SLC16A5

gene
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Also known as MCT5MCT6

Summary

SLC16A5 (solute carrier family 16 member 5, HGNC:10926) is a protein-coding gene on chromosome 17q25.1, encoding Monocarboxylate transporter 6 (O15375). Proton-linked monocarboxylate transporter.

This gene encodes a member of the monocarboxylate transporter family and the major facilitator superfamily. The encoded protein is localized to the cell membrane and acts as a proton-linked transporter of bumetanide. Transport by the encoded protein is inhibited by four loop diuretics, nateglinide, thiazides, probenecid, and glibenclamide. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9121 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 104 total
  • MANE Select transcript: NM_004695

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:10926
Approved symbolSLC16A5
Namesolute carrier family 16 member 5
Location17q25.1
Locus typegene with protein product
StatusApproved
AliasesMCT5, MCT6
Ensembl geneENSG00000170190
Ensembl biotypeprotein_coding
OMIM603879
Entrez9121

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 42 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000329783, ENST00000450736, ENST00000538213, ENST00000578376, ENST00000578847, ENST00000580123, ENST00000582048, ENST00000584118, ENST00000584207, ENST00000585293, ENST00000872974, ENST00000872975, ENST00000872976, ENST00000872977, ENST00000872978, ENST00000872979, ENST00000872980, ENST00000872981, ENST00000872982, ENST00000872983, ENST00000872984, ENST00000872985, ENST00000872986, ENST00000872987, ENST00000872988, ENST00000872989, ENST00000872990, ENST00000872991, ENST00000872992, ENST00000937151, ENST00000969581, ENST00000969582, ENST00000969583, ENST00000969584, ENST00000969585, ENST00000969586, ENST00000969587, ENST00000969588, ENST00000969589, ENST00000969590, ENST00000969591, ENST00000969592, ENST00000969593, ENST00000969594

RefSeq mRNA: 3 — MANE Select: NM_004695 NM_001271765, NM_001369668, NM_004695

CCDS: CCDS11713

Canonical transcript exons

ENST00000329783 — 7 exons

ExonStartEnd
ENSE000011749367510000775100816
ENSE000011749597508915175089304
ENSE000026948477510588075106162
ENSE000035083497509358975093835
ENSE000036923797509803875098181
ENSE000037853577510397075104180
ENSE000038510817508795475088044

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 97.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9737 / max 125.4906, expressed in 1267 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter IDTPM avgSamples expressed
1626963.50841043
1626951.2880718
1626940.5923323
1626930.3240158
1627020.094331
1626970.074223
1626980.043515
1626990.042113
1627010.00713

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
metanephros cortexUBERON:001053397.65gold quality
bronchial epithelial cellCL:000232893.92gold quality
mucosa of transverse colonUBERON:000499192.60gold quality
epithelium of bronchusUBERON:000203192.25gold quality
right uterine tubeUBERON:000130291.85gold quality
bronchusUBERON:000218591.54gold quality
pancreatic ductal cellCL:000207990.37gold quality
upper lobe of left lungUBERON:000895290.03gold quality
oocyteCL:000002389.96gold quality
upper lobe of lungUBERON:000894889.71gold quality
duodenumUBERON:000211489.28gold quality
right lungUBERON:000216789.15gold quality
epithelium of nasopharynxUBERON:000195188.53gold quality
monocyteCL:000057688.31gold quality
mononuclear cellCL:000084288.16gold quality
olfactory segment of nasal mucosaUBERON:000538687.91gold quality
granulocyteCL:000009487.90gold quality
leukocyteCL:000073887.80gold quality
bloodUBERON:000017887.34gold quality
transverse colonUBERON:000115787.04gold quality
adult mammalian kidneyUBERON:000008286.38gold quality
small intestine Peyer’s patchUBERON:000345486.19gold quality
left lobe of thyroid glandUBERON:000112085.57gold quality
small intestineUBERON:000210885.44gold quality
right atrium auricular regionUBERON:000663185.42gold quality
right lobe of thyroid glandUBERON:000111985.41gold quality
lungUBERON:000204885.09gold quality
lower lobe of lungUBERON:000894984.98silver quality
jejunal mucosaUBERON:000039984.69gold quality
apex of heartUBERON:000209884.57gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes13.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting SLC16A5, 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-4795-3P100.0074.624024
HSA-MIR-24-3P99.5969.971934
HSA-MIR-323A-5P98.5965.13651

Literature-anchored findings (GeneRIF, showing 3)

  • We demonstrated that SLC16A5 and ZNF206 displayed altered methylation patterns in the neuroblastoma genome (PMID:22911660)
  • Identify a novel association between protein-coding variation in SLC16A5 and cisplatin-induced ototoxic effects in testicular cancer patients. (PMID:28448657)
  • Solute carrier family 16 member 5 downregulation and its methylation might serve as a prognostic indicator of prostate cancer. (PMID:34549875)

Cross-species orthologs

18 orthologs

OrganismSymbolGene ID
danio_rerioslc16a5aENSDARG00000030472
danio_rerioslc16a5bENSDARG00000102668
mus_musculusSlc16a5ENSMUSG00000045775
rattus_norvegicusSlc16a5ENSRNOG00000023476
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), SLC16A7 (ENSG00000118596), SLC16A3 (ENSG00000141526), SLC16A2 (ENSG00000147100), SLC16A12 (ENSG00000152779), SLC16A1 (ENSG00000155380), SLC16A14 (ENSG00000163053), SLC16A9 (ENSG00000165449), SLC16A4 (ENSG00000168679), SLC16A11 (ENSG00000174326), SLC16A13 (ENSG00000174327)

Protein

Protein identifiers

Monocarboxylate transporter 6O15375 (reviewed: O15375)

Alternative names: Monocarboxylate transporter 5, Solute carrier family 16 member 5

All UniProt accessions (5): O15375, J3KS19, J3KT93, J3QL40, J3QQW5

UniProt curated annotations — full annotation on UniProt →

Function. Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in kidney.

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

Isoforms (2)

UniProt IDNamesCanonical?
O15375-11yes
O15375-22

RefSeq proteins (3): NP_001258694, NP_001356597, NP_004686* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR004743MCTFamily
IPR011701MFSFamily
IPR020846MFS_domDomain
IPR036259MFS_trans_sfHomologous_superfamily
IPR050327Proton-linked_MCTFamily

Pfam: PF07690

UniProt features (29 total): topological domain 13, transmembrane region 12, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O15375-F180.560.60

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 214 (showing top): MORF_RAGE, MORF_FLT1, MORF_MSH3, MORF_BRCA1, MORF_ATRX, MORF_ESR1, MORF_RAD51L3, GOBP_ORGANIC_ACID_TRANSPORT, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, BROWNE_HCMV_INFECTION_48HR_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, MORF_IL4, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, GOBP_ORGANIC_ANION_TRANSPORT, MODULE_71

GO Biological Process (2): monocarboxylic acid transport (GO:0015718), transmembrane transport (GO:0055085)

GO Molecular Function (4): monocarboxylic acid transmembrane transporter activity (GO:0008028), symporter activity (GO:0015293), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
carboxylic acid transport1
transport1
cellular process1
monocarboxylic acid transport1
carboxylic acid transmembrane transporter activity1
secondary active transmembrane transporter activity1
binding1
transporter activity1
transmembrane transport1
membrane1
cell periphery1
cellular anatomical structure1
basal plasma membrane1
plasma membrane region1

Protein interactions and networks

STRING

838 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
SLC16A5ACYP2P14621511
SLC16A5CBLL1Q75N03492
SLC16A5ATP5PDO75947478
SLC16A5SLC25A48Q6ZT89447
SLC16A5TPMTP51580444
SLC16A5SLC39A11Q8N1S5443
SLC16A5SLC37A1P57057437
SLC16A5ALS2CLQ60I27435
SLC16A5SLC26A8Q96RN1435
SLC16A5SLC5A6Q9Y289420
SLC16A5MCTS1Q9ULC4420
SLC16A5ARMC7Q9H6L4410
SLC16A5KCTD2Q14681410
SLC16A5LYG1Q8N1E2402
SLC16A5NT5CQ8TCD5401

IntAct

11 interactions, top by confidence:

ABTypeScore
SLC16A5HSPB8psi-mi:“MI:0915”(physical association)0.560
SLC16A5EFEMP2psi-mi:“MI:0915”(physical association)0.560
SLC16A5psi-mi:“MI:0915”(physical association)0.560
SLC16A5NDUFB3psi-mi:“MI:0914”(association)0.350
SLC16A5HSPB8psi-mi:“MI:0915”(physical association)0.000
EFEMP2SLC16A5psi-mi:“MI:0915”(physical association)0.000
SLC16A5psi-mi:“MI:0915”(physical association)0.000

BioGRID (24): SLC16A5 (Negative Genetic), SLC16A5 (Negative Genetic), SLC16A5 (Two-hybrid), SLC16A5 (Two-hybrid), EFEMP2 (Two-hybrid), SLC16A5 (Proximity Label-MS), SLC16A5 (Affinity Capture-RNA), BMPR2 (Affinity Capture-MS), BSG (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), CAMK2D (Affinity Capture-MS), EMB (Affinity Capture-MS), FN3KRP (Affinity Capture-MS), JUP (Affinity Capture-MS), NDUFB3 (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: A0A0C4VYV1, A0A2U8U2M7, A0A411PQP0, A0A4P8GFD0, A5ABG1, B0XWL0, B8N0F1, B8NJG7, I1RV24, O15375, Q08268, Q08777, Q0CZG9, Q4WKX3, Q53WP9, Q5ATG7, Q5AUY2, S0ECK8, S7Z7Z3, S8AKG0, W7MTI3, A0LNN5, B1AT66, G5E8K6, O35308, Q7RTX9, Q7TMR7, Q8K1C7, O15403, O15427, O35440, O35910, O60669, O70451, O95907, P53985, P53986, P53987, P53988, P57787

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance83
Likely benign9
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1288 predictions. Top by Δscore:

VariantEffectΔscore
17:75098035:CA:Cacceptor_loss1.0000
17:75098036:AG:Aacceptor_gain1.0000
17:75098036:AGG:Aacceptor_gain1.0000
17:75098037:GG:Gacceptor_gain1.0000
17:75098037:GGG:Gacceptor_gain1.0000
17:75098037:GGGC:Gacceptor_gain1.0000
17:75098177:CACAG:Cdonor_loss1.0000
17:75098178:ACAGG:Adonor_loss1.0000
17:75098179:CAGGT:Cdonor_loss1.0000
17:75098180:AGGTG:Adonor_loss1.0000
17:75098181:GGT:Gdonor_loss1.0000
17:75098182:GTG:Gdonor_loss1.0000
17:75098183:T:Adonor_loss1.0000
17:75100812:GGCCG:Gdonor_gain1.0000
17:75100813:GCCGG:Gdonor_gain1.0000
17:75100814:CCGGT:Cdonor_loss1.0000
17:75100815:CGG:Cdonor_loss1.0000
17:75100816:GGTG:Gdonor_loss1.0000
17:75100817:GTG:Gdonor_loss1.0000
17:75100818:T:Gdonor_loss1.0000
17:75103966:CCAG:Cacceptor_loss1.0000
17:75103967:CAGG:Cacceptor_loss1.0000
17:75103968:A:AGacceptor_gain1.0000
17:75103968:AG:Aacceptor_gain1.0000
17:75103969:G:Aacceptor_gain1.0000
17:75103969:G:GAacceptor_gain1.0000
17:75103969:GGGT:Gacceptor_gain1.0000
17:75103969:GGGTT:Gacceptor_gain1.0000
17:75104137:G:GTdonor_gain1.0000
17:75093585:CCA:Cacceptor_loss0.9900

AlphaMissense

3283 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:75100678:A:CS339R0.994
17:75100680:C:AS339R0.994
17:75100680:C:GS339R0.994
17:75100690:A:CS343R0.991
17:75100692:T:AS343R0.991
17:75100692:T:GS343R0.991
17:75104020:A:CS402R0.991
17:75104022:C:AS402R0.991
17:75104022:C:GS402R0.991
17:75098127:A:CS97R0.986
17:75098129:C:AS97R0.986
17:75098129:C:GS97R0.986
17:75098109:A:CS91R0.981
17:75098111:C:AS91R0.981
17:75098111:C:GS91R0.981
17:75100126:T:AW155R0.981
17:75100126:T:CW155R0.981
17:75100190:G:AG176D0.980
17:75098115:G:CG93R0.978
17:75100060:T:CF133L0.978
17:75100062:T:AF133L0.978
17:75100062:T:GF133L0.978
17:75100165:T:AW168R0.978
17:75100165:T:CW168R0.978
17:75100510:A:CS283R0.978
17:75100512:C:AS283R0.978
17:75100512:C:GS283R0.978
17:75100402:T:AW247R0.977
17:75100402:T:CW247R0.977
17:75100451:C:AA263D0.976

dbSNP variants (sampled 300 via entrez): RS1000143309 (17:75108020 CTT>C), RS1000262085 (17:75086515 G>A,T), RS1000396575 (17:75091069 C>T), RS1000429543 (17:75096182 T>C), RS1000438052 (17:75091915 C>T), RS1000452930 (17:75108280 C>G), RS1000594616 (17:75087867 C>A), RS1000864066 (17:75096337 C>CACCCCT), RS1000868218 (17:75100697 T>A), RS1001054824 (17:75106908 CA>C,CAA), RS1001197042 (17:75103195 T>G), RS1001232269 (17:75107416 G>A), RS1001549689 (17:75106628 C>T), RS1001753374 (17:75101796 A>C,G), RS1001777000 (17:75085940 T>G)

Disease associations

OMIM: gene MIM:603879 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST008103_113Bipolar disorder4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs4788863Toxicity3cisplatinNeoplasms;Ototoxicity;Testicular Neoplasms

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs4788863SLC16A531.751cisplatin

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC16 family of monocarboxylate transporters

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, decreases expression, affects expression, increases methylation6
Benzo(a)pyreneincreases expression, increases methylation3
sodium arsenitedecreases expression, increases expression2
Phenylmercuric Acetateaffects cotreatment, decreases expression2
Aflatoxin B1decreases methylation, increases expression2
aristolochic acid Iincreases expression1
GSK-J4decreases expression1
afuresertibincreases expression1
triphenyl phosphateaffects expression1
bisphenol Adecreases expression1
lead acetatedecreases expression1
tris(2-butoxyethyl) phosphateaffects expression1
arsenitedecreases methylation1
tris(1,3-dichloro-2-propyl)phosphateincreases expression1
cobaltous chloridedecreases expression1
cupric chloridedecreases expression1
CGP 52608affects binding, increases reaction1
monomethylarsonous aciddecreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
ICG 001increases expression1
abrinedecreases expression1
dorsomorphinaffects cotreatment, decreases expression1
jinfukangincreases expression, affects cotreatment1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidincreases expression1
Sunitinibdecreases expression1
Air Pollutantsaffects expression, increases abundance1
Calcitriolincreases expression, affects cotreatment1
Cisplatinincreases expression, affects cotreatment1
Estradiolaffects expression1
Gasolineaffects cotreatment, increases abundance, increases expression1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

CellosaurusNameCategorySex
CVCL_D4I7HCT116-SLC16A5-KO-c10Cancer cell lineMale
CVCL_D4I8HCT116-SLC16A5-KO-c4Cancer 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): bipolar disorder