SLC16A7

gene
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Also known as MCT2

Summary

SLC16A7 (solute carrier family 16 member 7, HGNC:10928) is a protein-coding gene on chromosome 12q14.1, encoding Monocarboxylate transporter 2 (O60669). Proton-coupled monocarboxylate symporter.

This gene is a member of the monocarboxylate transporter family. Members in this family transport metabolites, such as lactate, pyruvate, and ketone bodies. The protein encoded by this gene catalyzes the proton-linked transport of monocarboxylates and has the highest affinity for pyruvate. This protein has been reported to be more highly expressed in prostate and colorectal cancer specimens when compared to control specimens. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9194 — RefSeq curated summary.

At a glance

  • GWAS associations: 11
  • Clinical variants (ClinVar): 90 total
  • Druggable target: yes — 1 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_001270623

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:10928
Approved symbolSLC16A7
Namesolute carrier family 16 member 7
Location12q14.1
Locus typegene with protein product
StatusApproved
AliasesMCT2
Ensembl geneENSG00000118596
Ensembl biotypeprotein_coding
OMIM603654
Entrez9194

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 24 protein_coding, 6 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000261187, ENST00000546459, ENST00000547379, ENST00000547801, ENST00000548444, ENST00000548610, ENST00000549033, ENST00000549305, ENST00000549465, ENST00000549588, ENST00000549928, ENST00000550062, ENST00000551877, ENST00000552024, ENST00000552405, ENST00000552432, ENST00000858943, ENST00000858944, ENST00000858945, ENST00000858946, ENST00000858947, ENST00000858948, ENST00000858949, ENST00000858950, ENST00000858951, ENST00000858952, ENST00000858953, ENST00000858954, ENST00000858955, ENST00000858956, ENST00000958121, ENST00000958122, ENST00000958123

RefSeq mRNA: 3 — MANE Select: NM_001270623 NM_001270622, NM_001270623, NM_004731

CCDS: CCDS8961

Canonical transcript exons

ENST00000547379 — 6 exons

ExonStartEnd
ENSE000023424275977942359789841
ENSE000023643315965515259655250
ENSE000024099515959602959596236
ENSE000035031195977465759775475
ENSE000035110885977121959771362
ENSE000036646245970477259705018

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9673 / max 454.0499, expressed in 1556 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter IDTPM avgSamples expressed
1263598.59891472
1263603.36011083
1263671.291368
1263580.3777173
1263570.098636
1263630.089223
1263650.045821
1263640.035719
2067610.026820
2067620.015111

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
heart right ventricleUBERON:000208098.88gold quality
renal medullaUBERON:000036298.36gold quality
vena cavaUBERON:000408797.96gold quality
pericardiumUBERON:000240797.54gold quality
spermCL:000001997.16gold quality
tongue squamous epitheliumUBERON:000691996.26gold quality
cardia of stomachUBERON:000116295.34gold quality
male germ cellCL:000001594.84gold quality
left ventricle myocardiumUBERON:000656694.72gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450294.25gold quality
superior surface of tongueUBERON:000737194.24gold quality
body of tongueUBERON:001187693.92gold quality
nippleUBERON:000203093.87gold quality
myocardiumUBERON:000234993.57gold quality
pharyngeal mucosaUBERON:000035593.08gold quality
biceps brachiiUBERON:000150792.97gold quality
adrenal tissueUBERON:001830392.80gold quality
oral cavityUBERON:000016792.75gold quality
tongueUBERON:000172392.74gold quality
skin of hipUBERON:000155492.39gold quality
calcaneal tendonUBERON:000370192.29gold quality
cervix squamous epitheliumUBERON:000692292.29gold quality
esophagus squamous epitheliumUBERON:000692092.28gold quality
squamous epitheliumUBERON:000691491.98gold quality
saphenous veinUBERON:000731891.46gold quality
superficial temporal arteryUBERON:000161491.06gold quality
endothelial cellCL:000011590.96gold quality
cauda epididymisUBERON:000436090.94gold quality
gingivaUBERON:000182890.45gold quality
Brodmann (1909) area 23UBERON:001355490.12gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

ExperimentMarker?Max mean expression
E-MTAB-8142yes36.32
E-CURD-88yes22.57
E-CURD-46yes13.29
E-MTAB-6701yes11.42
E-GEOD-137537yes7.08
E-MTAB-7316no859.53
E-ANND-3no0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA

miRNA regulators (miRDB)

348 targeting SLC16A7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3646100.0073.565283
HSA-MIR-4668-3P100.0068.742635
HSA-MIR-4776-3P100.0068.731340
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-126-5P100.0072.713180
HSA-MIR-190A-3P100.0080.355520
HSA-MIR-4262100.0073.263931
HSA-MIR-5692A100.0074.406850
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-656-3P100.0072.152788
HSA-MIR-4425100.0067.591049
HSA-MIR-200B-3P100.0073.312693
HSA-MIR-200C-3P100.0073.352685
HSA-MIR-429100.0073.442698
HSA-MIR-3163100.0077.238605
HSA-MIR-340-5P100.0072.504437
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-366299.9973.825684
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-428299.9975.366408
HSA-MIR-453199.9969.703181
HSA-MIR-453499.9966.581907
HSA-MIR-548AW99.9972.573559
HSA-MIR-181A-5P99.9972.962995
HSA-MIR-181B-5P99.9972.972996
HSA-MIR-181C-5P99.9972.952996
HSA-MIR-181D-5P99.9973.042997
HSA-MIR-511-3P99.9968.851467

Literature-anchored findings (GeneRIF, showing 25)

  • MCT2 immunoreactivity was noted in astrocytic cell bodies from week 19 and spread subsequently to the astrocyte end-feet in contact with blood vessels of visual cortex. (PMID:14757520)
  • Gamma-hydroxybutyric acid (GHB) is a substrate for both MCT2 and MCT4. (PMID:17502341)
  • Colorectal neoplasms showed a loss of expression of MCT2 in plasma membranes. (PMID:18188595)
  • These data demonstrate neuronal MCT2 expression in human, but since a portion of it exhibits a distinct synaptic localization, it further supports a putative role for MCT2 in adjustment of energy supply to levels of activity. (PMID:18598673)
  • Data suggest that hypoxia increases lactate release from adipocytes and modulates MCT expression in a type-specific manner, with MCT1 and MCT4, but not MCT2 expression, being hypoxia-inducible transcription factor-1 (HIF-1) dependent. (PMID:19876643)
  • Ocular absorption of monocarboxylic acid drugs may be enhanced by MCT transporter SLC16A7, and the absorption route provided by this transporter may be utilized to improve the bioavailability of topically applied ophthalmic drugs. (PMID:20035863)
  • MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44, were analysed. (PMID:20454640)
  • data suggest that extracellular membrane-bound CAIV, but not cytosolic CAII, augments transport activity of MCT2 in a non-catalytic manner, possibly by facilitating a proton pathway other than His-88 (PMID:21680735)
  • Data show that a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. (PMID:21787388)
  • Light microscopic immunohistochemistry revealed significantly less perivascular MCT2 immunoreactivity in the hippocampal formation in medial temporal lobe epilepsy than in non-MTLE patients (PMID:22535546)
  • The monocarboxylate transporter 2 (MCT2) protein was tumor-selectively expressed in human colorectal malignancies and knockdown of MCT2 induces mitochondrial dysfunction, cell-cycle arrest, and senescence. (PMID:22964484)
  • this study provided evidence for the presence of MCT2 in prostate cancer, selectively labeling malignant glands. (PMID:23192371)
  • MCT2-3’ UTR SNP (+2626 G > A) had a strong association with oligoasthenoteratozoospermia. (PMID:24799634)
  • This study identified that CGPs was found to significantly correlate with the differential expression and methylation of genes encoding solute carrier family 16, member 7. (PMID:25243493)
  • SNPs in MCT1 and MCT2 genes may affect clinical outcomes and can be used to predict the response to adjuvant chemotherapy in CRC patients who received surgical treatment. (PMID:25492048)
  • Our findings suggest that SNPs in MCT1 and MCT2 genes may affect clinical outcomes and can be used to predict the response to adjuvant chemotherapy in NSCLC patients who received surgical treatment once validated in future study. (PMID:25578492)
  • Data suggest that monocarboxylate transporter 2 (MCT2) at peroxisomes is related to an increase in beta-oxidation levels which may be crucial for malignant transformation. (PMID:25639644)
  • SLC16A7 (MCT2) epigenetic regulation results in protein over-expression, affecting signalling and cellular phenotypes in prostate cancer (PMID:26035357)
  • Adipocytes promote malignant growth of breast tumors with MCT2 expression via beta-hydroxybutyrate. (PMID:28281525)
  • MCT2 dictates the mode of action of N-oxalylglycine (NOG) by determining its intracellular concentration (PMID:30297875)
  • the present study reports that the combination of tumour stroma percentage and tumour cell expression of cytoplasmic MCT-2 or nuclear LDH-5 is associated with poor prognosis. (PMID:30521130)
  • Cooperative transport mechanism of human monocarboxylate transporter 2. (PMID:32415067)
  • Identification of the essential extracellular aspartic acids conserved in human monocarboxylate transporters 1, 2, and 4. (PMID:32819565)
  • Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function. (PMID:35939682)
  • Functional heterogeneity of MCT1 and MCT4 in metabolic reprogramming affects osteosarcoma growth and metastasis. (PMID:36814318)

Cross-species orthologs

17 orthologs

OrganismSymbolGene ID
ENSDARG00000098258
mus_musculusSlc16a7ENSMUSG00000020102
rattus_norvegicusSlc16a7ENSRNOG00000007839
drosophila_melanogasterMct1FBGN0023549
drosophila_melanogasterCG14196FBGN0031002
drosophila_melanogasterCG8051FBGN0031012
drosophila_melanogasterSlnFBGN0033657
drosophila_melanogasterCG8468FBGN0033913
drosophila_melanogasterTargFBGN0033955
drosophila_melanogasterCG13907FBGN0035173
drosophila_melanogasteroutFBGN0259834
caenorhabditis_elegansWBGENE00003986
caenorhabditis_elegansWBGENE00010834
caenorhabditis_elegansWBGENE00015273
caenorhabditis_elegansWBGENE00015676
caenorhabditis_elegansWBGENE00020168
caenorhabditis_elegansWBGENE00021227

Paralogs (13): SLC16A8 (ENSG00000100156), SLC16A6 (ENSG00000108932), SLC16A10 (ENSG00000112394), SLC16A3 (ENSG00000141526), SLC16A2 (ENSG00000147100), SLC16A12 (ENSG00000152779), SLC16A1 (ENSG00000155380), SLC16A14 (ENSG00000163053), SLC16A9 (ENSG00000165449), SLC16A4 (ENSG00000168679), SLC16A5 (ENSG00000170190), SLC16A11 (ENSG00000174326), SLC16A13 (ENSG00000174327)

Protein

Protein identifiers

Monocarboxylate transporter 2O60669 (reviewed: O60669)

Alternative names: Solute carrier family 16 member 7

All UniProt accessions (9): O60669, F8VQS4, F8VS95, F8VVU7, F8VXG4, F8VYZ2, F8W0N3, F8W0U4, F8W1M4

UniProt curated annotations — full annotation on UniProt →

Function. Proton-coupled monocarboxylate symporter. Catalyzes the rapid transport across the plasma membrane of monocarboxylates such as L-lactate, pyruvate and ketone bodies, acetoacetate, beta-hydroxybutyrate and acetate. Dimerization is functionally required and both subunits work cooperatively in transporting substrate.

Subunit / interactions. Homodimer. Interacts with GRID2IP. Interacts with EMB; interaction mediates SLC16A7 targeting to the plasma membrane. Interacts with isoform 2 of BSG.

Subcellular location. Cell membrane. Basolateral cell membrane. Cytoplasm.

Tissue specificity. Detected in heart and in blood lymphocytes and monocytes (at protein level). High expression in testis, moderate to low in spleen, heart, kidney, pancreas, skeletal muscle, brain and leukocyte. Restricted expression in normal tissues, but widely expressed in cancer cells.

Activity regulation. Transport activity exhibits steep dependence on substrate concentration. Substrate concentration sensitivity of SLC16A7 arises from the strong inter-subunit cooperativity of the SLC16A7 dimer during transport. Inhibited by AR-C155858.

Similarity. Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.

RefSeq proteins (3): NP_001257551, NP_001257552, NP_004722 (=MANE)

Domains & families (InterPro)

IDNameType
IPR004743MCTFamily
IPR011701MFSFamily
IPR020846MFS_domDomain
IPR036259MFS_trans_sfHomologous_superfamily
IPR050327Proton-linked_MCTFamily

Pfam: PF07690

Catalyzed reactions (Rhea), 7 shown:

  • (S)-lactate(in) + H(+)(in) = (S)-lactate(out) + H(+)(out) (RHEA:29415)
  • pyruvate(out) + H(+)(out) = pyruvate(in) + H(+)(in) (RHEA:64720)
  • acetoacetate(out) + H(+)(out) = acetoacetate(in) + H(+)(in) (RHEA:71775)
  • 4-methyl-2-oxopentanoate(out) + H(+)(out) = 4-methyl-2-oxopentanoate(in) + H(+)(in) (RHEA:71779)
  • 3-methyl-2-oxobutanoate(out) + H(+)(out) = 3-methyl-2-oxobutanoate(in) + H(+)(in) (RHEA:71783)
  • (R)-3-hydroxybutanoate(out) + H(+)(out) = (R)-3-hydroxybutanoate(in) + H(+)(in) (RHEA:71795)
  • (S)-3-hydroxybutanoate(out) + H(+)(out) = (S)-3-hydroxybutanoate(in) + H(+)(in) (RHEA:71871)

UniProt features (48 total): mutagenesis site 14, topological domain 13, transmembrane region 12, sequence conflict 3, region of interest 2, chain 1, compositionally biased region 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDBMethodResolution (Å)
9L0CELECTRON MICROSCOPY3.2
9L0BELECTRON MICROSCOPY3.7
7BP3ELECTRON MICROSCOPY3.8

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O60669-F184.380.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 293 (may be protonated during monocarboxylate transport)

Mutagenesis-validated functional residues (14):

PositionPhenotype
18reduces pyruvate transmembrane transporter activity. no effect on protein abundance. does not affect cell surface locali
20reduces pyruvate transmembrane transporter activity. no effect on protein abundance. does not affect cell surface locali
34reduces pyruvate transmembrane transporter activity. no effect on protein abundance. does not affect cell surface locali
38reduces pyruvate transmembrane transporter activity. no effect on protein abundance. does not affect cell surface locali
70no effect on protein abundance. does not affect cell surface localization.
143reduces pyruvate transmembrane transporter activity. reduces pyruvate transmembrane transporter activity. no effect on p
147reduces pyruvate transmembrane transporter activity. reduces pyruvate transmembrane transporter activity. no effect on p
262no effect on protein abundance. does not affect cell surface localization.
293reduced proton-dependent active symport, but not pyruvate transport.
297reduces pyruvate transmembrane transporter activity. no effect on protein abundance. does not affect cell surface locali
305reduces pyruvate transmembrane transporter activity. no effect on protein abundance. does not affect cell surface locali
351reduces pyruvate transmembrane transporter activity. no effect on protein abundance. does not affect cell surface locali
355reduces pyruvate transmembrane transporter activity. no effect on protein abundance. does not affect cell surface locali
360reduces pyruvate transmembrane transporter activity. no effect on protein abundance. does not affect cell surface locali

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

IDPathway
R-HSA-433692Proton-coupled monocarboxylate transport
R-HSA-382551Transport of small molecules
R-HSA-425366
R-HSA-425407SLC-mediated transmembrane transport

MSigDB gene sets: 276 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, MODULE_162, GOZGIT_ESR1_TARGETS_DN, HALMOS_CEBPA_TARGETS_UP, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, BROWNE_HCMV_INFECTION_48HR_DN, SASAI_RESISTANCE_TO_NEOPLASTIC_TRANSFROMATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_ORGANIC_ANION_TRANSPORT

GO Biological Process (6): lactate transmembrane transport (GO:0035873), plasma membrane lactate transport (GO:0035879), transport across blood-brain barrier (GO:0150104), pyruvate transmembrane transport (GO:1901475), monocarboxylic acid transport (GO:0015718), transmembrane transport (GO:0055085)

GO Molecular Function (9): pyruvate secondary active transmembrane transporter activity (GO:0005477), lactate transmembrane transporter activity (GO:0015129), symporter activity (GO:0015293), identical protein binding (GO:0042802), pyruvate transmembrane transporter activity (GO:0050833), protein binding (GO:0005515), monocarboxylic acid transmembrane transporter activity (GO:0008028), secondary active monocarboxylate transmembrane transporter activity (GO:0015355), transmembrane transporter activity (GO:0022857)

GO Cellular Component (11): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), Schaffer collateral - CA1 synapse (GO:0098685), hippocampal mossy fiber to CA3 synapse (GO:0098686), parallel fiber to Purkinje cell synapse (GO:0098688), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
SLC-mediated transport of organic anions1
Transport of small molecules1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
carboxylic acid transmembrane transport2
lactate transmembrane transport2
monocarboxylic acid transmembrane transporter activity2
secondary active transmembrane transporter activity2
carboxylic acid transmembrane transporter activity2
synapse2
lactate transport1
vascular transport1
pyruvate transport1
carboxylic acid transport1
transport1
cellular process1
secondary active monocarboxylate transmembrane transporter activity1
pyruvate transmembrane transporter activity1
protein binding1
pyruvate transmembrane transport1
binding1
monocarboxylic acid transport1
transporter activity1
transmembrane transport1
nuclear lumen1
cytoplasm1
membrane1
cell periphery1
basal plasma membrane1
plasma membrane region1
thorny excrescence1
neuron to neuron synapse1
hippocampal mossy fiber expansion1
excitatory synapse1
postsynaptic density1
postsynaptic membrane1
postsynaptic specialization membrane1
intracellular anatomical structure1

Protein interactions and networks

STRING

936 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
SLC16A7EMBQ6PCB8883
SLC16A7BSGP35613799
SLC16A7SLC17A5Q9NRA2772
SLC16A7SLC2A3P11169606
SLC16A7SLC16A3O15427604
SLC16A7MCTS1Q9ULC4597
SLC16A7SLC2A1P11166588
SLC16A7SLC5A8Q8N695581
SLC16A7SLC5A12Q1EHB4580
SLC16A7SLC16A4O15374579
SLC16A7HCAR1Q9BXC0569
SLC16A7LDHAP00338507
SLC16A7PEX19P40855486
SLC16A7OXCT1P55809444
SLC16A7SLC16A8O95907435

IntAct

175 interactions, top by confidence:

ABTypeScore
SCRIBSLC16A7psi-mi:“MI:0407”(direct interaction)0.620
SNTB1SLC16A7psi-mi:“MI:0407”(direct interaction)0.620
SNTA1SLC16A7psi-mi:“MI:0407”(direct interaction)0.620
SLC16A7SNTA1psi-mi:“MI:0407”(direct interaction)0.620
SLC16A7SCRIBpsi-mi:“MI:0407”(direct interaction)0.620
IFITM3SLC16A7psi-mi:“MI:0915”(physical association)0.560
VAPASLC16A7psi-mi:“MI:0915”(physical association)0.560
SFXN1SLC16A7psi-mi:“MI:0915”(physical association)0.560
LEMD1SLC16A7psi-mi:“MI:0915”(physical association)0.560
CDIPTSLC16A7psi-mi:“MI:0915”(physical association)0.560
TIMM23SLC16A7psi-mi:“MI:0915”(physical association)0.560
SLC16A7VTI1Bpsi-mi:“MI:0915”(physical association)0.560
SLC16A7IFITM3psi-mi:“MI:0915”(physical association)0.560
SLC16A7COMTpsi-mi:“MI:0915”(physical association)0.560
SLC16A7VAPApsi-mi:“MI:0915”(physical association)0.560
GPR25SLC16A7psi-mi:“MI:0915”(physical association)0.560
SLC16A7FXYD6psi-mi:“MI:0915”(physical association)0.560
SLC16A7SFXN1psi-mi:“MI:0915”(physical association)0.560
SLC16A7SMAGPpsi-mi:“MI:0915”(physical association)0.560
SLC16A7ACSL5psi-mi:“MI:0915”(physical association)0.560
SLC16A7HMOX1psi-mi:“MI:0915”(physical association)0.560
SLC16A7LEMD1psi-mi:“MI:0915”(physical association)0.560

BioGRID (44): SLC16A7 (Two-hybrid), SLC16A7 (Two-hybrid), SLC16A7 (Two-hybrid), SLC16A7 (Two-hybrid), SLC16A7 (Two-hybrid), FXYD6 (Two-hybrid), IFITM3 (Two-hybrid), SFXN1 (Two-hybrid), GPR25 (Two-hybrid), SMAGP (Two-hybrid), LEMD1 (Two-hybrid), ACSL5 (Two-hybrid), TIMM23 (Two-hybrid), KTN1 (Proximity Label-MS), SLC16A7 (Affinity Capture-MS)

ESM2 similar proteins: A1L1W9, B0JZE1, D3Z5L6, D4A9K4, F1NJ67, G5E8K6, G8XYX6, O08966, O15375, O35308, O35440, O60669, O70324, O70451, O70461, O94956, P36021, P53985, P53986, P53987, P53988, Q03064, Q05B81, Q0IHM1, Q3MHW6, Q3U9N9, Q5EBA8, Q5TF39, Q63089, Q63344, Q68F72, Q6DCX5, Q6DEJ6, Q6NT16, Q6PDF3, Q6PEM8, Q7ZWG6, Q80T22, Q8BH31, Q8CE47

Diamond homologs: A0LNN5, B1AT66, I1RV24, O15375, O15403, O15427, O35440, O35910, O60669, O70451, O95907, P53985, P53986, P53987, P53988, P57787, P57788, Q03064, Q17QR6, Q3MHW6, Q63344, Q66HE2, Q7RTY0, Q7TMR7, Q8CE94, Q90632, D4A734, G5E8K6, O15374, O35308, O70461, Q503M4, Q5NC32, Q6GM59, Q6P2X9, Q6ZSM3, Q8BGC3, Q8NCK7, Q8R0M8, M0RCI4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Ras activation upon Ca2+ influx through NMDA receptor540.8×8e-06
Unblocking of NMDA receptors, glutamate binding and activation538.8×8e-06
Negative regulation of NMDA receptor-mediated neuronal transmission538.8×8e-06
Long-term potentiation534.0×1e-05
Assembly and cell surface presentation of NMDA receptors932.6×7e-10
Neurexins and neuroligins1028.1×4e-10
Protein-protein interactions at synapses622.8×1e-05
RND3 GTPase cycle518.5×2e-04

GO biological processes:

GO termPartnersFoldFDR
establishment or maintenance of epithelial cell apical/basal polarity1165.9×3e-15
protein localization to synapse647.4×4e-07
receptor clustering745.0×5e-08
regulation of postsynaptic membrane neurotransmitter receptor levels735.8×2e-07
cell-cell adhesion1010.5×6e-06
protein-containing complex assembly89.4×2e-04
protein localization to plasma membrane66.7×9e-03
chemical synaptic transmission75.6×9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

90 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance72
Likely benign5
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2579 predictions. Top by Δscore:

VariantEffectΔscore
12:59596232:ATAAA:Adonor_gain1.0000
12:59596233:TAAA:Tdonor_gain1.0000
12:59596234:AAA:Adonor_gain1.0000
12:59596235:AA:Adonor_gain1.0000
12:59596236:AG:Adonor_loss1.0000
12:59596237:G:GGdonor_gain1.0000
12:59596237:GTAA:Gdonor_loss1.0000
12:59655248:TCT:Tdonor_gain1.0000
12:59655251:G:GGdonor_gain1.0000
12:59705015:GGAG:Gdonor_gain1.0000
12:59705016:GAGG:Gdonor_gain1.0000
12:59711048:G:GTdonor_gain1.0000
12:59711066:C:CGdonor_gain1.0000
12:59771211:T:Aacceptor_gain1.0000
12:59771214:T:Aacceptor_gain1.0000
12:59771215:GTA:Gacceptor_loss1.0000
12:59771216:TA:Tacceptor_loss1.0000
12:59771217:A:AGacceptor_gain1.0000
12:59771218:G:GGacceptor_gain1.0000
12:59771218:GGT:Gacceptor_gain1.0000
12:59771218:GGTC:Gacceptor_gain1.0000
12:59771359:ACAGG:Adonor_loss1.0000
12:59771363:G:Cdonor_loss1.0000
12:59771364:T:Gdonor_loss1.0000
12:59596232:A:Gdonor_gain0.9900
12:59655150:A:AGacceptor_gain0.9900
12:59655151:G:GGacceptor_gain0.9900
12:59655151:GGA:Gacceptor_gain0.9900
12:59655247:CTCT:Cdonor_gain0.9900
12:59655249:CT:Cdonor_gain0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004014 (12:59774447 A>G,T), RS1000047756 (12:59739178 A>T), RS1000048362 (12:59697774 T>C), RS1000053169 (12:59767116 C>T), RS1000062088 (12:59752932 G>T), RS1000071756 (12:59596130 T>C), RS1000093985 (12:59651073 A>G), RS1000156159 (12:59722283 C>T), RS1000169446 (12:59663600 A>G), RS1000177268 (12:59703542 T>C), RS1000206515 (12:59612609 A>G), RS1000237616 (12:59612362 A>G), RS1000241573 (12:59759030 G>A), RS1000245426 (12:59676122 T>A,C), RS1000257494 (12:59754412 T>C)

Disease associations

OMIM: gene MIM:603654 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

StudyTraitp-value
GCST002911_5Calcium levels3.000000e-06
GCST002951_16Response to zileuton treatment in asthma (FEV1 change interaction)4.000000e-07
GCST005994_13Hematocrit4.000000e-08
GCST006575_49Takayasu arteritis4.000000e-06
GCST006575_56Takayasu arteritis6.000000e-06
GCST007005_6Logical memory (immediate recall) in normal cognition3.000000e-06
GCST007006_10Logical memory (delayed recall) in normal cognition2.000000e-07
GCST007324_166Adventurousness3.000000e-11
GCST007324_89Adventurousness5.000000e-09
GCST007325_287General risk tolerance (MTAG)1.000000e-12
GCST90014243_16Kawasaki disease2.000000e-06

EFO canonical traits (5, from GWAS)

EFO IDTrait name
EFO:0004838calcium measurement
EFO:0005921FEV change measurement
EFO:0004348hematocrit
EFO:0004874memory performance
EFO:0008579risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2073704 (SINGLE PROTEIN), CHEMBL4802068 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 159 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL3335793AZD39651159

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs3763980Efficacy3methotrexateJuvenile Rheumatoid Arthritis

PharmGKB variants

2 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs3763980SLC16A731.501methotrexate
rs12231740SLC16A70.000

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC16 family of monocarboxylate transporters

Most potent curated ligand interactions (3 total), top 3:

LigandActionAffinityParameter
BAY-8002Inhibitor8.3pIC50
7ACC2Inhibition7.96pIC50
AZD3965Inhibition7.7pKi

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
7.70Ki20nMAZD3965
6.60Ki251nMCHEMBL5723356
6.20IC50638nMMSC-4381

PubChem BioAssay actives

1 with measured affinity, of 11 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
5-[(4S)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-6-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione1931149: Binding affinity to MCT2 (unknown origin) assessed as inhibition constantki0.0200uM

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, affects expression, decreases methylation8
trichostatin Aincreases expression, affects cotreatment4
Air Pollutantsincreases abundance, decreases expression, affects cotreatment4
Tetrachlorodibenzodioxinaffects expression, affects cotreatment, increases expression4
sodium arsenitedecreases expression, increases abundance3
Acetaminophendecreases expression, increases expression3
Estradiolaffects cotreatment, decreases expression, increases expression3
Silicon Dioxidedecreases expression3
Smokedecreases expression, increases abundance3
Tretinoindecreases expression, increases expression, affects expression3
bisphenol Aincreases expression, increases methylation2
Phenylmercuric Acetateaffects cotreatment, increases expression2
Tobacco Smoke Pollutiondecreases expression, increases expression2
p-Chloromercuribenzoic Aciddecreases expression, affects cotreatment2
aristolochic acid Idecreases expression1
bisphenol Fincreases expression1
geldanamycinincreases expression1
testosterone enanthateaffects expression1
triphenyl phosphateaffects expression1
alpha-pineneaffects cotreatment, decreases expression, increases abundance1
methylselenic acidincreases expression1
coumarinincreases phosphorylation1
methacrylaldehydedecreases expression, increases abundance, affects cotreatment1
gallium arsenidedecreases expression1
tamibaroteneaffects expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression, increases expression1
2,2’,4,4’,5-brominated diphenyl etherincreases expression1
3-iodothyronamineaffects uptake1
bisphenol Bincreases expression1
abrinedecreases expression1

ChEMBL screening assays

5 unique, capped per target: 3 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL2075342FunctionalTP_TRANSPORTER: uptake in Xenopus laevis oocytesHuman monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter. — J Biol Chem
CHEMBL5234425BindingBinding affinity to MCT2 (unknown origin) assessed as inhibition constantMonocarboxylate transporter 1 and 4 inhibitors as potential therapeutics for treating solid tumours: A review with structure-activity relationship insights. — Eur J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_D4I9HCT116-SLC16A7-KO-c3Cancer cell lineMale
CVCL_D4IAHCT116-SLC16A7-KO-c7Cancer cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): Kawasaki disease, Takayasu arteritis