Details for: SLC35F4

Gene ID: 341880

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: SLC35F4

Ensembl ID: ENSG00000151812

Description: solute carrier family 35 member F4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 31.82
    rCSI 38%
    PRS 97.14
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 29.34
    rCSI 51.81%
    PRS 97.25
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 27.06
    rCSI 45.42%
    PRS 97.51
  • sncg GABAergic cortical interneuron CL4023015
    CSI 25.74
    rCSI 41.4%
    PRS 96.98
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 25.61
    rCSI 31.86%
    PRS 96.79
  • cerebellar granule cell CL0001031
    CSI 18.52
    rCSI 27.22%
    PRS 97.59
  • glioblast CL0000030
    CSI 16.89
    rCSI 26.94%
    PRS 97.67
  • retinal rod cell CL0000604
    CSI 16.08
    rCSI 28.35%
    PRS 97.9
  • retinal bipolar neuron CL0000748
    CSI 15.05
    rCSI 28.19%
    PRS 97.36
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 13.32
    rCSI 41.65%
    PRS 97.5
  • sst GABAergic cortical interneuron CL4023017
    CSI 12.67
    rCSI 16.33%
    PRS 97.53
  • inhibitory interneuron CL0000498
    CSI 10.48
    rCSI 24.2%
    PRS 97.24
  • interneuron CL0000099
    CSI 9.71
    rCSI 19.49%
    PRS 98.18
  • invaginating midget bipolar cell CL4033034
    CSI 9.19
    rCSI 54.25%
    PRS 95.58
  • parietal epithelial cell CL1000452
    CSI 9.17
    rCSI 24.51%
    PRS 98.47
  • amacrine cell CL0000561
    CSI 8.56
    rCSI 24.8%
    PRS 97.13
  • retinal ganglion cell CL0000740
    CSI 6.81
    rCSI 15.03%
    PRS 97.09
  • Bergmann glial cell CL0000644
    CSI 6.63
    rCSI 9.07%
    PRS 97.59
  • rod bipolar cell CL0000751
    CSI 5.94
    rCSI 10.67%
    PRS 97.87
  • dopaminergic neuron CL0000700
    CSI 5.52
    rCSI 31.19%
    PRS 96.32
  • glycinergic amacrine cell CL4030028
    CSI 5.26
    rCSI 13.7%
    PRS 96.79
  • basket cell CL0000118
    CSI 5.03
    rCSI 31.48%
    PRS 92.43
  • GABAergic neuron CL0000617
    CSI 4.86
    rCSI 16.28%
    PRS 95.02
  • starburst amacrine cell CL0004232
    CSI 4.59
    rCSI 38.64%
    PRS 94.08
  • cerebellar neuron CL1001611
    CSI 4.34
    rCSI 38.16%
    PRS 95.01
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 4.07
    rCSI 9.89%
    PRS 96.24
  • GABAergic amacrine cell CL4030027
    CSI 4.05
    rCSI 13.87%
    PRS 95.41
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 4.05
    rCSI 15.3%
    PRS 96.62
  • retinal cone cell CL0000573
    CSI 3.52
    rCSI 5.67%
    PRS 97.27
  • serotonergic neuron CL0000850
    CSI 2.82
    rCSI 12.59%
    PRS 94.37
  • L6b glutamatergic cortical neuron CL4023038
    CSI 2.64
    rCSI 8.24%
    PRS 97.14
  • diffuse bipolar 4 cell CL4033031
    CSI 2.53
    rCSI 29%
    PRS 93.21
  • direct pathway medium spiny neuron CL4023026
    CSI 2.36
    rCSI 56.44%
    PRS 95.61
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.17
    rCSI 52.24%
    PRS 95.47
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.84
    rCSI 10.82%
    PRS 96.69
  • central nervous system neuron CL2000029
    CSI 1.81
    rCSI 13.27%
    PRS 97.53
  • medium spiny neuron CL1001474
    CSI 1.75
    rCSI 15.05%
    PRS 97
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.43
    rCSI 5.14%
    PRS 96.62
  • ON midget ganglion cell CL4033046
    CSI 0.98
    rCSI 19.93%
    PRS 96.73
  • OFF midget ganglion cell CL4033047
    CSI 0.91
    rCSI 18.44%
    PRS 96.69
  • ON parasol ganglion cell CL4033052
    CSI 0.65
    rCSI 9.25%
    PRS 96.63

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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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 [SLC35F4](/gene/341880), or Solute Carrier Family 35 Member F4, is a protein-coding gene located on chromosome 14. As a member of the solute carrier (SLC) superfamily, it is predicted to function as a transporter protein embedded within the cell membrane ([GO:0016020](https://www.ebi.ac.uk/QuickGO/term/GO:0016020)). **Overall**, expression data reveals a highly specific and significant role for [SLC35F4](/gene/341880) within the central nervous system. It exhibits exceptionally high expression in various subtypes of inhibitory neurons, most notably in [VIP GABAergic cortical interneuron](/details-cell/CL4023016)s, [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064)s, and [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)s. This strong enrichment suggests a specialized function related to neuronal homeostasis, metabolism, or signaling, particularly within the GABAergic system. ## Cellular Roles and Expression Landscape The expression profile of [SLC35F4](/gene/341880) strongly points to a specialized role in the nervous system. The gene consistently ranks as a top marker across a diverse range of neuronal cell types, with a particular emphasis on inhibitory interneurons. It is most significantly expressed in multiple subtypes of cortical GABAergic interneurons, including those expressing VIP, lamp5, sncg, pvalb, and sst. This widespread importance across different classes of interneurons suggests a fundamental role in maintaining inhibitory tone and cortical circuit function. Beyond the cerebral cortex, [SLC35F4](/gene/341880) is also a significant marker in other key brain regions. It shows high expression in the [cerebellar granule cell](/details-cell/CL0001031), one of the most numerous neuronal types in the brain, as well as in specialized sensory neurons such as the [retinal rod cell](/details-cell/CL0000604) and [retinal bipolar neuron](/details-cell/CL0000748). This pattern indicates its function is not limited to a single circuit but is relevant to different modalities of neural processing, from motor coordination to vision. Interestingly, [SLC35F4](/gene/341880) also shows significant expression in [glioblast](/details-cell/CL0000030)s, suggesting a potential role in the pathophysiology of this brain tumor. The collective data portrays [SLC35F4](/gene/341880) as a key molecular component of diverse neuronal populations, with a potentially critical, albeit uncharacterized, transport function. ## Pathways and Molecular Function The functional annotation for [SLC35F4](/gene/341880) is currently sparse, with its primary known characteristic being its localization to the membrane ([GO:0016020](https://www.ebi.ac.uk/QuickGO/term/GO:0016020)). This is consistent with its classification as a solute carrier, which are integral membrane proteins responsible for transporting various substrates such as ions, metabolites, and nutrients across cellular membranes. The specific substrate(s) transported by [SLC35F4](/gene/341880) have not yet been identified. However, its high enrichment in GABAergic interneurons and other electrically active cells suggests its substrate may be crucial for processes such as neurotransmitter synthesis or recycling, maintenance of ion gradients, or neuronal metabolic support. Its characterization has been noted in large-scale genomic sequencing efforts ([Link](https://doi.org/10.1038/nature01348), [Link](https://doi.org/10.1038/35057062)). ## Research Directions The highly specific expression pattern of [SLC35F4](/gene/341880) in the central nervous system, coupled with its uncharacterized function, presents several compelling avenues for future research. **Proposed Hypotheses:** 1. Given its profound enrichment in multiple subtypes of cortical GABAergic interneurons, [SLC35F4](/gene/341880) likely transports a substrate essential for the metabolic or functional integrity of these inhibitory cells. The substrate could be a precursor for GABA synthesis, a key nutrient, or a molecule involved in cellular waste removal, the absence of which could lead to impaired inhibitory neurotransmission and circuit hyperexcitability. 2. The significant expression of [SLC35F4](/gene/341880) in [glioblast](/details-cell/CL0000030)s suggests that this transporter may be hijacked by tumor cells to facilitate rapid growth. It could be responsible for the uptake of a critical nutrient from the tumor microenvironment, and its activity may correlate with tumor grade or patient prognosis. 3. In the retina, the expression of [SLC35F4](/gene/341880) in both [retinal rod cell](/details-cell/CL0000604)s and [retinal bipolar neuron](/details-cell/CL0000748)s suggests a role in the visual processing pathway. It might be involved in transporting a key metabolite for phototransduction or in regulating the synaptic environment between photoreceptors and their downstream targets. **Key Experimental Approach:** To test the hypothesis that [SLC35F4](/gene/341880) is critical for GABAergic neuron function (Hypothesis 1), a multi-pronged approach could be employed. First, a conditional knockout mouse model could be created using a Vgat-Cre driver to specifically delete [SLC35F4](/gene/341880) in GABAergic neurons. Brain slices from these mice could be analyzed using whole-cell patch-clamp electrophysiology to measure changes in inhibitory postsynaptic currents (IPSCs) and neuronal firing properties. Concurrently, untargeted metabolomics on FACS-sorted GABAergic neurons from knockout versus wild-type mice could be performed to identify candidate substrates that accumulate or are depleted upon gene deletion, thereby revealing its transport function. **Therapeutic Potential:** The therapeutic potential of [SLC35F4](/gene/341880) is primarily linked to its expression in [glioblast](/details-cell/CL0000030)s. If its transport function is proven to be essential for tumor cell survival or proliferation, it would become a viable therapeutic target. An inhibitory strategy using small molecules to block its transport activity could selectively starve tumor cells or render them more vulnerable to conventional therapies. However, its widespread expression in critical neuron populations throughout the brain poses a significant risk for on-target neurological side effects. Therefore, any therapeutic agent would need to be highly specific or be delivered directly to the tumor site to minimize toxicity.

Genular Protein ID: 1041260672

Symbol: S35F4_HUMAN

Name: Solute carrier family 35 member F4

UniProtKB Accession Codes:

A4IF30 A6NDQ3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 2 KEGG 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 4 STRING 1 SUPFAM 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 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

Sequence Information:

  • Length: 521
  • Mass: 57809
  • Checksum: 8509C6BAB218E5B8
  • Sequence:
    • MDELLLDLFH KLTSGRQLAA GNGLCGISHK EQEVWKPGHN ILVKMRKEDK SLVWLIHSTL 
ARYTQVTNFL GTSRSSVTRC KPGANCPSSH SGISRQLSPL SVTEDSSAPI LELQNQGSSG 
VCGHRVERQN RSADDGTQTH SENSSQENRI KARCLSCTSM VLKGIWGLLI ILSVSSSWVG 
TTQIVKITYK NFYCPFFMTW FSTNWNIMFF PVYYSGHLAT AQEKQSPMKK FRECSRIFGE 
DGLTLKLFLK RTAPFSILWT LTNYLYLLAL KKLTATDVSA LFCCNKAFVF LLSWIVLKDR 
FMGVRIVAAI MAITGIVMMA YADNFHADSI IGVAFAVGSA STSALYKVLF KMFLGSANFG 
EAAHFVSTLG FFNLIFISFT PVILYFTKVE HWSSFAALPW GCLCGMAGLW LAFNILVNVG 
VVLTYPILIS IGTVLSVPGN AAVDLLKQEV IFNVVRLAAT IIICIGFLLM LLPEEWDEIT 
LRFINSLKEK KSEEHVDDVT DPSIHLRGRG RANGTVSIPL A

Genular Protein ID: 3982681324

Symbol: G3V4Z9_HUMAN

Name: N/A

UniProtKB Accession Codes:

G3V4Z9

Database IDs:

AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 2 KEGG 1 MANE-Select 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 Pfam 2 Proteomes 2 RefSeq 1 SAM 2 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 12508121

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

PubMed ID: 12508121

DOI: 10.1038/nature01348

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 485
  • Mass: 53607
  • Checksum: E0CA560646B5CFB9
  • Sequence:
    • MDVKAAPNGV ATIEDRILRI TGYYGYYPGY SSQKSTSRSS VTRCKPGANC PSSHSGISRQ 
LSPLSVTEDS SAPILELQNQ GSSGVCGHRV ERQNRSADDG TQTHSENSSQ ENRIKARCLS 
CTSMVLKGIW GLLIILSVSS SWVGTTQIVK ITYKNFYCPF FMTWFSTNWN IMFFPVYYSG 
HLATAQEKQS PMKKFRECSR IFGEDGLTLK LFLKRTAPFS ILWTLTNYLY LLALKKLTAT 
DVSALFCCNK AFVFLLSWIV LKDRFMGVRI VAAIMAITGI VMMAYADNFH ADSIIGVAFA 
VGSASTSALY KVLFKMFLGS ANFGEAAHFV STLGFFNLIF ISFTPVILYF TKVEHWSSFA 
ALPWGCLCGM AGLWLAFNIL VNVGVVLTYP ILISIGTVLS VPGNAAVDLL KQEVIFNVVR 
LAATIIICIG FLLMLLPEEW DEITLRFINS LKEKKSEEHV DDVTDPSIHL RGRGRANGTV 
SIPLA