Details for: SLC16A4

Gene ID: 9122

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: SLC16A4

Ensembl ID: ENSG00000168679

Description: solute carrier family 16 member 4

Cell Significance Landscape

Associated with

Significant Cells

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

  • cerebral cortex endothelial cell CL1001602
    CSI 4.83
    rCSI 8.35%
    PRS 84.15
  • conjunctival epithelial cell CL1000432
    CSI 4.02
    rCSI 6.14%
    PRS 89.15
  • melanocyte CL0000148
    CSI 3.57
    rCSI 2.64%
    PRS 85.72
  • vascular leptomeningeal cell CL4023051
    CSI 3.32
    rCSI 5.81%
    PRS 85.97
  • brush cell of tracheobronchial tree CL0002075
    CSI 3.23
    rCSI 9.58%
    PRS 95.21
  • extravillous trophoblast CL0008036
    CSI 3.12
    rCSI 3.87%
    PRS 88.22
  • myofibroblast cell CL0000186
    CSI 3.1
    rCSI 4.29%
    PRS 86.34
  • cardiac muscle cell CL0000746
    CSI 3.07
    rCSI 4.41%
    PRS 81.77
  • neural crest cell CL0011012
    CSI 3.04
    rCSI 2.41%
    PRS 82.28
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.76
    rCSI 3.02%
    PRS 91.19
  • chondrocyte CL0000138
    CSI 2.66
    rCSI 4.22%
    PRS 84.76
  • hepatic stellate cell CL0000632
    CSI 2.48
    rCSI 9.28%
    PRS 84.78
  • ependymal cell CL0000065
    CSI 2.46
    rCSI 4.98%
    PRS 71.66
  • adipocyte CL0000136
    CSI 2.42
    rCSI 3.1%
    PRS 81.46
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.39
    rCSI 2.76%
    PRS 82.53
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.38
    rCSI 3.37%
    PRS 87.25
  • retinal bipolar neuron CL0000748
    CSI 2.28
    rCSI 4.27%
    PRS 80.91
  • Mueller cell CL0000636
    CSI 2.25
    rCSI 5.14%
    PRS 83.05
  • choroid plexus epithelial cell CL0000706
    CSI 2.2
    rCSI 3.6%
    PRS 82.25
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.18
    rCSI 5.63%
    PRS 86.59
  • alveolar adventitial fibroblast CL4028006
    CSI 2.16
    rCSI 3.42%
    PRS 90.61
  • blood vessel smooth muscle cell CL0019018
    CSI 2.15
    rCSI 17.5%
    PRS 86.6
  • intestinal epithelial cell CL0002563
    CSI 2.14
    rCSI 2.23%
    PRS 87.31
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.02
    rCSI 2.6%
    PRS 77.37
  • epithelial cell of proximal tubule CL0002306
    CSI 1.99
    rCSI 4.87%
    PRS 82.9
  • cardiac neuron CL0010022
    CSI 1.98
    rCSI 6.34%
    PRS 88.2
  • enterocyte CL0000584
    CSI 1.9
    rCSI 3.07%
    PRS 86.76
  • stem cell CL0000034
    CSI 1.85
    rCSI 1.79%
    PRS 85.42
  • retinal pigment epithelial cell CL0002586
    CSI 1.83
    rCSI 3.63%
    PRS 86.14
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.73
    rCSI 2.91%
    PRS 76.15
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.73
    rCSI 2.06%
    PRS 76.24
  • retinal ganglion cell CL0000740
    CSI 1.71
    rCSI 3.78%
    PRS 78.84
  • renal interstitial pericyte CL1001318
    CSI 1.67
    rCSI 4.6%
    PRS 86.83
  • mesothelial cell CL0000077
    CSI 1.54
    rCSI 6.03%
    PRS 72.42
  • renal principal cell CL0005009
    CSI 1.53
    rCSI 3.97%
    PRS 88.95
  • keratocyte CL0002363
    CSI 1.5
    rCSI 3.61%
    PRS 90.88
  • fibroblast of cardiac tissue CL0002548
    CSI 1.5
    rCSI 7.18%
    PRS 90.49
  • placental villous trophoblast CL2000060
    CSI 1.37
    rCSI 2.11%
    PRS 87.96
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.22
    rCSI 3.54%
    PRS 88.77
  • syncytiotrophoblast cell CL0000525
    CSI 1.2
    rCSI 3.45%
    PRS 91.34
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.18
    rCSI 2.99%
    PRS 83.1
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.06
    rCSI 6.65%
    PRS 83.36
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.71
    rCSI 2.22%
    PRS 77.58
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.71
    rCSI 1.72%
    PRS 73.92

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 [SLC16A4](/details-gene/9122), or Solute Carrier Family 16 Member 4, encodes a protein known as Monocarboxylate Transporter 5 (MCT5). It functions as a transmembrane transporter, specifically facilitating the symport of monocarboxylic acids across the plasma membrane, as defined by its gene ontology annotations ([GO:0008028](https://www.ebi.ac.uk/QuickGO/term/GO:0008028)). **Overall**, expression data reveals that [SLC16A4](/details-gene/9122) is a significant marker for diverse cell types, including [cerebral cortex endothelial cell](/details-cell/CL1001602) and [conjunctival epithelial cell](/details-cell/CL1000432), suggesting a key role in metabolic transport at biological barriers. Its high significance in specialized cells such as [melanocyte](/details-cell/CL0000148) and [cardiac muscle cell](/details-cell/CL0000746) further indicates its importance in tissues with unique metabolic demands. The existence of this gene as part of a larger transporter family was confirmed in early cloning studies [Link](https://doi.org/10.1042/bj3290321). ## Cellular Roles and Expression Landscape The expression profile of [SLC16A4](/details-gene/9122) points to a broad yet specific role in cellular metabolism and transport across multiple tissues. **Overall**, its most significant expression is observed in [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 4.83), suggesting a specialized function in transport across the blood-brain barrier. High significance is also noted in other barrier-forming cells like [conjunctival epithelial cell](/details-cell/CL1000432) (CSI: 4.02) and structural cells like [myofibroblast cell](/details-cell/CL0000186) (CSI: 3.10) and [chondrocyte](/details-cell/CL0000138) (CSI: 2.66). Furthermore, [SLC16A4](/details-gene/9122) is highly expressed in metabolically active and specialized cell types. Its prominence in [melanocyte](/details-cell/CL0000148) (CSI: 3.57) suggests a potential role in transporting metabolites related to pigment production. In [cardiac muscle cell](/details-cell/CL0000746) (CSI: 3.07), it may be involved in the shuttling of energy substrates like lactate. The gene's presence in developmental cell types such as [neural crest cell](/details-cell/CL0011012) and [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) implies a role during cellular differentiation and migration. This diverse expression pattern underscores its importance as a workhorse transporter tailored to the specific metabolic needs of various cell lineages. ## Pathways and Molecular Function The function of [SLC16A4](/details-gene/9122) is centered on its role as a transmembrane transporter. Its annotation within the Gene Ontology framework specifies its involvement in `Carboxylic acid transmembrane transport` ([GO:1905039](https://www.ebi.ac.uk/QuickGO/term/GO:1905039)). **Molecular Function:** At the molecular level, it exhibits `Monocarboxylic acid transmembrane transporter activity` ([GO:0008028](https://www.ebi.ac.uk/QuickGO/term/GO:0008028)) and `symporter activity` ([GO:0015293](https://www.ebi.ac.uk/QuickGO/term/GO:0015293)). This indicates it cotransports monocarboxylates (such as lactate, pyruvate, or ketone bodies) with another ion, likely H+, in the same direction across the cell membrane. The protein is an integral component of the `plasma membrane` ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)). This transport function is consistent with its expression profile. For instance, in [cerebral cortex endothelial cell](/details-cell/CL1001602), it likely facilitates the transport of energy substrates to the brain. In [cardiac muscle cell](/details-cell/CL0000746), it may contribute to the utilization of lactate as a fuel source. ## Research Directions The specific substrates and regulatory mechanisms of [SLC16A4](/details-gene/9122) in different cellular contexts remain largely uncharacterized, offering several avenues for future research. **Proposed Hypotheses:** 1. Given its top-ranking expression in [cerebral cortex endothelial cell](/details-cell/CL1001602), [SLC16A4](/details-gene/9122) may be a primary transporter for ketone bodies or other alternative energy substrates across the blood-brain barrier, a role that could become critical during periods of fasting or in neurodegenerative conditions associated with impaired glucose metabolism. 2. The high significance of [SLC16A4](/details-gene/9122) in [melanocyte](/details-cell/CL0000148) suggests it may be responsible for the efflux of acidic byproducts of melanogenesis, thereby helping to maintain intracellular pH homeostasis and supporting sustained pigment production. 3. In [cardiac muscle cell](/details-cell/CL0000746), [SLC16A4](/details-gene/9122) might function as a regulated lactate importer, allowing the heart to efficiently use lactate produced by other tissues (e.g., skeletal muscle) as a preferred oxidative fuel, particularly during exercise. **Key Experimental Approach:** To test the hypothesis regarding its role in melanocytes (Hypothesis 2), one could utilize a CRISPR-Cas9 knockout of [SLC16A4](/details-gene/9122) in a human melanoma cell line or primary melanocytes. The functional consequences could be assessed by measuring changes in intracellular pH upon stimulation of melanogenesis, quantifying melanin production, and using mass spectrometry-based metabolomics to identify retained monocarboxylate species within the knockout cells compared to wild-type controls. **Therapeutic Potential:** As a solute carrier, [SLC16A4](/details-gene/9122) represents a potentially druggable target. Its specific expression pattern could be exploited for therapeutic benefit. For diseases characterized by metabolic reprogramming, such as melanoma (arising from [melanocyte](/details-cell/CL0000148)), **inhibition** of [SLC16A4](/details-gene/9122) could disrupt tumor metabolism and survival. Conversely, strategies aimed at **activation** or enhancing its transport function might be beneficial in neurological disorders where augmenting energy substrate delivery across the blood-brain barrier is desired. The development of specific small-molecule modulators would be a critical first step in exploring these possibilities.

Genular Protein ID: 1445128462

Symbol: MOT5_HUMAN

Name: Monocarboxylate transporter 5

UniProtKB Accession Codes:

O15374 A8K3V5 B2R9C9 B4DJ67 B4DPX7 E7EPY8 G3V175 Q5T612 Q8WU09

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 5 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 10 Ensembl 5 ExpressionAtlas 1 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 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 5 RNAct 1 RefSeq 6 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9425115

Title: Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past.

PubMed ID: 9425115

DOI: 10.1042/bj3290321

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 487
  • Mass: 54022
  • Checksum: 3CF236C69CC29631
  • Sequence:
    • MLKREGKVQP YTKTLDGGWG WMIVIHFFLV NVFVMGMTKT FAIFFVVFQE EFEGTSEQIG 
WIGSIMSSLR FCAGPLVAII CDILGEKTTS ILGAFVVTGG YLISSWATSI PFLCVTMGLL 
PGLGSAFLYQ VAAVVTTKYF KKRLALSTAI ARSGMGLTFL LAPFTKFLID LYDWTGALIL 
FGAIALNLVP SSMLLRPIHI KSENNSGIKD KGSSLSAHGP EAHATETHCH ETEESTIKDS 
TTQKAGLPSK NLTVSQNQSE EFYNGPNRNR LLLKSDEESD KVISWSCKQL FDISLFRNPF 
FYIFTWSFLL SQLAYFIPTF HLVARAKTLG IDIMDASYLV SVAGILETVS QIISGWVADQ 
NWIKKYHYHK SYLILCGITN LLAPLATTFP LLMTYTICFA IFAGGYLALI LPVLVDLCRN 
STVNRFLGLA SFFAGMAVLS GPPIAGWLYD YTQTYNGSFY FSGICYLLSS VSFFFVPLAE 
RWKNSLT