MPC2

Summary

MPC2 (mitochondrial pyruvate carrier 2, HGNC:24515) is a protein-coding gene on chromosome 1q24.2, encoding Mitochondrial pyruvate carrier 2 (O95563). Mediates the uptake of pyruvate into mitochondria to maintain the balance between glycolysis and oxidative phosphorylation.

Enables identical protein binding activity. Involved in mitochondrial pyruvate transmembrane transport. Located in mitochondrial inner membrane.

Source: NCBI Gene 25874 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial pyruvate carrier deficiency (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001143674

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24515
Approved symbol	MPC2
Name	mitochondrial pyruvate carrier 2
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564B167, SLC54A2
Ensembl gene	ENSG00000143158
Ensembl biotype	protein_coding
OMIM	614737
Entrez	25874

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000271373, ENST00000367846, ENST00000458574, ENST00000856458, ENST00000856459, ENST00000856460, ENST00000856461, ENST00000856462, ENST00000856463, ENST00000936468, ENST00000936469, ENST00000936470, ENST00000936471

RefSeq mRNA: 2 — MANE Select: NM_001143674 NM_001143674, NM_015415

CCDS: CCDS1266

Canonical transcript exons

ENST00000271373 — 6 exons

Exon	Start	End
ENSE00000958426	167924497	167924537
ENSE00000958427	167920547	167920631
ENSE00000958428	167919979	167920090
ENSE00001445754	167935733	167935898
ENSE00001445755	167936939	167937072
ENSE00001445757	167916675	167918359

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.2289 / max 592.7257, expressed in 1825 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15797	41.7698	1823
15798	1.0820	677
15796	0.6704	392
15810	0.5977	210
15802	0.4227	232
15808	0.3950	49
15799	0.2596	104
15806	0.2085	48
15800	0.2063	79
15803	0.1764	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.55	gold quality
adult organism	UBERON:0007023	98.47	gold quality
male germ cell	CL:0000015	98.37	gold quality
diaphragm	UBERON:0001103	97.97	gold quality
left testis	UBERON:0004533	97.72	gold quality
right testis	UBERON:0004534	97.52	gold quality
heart right ventricle	UBERON:0002080	97.48	gold quality
renal medulla	UBERON:0000362	97.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.01	gold quality
left ventricle myocardium	UBERON:0006566	96.87	gold quality
liver	UBERON:0002107	96.78	gold quality
colonic mucosa	UBERON:0000317	96.75	gold quality
jejunal mucosa	UBERON:0000399	96.58	gold quality
right lobe of liver	UBERON:0001114	96.53	gold quality
adult mammalian kidney	UBERON:0000082	96.45	gold quality
testis	UBERON:0000473	96.43	gold quality
body of tongue	UBERON:0011876	96.37	gold quality
triceps brachii	UBERON:0001509	96.31	gold quality
jejunum	UBERON:0002115	96.21	gold quality
cardiac ventricle	UBERON:0002082	96.18	gold quality
heart left ventricle	UBERON:0002084	96.16	gold quality
biceps brachii	UBERON:0001507	95.98	gold quality
skeletal muscle tissue	UBERON:0001134	95.92	gold quality
vastus lateralis	UBERON:0001379	95.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.88	gold quality
nephron tubule	UBERON:0001231	95.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.67	gold quality
vena cava	UBERON:0004087	95.64	gold quality
quadriceps femoris	UBERON:0001377	95.61	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	1351.37
E-HCAD-10	yes	1071.58
E-GEOD-124472	yes	838.18
E-HCAD-4	yes	159.71
E-MTAB-6701	yes	114.12
E-HCAD-6	yes	67.16
E-GEOD-134144	yes	30.88
E-HCAD-31	yes	28.46
E-MTAB-5061	yes	27.36
E-CURD-122	yes	19.41
E-MTAB-10553	yes	18.58
E-MTAB-9388	yes	12.66
E-HCAD-1	yes	9.46
E-HCAD-9	yes	9.21
E-HCAD-13	yes	7.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting MPC2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4261	99.59	70.30	3415

Literature-anchored findings (GeneRIF, showing 17)

• found no significant difference (P > 0.05) in either allele or genotype frequency in the SNPs between patients and controls. (PMID:23933155)
• Tumor cells expressing MPC1 and MPC2 display increased mitochondrial pyruvate oxidation, with no changes in cell growth in adherent culture. (PMID:25458841)
• These results reveal a novel post-translational regulation of MPC1 by Sirt3, which is important for its activity and colon cancer cell growth. (PMID:26577410)
• a significant association between MPC2 variant rs10489202 and Schizophrenia susceptibility in Han Chinese (Meta-Analysis) (PMID:27460766)
• Our study indicates that MPC1 and MPC2 expressions are of prognostic values in PCAs and that positive expression of MPC1 or MPC2 is a predictor of favorable outcome. (PMID:27852261)
• Results indicate mitochondrial pyruvate transporter (MPC) to be the key regulatory junction perturbed by virulent strains of Mycobacterium tuberculosis leading to alteration of mitochondrial metabolic flux and regulation of acetyl-CoA formation. (PMID:28263840)
• In contrast to MPC1, which co-purifies with a host chaperone, we demonstrated that MPC2 homo-oligomers promote efficient pyruvate transport into proteoliposomes. The derived functional requirements and kinetic features of MPC2 resemble those previously demonstrated for MPC in the literature (PMID:29472561)
• Hypoxia induces lactate secretion and glycolytic efflux by downregulating MPC1/MPC2 levels in HUVEC cells. (PMID:29845198)
• MPC2 rs10489202 was genome-wide significantly associated with schizophrenia. The expression quantitative trait loci analysis in lymphoblastoid cell lines from East Asian donors revealed that MPC2 rs10489202 was specifically and significantly associated with the expression of TIPRL gene. (PMID:30087317)
• characterization of the rat ortholog (PMID:3022128)
• The data demonstrated that CtBP1 directly bound to the promoters of MPC1 and MPC2 and transcriptionally repressed them, leading to increased levels of free NADH in the cytosol and nucleus, thus positively feeding back CtBP1’s functions. (PMID:30356033)
• Characteristic Analysis of Homo- and Heterodimeric Complexes of Human Mitochondrial Pyruvate Carrier Related to Metabolic Diseases. (PMID:32403431)
• Mitochondrial pyruvate carrier: a potential target for diabetic nephropathy. (PMID:32664896)
• The Multifaceted Pyruvate Metabolism: Role of the Mitochondrial Pyruvate Carrier. (PMID:32708919)
• Decreased Expression of MPC2 Contributes to Aerobic Glycolysis and Colorectal Cancer Proliferation by Activating mTOR Pathway. (PMID:33791391)
• Structural Insights into the Human Mitochondrial Pyruvate Carrier Complexes. (PMID:34664967)
• MPC2 variants disrupt mitochondrial pyruvate metabolism and cause an early-onset mitochondriopathy. (PMID:36417180)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpc2b	ENSDARG00000024478
danio_rerio	mpc2a	ENSDARG00000037679
mus_musculus	Mpc2	ENSMUSG00000026568
rattus_norvegicus	Mpc2	ENSRNOG00000003150
drosophila_melanogaster	CG9396	FBGN0037714
drosophila_melanogaster	CG9399	FBGN0037715
drosophila_melanogaster	CG32832	FBGN0052832
caenorhabditis_elegans	mpc-2	WBGENE00018765

Paralogs (2): MPC1 (ENSG00000060762), MPC1L (ENSG00000238205)

Protein

Protein identifiers

Mitochondrial pyruvate carrier 2 — O95563 (reviewed: O95563)

Alternative names: Brain protein 44

All UniProt accessions (2): O95563, Q5R3B4

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the uptake of pyruvate into mitochondria to maintain the balance between glycolysis and oxidative phosphorylation. Plays an essential role in cellular metabolism.

Subunit / interactions. Heterodimer; dimerises with MPC1 or MPC1L to form a functional mitochondrial pyruvate carrier. May form a homodimer.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.

RefSeq proteins (2): NP_001137146, NP_056230 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005336	MPC	Family

Pfam: PF03650

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (26 total): helix 8, mutagenesis site 6, topological domain 4, transmembrane region 3, strand 2, binding site 2, chain 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
9MNZ	ELECTRON MICROSCOPY	2.73
9MNY	ELECTRON MICROSCOPY	2.78
9MO0	ELECTRON MICROSCOPY	2.83
8YW9	ELECTRON MICROSCOPY	3.01
9MNX	ELECTRON MICROSCOPY	3.11
8YW8	ELECTRON MICROSCOPY	3.17
8YW6	ELECTRON MICROSCOPY	3.18
9O9T	ELECTRON MICROSCOPY	3.31
9MNW	ELECTRON MICROSCOPY	3.35
9KNY	ELECTRON MICROSCOPY	3.4
9KNW	ELECTRON MICROSCOPY	3.41
9O9S	ELECTRON MICROSCOPY	3.57
9GIV	ELECTRON MICROSCOPY	3.65
9GIX	ELECTRON MICROSCOPY	3.65
9KNX	ELECTRON MICROSCOPY	3.72
9GIY	ELECTRON MICROSCOPY	3.79
9GIW	ELECTRON MICROSCOPY	3.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95563-F1	89.34	0.53

Antibody-complex structures (SAbDab): 10 — 8YW6, 8YW8, 8YW9, 9GIX, 9KNW, 9KNX, 9KNY, 9MNX, 9MNY, 9MNZ

Functional residue map

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

Ligand- & substrate-binding residues (2): 49; 82

Mutagenesis-validated functional residues (6):

Position	Phenotype
49	impairs pyruvate uptake.
66	impairs pyruvate uptake.
71	abolishes pyruvate uptake.
82	impairs pyruvate uptake.
100	impairs pyruvate uptake.
110	abolishes pyruvate uptake.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-70268	Pyruvate metabolism
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism

MSigDB gene sets: 286 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, TGCGCANK_UNKNOWN, RORA1_01, GCANCTGNY_MYOD_Q6, GOBP_INSULIN_SECRETION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, AREB6_03, MAZ_Q6, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2

GO Biological Process (3): pyruvate decarboxylation to acetyl-CoA (GO:0006086), pyruvate import into mitochondria (GO:0006850), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774)

GO Molecular Function (3): identical protein binding (GO:0042802), pyruvate transmembrane transporter activity (GO:0050833), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), inner mitochondrial membrane protein complex (GO:0098800), mitochondrial pyruvate carrier complex (GO:7770001), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyruvate transmembrane transport	2
intracellular membrane-bounded organelle	2
dihydrolipoyl dehydrogenase (NADH) activity	1
pyruvate dehydrogenase (acetyl-transferring) activity	1
dihydrolipoyllysine-residue acetyltransferase activity	1
acetyl-CoA biosynthetic process	1
pyruvate metabolic process	1
aerobic respiration	1
import into the mitochondrion	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
protein binding	1
monocarboxylic acid transmembrane transporter activity	1
binding	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial inner membrane	1
membrane protein complex	1
mitochondrial protein-containing complex	1
inner mitochondrial membrane protein complex	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPC2	MPC1	Q9Y5U8	997
MPC2	MPC1L	P0DKB6	711
MPC2	VDAC1	P21796	513
MPC2	PC	P11498	501
MPC2	MPZL1	O95297	460
MPC2	MAGED1	Q9Y5V3	452
MPC2	MDH2	P40926	448
MPC2	PDHB	P11177	433
MPC2	ACTC1	P04270	430
MPC2	PDHA1	P08559	429
MPC2	PDHX	O00330	428
MPC2	COQ10A	Q96MF6	410
MPC2	COG3	Q96JB2	398
MPC2	RELN	P78509	392
MPC2	H2AC6	Q93077	392

IntAct

122 interactions, top by confidence:

A	B	Type	Score
MPC2	MPC1	psi-mi:“MI:0915”(physical association)	0.860
MPC2	MPC1	psi-mi:“MI:0407”(direct interaction)	0.860
MPC1	MPC2	psi-mi:“MI:0915”(physical association)	0.860
MPC1	MPC2	psi-mi:“MI:0914”(association)	0.860
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MPC2	MPC1L	psi-mi:“MI:0407”(direct interaction)	0.650
EIF3F	EIF3CL	psi-mi:“MI:0914”(association)	0.640
MPC2	DIABLO	psi-mi:“MI:0915”(physical association)	0.560
MPC2	TEX44	psi-mi:“MI:0915”(physical association)	0.560
MPC2	SYT16	psi-mi:“MI:0915”(physical association)	0.560
TIMM17B	MPC2	psi-mi:“MI:0915”(physical association)	0.560
MPC2	SPG21	psi-mi:“MI:0915”(physical association)	0.560
MPC2	MPC2	psi-mi:“MI:0915”(physical association)	0.560
MPC2	SNX1	psi-mi:“MI:0915”(physical association)	0.560
MPC2	MICOS10	psi-mi:“MI:0915”(physical association)	0.560
MPC2	APOC1	psi-mi:“MI:0915”(physical association)	0.560
MPC2	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
MPC2	RHBDD2	psi-mi:“MI:0915”(physical association)	0.560
DR1	MPC2	psi-mi:“MI:0915”(physical association)	0.560
EEF1D	MPC2	psi-mi:“MI:0915”(physical association)	0.560
BRK1	MPC2	psi-mi:“MI:0915”(physical association)	0.560
GTF3C3	MPC2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (75): MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), MPC2 (Affinity Capture-RNA), MPC2 (Two-hybrid), RPLP1 (Two-hybrid)

ESM2 similar proteins: A0JNC1, A2VE61, B2RZ37, D4A9I3, O75844, O95563, O95674, Q00765, Q0VCK9, Q0VFK3, Q29RM3, Q29S14, Q401C0, Q5BL21, Q5R4Z3, Q5R7B1, Q5R9I4, Q5R9K4, Q5RDV3, Q5RE33, Q5ZKJ0, Q60870, Q68EQ9, Q68EY2, Q6DD32, Q6GM44, Q6INE8, Q6NYY9, Q6P360, Q6P3N5, Q6PBX9, Q80W54, Q8BG21, Q8BXA5, Q8R1Z9, Q91ZQ0, Q940S0, Q96GC9, Q96KA5, Q99KU0

Diamond homologs: O01578, O49636, O95563, P38718, P38857, P53311, Q09896, Q5R4Z3, Q8L7H8, Q8LD38, Q949R9, Q9D023, Q3ZCG2, Q7KSC4, Q9Y5U8, P63030, P63031, P0DKB6, Q21828, O74847, Q55GU3, P53157, Q2M2T3, Q55GU4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MPC2	“form complex”	“Mitochondrial pyruvate carrier complex”	binding
MPC2	“form complex”	“Mitochondrial pyruvate carrier complex, testis variant”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

657 predictions. Top by Δscore:

Variant	Effect	Δscore
1:167920628:ACCC:A	acceptor_gain	1.0000
1:167920629:CCCC:C	acceptor_gain	1.0000
1:167924495:AC:A	donor_gain	1.0000
1:167924496:CC:C	donor_gain	1.0000
1:167924535:GAC:G	acceptor_gain	1.0000
1:167924536:ACCT:A	acceptor_loss	1.0000
1:167924538:C:CC	acceptor_gain	1.0000
1:167924538:CTGAA:C	acceptor_loss	1.0000
1:167924539:T:C	acceptor_loss	1.0000
1:167935727:CATTA:C	donor_loss	1.0000
1:167935728:ATTAC:A	donor_loss	1.0000
1:167935729:TTACC:T	donor_loss	1.0000
1:167935730:TACC:T	donor_loss	1.0000
1:167935732:CCTG:C	donor_gain	1.0000
1:167920542:TTTA:T	donor_loss	0.9900
1:167920543:TTACC:T	donor_loss	0.9900
1:167920544:TACCT:T	donor_loss	0.9900
1:167920545:AC:A	donor_loss	0.9900
1:167920546:C:A	donor_loss	0.9900
1:167920627:AACCC:A	acceptor_gain	0.9900
1:167920629:CCC:C	acceptor_gain	0.9900
1:167920630:CCC:C	acceptor_gain	0.9900
1:167920643:C:CT	acceptor_gain	0.9900
1:167920645:CA:C	acceptor_gain	0.9900
1:167920646:A:AC	acceptor_gain	0.9900
1:167920646:A:C	acceptor_gain	0.9900
1:167924495:A:AC	donor_gain	0.9900
1:167924495:ACC:A	donor_gain	0.9900
1:167924496:C:CC	donor_gain	0.9900
1:167924496:CCC:C	donor_gain	0.9900

AlphaMissense

815 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:167920090:C:T	G79E	1.000
1:167920015:C:T	G104E	0.999
1:167920016:C:G	G104R	0.999
1:167920016:C:T	G104R	0.999
1:167920026:A:C	N100K	0.999
1:167920026:A:T	N100K	0.999
1:167920055:G:A	P91S	0.999
1:167920060:A:T	I89N	0.999
1:167920082:A:G	W82R	0.999
1:167920082:A:T	W82R	0.999
1:167920547:C:A	G79W	0.999
1:167920547:C:G	G79R	0.999
1:167920547:C:T	G79R	0.999
1:167920549:G:A	T78I	0.999
1:167924499:A:G	W50R	0.999
1:167924499:A:T	W50R	0.999
1:167924521:G:C	F42L	0.999
1:167924521:G:T	F42L	0.999
1:167924523:A:G	F42L	0.999
1:167920007:C:G	G107R	0.998
1:167920007:C:T	G107R	0.998
1:167920039:A:G	L96P	0.998
1:167920054:G:T	P91Q	0.998
1:167920055:G:C	P91A	0.998
1:167920060:A:C	I89S	0.998
1:167920060:A:G	I89T	0.998
1:167920090:C:A	G79V	0.998
1:167920558:A:C	L75W	0.998
1:167920558:A:G	L75S	0.998
1:167920607:C:G	D59H	0.998

dbSNP variants (sampled 300 via entrez): RS1000063971 (1:167933099 A>G), RS1000325636 (1:167930011 T>A), RS1000331734 (1:167933456 C>A,T), RS1000437960 (1:167923016 C>T), RS1000470560 (1:167918801 G>A), RS1000621338 (1:167923281 T>C), RS1000735448 (1:167919047 A>G), RS1000958865 (1:167924342 A>C,G), RS1001036146 (1:167937363 C>G,T), RS1001100366 (1:167935299 G>A), RS1001164709 (1:167917440 A>C,G), RS1001332206 (1:167931553 A>C), RS1001550865 (1:167931286 C>A,G,T), RS1001765173 (1:167937743 A>T), RS1001861455 (1:167936765 C>T)

Disease associations

OMIM: gene MIM:614737 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial pyruvate carrier deficiency	Moderate	Autosomal recessive
metabolic disease	Limited	Autosomal recessive

Mondo (2): mitochondrial pyruvate carrier deficiency (MONDO:0013877), metabolic disease (MONDO:0005066)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001301_1	Schizophrenia	1.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008659	Metabolic Diseases	C18.452

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295686 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 331 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL146624	MITOGLITAZONE	2	331

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC54 Mitochondrial pyruvate carriers

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
UK-5099	Inhibition	7.28	pIC50
α-cyanocinnamate	Inhibition	6.7	pIC50
α-Cyano-5-phenyl-2,4-pentadienic acid	Inhibition	6.7	pIC50
zaprinast	Inhibition	6.52	pIC50
entacapone	Inhibition	6.22	pIC50
mitoglitazone	Inhibition	5.89	pIC50
α-cyano-4-hydroxycinnamate	Inhibition	5.82	pIC50
nitrofurantoin	Inhibition	5.48	pIC50
lonidamine	Inhibition	5.34	pIC50

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.92	IC50	1200	nM	MITOGLITAZONE
5.92	IC50	1200	nM	CHEMBL4291468

PubChem BioAssay actives

2 with measured affinity, of 2 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[[4-[2-(5-ethyl-2-pyridinyl)-2-oxoethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione	1419250: Displacement of photoprobe from MPC2 (unknown origin)	ic50	1.2000	uM
5-[[4-[2-(3-methoxyphenyl)-2-oxoethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione	1419250: Displacement of photoprobe from MPC2 (unknown origin)	ic50	1.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects expression	3
Valproic Acid	decreases methylation, increases expression	3
Aflatoxin B1	decreases expression, decreases methylation	3
Acetaminophen	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
brequinar	decreases expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
enzalutamide	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	increases expression	1
Cyclophosphamide	affects response to substance	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	increases expression	1
Fluorouracil	affects response to substance	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Mitoxantrone	affects response to substance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4265674	Binding	Displacement of photoprobe from MPC2 (unknown origin)	PPARγ-sparing thiazolidinediones as insulin sensitizers. Design, synthesis and selection of compounds for clinical development. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4RI	HuH7-MPC2-KO-c10	Cancer cell line	Male
CVCL_D4RJ	HuH7-MPC2-KO-c12	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00192621	PHASE4	COMPLETED	Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects
NCT01443806	PHASE4	COMPLETED	Characterisation of the Human Carboxylesterase 1 (CES1) Mutations in Thailand
NCT02645279	PHASE4	UNKNOWN	Comparison of Oral 30 % Dextrose and iv Midazolam Sedation During MRI in Neonates
NCT04653779	PHASE4	UNKNOWN	A Clinical Trial to Evaluate the Preference Regarding Convenience of Medication and Efficacy/Safety of SUGAMET®XR Tablet 5/1000mg
NCT05084079	PHASE4	UNKNOWN	Different Initial Insulin Dose Regimens on Time to Achieve Glycemic Targets and Treatment Safety in SIIT
NCT05855577	PHASE4	NOT_YET_RECRUITING	Motor Function Efficacy of Pharmacological Treatments Targeting Energy Metabolism, in Parkinson’s Patients
NCT06003153	PHASE4	RECRUITING	GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
NCT06009653	PHASE4	WITHDRAWN	Effects of Tirzepatide Plus Intensive Lifestyle Therapy on Body Weight and Metabolic Health in Latinos With Obesity
NCT00387114	PHASE3	TERMINATED	Effect of an Anti-Oxidant Treatment on Resistin Serum Levels.A Randomized Study
NCT00546052	PHASE3	COMPLETED	A 52 Week Study to Evaluate the Effects of Losartan With or Without HCTZ on Plasma Glucose, Metabolic Parameters, Blood Pressure in Hypertensive Patients With Metabolic Syndrome (0954A-331)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00935766	PHASE3	TERMINATED	Effect of Fish Oil (Omega-3 Fatty Acids) on Arteries
NCT01286909	PHASE3	UNKNOWN	Efficacy of Laflavon in Lowering Triglycerides and Raising High-Density Lipoprotein (HDL)
NCT01343680	PHASE3	TERMINATED	Trial of Two Central Venous Catheter (CVC) Flushing Schemes in Pediatric Hematology and Oncology Patients
NCT04371978	PHASE3	TERMINATED	Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19
NCT04809220	PHASE3	COMPLETED	A Study of Two Doses of Dulaglutide (LY2189265) in Japanese Patients With Type 2 Diabetes
NCT05260021	PHASE3	COMPLETED	A Study to Evaluate Tirzepatide (LY3298176) in Pediatric and Adolescent Participants With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin or Basal Insulin or Both
NCT05425745	PHASE3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05505994	PHASE3	UNKNOWN	The Efficacy and Safety of DWP16001 in Combination With Metformin in T2DM Patients Inadequately Controlled on Metformin
NCT05691712	PHASE3	COMPLETED	A Study of Tirzepatide (LY3298176) in Chinese Participants With Type 2 Diabetes
NCT06568471	PHASE3	RECRUITING	A Study on Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT07613307	PHASE3	NOT_YET_RECRUITING	A Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes Who Observe Ramadan Fasting
NCT00001723	PHASE2	COMPLETED	Safety and Efficacy of Xenical in Children and Adolescents With Obesity-Related Diseases
NCT00119379	PHASE2	COMPLETED	Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults
NCT00362180	PHASE2	COMPLETED	Measure Liver Fat Content After ISIS 301012 (Mipomersen) Administration
NCT00446264	PHASE2	COMPLETED	Islet Allotransplantation With Steroid Free Immunosuppression
NCT00477594	PHASE2	COMPLETED	Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00622765	PHASE2	COMPLETED	A Study of the Safety and Effectiveness of JNJ-16269110 (R256918) in Overweight and Obese Patients
NCT00707746	PHASE2	COMPLETED	Safety and Efficacy Study of ISIS 301012 (Mipomersen) Administration in High Risk Statin Intolerant Subjects
NCT01041677	PHASE2	COMPLETED	A Study of the Safety of R256918 in Obese Patients
NCT01135537	PHASE2	TERMINATED	Pharmacokinetics of Thymoglobulin in Paediatric Haematopoietic Stem-cell Transplants
NCT01596699	PHASE2	TERMINATED	Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
NCT01927913	PHASE2	WITHDRAWN	Treatment of Iron Overload Requiring Chelation Therapy
NCT01968720	PHASE2	COMPLETED	Pilot Study To Assess CAT-2003 in Patients With Severe Hypertriglyceridemia
NCT02019667	PHASE2	COMPLETED	Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency
NCT02102737	PHASE2	COMPLETED	Comparison of A New Technique of Measure of the Insulin Resistance By Scintigraphy With the Reference Technique
NCT02512679	PHASE2	TERMINATED	Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
NCT02587572	PHASE2	WITHDRAWN	Safety and Efficacy Trial Using Allogeneic Human Mesenchymal Stem Cells: The SIRONA Trial