Details for: TEDC1

Gene ID: 283643

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: TEDC1

Ensembl ID: ENSG00000185347

Description: tubulin epsilon and delta complex 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • intestine goblet cell CL0019031
    CSI 3.52
    rCSI 3.13%
    PRS 99.32
  • deuterosomal cell CL4033044
    CSI 1.3
    rCSI 4.39%
    PRS 98.34

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • Node Size: Proportional to Target Cell CSI magnitude
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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 [TEDC1](/details-gene/283643) (Tubulin Epsilon and Delta Complex 1) is a protein-coding gene located on chromosome 14q32.33. Functional annotations strongly associate it with cytoskeletal structures, specifically the [centriole](/details-cell/GO:0005814) and [cilium](/details-cell/GO:0005929). Expression data highlights its significant role in specialized cell types, including [intestine goblet cell](/details-cell/CL0019031) and [deuterosomal cell](/details-cell/CL4033044), suggesting a function in processes related to secretion and the formation of multiciliated structures. Clinically, biallelic mutations in [TEDC1](/details-gene/283643) have been implicated in congenital microcephaly, underscoring its critical role in proper cellular and developmental processes [Link](https://doi.org/10.1007/s11033-023-09136-3). ## Cellular Roles and Expression Landscape The expression profile of [TEDC1](/details-gene/283643) indicates a highly specialized function rather than a ubiquitous housekeeping role. **Overall**, the gene shows its most significant expression in distinct cell populations characterized by complex microtubule-based organelles. Its highest significance is observed in [intestine goblet cell](/details-cell/CL0019031) (CSI: 3.52), which are specialized for producing and secreting mucus. This suggests [TEDC1](/details-gene/283643) may be involved in organizing the microtubule network required for the extensive trafficking of mucin granules. A significant signal is also seen in [deuterosomal cell](/details-cell/CL4033044) (CSI: 1.30). These cells are precursors to multiciliated epithelial cells and are defined by the presence of deuterosomes, which are structures that template the massive amplification of centrioles (basal bodies) needed to form multiple motile cilia. This expression pattern is highly consistent with the gene's annotated localization to the [centriole](/details-cell/GO:0005814) and its likely involvement in ciliogenesis. ## Pathways and Molecular Function The known functions of [TEDC1](/details-gene/283643) are closely tied to the biology of the cilium and centriole, which act as critical signaling and organizational hubs within the cell. * **Cellular Component:** [TEDC1](/details-gene/283643) is primarily localized to the [cytoplasm](/details-cell/GO:0005737), with specific enrichment in the [centriole](/details-cell/GO:0005814) and the [cilium](/details-cell/GO:0005929). Centrioles are essential for forming the centrosome, which organizes microtubules during interphase and the mitotic spindle during cell division. They also function as basal bodies that template the growth of cilia. * **Biological Process:** The gene is implicated in the [positive regulation of smoothened signaling pathway](/details-cell/GO:0045880). The Smoothened receptor is a core component of the Hedgehog signaling pathway, a crucial pathway in embryonic development whose signal transduction is often mediated through the primary cilium. This suggests [TEDC1](/details-gene/283643) may function within the cilium to modulate developmental signaling. * **Molecular Function:** Its annotated role in [protein binding](/details-cell/GO:0005515) suggests it likely functions as part of a larger protein complex, possibly scaffolding or regulating other proteins involved in centriole duplication or ciliary function. ## Research Directions The association of [TEDC1](/details-gene/283643) with ciliogenesis and a severe neurodevelopmental disorder like microcephaly provides a clear direction for future investigation. Its specific expression pattern and role in a key developmental pathway highlight its importance. ### Proposed Hypotheses: 1. **Hypothesis 1: Defective Neurogenesis via Centriole Instability.** Biallelic loss-of-function mutations in [TEDC1](/details-gene/283643) disrupt centriole duplication or stability in neural progenitor cells during corticogenesis. This leads to mitotic errors, cell cycle arrest, or apoptosis, ultimately reducing the pool of neurons and causing microcephaly, as has been recently suggested [Link](https://doi.org/10.1007/s11033-023-09136-3). 2. **Hypothesis 2: Dysregulation of Ciliary Signaling.** [TEDC1](/details-gene/283643) is essential for the structural integrity or signaling capacity of the primary cilium in developing neurons. Its absence impairs Hedgehog signal transduction, which is critical for patterning and proliferation in the developing brain, thereby contributing to microcephaly. 3. **Hypothesis 3: Impaired Mucociliary Function.** Given its expression in [deuterosomal cell](/details-cell/CL4033044) and [intestine goblet cell](/details-cell/CL0019031), loss of [TEDC1](/details-gene/283643) function may contribute to a broader ciliopathy phenotype, potentially affecting mucociliary clearance in the respiratory or gastrointestinal tracts, which may be a secondary manifestation in affected individuals. ### Key Experimental Approach: To test Hypothesis 1, one could use CRISPR-Cas9 to introduce patient-derived mutations into human induced pluripotent stem cells (iPSCs). These edited iPSCs and isogenic controls would be differentiated into cerebral organoids. The impact of [TEDC1](/details-gene/283643) mutation on neural progenitor cell proliferation and survival would be assessed by quantifying organoid size and performing immunohistochemistry for markers of mitosis (e.g., Phospho-Histone H3) and apoptosis (e.g., Cleaved Caspase-3). High-resolution microscopy could be used to directly visualize centriole numbers and mitotic spindle integrity in neural progenitors within the organoids. ### Therapeutic Potential: Given that pathogenic variants in [TEDC1](/details-gene/283643) cause a severe congenital disorder, its primary clinical utility is in the realm of genetic diagnostics for individuals with microcephaly. Direct therapeutic intervention via small molecule inhibitors or activators is unlikely to be a viable strategy for a developmental disease caused by a loss-of-function mutation. In the long term, [TEDC1](/details-gene/283643) could be a candidate for gene replacement therapies aimed at correcting the genetic defect in affected cell lineages, though the technical and ethical challenges of such an approach for a neurodevelopmental condition remain substantial.

Genular Protein ID: 1750857280

Symbol: TEDC1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q86SX3 B5MDG3 E9PAQ4 Q86TT3 Q86TT4 Q86TT5 Q96B41 Q9H7H4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 5 CTD 1 DIP 1 DMDM 1 DNASU 1 EMBL 8 Ensembl 6 ExpressionAtlas 1 GO 4 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 6 Pumba 1 RNAct 1 RefSeq 4 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 28796488

Title: Direct Interaction of Chivosazole F with Actin Elicits Cell Responses Similar to Latrunculin A but Distinct from Chondramide.

PubMed ID: 28796488

DOI: 10.1021/acschembio.7b00385

PubMed ID: 38252227

Title: Second report of TEDC1-related microcephaly caused by a novel biallelic mutation in an Iranian consanguineous family.

PubMed ID: 38252227

DOI: 10.1007/s11033-023-09136-3

Sequence Information:

  • Length: 495
  • Mass: 54231
  • Checksum: 3E34FACE82E0EACF
  • Sequence:
    • MGRRRQRVDP AAGARAGALP EAIAALSRSL PSGPSPEIFR RAKFDRPEAT SALWQLLFRV 
LSPLPAGNAL ASLALEVQAR LVKSALCSQG YPRLALAQLP EDGSQGSREL LLALSWLLAR 
GPVPEQMLAQ ARVPLGDEMT VCQCEALASP GPPAPHMEAE GPVDVRHVQW LMGKLRFRWR 
QLVSSQQEQC ALLSKIHLYT RGCHSDQSLS HLSVTEAEML RDPEGGQQVS GAGAAQNLDL 
AYPKCLHSFC TPGMGPRTFW NDLWLVCEQP GLLPGDWAAP LDPGGASACS LLSPFRALLR 
TLERENQRLE AVLAWRRSEL VFWRWMDTVL GTCAPEVPAA ASQPTFLPWV PERGGGELDL 
VVRELQALEE ELREAAERRR AAWEAKAGGC GRGPEWSAAR RASREAVEKE LGALQQCWER 
DGGPAQPHGP HRLVRREDGA AGDRDLRAAV VIRTLRSQEA CLEAVLRRLQ GQCRQELARL 
VGARPGLIWI PPPGR