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    SLC16A3 solute carrier family 16 member 3 [ Homo sapiens (human) ]

    Gene ID: 9123, updated on 3-Nov-2024

    Summary

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    Official Symbol
    SLC16A3provided by HGNC
    Official Full Name
    solute carrier family 16 member 3provided by HGNC
    Primary source
    HGNC:HGNC:10924
    See related
    Ensembl:ENSG00000141526 MIM:603877; AllianceGenome:HGNC:10924
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MCT3; MCT4; MCT 3; MCT 4; MCT-3; MCT-4
    Summary
    Lactic acid and pyruvate transport across plasma membranes is catalyzed by members of the proton-linked monocarboxylate transporter (MCT) family, which has been designated solute carrier family-16. Each MCT appears to have slightly different substrate and inhibitor specificities and transport kinetics, which are related to the metabolic requirements of the tissues in which it is found. The MCTs, which include MCT1 (SLC16A1; MIM 600682) and MCT2 (SLC16A7; MIM 603654), are characterized by 12 predicted transmembrane domains (Price et al., 1998 [PubMed 9425115]).[supplied by OMIM, Mar 2008]
    Expression
    Broad expression in placenta (RPKM 10.2), appendix (RPKM 8.8) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SLC16A3 in Genome Data Viewer
    Location:
    17q25.3
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (82217934..82240086)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (83097177..83108820)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (80186311..80197962)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:80054421-80055336 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9192 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9193 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9194 Neighboring gene small nucleolar RNA, C/D box 134 Neighboring gene fatty acid synthase Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:80061739-80062652 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:80062653-80063566 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12986 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12987 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12988 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:80065397-80066310 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12989 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:80074745-80075652 Neighboring gene coiled-coil domain containing 57 Neighboring gene uncharacterized LOC124904119 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12990 Neighboring gene Sharpr-MPRA regulatory region 9641 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:80131430-80132220 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:80133010-80133799 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:80137557-80138524 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:80138525-80139491 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr17:80163065-80163866 and GRCh37_chr17:80163867-80164668 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9195 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:80171129-80172071 Neighboring gene Sharpr-MPRA regulatory region 4733 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12994 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:80183365-80183517 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9196 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9197 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9198 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9199 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9200 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9201 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9202 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9203 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12995 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:80195135-80195906 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:80196677-80197447 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12996 Neighboring gene microRNA 6787 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr17:80210177-80211376 Neighboring gene casein kinase 1 delta Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:80223561-80224292 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9204 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9205 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9206 Neighboring gene uncharacterized LOC124904089 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:80234577-80235076 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9207 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9208 Neighboring gene long intergenic non-protein coding RNA 1970

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Monocarboxylate transporter 4 (MCT4) is a high affinity transporter capable of exporting lactate in high-lactate microenvironments. Contreras-Baeza Y, et al. J Biol Chem, 2019 Dec 27. PMID 31719150, Free PMC Article
    2. Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma. Long Y, et al. Cancer Med, 2018 Sep. PMID 30051648, Free PMC Article
    3. MCT4 as a potential therapeutic target to augment gemcitabine chemosensitivity in resected pancreatic cancer. Lee SH, et al. Cell Oncol (Dordr), 2021 Dec. PMID 34791637
    4. Targeting tumor-intrinsic SLC16A3 to enhance anti-PD-1 efficacy via tumor immune microenvironment reprogramming. Yu T, et al. Cancer Lett, 2024 May 1. PMID 38522774
    5. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4). Ziegler K, et al. Arch Biochem Biophys, 2016 Jun 1. PMID 26854723, Free PMC Article

    See all (67) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Bone Morphogenetic Protein-4 Promotes Phenotypic Modulation via SMAD-4/MCT-4 Axis in Vascular Smooth Muscle Cells.
      Title: Bone Morphogenetic Protein-4 Promotes Phenotypic Modulation via SMAD-4/MCT-4 Axis in Vascular Smooth Muscle Cells.
    2. Targeting tumor-intrinsic SLC16A3 to enhance anti-PD-1 efficacy via tumor immune microenvironment reprogramming.
      Title: Targeting tumor-intrinsic SLC16A3 to enhance anti-PD-1 efficacy via tumor immune microenvironment reprogramming.
    3. Involvement of SLC16A1/MCT1 and SLC16A3/MCT4 in l-lactate transport in the hepatocellular carcinoma cell line.
      Title: Involvement of SLC16A1/MCT1 and SLC16A3/MCT4 in l-lactate transport in the hepatocellular carcinoma cell line.
    4. Monocarboxylate transporter 4 inhibition potentiates hepatocellular carcinoma immunotherapy through enhancing T cell infiltration and immune attack.
      Title: Monocarboxylate transporter 4 inhibition potentiates hepatocellular carcinoma immunotherapy through enhancing T cell infiltration and immune attack.
    5. Identification and Validation of a Prognostic Model Based on Three MVI-Related Genes in Hepatocellular Carcinoma.
      Title: Identification and Validation of a Prognostic Model Based on Three MVI-Related Genes in Hepatocellular Carcinoma.
    6. MCT4 as a potential therapeutic target to augment gemcitabine chemosensitivity in resected pancreatic cancer.
      Title: MCT4 as a potential therapeutic target to augment gemcitabine chemosensitivity in resected pancreatic cancer.
    7. The tissue expression of MCT3, MCT8, and MCT9 genes in women with breast cancer.
      Title: The tissue expression of MCT3, MCT8, and MCT9 genes in women with breast cancer.
    8. these data suggest that the key effect of MCT4 depletion on NK cells probably utilizes inductive autophagy as a compensatory metabolic mechanism to minimize the acidic extracellular microenvironment associated with lactate export in tumors.
      Title: Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma.
    9. MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid.
      Title: Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).
    10. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC138472, MGC138474

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding HDA PubMed 
    enables lactate:proton symporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables lactate:proton symporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables monocarboxylic acid transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables pyruvate transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in lactate transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in pyruvate catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in pyruvate transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in apical plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in basolateral plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in basolateral plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lateral plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in nuclear membrane IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    monocarboxylate transporter 4
    Names
    monocarboxylate transporter 3
    solute carrier family 16 (monocarboxylate transporter), member 3
    solute carrier family 16 (monocarboxylic acid transporters), member 3
    solute carrier family 16, member 3 (monocarboxylic acid transporter 4)

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001042422.3 → NP_001035887.1  monocarboxylate transporter 4

      See identical proteins and their annotated locations for NP_001035887.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same protein.
      Source sequence(s)
      AC132872
      Consensus CDS
      CCDS11804.1
      UniProtKB/Swiss-Prot
      B3KXG8, O15427, Q2M1P8
      UniProtKB/TrEMBL
      Q53G91
      Related
      ENSP00000464625.2, ENST00000584689.6
      Conserved Domains (1) summary
      cl26868
      Location:8 → 444
      2A0111; oxalate/formate antiporter family transporter

    2. NM_001042423.3 → NP_001035888.1  monocarboxylate transporter 4

      See identical proteins and their annotated locations for NP_001035888.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same protein.
      Source sequence(s)
      AC132872
      Consensus CDS
      CCDS11804.1
      UniProtKB/Swiss-Prot
      B3KXG8, O15427, Q2M1P8
      UniProtKB/TrEMBL
      Q53G91
      Related
      ENSP00000376150.1, ENST00000392339.6
      Conserved Domains (1) summary
      cl26868
      Location:8 → 444
      2A0111; oxalate/formate antiporter family transporter

    3. NM_001206950.2 → NP_001193879.1  monocarboxylate transporter 4

      See identical proteins and their annotated locations for NP_001193879.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2, 3, 4, 5 and 6 encode the same protein.
      Source sequence(s)
      AC132872
      Consensus CDS
      CCDS11804.1
      UniProtKB/Swiss-Prot
      B3KXG8, O15427, Q2M1P8
      UniProtKB/TrEMBL
      Q53G91
      Related
      ENSP00000376152.1, ENST00000392341.6
      Conserved Domains (1) summary
      cl26868
      Location:8 → 444
      2A0111; oxalate/formate antiporter family transporter

    4. NM_001206951.2 → NP_001193880.1  monocarboxylate transporter 4

      See identical proteins and their annotated locations for NP_001193880.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same protein.
      Source sequence(s)
      AC132872
      Consensus CDS
      CCDS11804.1
      UniProtKB/Swiss-Prot
      B3KXG8, O15427, Q2M1P8
      UniProtKB/TrEMBL
      Q53G91
      Related
      ENSP00000483212.1, ENST00000617373.5
      Conserved Domains (1) summary
      cl26868
      Location:8 → 444
      2A0111; oxalate/formate antiporter family transporter

    5. NM_001206952.2 → NP_001193881.1  monocarboxylate transporter 4

      See identical proteins and their annotated locations for NP_001193881.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same protein.
      Source sequence(s)
      AC132872
      Consensus CDS
      CCDS11804.1
      UniProtKB/Swiss-Prot
      B3KXG8, O15427, Q2M1P8
      UniProtKB/TrEMBL
      Q53G91
      Related
      ENSP00000482013.1, ENST00000619321.2
      Conserved Domains (1) summary
      cl26868
      Location:8 → 444
      2A0111; oxalate/formate antiporter family transporter

    6. NM_004207.4 → NP_004198.1  monocarboxylate transporter 4

      See identical proteins and their annotated locations for NP_004198.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same protein.
      Source sequence(s)
      AC132872
      Consensus CDS
      CCDS11804.1
      UniProtKB/Swiss-Prot
      B3KXG8, O15427, Q2M1P8
      UniProtKB/TrEMBL
      Q53G91
      Related
      ENSP00000462405.1, ENST00000582743.6
      Conserved Domains (1) summary
      cl26868
      Location:8 → 444
      2A0111; oxalate/formate antiporter family transporter

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      82217934..82240086
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024451023.2 → XP_024306791.1  monocarboxylate transporter 4 isoform X1

      UniProtKB/Swiss-Prot
      B3KXG8, O15427, Q2M1P8
      UniProtKB/TrEMBL
      Q53G91
      Related
      ENSP00000463880.2, ENST00000580098.6
      Conserved Domains (1) summary
      cl26868
      Location:8 → 444
      2A0111; oxalate/formate antiporter family transporter

    2. XM_047437036.1 → XP_047292992.1  monocarboxylate transporter 4 isoform X1

      UniProtKB/Swiss-Prot
      B3KXG8, O15427, Q2M1P8

    3. XM_047437037.1 → XP_047292993.1  monocarboxylate transporter 4 isoform X1

      UniProtKB/Swiss-Prot
      B3KXG8, O15427, Q2M1P8

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      83097177..83108820
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O15427.1 GenPept UniProtKB/Swiss-Prot:O15427

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