Details for: POU3F4

Gene ID: 5456

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: POU3F4

Ensembl ID: ENSG00000196767

Description: POU class 3 homeobox 4

Cell Significance Landscape

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 13.52
    rCSI 28.76%
    PRS 94.2
  • glioblast CL0000030
    CSI 5.38
    rCSI 8.59%
    PRS 94.22
  • interneuron CL0000099
    CSI 4.66
    rCSI 9.37%
    PRS 95.4
  • radial glial cell CL0000681
    CSI 4.27
    rCSI 5.93%
    PRS 97.28
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 3.62
    rCSI 4.64%
    PRS 96.13
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 3.48
    rCSI 10.28%
    PRS 97.26
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.35
    rCSI 5.92%
    PRS 92.64
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.02
    rCSI 3.49%
    PRS 94.04
  • forebrain radial glial cell CL0013000
    CSI 2.5
    rCSI 8.02%
    PRS 97.55
  • neural cell CL0002319
    CSI 1.62
    rCSI 6.11%
    PRS 90.19

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.

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  • 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 [POU3F4](/details-gene/5456) is a protein-coding gene located on the X chromosome that encodes POU class 3 homeobox 4, a transcription factor critical for embryonic development. As a member of the POU domain family, it plays a fundamental role in regulating gene expression by binding to specific DNA sequences. Its expression is highly significant in various neural precursor and glial cell types, underscoring its essential function in the developing central nervous system. Functionally, [POU3F4](/details-gene/5456) is integral to processes such as [brain development](/details-go/GO:0007420) and, most notably, [cochlea morphogenesis](/details-go/GO:0090103). Mutations in this gene are clinically associated with X-linked deafness type 3 (DFN3) ([153245](https://omim.org/entry/300039)), a condition characterized by mixed conductive and sensorineural hearing loss, as established in multiple studies [Link](https://doi.org/10.1126/science.7839145), [Link](https://doi.org/10.1093/hmg/4.8.1467). ## Cellular Roles and Expression Landscape The expression profile of [POU3F4](/details-gene/5456) highlights its specialized role as a key regulator in neurogenesis and neural development. **Overall**, the gene shows its highest significance in [progenitor cell](/details-cell/CL0011026)s (CSI: 13.52), suggesting a primary function in maintaining or directing the fate of undifferentiated neural precursors. This is further supported by its high significance in more committed neural lineages, including [glioblast](/details-cell/CL0000030) (CSI: 5.38), [interneuron](/details-cell/CL0000099) (CSI: 4.66), and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) (CSI: 3.62). The gene's prominence in specialized developmental cell types, such as [radial glial cell](/details-cell/CL0000681) (CSI: 4.27) and [forebrain radial glial cell](/details-cell/CL0013000) (CSI: 2.50), is consistent with its role in orchestrating the cellular architecture of the developing brain. Its activity within specific neuronal subtypes, like the [cerebral cortex GABAergic interneuron](/details-cell/CL0010011), further points to a function in neuronal differentiation and subtype specification. The collective expression data firmly establish [POU3F4](/details-gene/5456) as a critical transcriptional controller within the developing central nervous system. ## Pathways and Molecular Function [POU3F4](/details-gene/5456) functions primarily as a [DNA-binding transcription factor activity, rna polymerase ii-specific](/details-go/GO:0000981). Located within the [nucleus](/details-go/GO:0005634), it binds to [chromatin](/details-go/GO:0000785) to execute its function in the [regulation of transcription by rna polymerase ii](/details-go/GO:0006357). This core molecular activity drives its involvement in higher-order biological processes. Its role in [brain development](/details-go/GO:0007420) is consistent with its high expression in various neural progenitor and glial cells. Critically, its function is directly implicated in [cochlea morphogenesis](/details-go/GO:0090103) and the [sensory perception of sound](/details-go/GO:0007605), providing a direct molecular explanation for the deafness phenotype associated with its mutation [Link](https://doi.org/10.1126/science.7839145). The gene product is also known to engage in [protein binding](/details-go/GO:0005515), suggesting it may interact with other transcriptional regulators to form larger protein complexes that fine-tune gene expression during development [Link](https://doi.org/10.1016/s0169-328x(96)00238-0). ## Research Directions The well-established link between [POU3F4](/details-gene/5456) mutations and congenital deafness (DFN3) provides a strong foundation for further investigation into its precise molecular mechanisms during inner ear development. **Proposed Hypotheses:** 1. [POU3F4](/details-gene/5456) acts as a pioneer transcription factor in otic progenitor cells, where it is required to establish chromatin accessibility at key gene loci that govern the differentiation of sensory hair cells and supporting cells of the cochlea. Its absence leads to a failure in lineage commitment, resulting in the structural and functional deficits observed in DFN3. 2. Beyond the cochlea, the high significance of [POU3F4](/details-gene/5456) in [glioblast](/details-cell/CL0000030)s suggests a potential role in glial cell tumorigenesis. Its misexpression or reactivation in mature glial cells may contribute to the maintenance of a de-differentiated, proliferative state characteristic of glioblastoma. **Experimental Approach:** To test the first hypothesis, a powerful approach would be to utilize human induced pluripotent stem cell (iPSC)-derived inner ear organoids. 1. Generate an isogenic [POU3F4](/details-gene/5456) knockout iPSC line using CRISPR-Cas9 genome editing, alongside a wild-type control. 2. Differentiate both cell lines into cochlear organoids, which recapitulate aspects of inner ear development *in vitro*. 3. Perform single-cell RNA-sequencing (scRNA-seq) and single-cell ATAC-sequencing (scATAC-seq) at key developmental time points. 4. This combined analysis would reveal how the loss of [POU3F4](/details-gene/5456) alters the transcriptional landscape and chromatin accessibility profiles of developing otic cell types, identifying the specific downstream gene regulatory networks that are disrupted and lead to abnormal cochlear morphogenesis. **Therapeutic Potential:** As a developmental transcription factor, direct pharmacological targeting of [POU3F4](/details-gene/5456) is challenging and likely to have significant off-target effects. However, for the monogenic disorder DFN3, which results from loss-of-function mutations, [POU3F4](/details-gene/5456) represents a candidate for gene replacement therapy. A strategy involving adeno-associated virus (AAV)-mediated delivery of a functional [POU3F4](/details-gene/5456) gene to the developing inner ear could potentially restore normal cochlear development and prevent hearing loss. This approach would require careful optimization of delivery timing and cell-type specificity to be viable.

Genular Protein ID: 3429189517

Symbol: PO3F4_HUMAN

Name: POU domain, class 3, transcription factor 4

UniProtKB Accession Codes:

P49335 B2RC71 Q5H9G9 Q99410

Database IDs:

AGR 1 AlphaFoldDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 GO 11 Gene3D 2 GeneCards 1 GeneReviews 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 InParanoid 1 InterPro 8 KEGG 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 Orphanet 2 OrthoDB 1 PANTHER 2 PIR 1 PIRSF 1 PRINTS 1 PRO 1 PROSITE 5 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7839145

Title: Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.

PubMed ID: 7839145

DOI: 10.1126/science.7839145

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 9105675

Title: The class III POU factor Brn-4 interacts with other class III POU factors and the heterogeneous nuclear ribonucleoprotein U.

PubMed ID: 9105675

DOI: 10.1016/s0169-328x(96)00238-0

PubMed ID: 7581392

Title: Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3.

PubMed ID: 7581392

DOI: 10.1093/hmg/4.8.1467

PubMed ID: 9298820

Title: The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation.

PubMed ID: 9298820

DOI: 10.1002/(sici)1098-1004(1997)10:3<207::aid-humu5>3.0.co;2-f

PubMed ID: 9778298

Title: A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed deafness (DFN3).

PubMed ID: 9778298

DOI: 10.1097/00005537-199810000-00022

Sequence Information:

  • Length: 361
  • Mass: 39427
  • Checksum: DE30602CFAC4683A
  • Sequence:
    • MATAASNPYS ILSSTSLVHA DSAGMQQGSP FRNPQKLLQS DYLQGVPSNG HPLGHHWVTS 
LSDGGPWSST LATSPLDQQD VKPGREDLQL GAIIHHRSPH VAHHSPHTNH PNAWGASPAP 
NPSITSSGQP LNVYSQPGFT VSGMLEHGGL TPPPAAASAQ SLHPVLREPP DHGELGSHHC 
QDHSDEETPT SDELEQFAKQ FKQRRIKLGF TQADVGLALG TLYGNVFSQT TICRFEGLQL 
SFKNMCKLKP LLNKWLEEAD SSTGSPTSID KIAAQGRKRK KRTSIEVSVK GVLETHFLKC 
PKPAAQEISS LADSLQLEKE VVRVWFCNRR QKEKRMTPPG DQQPHEVYSH TVKTDTSCHD 
L

Genular Protein ID: 2061667775

Symbol: A0A2R8Y739_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A2R8Y739

Database IDs:

ARBA 7 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 GO 9 Gene3D 2 GeneTree 1 HGNC 1 InterPro 8 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRINTS 1 PROSITE 7 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 1 RefSeq 1 RuleBase 2 SAM 1 SMART 2 SMR 1 SUPFAM 2 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

Sequence Information:

  • Length: 361
  • Mass: 39441
  • Checksum: DE30658CF9646E3A
  • Sequence:
    • MATAASNPYS ILSSTSLVHA DSAGMQQGSP FRNPQKLLQS DYLQGVPSNG HPLGHHWVTS 
LSDGGPWSST LATSPLDQQD VKPGREDLQL GAIIHHRSPH VAHHSPHTNH PNAWGASPAP 
NPSITSSGQP LNVYSQPGFT VSGMLEHGGL TPPPAAASAQ SLHPVLREPP DHGELGSHHC 
QDHSDEETPT SDELEQFAKQ FKQRRIKLGF TQADVGLALG TLYGNVFSQT TICRFEALQL 
SFKNMCKLKP LLNKWLEEAD SSTGSPTSID KIAAQGRKRK KRTSIEVSVK GVLETHFLKC 
PKPAAQEISS LADSLQLEKE VVRVWFCNRR QKEKRMTPPG DQQPHEVYSH TVKTDTSCHD 
L