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

Gene ID: 9123, updated on 11-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (82217934..82240086)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (83097177..83108820)
105.20220307 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
  • 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. 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
  2. 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
  3. 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
  4. Involvement of SLC16A1/MCT1 and SLC16A3/MCT4 in l-lactate transport in the hepatocellular carcinoma cell line. Mukai Y, et al. Biopharm Drug Dispos, 2022 Oct. PMID 36104287
  5. Monocarboxylate transporter 4 inhibition potentiates hepatocellular carcinoma immunotherapy through enhancing T cell infiltration and immune attack. Fang Y, et al. Hepatology, 2023 Jan 1. PMID 35043976

See all (57) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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).
  8. 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.
  9. Observational study of gene-disease association. (HuGE Navigator)
    Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
  10. Ocular absorption of monocarboxylic acid drugs may be enhanced by MCT transporter SLC16A3, and the absorption route provided by the transporter may be utilized to improve the bioavailability of topically applied ophthalmic drugs.
    Title: Monocarboxylate transport in human corneal epithelium and cell lines.
Submit: New GeneRIF Correction See all GeneRIFs (11)

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 monocarboxylic acid transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein catabolic process 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
  
is_active_in synapse IDA
Inferred from Direct Assay
more info
 PubMed 

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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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_2023_10

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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