systems. The gene's most significant expression is observed in [rod bipolar cell](/details-cell/CL0000751) (CSI: 8.80), a specialized neuron in the retina, with notable expression also found in [Mueller cell](/details-cell/CL0000636)s. This suggests a potentially critical, though currently under-characterized, role in retinal function and signal integration. Beyond the nervous system, [THAP12](/details-gene/5612) is a significant marker within the hematopoietic and immune systems. It is highly expressed in [progenitor cell](/details-cell/CL0011026) (CSI: 7.57) and [hematopoietic multipotent progenitor cell](/details-cell/CL0000837) (CSI: 3.67), pointing towards a role in cellular differentiation or the maintenance of pluripotency. Furthermore, it demonstrates a consistent and significant presence across various T lymphocyte populations, including [central memory CD4-positive, alpha-beta T cell](/details-cell/CL0000904) (CSI: 4.81), [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) (CSI: 4.64), and [CD8-positive, alpha-beta memory T cell](/details-cell/CL0000909) (CSI: 4.26). This widespread expression across T cell subsets suggests a fundamental role in regulating T cell activation, memory formation, or quiescence. ## Pathways and Molecular Function The molecular functions of [THAP12](/details-gene/5612) are consistent with its role as a regulatory protein located in the [nucleus](/details-cell/GO:0005634) ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)). Its annotated functions include DNA binding ([GO:0003677](https://www.ebi.ac.uk/QuickGO/term/GO:0003677)), protein binding ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)), and protein dimerization activity ([GO:0046983](https://www.ebi.ac.uk/QuickGO/term/GO:0046983)). These molecular activities underpin its primary biological processes. The most well-defined role for [THAP12](/details-gene/5612) is in signal transduction ([GO:0007165](https://www.ebi.ac.uk/QuickGO/term/GO:0007165)), specifically through its characterization as a repressor of the protein kinase PKR ([Link](https://doi.org/10.1128/mcb.18.2.859)). As PKR is a key component of the cellular stress response and a regulator of translation and cell growth, the inhibitory action of [THAP12](/details-gene/5612) directly aligns with its involvement in the negative regulation of cell population proliferation ([GO:0008285](https://www.ebi.ac.uk/QuickGO/term/GO:0008285)). This function likely explains its significance in the tightly controlled proliferative environments of hematopoietic progenitors and T lymphocytes. ## Research Directions The specific expression pattern and known molecular function of [THAP12](/details-gene/5612) suggest several avenues for future research. The data points to a dual role in both the immune system and the retina, which warrants further investigation. **Proposed Hypotheses:** 1. Given its role as a negative regulator of proliferation and its high significance in multiple memory T cell subsets, [THAP12](/details-gene/5612) may function as a key gatekeeper for T cell quiescence. Its expression could be critical for establishing and maintaining a stable memory T cell pool by preventing spurious activation and exhaustion. 2. The exceptionally high CSI in [rod bipolar cell](/details-cell/CL0000751) suggests a specialized, non-proliferative role in the retina. [THAP12](/details-gene/5612) may modulate local protein synthesis or specific signaling cascades via its interaction with PKR to fine-tune synaptic transmission or neuronal homeostasis in response to visual stimuli. **Experimental Approach:** To test the first hypothesis regarding T cell quiescence, a loss-of-function study would be highly informative. A specific experimental plan could involve: * **Methodology:** Use CRISPR-Cas9 to knock out [THAP12](/details-gene/5612) in primary human naive CD8+ T cells. * **Assay:** Culture both knockout and wild-type control T cells and stimulate them through the T cell receptor (TCR). * **Readouts:** Measure proliferation using CFSE dilution assays, assess activation marker expression (e.g., CD69, CD25) via flow cytometry, and quantify cytokine production (e.g., IFN-gamma, TNF-alpha) by ELISA. * **Expected Outcome:** If the hypothesis is correct, [THAP12](/details-gene/5612)-deficient T cells would be expected to exhibit hyper-proliferation, enhanced activation, and potentially a faster transition towards an exhausted phenotype upon chronic stimulation compared to controls. **Therapeutic Potential:** The function of [THAP12](/details-gene/5612) as a repressor of proliferation suggests it could act as a tumor suppressor. Loss-of-function mutations could contribute to uncontrolled cell growth, particularly in hematological malignancies. However, in the context of immunotherapy, its role as a potential brake on T cell activation makes it an intriguing, albeit challenging, target. Inhibition of [THAP12](/details-gene/5612) or its downstream pathways could potentially enhance the efficacy of T cell-based therapies against cancer. As a nuclear DNA-binding protein, it is not easily targetable with conventional small molecules or antibodies, suggesting that strategies aimed at modulating its expression or downstream effectors may be more feasible.

Genular Protein ID: 3869746474

Symbol: P52K_HUMAN

Name: 52 kDa repressor of the inhibitor of the protein kinase

UniProtKB Accession Codes:

O43422 A8K728 Q17RY9 Q8WTW1 Q9Y3Z4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 6 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9447982

Title: Regulation of interferon-induced protein kinase PKR: modulation of P58IPK inhibitory function by a novel protein, P52rIPK.

PubMed ID: 9447982

DOI: 10.1128/mcb.18.2.859

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

Sequence Information:

  • Length: 761
  • Mass: 87704
  • Checksum: 88809CFE52399C13
  • Sequence:
    • MPNFCAAPNC TRKSTQSDLA FFRFPRDPAR CQKWVENCRR ADLEDKTPDQ LNKHYRLCAK 
HFETSMICRT SPYRTVLRDN AIPTIFDLTS HLNNPHSRHR KRIKELSEDE IRTLKQKKID 
ETSEQEQKHK ETNNSNAQNP SEEEGEGQDE DILPLTLEEK ENKEYLKSLF EILILMGKQN 
IPLDGHEADE IPEGLFTPDN FQALLECRIN SGEEVLRKRF ETTAVNTLFC SKTQQRQMLE 
ICESCIREET LREVRDSHFF SIITDDVVDI AGEEHLPVLV RFVDESHNLR EEFIGFLPYE 
ADAEILAVKF HTMITEKWGL NMEYCRGQAY IVSSGFSSKM KVVASRLLEK YPQAIYTLCS 
SCALNMWLAK SVPVMGVSVA LGTIEEVCSF FHRSPQLLLE LDNVISVLFQ NSKERGKELK 
EICHSQWTGR HDAFEILVEL LQALVLCLDG INSDTNIRWN NYIAGRAFVL CSAVSDFDFI 
VTIVVLKNVL SFTRAFGKNL QGQTSDVFFA AGSLTAVLHS LNEVMENIEV YHEFWFEEAT 
NLATKLDIQM KLPGKFRRAH QGNLESQLTS ESYYKETLSV PTVEHIIQEL KDIFSEQHLK 
ALKCLSLVPS VMGQLKFNTS EEHHADMYRS DLPNPDTLSA ELHCWRIKWK HRGKDIELPS 
TIYEALHLPD IKFFPNVYAL LKVLCILPVM KVENERYENG RKRLKAYLRN TLTDQRSSNL 
ALLNINFDIK HDLDLMVDTY IKLYTSKSEL PTDNSETVEN T