SLC16A8

Summary

SLC16A8 (solute carrier family 16 member 8, HGNC:16270) is a protein-coding gene on chromosome 22q13.1, encoding Monocarboxylate transporter 3 (O95907). Probable retinal pigment epithelium (RPE)-specific proton-coupled L-lactate transporter.

SLC16A8 is a member of a family of proton-coupled monocarboxylate transporters that mediate lactate transport across cell membranes (Yoon et al., 1999 [PubMed 10493836]).

Source: NCBI Gene 23539 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 108 total
• Druggable target: yes
• MANE Select transcript: NM_013356

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16270
Approved symbol	SLC16A8
Name	solute carrier family 16 member 8
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	MCT3, REMP
Ensembl gene	ENSG00000100156
Ensembl biotype	protein_coding
OMIM	610409
Entrez	23539

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000320521, ENST00000427592, ENST00000469516, ENST00000681075, ENST00000902580, ENST00000902581, ENST00000902582, ENST00000902583, ENST00000902584

RefSeq mRNA: 2 — MANE Select: NM_013356 NM_001394131, NM_013356

CCDS: CCDS13966

Canonical transcript exons

ENST00000681075 — 6 exons

Exon	Start	End
ENSE00000654155	38081889	38082032
ENSE00001261194	38080840	38081679
ENSE00001702978	38083042	38083361
ENSE00003915100	38082660	38082881
ENSE00003930295	38078137	38078704
ENSE00003938202	38083988	38084184

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 96.39.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1004 / max 77.4322, expressed in 27 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194111	0.0861	25
194112	0.0143	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	96.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.64	gold quality
nucleus accumbens	UBERON:0001882	81.46	gold quality
sural nerve	UBERON:0015488	81.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.29	gold quality
right uterine tube	UBERON:0001302	79.47	gold quality
putamen	UBERON:0001874	78.98	gold quality
spinal cord	UBERON:0002240	78.49	gold quality
descending thoracic aorta	UBERON:0002345	78.42	gold quality
tibial nerve	UBERON:0001323	78.41	gold quality
ascending aorta	UBERON:0001496	77.51	gold quality
thoracic aorta	UBERON:0001515	77.41	gold quality
caudate nucleus	UBERON:0001873	77.41	gold quality
pituitary gland	UBERON:0000007	76.17	gold quality
adenohypophysis	UBERON:0002196	76.16	gold quality
right coronary artery	UBERON:0001625	75.14	gold quality
aorta	UBERON:0000947	74.42	gold quality
cervix squamous epithelium	UBERON:0006922	73.92	gold quality
substantia nigra	UBERON:0002038	73.76	gold quality
hypothalamus	UBERON:0001898	73.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.53	gold quality
left coronary artery	UBERON:0001626	73.40	gold quality
tendon of biceps brachii	UBERON:0008188	73.40	silver quality
right frontal lobe	UBERON:0002810	73.36	gold quality
amygdala	UBERON:0001876	73.33	gold quality
prefrontal cortex	UBERON:0000451	73.32	gold quality
coronary artery	UBERON:0001621	73.10	gold quality
oocyte	CL:0000023	72.93	silver quality
midbrain	UBERON:0001891	72.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	15.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting SLC16A8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-4653-5P	97.22	67.72	1429

Literature-anchored findings (GeneRIF, showing 2)

• The expression level of LIPC, SLC16A8, and TIMP-3 was significantly associated with age-related macular degeneration pathology. (PMID:27966779)
• A Splice Variant in SLC16A8 Gene Leads to Lactate Transport Deficit in Human iPS Cell-Derived Retinal Pigment Epithelial Cells. (PMID:33477551)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc16a8	ENSDARG00000045153
mus_musculus	Slc16a8	ENSMUSG00000032988
rattus_norvegicus	Slc16a8	ENSRNOG00000012090
drosophila_melanogaster	Mct1	FBGN0023549
drosophila_melanogaster	CG14196	FBGN0031002
drosophila_melanogaster	CG8051	FBGN0031012
drosophila_melanogaster	Sln	FBGN0033657
drosophila_melanogaster	CG8468	FBGN0033913
drosophila_melanogaster	Targ	FBGN0033955
drosophila_melanogaster	CG13907	FBGN0035173
drosophila_melanogaster	out	FBGN0259834
caenorhabditis_elegans		WBGENE00003986
caenorhabditis_elegans		WBGENE00010834
caenorhabditis_elegans		WBGENE00015273
caenorhabditis_elegans		WBGENE00015676
caenorhabditis_elegans		WBGENE00020168
caenorhabditis_elegans		WBGENE00021227

Paralogs (13): SLC16A6 (ENSG00000108932), SLC16A10 (ENSG00000112394), SLC16A7 (ENSG00000118596), 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 3 — O95907 (reviewed: O95907)

Alternative names: Solute carrier family 16 member 8

All UniProt accessions (1): O95907

UniProt curated annotations — full annotation on UniProt →

Function. Probable retinal pigment epithelium (RPE)-specific proton-coupled L-lactate transporter. May facilitate transport of lactate and H(+) out of the retina and could therefore play a role in pH and ion homeostasis of the outer retina.

Subcellular location. Basolateral cell membrane.

Tissue specificity. Retinal pigment epithelium.

Domain organisation. The two basolateral sorting signals (BSS) are required to direct SLC16A8 to the basolateral membrane.

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

RefSeq proteins (1): NP_037488* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004743	MCT	Family
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR050327	Proton-linked_MCT	Family

Pfam: PF07690

Catalyzed reactions (Rhea), 1 shown:

• (S)-lactate(in) + H(+)(in) = (S)-lactate(out) + H(+)(out) (RHEA:29415)

UniProt features (41 total): topological domain 13, transmembrane region 12, mutagenesis site 5, region of interest 4, compositionally biased region 4, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95907-F1	77.38	0.50

Functional residue map

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

Mutagenesis-validated functional residues (5):

Position	Phenotype
465–469	affects subcellular localization leading to apical localization.
471	abolishes basolateral membrane localization; when associated with a-472.
472	abolishes basolateral membrane localization; when associated with a-471.
481	affects subcellular localization leading to apical localization; when associated with a-482.
482	affects subcellular localization leading to apical localization; when associated with a-481.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-210991	Basigin interactions
R-HSA-433692	Proton-coupled monocarboxylate transport
R-HSA-109582	Hemostasis
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 74 (showing top): AREB6_01, TGACCTY_ERR1_Q2, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, MODULE_368, GOBP_ORGANIC_ANION_TRANSPORT, MODULE_71, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_TRANSMEMBRANE_TRANSPORT, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, MODULE_218, GOCC_APICAL_PART_OF_CELL, WGGAATGY_TEF1_Q6, chr22q13

GO Biological Process (4): lactate transport (GO:0015727), monocarboxylic acid transport (GO:0015718), lactate transmembrane transport (GO:0035873), transmembrane transport (GO:0055085)

GO Molecular Function (4): monocarboxylic acid transmembrane transporter activity (GO:0008028), lactate transmembrane transporter activity (GO:0015129), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), apical part of cell (GO:0045177)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1
SLC-mediated transport of organic anions	1
Hemostasis	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monocarboxylic acid transport	2
cellular anatomical structure	2
plasma membrane region	2
organic hydroxy compound transport	1
carboxylic acid transport	1
lactate transport	1
carboxylic acid transmembrane transport	1
transport	1
cellular process	1
carboxylic acid transmembrane transporter activity	1
monocarboxylic acid transmembrane transporter activity	1
lactate transmembrane transport	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
basal plasma membrane	1
apical part of cell	1

Protein interactions and networks

STRING

772 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC16A8	BSG	P35613	980
SLC16A8	SLC17A5	Q9NRA2	775
SLC16A8	EMB	Q6PCB8	706
SLC16A8	B3GLCT	Q6Y288	671
SLC16A8	FILIP1L	Q4L180	668
SLC16A8	ARMS2	P0C7Q2	648
SLC16A8	CLIC4	Q9Y696	629
SLC16A8	AQP1	P29972	599
SLC16A8	HRH3	Q9Y5N1	588
SLC16A8	COL8A1	P27658	580
SLC16A8	CFH	P08603	553
SLC16A8	RAD51B	O15315	550
SLC16A8	HIVEP2	P31629	548
SLC16A8	VTN	P01141	531
SLC16A8	MCTS1	Q9ULC4	526

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SLC16A8	NTHL1	psi-mi:“MI:0914”(association)	0.350
SLC16A8	C15orf61	psi-mi:“MI:0914”(association)	0.350
DNAJB9	SLC16A8	psi-mi:“MI:0915”(physical association)	0.000
RAB1A	SLC16A8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (87): SLC16A8 (Negative Genetic), SLC16A8 (Negative Genetic), SLC16A8 (Negative Genetic), SLC16A8 (Positive Genetic), SLC16A8 (Positive Genetic), SLC16A8 (Positive Genetic), SLC16A8 (Two-hybrid), SLC16A8 (Two-hybrid), DPP9 (Affinity Capture-MS), NTHL1 (Affinity Capture-MS), CORO2A (Affinity Capture-MS), ABCD3 (Affinity Capture-MS), ALG10 (Affinity Capture-MS), ATP13A1 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2HW92, A6NDV4, A6NFX1, A6QLK4, B1AWJ5, F1NCD6, F1NJ67, F1PZV2, O35308, O35595, O70461, O95907, Q08DX7, Q0IHM1, Q0P5C0, Q0P5M9, Q13286, Q14728, Q29611, Q2YDU8, Q3T9M1, Q3U481, Q501I9, Q5R8G5, Q5R9A1, Q5U419, Q60HH0, Q61124, Q66H95, Q6NUT3, Q6UXD7, Q6ZMD2, Q7RTT9, Q8BFQ6, Q8CE47, Q8NA29, Q8R0G7, Q8R139, Q8TB61, Q8VCW4

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

837 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38078701:CGGC:C	acceptor_gain	1.0000
22:38078702:GGC:G	acceptor_gain	1.0000
22:38078702:GGCC:G	acceptor_loss	1.0000
22:38078705:C:CA	acceptor_loss	1.0000
22:38078705:C:CC	acceptor_gain	1.0000
22:38078706:T:A	acceptor_loss	1.0000
22:38080825:T:TA	donor_gain	1.0000
22:38078700:GCGGC:G	acceptor_gain	0.9900
22:38078701:CGGCC:C	acceptor_gain	0.9900
22:38078703:GC:G	acceptor_gain	0.9900
22:38078704:CC:C	acceptor_gain	0.9900
22:38080787:C:A	donor_gain	0.9900
22:38081883:CCTCA:C	donor_loss	0.9900
22:38081884:CTCA:C	donor_loss	0.9900
22:38081885:TCACC:T	donor_loss	0.9900
22:38081886:CACC:C	donor_loss	0.9900
22:38081888:C:CG	donor_loss	0.9900
22:38082658:AC:A	donor_gain	0.9900
22:38082659:CC:C	donor_gain	0.9900
22:38080786:T:TA	donor_gain	0.9800
22:38080819:C:CA	donor_gain	0.9800
22:38082651:GACAC:G	donor_loss	0.9800
22:38082652:ACAC:A	donor_loss	0.9800
22:38082653:CACTG:C	donor_loss	0.9800
22:38082654:ACTGA:A	donor_loss	0.9800
22:38082655:CTGAC:C	donor_loss	0.9800
22:38082656:TGA:T	donor_loss	0.9800
22:38082657:GACCC:G	donor_loss	0.9800
22:38082658:A:T	donor_loss	0.9800
22:38082699:AGG:A	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000117251 (22:38085582 C>T), RS1000207978 (22:38082187 G>A,T), RS1000302957 (22:38082371 AG>A,AGG), RS1000372195 (22:38077714 T>C), RS1000510470 (22:38085721 G>A), RS1000531063 (22:38082401 C>T), RS1000583511 (22:38082197 C>A,T), RS1001272547 (22:38086041 C>G), RS1001473659 (22:38081186 G>A), RS1002546430 (22:38078977 A>G), RS1002883632 (22:38082471 G>C), RS1002887993 (22:38078673 C>T), RS1003479178 (22:38083697 C>T), RS1003551950 (22:38080135 C>G), RS1003552948 (22:38083724 G>C)

Disease associations

OMIM: gene MIM:610409 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001884_7	Age-related macular degeneration	2.000000e-11
GCST003219_52	Advanced age-related macular degeneration	6.000000e-11
GCST004347_8	Glioma	9.000000e-07
GCST004349_3	Glioblastoma	2.000000e-10
GCST010703_11	Brain morphology (MOSTest)	9.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3308921 (SINGLE PROTEIN), CHEMBL4802068 (SELECTIVITY GROUP)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC16 family of monocarboxylate transporters

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.20	IC50	638	nM	MSC-4381

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1226690	Binding	Inhibition of human MCT3 expressed in INS1 cells assessed as reduction in intracellular acidification at 100 nM after 1 hr by L-Lactate uptake based BCECF staining	Monocarboxylate transporter MCT1 is a target for immunosuppression. — Nat Chem Biol

Clinical trials (associated diseases)

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