Details for: FSTL4

Gene ID: 23105

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: FSTL4

Ensembl ID: ENSG00000053108

Description: follistatin like 4

Cell Significance Landscape

Associated with

  • Brain-derived neurotrophic factor binding
    (GO:0048403)
  • Calcium ion binding
    (GO:0005509)
  • Cell differentiation
    (GO:0030154)
  • Extracellular region
    (GO:0005576)
  • Negative regulation of brain-derived neurotrophic factor receptor signaling pathway
    (GO:0031549)
  • Negative regulation of collateral sprouting
    (GO:0048671)
  • Negative regulation of dendritic spine development
    (GO:0061000)
  • Regulation of bmp signaling pathway
    (GO:0030510)
  • Secretory granule
    (GO:0030141)

Significant Cells

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

  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 23.29
    rCSI 55.71%
    PRS 83.93
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 22.08
    rCSI 53.67%
    PRS 79.7
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 22.04
    rCSI 47.81%
    PRS 82.89
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 19.13
    rCSI 23.79%
    PRS 79.68
  • interneuron CL0000099
    CSI 15.93
    rCSI 31.98%
    PRS 87.56
  • L6b glutamatergic cortical neuron CL4023038
    CSI 15.4
    rCSI 48.14%
    PRS 82.98
  • sst GABAergic cortical interneuron CL4023017
    CSI 15.4
    rCSI 19.85%
    PRS 82.9
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 13.91
    rCSI 43.5%
    PRS 84.68
  • retinal cone cell CL0000573
    CSI 13.28
    rCSI 21.37%
    PRS 85.77
  • retinal bipolar neuron CL0000748
    CSI 13.19
    rCSI 24.7%
    PRS 85.51
  • neuron CL0000540
    CSI 13.05
    rCSI 34.74%
    PRS 82.05
  • retinal ganglion cell CL0000740
    CSI 13
    rCSI 28.72%
    PRS 83.78
  • GABAergic amacrine cell CL4030027
    CSI 12.99
    rCSI 44.5%
    PRS 81.52
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 12.95
    rCSI 42.55%
    PRS 82.69
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 12.64
    rCSI 45.48%
    PRS 80
  • neural cell CL0002319
    CSI 12.59
    rCSI 47.52%
    PRS 79.99
  • glutamatergic neuron CL0000679
    CSI 11.61
    rCSI 23.86%
    PRS 82.41
  • basal cell CL0000646
    CSI 11.16
    rCSI 14.92%
    PRS 90.12
  • amacrine cell CL0000561
    CSI 10.65
    rCSI 30.87%
    PRS 85.43
  • VIP GABAergic cortical interneuron CL4023016
    CSI 10.61
    rCSI 12.67%
    PRS 81.9
  • cerebral cortex neuron CL0010012
    CSI 8.95
    rCSI 36.45%
    PRS 86.41
  • inhibitory interneuron CL0000498
    CSI 8.87
    rCSI 20.47%
    PRS 85.06
  • cerebral cortex endothelial cell CL1001602
    CSI 8.24
    rCSI 14.25%
    PRS 88.18
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 8.08
    rCSI 14.27%
    PRS 81.15
  • H2 horizontal cell CL0004218
    CSI 8.08
    rCSI 40.17%
    PRS 87.91
  • retinal rod cell CL0000604
    CSI 8.01
    rCSI 14.12%
    PRS 89.11
  • S cone cell CL0003050
    CSI 7.78
    rCSI 34.17%
    PRS 89.22
  • cerebellar granule cell CL0001031
    CSI 7.78
    rCSI 11.43%
    PRS 88.52
  • rod bipolar cell CL0000751
    CSI 7.65
    rCSI 13.75%
    PRS 88.33
  • flat midget bipolar cell CL4033033
    CSI 7.64
    rCSI 54.62%
    PRS 84.31
  • astrocyte of the cerebral cortex CL0002605
    CSI 7.28
    rCSI 16.31%
    PRS 82.07
  • sncg GABAergic cortical interneuron CL4023015
    CSI 6.62
    rCSI 10.65%
    PRS 82.85
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 6.41
    rCSI 37.77%
    PRS 82.24
  • kidney connecting tubule epithelial cell CL1000768
    CSI 6.2
    rCSI 15.72%
    PRS 87.88
  • neutrophil CL0000775
    CSI 6.15
    rCSI 34.42%
    PRS 90.17
  • invaginating midget bipolar cell CL4033034
    CSI 6.12
    rCSI 36.12%
    PRS 84.82
  • glycinergic amacrine cell CL4030028
    CSI 5.93
    rCSI 15.46%
    PRS 87.59
  • renal principal cell CL0005009
    CSI 5.82
    rCSI 15.12%
    PRS 92.34
  • central nervous system neuron CL2000029
    CSI 5.72
    rCSI 42.01%
    PRS 85.82
  • lung neuroendocrine cell CL1000223
    CSI 5.33
    rCSI 7.89%
    PRS 93.71
  • ON parasol ganglion cell CL4033052
    CSI 4.14
    rCSI 58.81%
    PRS 86.19
  • serotonergic neuron CL0000850
    CSI 3.97
    rCSI 17.71%
    PRS 79.83
  • dopaminergic neuron CL0000700
    CSI 3.79
    rCSI 21.44%
    PRS 83.37
  • myoepithelial cell CL0000185
    CSI 3.63
    rCSI 9.18%
    PRS 94.36
  • conjunctival epithelial cell CL1000432
    CSI 3.59
    rCSI 5.48%
    PRS 91.68
  • GABAergic neuron CL0000617
    CSI 3.54
    rCSI 11.87%
    PRS 81.04
  • epithelial cell of proximal tubule CL0002306
    CSI 3.5
    rCSI 8.56%
    PRS 87.36
  • OFFx cell CL4033036
    CSI 3.33
    rCSI 15.65%
    PRS 84.13
  • medium spiny neuron CL1001474
    CSI 3.22
    rCSI 27.77%
    PRS 85.79
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 3.13
    rCSI 11.83%
    PRS 82.07
  • cerebellar neuron CL1001611
    CSI 3.03
    rCSI 26.7%
    PRS 81.82
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.88
    rCSI 4.83%
    PRS 81.89
  • basket cell CL0000118
    CSI 2.76
    rCSI 17.29%
    PRS 75.12
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.42
    rCSI 4.4%
    PRS 87.26
  • direct pathway medium spiny neuron CL4023026
    CSI 2.4
    rCSI 57.38%
    PRS 79.65
  • ON midget ganglion cell CL4033046
    CSI 2.39
    rCSI 48.62%
    PRS 85.24
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.37
    rCSI 57.19%
    PRS 79.74
  • pancreatic A cell CL0000171
    CSI 2.22
    rCSI 2.33%
    PRS 93.99
  • OFF midget ganglion cell CL4033047
    CSI 2.16
    rCSI 44.02%
    PRS 85.91
  • retina horizontal cell CL0000745
    CSI 1.97
    rCSI 3%
    PRS 89.76
  • starburst amacrine cell CL0004232
    CSI 1.82
    rCSI 15.31%
    PRS 80.73
  • H1 horizontal cell CL0004217
    CSI 1.78
    rCSI 7.06%
    PRS 87.31
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.27
    rCSI 13.42%
    PRS 89.48
  • group 2 innate lymphoid cell CL0001069
    CSI 0.81
    rCSI 4.37%
    PRS 98.07

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 [FSTL4](/details-gene/23105) (Follistatin Like 4) is a protein-coding gene located on chromosome 5q31.1. It encodes a secreted protein that belongs to the follistatin family, characterized by its involvement in cellular regulation and signaling. Expression data indicates that [FSTL4](/details-gene/23105) is a highly specific marker for various neuronal populations, particularly within the cerebral cortex and retina. Functional annotations suggest it plays a key role in modulating neuronal development and signaling, primarily through the negative regulation of the brain-derived neurotrophic factor (BDNF) signaling pathway and the regulation of BMP signaling. Its extracellular localization and high specificity for neurons point towards a function in intercellular communication within the central nervous system. ## Cellular Roles and Expression Landscape The expression profile of [FSTL4](/details-gene/23105) demonstrates a profound and specific role within the nervous system. **Overall**, the gene shows the highest significance in a diverse array of neuronal subtypes, establishing it as a key marker for both excitatory and inhibitory circuits in the brain and retina. Its most significant expression is observed in cortical glutamatergic neurons, including [L4 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4030063) (CSI: 23.29), [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040) (CSI: 22.08), and [L2/3 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4030059) (CSI: 22.04). This suggests a fundamental role in the function of the brain's primary excitatory projection neurons. Concurrently, [FSTL4](/details-gene/23105) is also a significant marker for inhibitory [interneurons](/details-cell/CL0000099), such as [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 19.13) and [sst GABAergic cortical interneurons](/details-cell/CL4023017) (CSI: 15.40). This co-expression in both excitatory and inhibitory cell types points to a broader role in regulating cortical circuit balance and activity. Furthermore, its high significance in specialized sensory neurons, including [retinal cone cells](/details-cell/CL0000573) (CSI: 13.28), [retinal bipolar neurons](/details-cell/CL0000748) (CSI: 13.19), and [retinal ganglion cells](/details-cell/CL0000740) (CSI: 13.00), highlights its importance in the visual system. The consistent and high expression across these distinct [neuron](/details-cell/CL0000540) populations, coupled with a lack of significant expression in non-neuronal cell types in the provided data, underscores its highly specialized function within the central nervous system. ## Pathways and Molecular Function [FSTL4](/details-gene/23105) is annotated as a secreted, extracellular protein ([GO:0005576](https://www.ebi.ac.uk/QuickGO/term/GO:0005576)) that functions as a signaling modulator. Its molecular functions are directly tied to its neuronal expression pattern. A primary annotated role is the **negative regulation of the brain-derived neurotrophic factor (BDNF) receptor signaling pathway** ([GO:0031549](https://www.ebi.ac.uk/QuickGO/term/GO:0031549)) through direct BDNF binding ([GO:0048403](https://www.ebi.ac.uk/QuickGO/term/GO:0048403)). BDNF is a critical neurotrophin that promotes neuronal survival, differentiation, and synaptic plasticity. By antagonizing BDNF signaling, [FSTL4](/details-gene/23105) may serve as a crucial homeostatic brake on these processes. This is consistent with its roles in the negative regulation of collateral sprouting ([GO:0048671](https://www.ebi.ac.uk/QuickGO/term/GO:0048671)) and dendritic spine development ([GO:0061000](https://www.ebi.ac.uk/QuickGO/term/GO:0061000)), processes that are highly dependent on neurotrophin activity. Additionally, [FSTL4](/details-gene/23105) is implicated in the **regulation of the BMP signaling pathway** ([GO:0030510](https://www.ebi.ac.uk/QuickGO/term/GO:0030510)), another key pathway involved in cell differentiation ([GO:0030154](https://www.ebi.ac.uk/QuickGO/term/GO:0030154)) and development throughout the nervous system. The protein's ability to bind calcium ions ([GO:0005509](https://www.ebi.ac.uk/QuickGO/term/GO:0005509)) is also a feature common to many extracellular proteins involved in signaling and matrix interactions. ## Research Directions The specific expression of [FSTL4](/details-gene/23105) in diverse neuronal populations and its function as an extracellular inhibitor of key neurodevelopmental pathways suggest it is a critical regulator of neural circuit formation and plasticity. **Testable Hypotheses:** 1. Given its role as a negative regulator of BDNF signaling and dendritic spine development ([GO:0061000](https://www.ebi.ac.uk/QuickGO/term/GO:0061000)), the targeted knockout of [FSTL4](/details-gene/23105) in cortical glutamatergic neurons will lead to increased dendritic spine density and enhanced long-term potentiation, potentially at the cost of circuit stability. 2. Based on its high expression in multiple retinal cell types, [FSTL4](/details-gene/23105) may function as a locally secreted factor that modulates BMP signaling to maintain the structural integrity and synaptic organization of the outer and inner plexiform layers of the retina. **Proposed Experiment:** To test the first hypothesis, one could utilize a conditional knockout mouse model (e.g., Cre-Lox) to selectively delete [FSTL4](/details-gene/23105) in excitatory neurons of the cerebral cortex. *In vivo* two-photon microscopy could then be employed to longitudinally image and quantify dendritic spine density and dynamics in these neurons compared to wild-type controls. Concurrently, electrophysiological recordings from cortical slices could be used to assess changes in synaptic transmission and plasticity, specifically by measuring parameters of long-term potentiation (LTP). **Therapeutic Potential:** As a secreted, extracellular antagonist of the pro-survival and pro-plasticity BDNF pathway, [FSTL4](/details-gene/23105) represents a compelling therapeutic target. In neurodegenerative diseases such as Alzheimer's disease or in major depressive disorder, where BDNF levels are often reduced and synaptic connections are lost, **inhibition** of [FSTL4](/details-gene/23105) activity could be a viable strategy. A therapeutic agent, such as a neutralizing monoclonal antibody or a small molecule inhibitor, could disinhibit BDNF signaling, thereby promoting neuronal survival and enhancing synaptic plasticity. The high specificity of [FSTL4](/details-gene/23105) expression to the nervous system may help limit off-target effects of such a therapy.

Genular Protein ID: 1889151987

Symbol: FSTL4_HUMAN

Name: Follistatin-related protein 4

UniProtKB Accession Codes:

Q6MZW2 Q8TBU0 Q9UPU1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 3 CTD 1 ChEBI 5 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 ExpressionAtlas 1 GO 9 Gene3D 4 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 12 KEGG 1 MANE-Select 1 MEROPS 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 RefSeq 2 SMART 3 SMR 1 STRING 1 SUPFAM 4 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

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: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

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: 10470851

Title: Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 10470851

DOI: 10.1093/dnares/6.3.197

PubMed ID: 15527507

Title: An enigmatic fourth runt domain gene in the fugu genome: ancestral gene loss versus accelerated evolution.

PubMed ID: 15527507

DOI: 10.1186/1471-2148-4-43

Sequence Information:

  • Length: 842
  • Mass: 93096
  • Checksum: 9EEE073CD3C99517
  • Sequence:
    • MKPGGFWLHL TLLGASLPAA LGWMDPGTSR GPDVGVGESQ AEEPRSFEVT RREGLSSHNE 
LLASCGKKFC SRGSRCVLSR KTGEPECQCL EACRPSYVPV CGSDGRFYEN HCKLHRAACL 
LGKRITVIHS KDCFLKGDTC TMAGYARLKN VLLALQTRLQ PLQEGDSRQD PASQKRLLVE 
SLFRDLDADG NGHLSSSELA QHVLKKQDLD EDLLGCSPGD LLRFDDYNSD SSLTLREFYM 
AFQVVQLSLA PEDRVSVTTV TVGLSTVLTC AVHGDLRPPI IWKRNGLTLN FLDLEDINDF 
GEDDSLYITK VTTIHMGNYT CHASGHEQLF QTHVLQVNVP PVIRVYPESQ AQEPGVAASL 
RCHAEGIPMP RITWLKNGVD VSTQMSKQLS LLANGSELHI SSVRYEDTGA YTCIAKNEVG 
VDEDISSLFI EDSARKTLAN ILWREEGLSV GNMFYVFSDD GIIVIHPVDC EIQRHLKPTE 
KIFMSYEEIC PQREKNATQP CQWVSAVNVR NRYIYVAQPA LSRVLVVDIQ AQKVLQSIGV 
DPLPAKLSYD KSHDQVWVLS WGDVHKSRPS LQVITEASTG QSQHLIRTPF AGVDDFFIPP 
TNLIINHIRF GFIFNKSDPA VHKVDLETMM PLKTIGLHHH GCVPQAMAHT HLGGYFFIQC 
RQDSPASAAR QLLVDSVTDS VLGPNGDVTG TPHTSPDGRF IVSAAADSPW LHVQEITVRG 
EIQTLYDLQI NSGISDLAFQ RSFTESNQYN IYAALHTEPD LLFLELSTGK VGMLKNLKEP 
PAGPAQPWGG THRIMRDSGL FGQYLLTPAR ESLFLINGRQ NTLRCEVSGI KGGTTVVWVG 
EV