SLC16A11

Summary

SLC16A11 (solute carrier family 16 member 11, HGNC:23093) is a protein-coding gene on chromosome 17p13.1, encoding Monocarboxylate transporter 11 (Q8NCK7). Proton-linked monocarboxylate transporter.

Enables pyruvate transmembrane transporter activity. Involved in lipid metabolic process. Located in endoplasmic reticulum membrane and plasma membrane.

Source: NCBI Gene 162515 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_001370549

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23093
Approved symbol	SLC16A11
Name	solute carrier family 16 member 11
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90193, MCT11
Ensembl gene	ENSG00000174326
Ensembl biotype	protein_coding
OMIM	615765
Entrez	162515

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000573338, ENST00000574600, ENST00000662352, ENST00000673828, ENST00000892155, ENST00000892156

RefSeq mRNA: 3 — MANE Select: NM_001370549 NM_001370549, NM_001370553, NM_153357

CCDS: CCDS11086, CCDS92241

Canonical transcript exons

ENST00000574600 — 5 exons

Exon	Start	End
ENSE00001203799	7042930	7043073
ENSE00001285624	7041996	7042763
ENSE00002659772	7043312	7043519
ENSE00003903200	7041621	7041908
ENSE00003903771	7043775	7044092

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 94.05.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0084 / max 32.9744, expressed in 591 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164088	0.5750	344
164087	0.4334	178

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	94.05	gold quality
right lobe of thyroid gland	UBERON:0001119	81.36	gold quality
left lobe of thyroid gland	UBERON:0001120	81.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.80	gold quality
thyroid gland	UBERON:0002046	79.09	gold quality
parotid gland	UBERON:0001831	77.50	silver quality
minor salivary gland	UBERON:0001830	76.69	gold quality
saliva-secreting gland	UBERON:0001044	76.02	gold quality
palpebral conjunctiva	UBERON:0001812	75.27	silver quality
skin of abdomen	UBERON:0001416	73.42	gold quality
mouth mucosa	UBERON:0003729	73.42	gold quality
skin of leg	UBERON:0001511	73.22	gold quality
right lobe of liver	UBERON:0001114	71.57	gold quality
zone of skin	UBERON:0000014	71.04	gold quality
right lung	UBERON:0002167	70.16	gold quality
left uterine tube	UBERON:0001303	69.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.01	gold quality
right atrium auricular region	UBERON:0006631	68.27	gold quality
pituitary gland	UBERON:0000007	68.22	gold quality
lower esophagus mucosa	UBERON:0035834	68.18	gold quality
apex of heart	UBERON:0002098	68.06	gold quality
cerebellar hemisphere	UBERON:0002245	67.91	gold quality
cerebellar cortex	UBERON:0002129	67.90	gold quality
metanephros cortex	UBERON:0010533	67.66	gold quality
cardiac atrium	UBERON:0002081	67.56	gold quality
granulocyte	CL:0000094	67.16	gold quality
body of pancreas	UBERON:0001150	67.05	gold quality
cortex of kidney	UBERON:0001225	66.99	gold quality
cerebellum	UBERON:0002037	66.96	gold quality
esophagus mucosa	UBERON:0002469	66.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.09

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 14)

• Despite type 2 diabetes having been well studied by GWAS in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism. (PMID:24390345)
• Genetic association studies show that common variants in ABCA1 and SLC16A11 are involved in type 2 diabetes (T2D) susceptibility. Particularly, the variants rs10811661 (CDKN2A/2B) and rs9282541 (ABCA1) are associated with T2D in adult Maya population. (PMID:25839936)
• Our study identified an association between the SLC16A11 variant rs75493593 and type 2 diabetes in American Indians, where the effect on diabetes was much more pronounced in nonobese individuals. rs75493593 was also associated with RNASEK gene expression. (PMID:26487785)
• rs13342232 might be involved in the risk of pediatric-onset type 2 diabetes in Mexican families (PMID:28101933)
• Study demonstrates that disruption of SLC16A11 in primary human hepatocytes leads to Type 2 diabetes (T2D)-relevant changes in fatty acid and lipid metabolism; these results implicate reduced SLC16A11 function in liver as a causal factor for T2D. (PMID:28666119)
• The T2D risk haplotype in the SLC16A11 region includes a cis-eQTL that decreases SLC16A11 expression in a dose-dependent manner in liver tissue. (PMID:28666119)
• Individuals carrying the SLC16A11 risk haplotype exhibited decreased insulin action. Higher serum ALT and GGT levels were found in carriers with type 2 diabetes, and larger adipocytes in subcutaneous fat in the size distribution in carrier women with normal weight. (PMID:30475225)
• Mouse model carrying the reconstituted T2D risk haplotype of SLC16A11 displays elevated blood and liver triglycerides, glucose intolerance, insulin resistance, and increased levels of lipin 1 protein in the liver in response to a high-fat diet. Human LPIN1 levels are increased in HepG2 cells overexpressing the mutant SLC16A11. (PMID:30673611)
• Mouse model carrying the reconstituted T2D risk haplotype of human SLC16A11 displays elevated blood and liver triglycerides, glucose intolerance, insulin resistance, and increased levels of lipin 1 protein in the liver in response to a high-fat diet. Human LPIN1 levels are increased in HepG2 cells overexpressing the mutant SLC16A11. (PMID:30673611)
• The previously reported effects of SLC16A11 variants shown to be associated with diabetes in Mexicans was replicated in a large Mexican-American sample, but these effects were not significant in five non-Mexican Hispanic/Latino groups sampled from U.S. populations. (PMID:30696834)
• The association between SLC16A11 haplotype and lipid metabolism in Japanese patients with type 2 diabetes. (PMID:33561739)
• Genetic variants in the SLC16A11 gene are associated with increased BMI and insulin levels in nondiabetic Chilean population. (PMID:33909378)
• Downregulation of SLC16A11 is Present in Offspring of Mothers with Gestational Diabetes. (PMID:35831226)
• Epistasis Between HLA-DRB1*16:02:01 and SLC16A11 T-C-G-T-T Reduces Odds for Type 2 Diabetes in Southwest American Indians. (PMID:38530923)

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-246g23.4	ENSDARG00000013775
danio_rerio	zgc:114041	ENSDARG00000052109
mus_musculus	Slc16a11	ENSMUSG00000040938
rattus_norvegicus	Slc16a11	ENSRNOG00000018748
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): SLC16A8 (ENSG00000100156), SLC16A6 (ENSG00000108932), SLC16A10 (ENSG00000112394), SLC16A7 (ENSG00000118596), SLC16A3 (ENSG00000141526), SLC16A2 (ENSG00000147100), SLC16A12 (ENSG00000152779), SLC16A1 (ENSG00000155380), SLC16A14 (ENSG00000163053), SLC16A9 (ENSG00000165449), SLC16A4 (ENSG00000168679), SLC16A5 (ENSG00000170190), SLC16A13 (ENSG00000174327)

Protein

Protein identifiers

Monocarboxylate transporter 11 — Q8NCK7 (reviewed: Q8NCK7)

Alternative names: Solute carrier family 16 member 11

All UniProt accessions (2): A0A669KBK5, I3L431

UniProt curated annotations — full annotation on UniProt →

Function. Proton-linked monocarboxylate transporter. It catalyzes the transport of pyruvate across the plasma membrane. Probably involved in hepatic lipid metabolism: overexpression results in an increase of triacylglycerol(TAG) levels, small increases in intracellular diacylglycerols and decreases in lysophosphatidylcholine, cholesterol ester and sphingomyelin lipids.

Subunit / interactions. Interacts with isoform 2 of BSG.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane.

Tissue specificity. Expressed in liver, salivary gland and thyroid.

Disease relevance. Type 2 diabetes mellitus (T2D) [MIM:125853] A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility is associated with variants affecting the gene represented in this entry. A risk haplotype spanning SLC16A11 is associated with a 20% increased risk for T2D. The haplotype includes 5 SLC16A11 variants in strong linkage disequilibrium: variants Ile-89, Gly-103, Ser-316, Thr-419 and a silent variant. This risk haplotype probably derives from H.sapiens neanderthalensis (Neanderthal) introgression and is present at 50% frequency in Native-American samples, 10% in east Asian, while it is rare in European and African samples populations. The risk haplotype contains a cis-eQTL that is responsible for reduced SLC16A11 expression in liver.

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

RefSeq proteins (3): NP_001357478, NP_001357482, NP_699188 (=MANE)

Domains & families (InterPro)

ID	Name	Type
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:

• pyruvate(out) + H(+)(out) = pyruvate(in) + H(+)(in) (RHEA:64720)

UniProt features (22 total): transmembrane region 12, sequence variant 4, topological domain 2, compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCK7-F1	83.37	0.61

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, BENPORATH_ES_WITH_H3K27ME3, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_LIPID_METABOLIC_PROCESS, CHIANG_LIVER_CANCER_SUBCLASS_INTERFERON_DN, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, CHIANG_LIVER_CANCER_SUBCLASS_CTNNB1_UP, TGGAAA_NFAT_Q4_01, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOCARBOXYLIC_ACID_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (2): lipid metabolic process (GO:0006629), transmembrane transport (GO:0055085)

GO Molecular Function (4): monocarboxylic acid transmembrane transporter activity (GO:0008028), symporter activity (GO:0015293), pyruvate transmembrane transporter activity (GO:0050833), transmembrane transporter activity (GO:0022857)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
transport	1
cellular process	1
monocarboxylic acid transport	1
carboxylic acid transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
monocarboxylic acid transmembrane transporter activity	1
pyruvate transmembrane transport	1
transporter activity	1
transmembrane transport	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC16A11	CDC123	O75794	478
SLC16A11	BSG	P35613	462
SLC16A11	ZNF521	Q96K83	446
SLC16A11	KCNQ1	P51787	436
SLC16A11	C2CD4A	Q8NCU7	433
SLC16A11	SLC6A11	P48066	427
SLC16A11	SLC30A8	Q8IWU4	424
SLC16A11	RBM11	P57052	423
SLC16A11	CDKAL1	Q5VV42	418
SLC16A11	TCF7L2	Q9NQB0	418
SLC16A11	C2CD4B	A6NLJ0	417
SLC16A11	R3HDML	Q9H3Y0	405
SLC16A11	INS-IGF2	F8WCM5	402
SLC16A11	SLC12A1	Q13621	398
SLC16A11	CCDC57	Q2TAC2	375

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SLC16A11	H2AB2	psi-mi:“MI:0914”(association)	0.530
SLC16A11	BSG	psi-mi:“MI:0915”(physical association)	0.500
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC16A11	PABPC4	psi-mi:“MI:0914”(association)	0.350
SLC16A11	PTPRF	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): EMB (Affinity Capture-MS), H2AFB3 (Affinity Capture-MS), TOMM34 (Affinity Capture-MS), UFSP2 (Affinity Capture-MS), SLC16A11 (Affinity Capture-RNA), H2AFB3 (Affinity Capture-MS), UFSP2 (Affinity Capture-MS), EMB (Affinity Capture-MS), BAG6 (Affinity Capture-MS), EMB (Affinity Capture-MS), HSPA1L (Affinity Capture-MS), LRRC8A (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), PTPRF (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2HW92, A1L1W9, A6QLW8, F1NJ67, F1PZV2, G5E8K6, O35308, O35440, O70461, O95528, O95907, P30936, P32745, P36021, Q00788, Q08DX7, Q13286, Q1RPP5, Q2YDU8, Q32NY4, Q3U481, Q3U9N9, Q3YAW7, Q5NC32, Q5R540, Q60HH0, Q6DFR1, Q6NUT3, Q6PEM8, Q6UXD7, Q6ZMD2, Q7RTT9, Q7ZWG6, Q8CE47, Q8K078, Q8MK48, Q8NCK7, Q8NE01, Q8R0G7, Q8TF71

Diamond homologs: D4A734, G5E8K6, O15374, O15427, O35308, O35440, O35910, O60669, O70451, O70461, O95907, P53985, P53986, P53987, P53988, P57787, P57788, Q03064, Q17QR6, Q3MHW6, Q503M4, Q5NC32, Q63344, Q66HE2, Q6GM59, Q6P2X9, Q6ZSM3, Q7RTY0, Q8BGC3, Q8CE94, Q8NCK7, Q8R0M8, Q90632, A0LNN5, M0RCI4, O15375, Q5R5M4, Q5ZJU0, Q7RTY1, Q7TM99

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

705 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7042923:C:A	donor_gain	1.0000
17:7042922:T:TA	donor_gain	0.9900
17:7043310:A:AC	donor_gain	0.9900
17:7043311:C:CC	donor_gain	0.9900
17:7043311:CTGG:C	donor_gain	0.9900
17:7043317:G:GA	donor_gain	0.9900
17:7043355:AGTGT:A	donor_gain	0.9900
17:7042890:T:TA	donor_gain	0.9700
17:7042924:CCTCA:C	donor_loss	0.9700
17:7042925:CTCAC:C	donor_loss	0.9700
17:7042927:CACC:C	donor_loss	0.9700
17:7042928:A:C	donor_loss	0.9700
17:7043154:C:A	donor_gain	0.9700
17:7043312:TGGC:T	donor_gain	0.9700
17:7043359:T:TA	donor_gain	0.9700
17:7043843:C:A	donor_gain	0.9700
17:7042929:CCAG:C	donor_gain	0.9600
17:7043265:CGG:C	donor_gain	0.9600
17:7043305:C:CA	donor_gain	0.9600
17:7043842:T:TA	donor_gain	0.9600
17:7043282:T:A	donor_gain	0.9500
17:7043586:C:A	donor_gain	0.9500
17:7042928:A:AC	donor_gain	0.9400
17:7042929:C:CC	donor_gain	0.9400
17:7043264:A:AC	donor_gain	0.9400
17:7043265:C:CC	donor_gain	0.9400
17:7043774:CCCGA:C	donor_gain	0.9200
17:7042475:AGG:A	donor_gain	0.9100
17:7043567:T:TA	donor_gain	0.8900
17:7043179:TG:T	donor_gain	0.8800

AlphaMissense

576 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7043072:G:C	S92R	0.995
17:7043072:G:T	S92R	0.995
17:7043312:T:G	S92R	0.995
17:7043014:C:G	G112R	0.985
17:7043016:C:T	G111E	0.984
17:7043060:G:C	S96R	0.984
17:7043060:G:T	S96R	0.984
17:7043062:T:G	S96R	0.984
17:7043425:C:T	G54E	0.983
17:7043013:C:T	G112D	0.982
17:7043051:G:C	S99R	0.981
17:7043051:G:T	S99R	0.981
17:7043053:T:G	S99R	0.981
17:7043065:C:G	G95R	0.979
17:7043343:G:C	S81R	0.979
17:7043343:G:T	S81R	0.979
17:7043345:T:G	S81R	0.979
17:7043426:C:G	G54R	0.979
17:7043426:C:T	G54R	0.979
17:7043017:C:A	G111W	0.977
17:7043017:C:G	G111R	0.975
17:7043017:C:T	G111R	0.975
17:7043426:C:A	G54W	0.973
17:7043438:C:G	G50R	0.968
17:7043438:C:T	G50R	0.968
17:7043016:C:A	G111V	0.965
17:7043064:C:T	G95D	0.965
17:7043417:G:T	R57S	0.962
17:7043329:G:T	A86D	0.957
17:7043437:C:T	G50E	0.957

dbSNP variants (sampled 300 via entrez): RS1000066497 (17:7044938 C>T), RS1000138744 (17:7042369 G>A,C), RS1000535247 (17:7041242 A>G), RS1001308159 (17:7045098 C>T), RS1003727780 (17:7043167 G>A,C), RS1004197454 (17:7044552 C>T), RS1004540210 (17:7045998 A>G), RS1005307707 (17:7045162 T>C), RS1005733247 (17:7045561 G>A), RS1008995833 (17:7045993 A>G), RS1009973214 (17:7044843 G>C,T), RS1010004211 (17:7044648 A>T), RS1010796102 (17:7042648 C>G,T), RS1010981493 (17:7043749 T>A), RS1013251565 (17:7044606 G>A)

Disease associations

OMIM: gene MIM:615765 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002317_1	Type 2 diabetes	5.000000e-15
GCST007847_28	Type 2 diabetes	6.000000e-16
GCST010118_61	Type 2 diabetes	9.000000e-24
GCST012043_7	Childhood onset type 2 diabetes	4.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
potassium perchlorate	decreases expression	1
terbufos	increases methylation	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
tebuconazole	decreases expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Fonofos	increases methylation	1
Environmental Pollutants	affects expression	1
N-Nitrosopyrrolidine	decreases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases methylation	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Sodium Selenite	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4EH	1321N1-SLC16A11-KO-c17	Cancer cell line	Male
CVCL_D4EI	1321N1-SLC16A11-KO-c8	Cancer cell line	Male

Clinical trials (associated diseases)

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