Details for: TUB

Gene ID: 7275

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: TUB

Ensembl ID: ENSG00000166402

Description: TUB bipartite transcription factor

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • astrocyte of the cerebral cortex CL0002605
    CSI 5.46
    rCSI 12.25%
    PRS 63.18
  • epithelial cell of proximal tubule CL0002306
    CSI 5.36
    rCSI 13.08%
    PRS 72.57
  • retinal rod cell CL0000604
    CSI 3.54
    rCSI 6.24%
    PRS 75.84
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.73
    rCSI 6.23%
    PRS 74
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.7
    rCSI 6.57%
    PRS 60.34
  • ciliated cell CL0000064
    CSI 2.54
    rCSI 4.12%
    PRS 75.18
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.5
    rCSI 4.41%
    PRS 61.69
  • vascular leptomeningeal cell CL4023051
    CSI 2.19
    rCSI 3.84%
    PRS 74.16
  • ependymal cell CL0000065
    CSI 2.11
    rCSI 4.29%
    PRS 58.85
  • rod bipolar cell CL0000751
    CSI 2.06
    rCSI 3.7%
    PRS 73.65
  • direct pathway medium spiny neuron CL4023026
    CSI 2.06
    rCSI 49.21%
    PRS 60.67
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.05
    rCSI 2.91%
    PRS 76.89
  • interneuron CL0000099
    CSI 2.01
    rCSI 4.04%
    PRS 70.48
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.92
    rCSI 2.29%
    PRS 62.45
  • retinal pigment epithelial cell CL0002586
    CSI 1.91
    rCSI 3.8%
    PRS 75.95
  • retina horizontal cell CL0000745
    CSI 1.91
    rCSI 2.92%
    PRS 77.1
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.86
    rCSI 2.31%
    PRS 60.29
  • retinal cone cell CL0000573
    CSI 1.76
    rCSI 2.83%
    PRS 70.4
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.53
    rCSI 1.98%
    PRS 63.48
  • ciliated epithelial cell CL0000067
    CSI 1.44
    rCSI 1.26%
    PRS 69.53
  • medium spiny neuron CL1001474
    CSI 1.39
    rCSI 11.98%
    PRS 68.47
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.35
    rCSI 2.26%
    PRS 62.34
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.25
    rCSI 2.99%
    PRS 67.2
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.24
    rCSI 2%
    PRS 63.91
  • S cone cell CL0003050
    CSI 1.23
    rCSI 5.43%
    PRS 75.26
  • amacrine cell CL0000561
    CSI 1.19
    rCSI 3.45%
    PRS 69.8
  • peripheral nervous system neuron CL2000032
    CSI 1.15
    rCSI 1.57%
    PRS 71.9
  • retinal ganglion cell CL0000740
    CSI 0.81
    rCSI 1.8%
    PRS 66.04
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.75
    rCSI 2.35%
    PRS 64
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.68
    rCSI 4.27%
    PRS 71.9
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.68
    rCSI 4.01%
    PRS 63.06
  • parietal epithelial cell CL1000452
    CSI 0.67
    rCSI 1.78%
    PRS 72.01
  • dopaminergic neuron CL0000700
    CSI 0.64
    rCSI 3.6%
    PRS 66.28
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.58
    rCSI 1.81%
    PRS 66.35
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.54
    rCSI 2.03%
    PRS 62.83
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.51
    rCSI 1.84%
    PRS 60.24
  • OFF midget ganglion cell CL4033047
    CSI 0.4
    rCSI 8.17%
    PRS 71.34
  • ON parasol ganglion cell CL4033052
    CSI 0.3
    rCSI 4.25%
    PRS 71.32
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.29
    rCSI 6.89%
    PRS 61.23
  • central nervous system neuron CL2000029
    CSI 0.26
    rCSI 1.88%
    PRS 67.71

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 [TUB](/details-gene/7275) encodes the tubby protein homolog, a member of a novel family of bipartite transcription factors. This gene is implicated in a range of critical cellular processes, most notably those related to cilia function, G protein-coupled receptor signaling, and phagocytosis. Its expression pattern is highly specific, showing significant enrichment in specialized cells of the central nervous system, retina, and kidney. **Overall**, [TUB](/details-gene/7275) is a key marker for cell types such as [astrocytes of the cerebral cortex](/details-cell/CL0002605), [epithelial cells of the proximal tubule](/details-cell/CL0002306), and [retinal rod cells](/details-cell/CL0000604). Clinically, homozygous mutations in [TUB](/details-gene/7275) are associated with a syndrome characterized by early-onset retinal dystrophy and obesity ([Link](https://doi.org/10.1002/humu.22482)), consistent with its fundamental roles in photoreceptor maintenance and metabolic regulation ([OMIM: 601197](https://omim.org/entry/601197)). ## Cellular Roles and Expression Landscape The expression profile of [TUB](/details-gene/7275) highlights its importance in highly specialized, terminally differentiated cells across multiple tissues. * **Central Nervous System and Retina:** [TUB](/details-gene/7275) shows its highest significance in the CNS, particularly in [astrocytes of the cerebral cortex](/details-cell/CL0002605) (CSI: 5.46). It is also a defining feature of numerous neuronal subtypes, including various [interneurons](/details-cell/CL0000099) and [projecting glutamatergic neurons](/details-cell/CL4023040). Its critical role in vision is underscored by its high significance in [retinal rod cells](/details-cell/CL0000604) (CSI: 3.54), [rod bipolar cells](/details-cell/CL0000751), and [retinal pigment epithelial cells](/details-cell/CL0002586). This expression pattern aligns directly with the clinical presentation of retinal dystrophy observed in patients with [TUB](/details-gene/7275) mutations ([Link](https://doi.org/10.1002/humu.22482)). * **Epithelial and Ciliated Cells:** A second major expression domain is in specialized epithelial and ciliated cell types. [TUB](/details-gene/7275) is exceptionally significant in [epithelial cells of the proximal tubule](/details-cell/CL0002306) in the kidney (CSI: 5.36). Furthermore, its high significance in [ciliated columnar cells of the tracheobronchial tree](/details-cell/CL0002145) and [ependymal cells](/details-cell/CL0000065) is consistent with its established role in ciliary biology. This dual-domain expression pattern suggests that [TUB](/details-gene/7275) integrates cellular signaling with the structural and transport functions of cilia, which are critical for sensory perception in the retina, fluid homeostasis in the kidney, and neuronal function in the brain. ## Pathways and Molecular Function Functional annotation data reveals that [TUB](/details-gene/7275) operates at the intersection of intracellular transport, sensory signaling, and cellular clearance. * **Ciliary Function:** A predominant function of [TUB](/details-gene/7275) is its involvement in cilia-related processes. It is annotated with roles in [Intraciliary transport](/details-go/GO:0042073), [Protein localization to cilium](/details-go/GO:0061512), and is a component of the [cilium](/details-go/GO:0005929) itself. This is particularly relevant for its function in photoreceptors, where the outer segment is a highly modified primary cilium, and its dysfunction leads to [Photoreceptor cell maintenance](/details-go/GO:0045494) defects. * **Signaling and Receptor Localization:** [TUB](/details-gene/7275) is a key player in signal transduction, specifically in the [Regulation of g protein-coupled receptor signaling pathway](/details-go/GO:0008277) and through direct [G protein-coupled receptor binding](/details-go/GO:0001664). This function likely underpins its role in sensory processes such as vision and the [Sensory perception of sound](/details-go/GO:0007605). * **Phagocytosis:** The protein is also involved in [Phagocytosis, recognition](/details-go/GO:0006910) and the [Positive regulation of phagocytosis](/details-go/GO:0050766). Research suggests that tubby family proteins can act as "eat-me" signals on the surface of apoptotic cells, facilitating their clearance ([Link](https://doi.org/10.1016/j.yexcr.2009.10.008)). This function is highly relevant in the retina, where [retinal pigment epithelial cells](/details-cell/CL0002586) must phagocytose shed photoreceptor outer segments, and in the brain, where glial cells like [astrocytes](/details-cell/CL0002605) clear cellular debris. ## Research Directions The specific expression pattern and multifaceted functions of [TUB](/details-gene/7275) suggest several avenues for future investigation. **Testable Hypotheses:** 1. Given its high expression in [astrocytes of the cerebral cortex](/details-cell/CL0002605) and its documented role in phagocytosis, we hypothesize that [TUB](/details-gene/7275) functions as a critical signaling molecule for glial-mediated clearance of apoptotic neurons and synaptic pruning in the CNS. Dysregulation of this process could contribute to the pathology of neurodegenerative diseases. 2. Based on its high significance in the [epithelial cell of proximal tubule](/details-cell/CL0002306) and its established role in ciliary transport, we hypothesize that [TUB](/details-gene/7275) is essential for the function of primary cilia in renal tubules, likely in sensing fluid flow or mediating signaling pathways that regulate ion transport. Loss of this function may predispose individuals to renal ciliopathies. **Proposed Experimental Approach:** To test the first hypothesis regarding the role of [TUB](/details-gene/7275) in astrocytic phagocytosis, a targeted experiment could be designed. CRISPR-Cas9 could be used to knock out [TUB](/details-gene/7275) in human induced pluripotent stem cell (iPSC)-derived [astrocytes](/details-cell/CL0002605). The phagocytic capacity of these knockout astrocytes, compared to isogenic controls, could be assessed by co-culturing them with pHrodo-labeled apoptotic human neurons. The uptake of neuronal material would be quantified by flow cytometry and visualized using confocal microscopy. A subsequent transcriptomic analysis (RNA-seq) could identify downstream signaling and effector pathways disrupted by the loss of [TUB](/details-gene/7275). **Therapeutic Potential:** As [TUB](/details-gene/7275)-associated disease is a recessive, loss-of-function disorder, the therapeutic strategy would be **activation** or gene replacement, not inhibition. Systemic targeting is challenging due to its widespread expression in vital tissues. However, for the retinal dystrophy component, [TUB](/details-gene/7275) represents a promising candidate for AAV-mediated gene therapy. Delivering a functional copy of the gene directly to retinal cells could restore protein function, prevent photoreceptor death, and preserve vision, a strategy that has proven successful for other inherited retinal diseases.

Genular Protein ID: 3773615461

Symbol: TUB_HUMAN

Name: Tubby protein homolog

UniProtKB Accession Codes:

P50607 D3DQU4 O00293 Q6B007

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 5 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 19 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 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 PDB 1 PDBsum 1 PRINTS 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 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: 8612280

Title: Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.

PubMed ID: 8612280

DOI: 10.1016/s0092-8674(00)81104-6

PubMed ID: 9096357

Title: Molecular characterization of TUB, TULP1, and TULP2, members of the novel tubby gene family and their possible relation to ocular diseases.

PubMed ID: 9096357

DOI: 10.1073/pnas.94.7.3128

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: 19837063

Title: Identification of tubby and tubby-like protein 1 as eat-me signals by phage display.

PubMed ID: 19837063

DOI: 10.1016/j.yexcr.2009.10.008

PubMed ID: 24375934

Title: A homozygous mutation in the TUB gene associated with retinal dystrophy and obesity.

PubMed ID: 24375934

DOI: 10.1002/humu.22482

Sequence Information:

  • Length: 506
  • Mass: 55651
  • Checksum: B2A7D230795346C3
  • Sequence:
    • MTSKPHSDWI PYSVLDDEGR NLRQQKLDRQ RALLEQKQKK KRQEPLMVQA NADGRPRSRR 
ARQSEEQAPL VESYLSSSGS TSYQVQEADS LASVQLGATR PTAPASAKRT KAAATAGGQG 
GAARKEKKGK HKGTSGPAAL AEDKSEAQGP VQILTVGQSD HAQDAGETAA GGGERPSGQD 
LRATMQRKGI SSSMSFDEDE EDEEENSSSS SQLNSNTRPS SATSRKSVRE AASAPSPTAP 
EQPVDVEVQD LEEFALRPAP QGITIKCRIT RDKKGMDRGM YPTYFLHLDR EDGKKVFLLA 
GRKRKKSKTS NYLISVDPTD LSRGGDSYIG KLRSNLMGTK FTVYDNGVNP QKASSSTLES 
GTLRQELAAV CYETNVLGFK GPRKMSVIVP GMNMVHERVS IRPRNEHETL LARWQNKNTE 
SIIELQNKTP VWNDDTQSYV LNFHGRVTQA SVKNFQIIHG NDPDYIVMQF GRVAEDVFTM 
DYNYPLCALQ AFAIALSSFD SKLACE