Details for: TCFL5

Gene ID: 10732

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: TCFL5

Ensembl ID: ENSG00000101190

Description: transcription factor like 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Cell differentiation
    (GO:0030154)
  • Chromatin
    (GO:0000785)
  • Dna-binding transcription factor activity
    (GO:0003700)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Dna-binding transcription repressor activity, rna polymerase ii-specific
    (GO:0001227)
  • Dna binding
    (GO:0003677)
  • Male germ cell nucleus
    (GO:0001673)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Nucleus
    (GO:0005634)
  • Protein dimerization activity
    (GO:0046983)
  • Regulation of cell differentiation
    (GO:0045595)
  • Regulation of cell population proliferation
    (GO:0042127)
  • Regulation of dna-templated transcription
    (GO:0006355)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Sequence-specific double-stranded dna binding
    (GO:1990837)
  • Spermatogenesis
    (GO:0007283)
  • Transcription by rna polymerase ii
    (GO:0006366)

Significant Cells

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

  • melanocyte CL0000148
    CSI 3.63
    rCSI 2.69%
    PRS 97.14
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.08
    rCSI 3.83%
    PRS 93.53
  • blood vessel endothelial cell CL0000071
    CSI 2.82
    rCSI 5.85%
    PRS 97.75
  • ependymal cell CL0000065
    CSI 2.63
    rCSI 5.34%
    PRS 90.79
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.54
    rCSI 3.03%
    PRS 94.51
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.38
    rCSI 3.83%
    PRS 94.5
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.24
    rCSI 2.89%
    PRS 95.05
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.06
    rCSI 3.64%
    PRS 94.42
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.76
    rCSI 3.94%
    PRS 94.49
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.64
    rCSI 2.76%
    PRS 94.71
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.03
    rCSI 2.5%
    PRS 93.08
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.94
    rCSI 2.95%
    PRS 94.76
  • endothelial cell of placenta CL0009092
    CSI 0.87
    rCSI 4.27%
    PRS 98.49
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.82
    rCSI 2.95%
    PRS 93.46

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)

Loading network (please wait)...

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 [TCFL5](/details-gene/10732) encodes Transcription Factor-Like 5, a protein characterized by a basic helix-loop-helix (bHLH) motif. As a DNA-binding transcription factor, it is primarily localized to the nucleus and plays roles in regulating gene expression, cell differentiation, and proliferation. Functional annotations suggest it often acts as a transcriptional repressor. **Overall**, expression data reveals high significance in diverse cell types, including [melanocyte](/details-cell/CL0000148) and multiple subtypes of cortical GABAergic interneurons, indicating a potential role in nervous system development and pigment cell biology. Furthermore, literature strongly supports a highly specific and crucial function in male germline development, particularly during spermatogenesis ([Link](https://doi.org/10.1159/000015061)). ## Cellular Roles and Expression Landscape The expression profile of [TCFL5](/details-gene/10732) points to specialized roles in distinct cellular lineages. In the **Overall** context, it is most significant in [melanocyte](/details-cell/CL0000148) (CSI: 3.63), suggesting a key function in the identity or regulation of this cell type. A prominent feature of its expression pattern is its high significance across a wide array of inhibitory neurons in the central nervous system. This includes [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 3.08), [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 2.54), [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 2.38), and [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 2.24). This consistent high ranking across functionally distinct interneuron classes suggests [TCFL5](/details-gene/10732) may be a core regulator involved in the development, specification, or maintenance of cortical inhibitory circuits. Its significance also extends to other neural cell types, such as [ependymal cell](/details-cell/CL0000065) and [astrocyte of the cerebral cortex](/details-cell/CL0002605). Notably, research has identified a highly specific and critical role for [TCFL5](/details-gene/10732) in the male germline, where it is expressed in primary spermatocytes during the pachytene stage of meiosis ([Link](https://doi.org/10.1159/000015061)). This context-specific expression, not captured in the provided somatic cell-focused dataset, underscores its essential function in [Spermatogenesis](/details-go/GO:0007283). ## Pathways and Molecular Function The molecular functions of [TCFL5](/details-gene/10732) are centered on its identity as a transcription factor. Gene Ontology annotations confirm its role in [Dna-binding transcription factor activity, rna polymerase ii-specific](/details-go/GO:0000981) and [Protein dimerization activity](/details-go/GO:0046983), the latter being a common feature of bHLH proteins. Evidence points specifically towards a repressor function, as indicated by its annotation for [Dna-binding transcription repressor activity, rna polymerase ii-specific](/details-go/GO:0001227) and its involvement in the [Negative regulation of transcription by rna polymerase ii](/details-go/GO:0000122) pathway. Biologically, these molecular activities are linked to high-level processes such as [Cell differentiation](/details-go/GO:0030154) and the [Regulation of cell population proliferation](/details-go/GO:0042127). Its involvement in differentiation is consistent with its specific expression in terminally differentiated cell types like neurons and melanocytes. Its well-documented role in [Spermatogenesis](/details-go/GO:0007283), a complex developmental process involving both proliferation and differentiation, integrates its known molecular functions within a critical physiological context. ## Research Directions The specific expression patterns and annotated functions of [TCFL5](/details-gene/10732) provide a foundation for several testable hypotheses regarding its biological roles and potential involvement in disease. 1. **Hypothesis 1:** Given its high significance across multiple GABAergic interneuron subtypes, [TCFL5](/details-gene/10732) may act as a terminal selector gene required for establishing or maintaining the mature identity and function of these inhibitory neurons. Its dysregulation could contribute to neurodevelopmental disorders characterized by an imbalance of excitation and inhibition. 2. **Hypothesis 2:** Based on its top-ranking significance in [melanocyte](/details-cell/CL0000148), [TCFL5](/details-gene/10732) may regulate a transcriptional program essential for melanogenesis or melanocyte survival. Its aberrant expression could therefore be a driver or marker in melanoma. 3. **Hypothesis 3:** In the context of its specific expression in pachytene spermatocytes, [TCFL5](/details-gene/10732) may function as a transcriptional repressor that silences somatic gene programs, thereby ensuring the fidelity of the germline genetic and epigenetic state during meiosis. To test the role of [TCFL5](/details-gene/10732) in cortical interneuron development (Hypothesis 1), a conditional knockout mouse model could be generated using a pan-GABAergic Cre driver (e.g., *Gad2-Cre* or *Dlx5/6-Cre*). Analysis of the cortex in these knockout animals using single-cell RNA sequencing and patch-clamp electrophysiology would reveal defects in interneuron subtype specification, gene expression networks, and synaptic properties. As a transcription factor with cell-type-specific expression, [TCFL5](/details-gene/10732) presents a challenging but potentially valuable therapeutic target. Direct inhibition of transcription factors is notoriously difficult; however, if its overexpression is implicated in pathologies like melanoma, strategies could focus on inhibiting its protein-protein interactions (e.g., dimerization) or targeting its critical downstream effectors. Conversely, its essential role in spermatogenesis suggests that inhibiting its function could be explored as a target for non-hormonal male contraception.

Genular Protein ID: 3129002383

Symbol: TCFL5_HUMAN

Name: Transcription factor-like 5 protein

UniProtKB Accession Codes:

Q9UL49 O94771 Q9BYW0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 17 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 3 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 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11306602

Title: Dominant T- and B-cell epitopes in an autoantigen linked to Chagas' disease.

PubMed ID: 11306602

DOI: 10.1172/jci10734

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

PubMed ID: 9763657

Title: Cloning of TCFL5 encoding a novel human basic helix-loop-helix motif protein that is specifically expressed in primary spermatocytes at the pachytene stage.

PubMed ID: 9763657

DOI: 10.1159/000015061

Sequence Information:

  • Length: 500
  • Mass: 52697
  • Checksum: 39918DCA21A94E7B
  • Sequence:
    • MSGPGPREPP PEAGAAGGEA AVEGAGGGDA ALGEPGLSFT TTDLSLVEMT EVEYTQLQHI 
LCSHMEAAAD GELETRLNSA LLAAAGPGAG AGGFAAGGQG GAAPVYPVLC PSALAADAPC 
LGHIDFQELR MMLLSEAGAA EKTSGGGDGA RARADGAAKE GAGAAAAAAG PDGAPEARAK 
PAVRVRLEDR FNSIPAEPPP APRGPEPPEP GGALNNLVTL IRHPSELMNV PLQQQNKCTA 
LVKNKTAATT TALQFTYPLF TTNACSTSGN SNLSQTQSSS NSCSVLEAAK HQDIGLPRAF 
SFCYQQEIES TKQTLGSRNK VLPEQVWIKV GEAALCKQAL KRNRSRMRQL DTNVERRALG 
EIQNVGEGAT ATQGAWQSSE SSQANLGEQA QSGPQGGRSQ RRERHNRMER DRRRRIRICC 
DELNLLVPFC NAETDKATTL QWTTAFLKYI QERHGDSLKK EFESVFCGKT GRRLKLTRPD 
SLVTCPAQGS LQSSPSMEIK

Genular Protein ID: 300787290

Symbol: Q86TP4_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q86TP4

Database IDs:

ARBA 5 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 7 Gene3D 1 InterPro 3 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 2 SAM 1 SMART 1 SUPFAM 1

Citations:

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

Sequence Information:

  • Length: 483
  • Mass: 52265
  • Checksum: 9DB370986A5157DE
  • Sequence:
    • MTEVEYTQLQ HILCSHMEAA ADGELETRLN SALLAAAGPG AGAGGFAAGG QGGAAPVYPV 
LCPSALAADA PCLGHIDFQE LRMMLLSEAG AAEKTSGGGD GARARADGAA KEGAGAAAAA 
AGPDGAPEAR AKPAVRVRLE DRFNSIPAEP PPAPRGPEPP EPGGALNNLV TLIRHPSELM 
NVPLQQQNKC TALVKNKTAA TTTALQFTYP LFTTNACSTS GNSDLSQTQS SSNSCSVLEA 
AKHQDIGLPR AFSFCYQQEI ESTKQTLGSR NKVLPEQVWI KVGEAALCKQ ALKRNRSRMR 
QLDTNVERRA LGEIQNVGEG ATATQGAWQS SESSQANLGE QAQSGPQGGR SQRRERHNRM 
ERDRRRRIRI CCDELNLLVP FCNAETDKAT TLQWTTAFLK YIQERHGDSL KKVLSTNSRY 
VMLWTCFLKM KSAVDGKNPQ HAYRTANHKW LCLHEARSFA FEVSIWAHFQ LFRVRIPEGF 
LSI