MPC1

Summary

MPC1 (mitochondrial pyruvate carrier 1, HGNC:21606) is a protein-coding gene on chromosome 6q27, encoding Mitochondrial pyruvate carrier 1 (Q9Y5U8). Mediates the uptake of pyruvate into mitochondria to maintain the balance between glycolysis and oxidative phosphorylation.

The protein encoded by this gene is part of an MPC1/MPC2 heterodimer that is responsible for transporting pyruvate into mitochondria. The encoded protein is found in the inner mitochondrial membrane. Defects in this gene are a cause of mitochondrial pyruvate carrier deficiency. Several transcript variants, some protein coding and one non-protein coding, have been found for this gene.

Source: NCBI Gene 51660 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 61 total — 2 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_016098

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21606
Approved symbol	MPC1
Name	mitochondrial pyruvate carrier 1
Location	6q27
Locus type	gene with protein product
Status	Approved
Aliases	dJ68L15.3, CGI-129, SLC54A1
Ensembl gene	ENSG00000060762
Ensembl biotype	protein_coding
OMIM	614738
Entrez	51660

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000360961, ENST00000366868, ENST00000475708, ENST00000487218, ENST00000621630, ENST00000922734

RefSeq mRNA: 6 — MANE Select: NM_016098 NM_001270879, NM_001376566, NM_001376567, NM_001376568, NM_001376569, NM_016098

CCDS: CCDS5293

Canonical transcript exons

ENST00000360961 — 5 exons

Exon	Start	End
ENSE00001386817	166364919	166365453
ENSE00002722984	166382806	166382940
ENSE00003485662	166365974	166366106
ENSE00003537776	166366795	166366891
ENSE00003572699	166370218	166370221

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.3396 / max 604.8128, expressed in 1824 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76679	33.0795	1813
76680	10.5575	1799
76678	2.2317	1004
76681	0.3454	189
76676	0.1254	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.52	gold quality
cardiac ventricle	UBERON:0002082	99.08	gold quality
heart left ventricle	UBERON:0002084	99.07	gold quality
right atrium auricular region	UBERON:0006631	99.07	gold quality
apex of heart	UBERON:0002098	99.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.95	gold quality
cardiac atrium	UBERON:0002081	98.90	gold quality
right lobe of liver	UBERON:0001114	98.76	gold quality
heart	UBERON:0000948	98.68	gold quality
spinal cord	UBERON:0002240	98.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.30	gold quality
metanephros cortex	UBERON:0010533	98.21	gold quality
adult mammalian kidney	UBERON:0000082	98.04	gold quality
parotid gland	UBERON:0001831	98.02	gold quality
myocardium	UBERON:0002349	97.99	gold quality
caudate nucleus	UBERON:0001873	97.98	gold quality
body of tongue	UBERON:0011876	97.97	gold quality
left ventricle myocardium	UBERON:0006566	97.91	gold quality
liver	UBERON:0002107	97.86	gold quality
rectum	UBERON:0001052	97.84	gold quality
renal medulla	UBERON:0000362	97.83	gold quality
substantia nigra	UBERON:0002038	97.77	gold quality
corpus callosum	UBERON:0002336	97.76	gold quality
muscle of leg	UBERON:0001383	97.72	gold quality
putamen	UBERON:0001874	97.70	gold quality
anterior cingulate cortex	UBERON:0009835	97.65	gold quality
gastrocnemius	UBERON:0001388	97.62	gold quality
cingulate cortex	UBERON:0003027	97.59	gold quality
nucleus accumbens	UBERON:0001882	97.52	gold quality
midbrain	UBERON:0001891	97.50	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	16.94
E-HCAD-10	yes	14.75
E-GEOD-93593	yes	8.84
E-GEOD-99795	no	55.85
E-HCAD-13	no	3.09
E-CURD-112	no	2.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting MPC1, 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-4776-3P	100.00	68.73	1340
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676

Literature-anchored findings (GeneRIF, showing 30)

• the apparent occurrence of an unusual TG 3’ splice site in intron 1 is discussed (PMID:17672918)
• genetic studies of 3 families with children suffering from lactic acidosis and hyperpyruvatemia revealed a causal locus that mapped to MPC1 (BRP44L) changing single amino acids that are conserved throughout eukaryotes; data demonstrate that Mpc1 and Mpc2 form an essential part of the mitochondrial pyruvate carrier (PMID:22628558)
• Tumor cells expressing MPC1 and MPC2 display increased mitochondrial pyruvate oxidation, with no changes in cell growth in adherent culture. (PMID:25458841)
• GTPBP3 plays a role in the regulation of MCP1 protein through AMPK signaling. (PMID:26642043)
• Low MPC1 expression is associated with prostate cancer. (PMID:26895100)
• 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)
• Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, the authors found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. (PMID:28397687)
• Levels of lactate and mitochondrial pyruvate carrier (MPC1) mRNA were determined to scrutinize the prevalence of aerobic glycolysis..MT-RNR2 plays its anti-apoptotic role partly by avoiding deploying energy from complete oxidation of organic compounds to inorganic wastes. Thus MT-RNR2 can potentially serve as a new biomarker in the diagnosis of bladder carcinoma especially that it is present in blood circulation (PMID:28462847)
• Low MPC1 expression is associated with epithelial-mesenchymal transition in cholangiocarcinoma. (PMID:29286150)
• 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)
• PGC1alpha reversed the Warburg effect by upregulating the expression of pyruvate dehydrogenase E1 alpha 1 subunit and mitochondrial pyruvate carrier 1 to increase pyruvate flux into the mitochondria for oxidation, whereas simultaneously promoting mitochondrial biogenesis and fusion to mediate the metabolic switch to oxidative phosphorylation. (PMID:29700317)
• Hypoxia induces lactate secretion and glycolytic efflux by downregulating MPC1/MPC2 levels in HUVEC cells. (PMID:29845198)
• Studied role of mitochondrial pyruvate carrier 1 (MPC1) as a possible biomarker in the prognosis of renal cell carcinoma. (PMID:30291323)
• 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)
• MPC1 was lowly expressed in lung adenocarcinoma tissues and positively correlated with overall survival of lung adenocarcinoma patients. MPC1 suppressed tumor progression via interacting with mito-STAT3, disrupting STAT3 distribution and inhibiting cyto-STAT3 activation. (PMID:30770798)
• The present study has shown that reduced MPC1 expression is involved in EMT in pancreatic cancer and CRC cell lines. Such changes have not been observed in MPC2. The tendency for MPC1 expression in carcinomas to be lower in comparison to normal cells promotes EMT through glutamine metabolism. (PMID:30801869)
• The mitochondrial pyruvate carrier (MPC) links glycolysis and mitochondrial metabolism. Retina-specific deletion of MPC1 results in progressive retinal degeneration and decline of visual function in both rod and cone photoreceptors. (PMID:30808746)
• MPC1 deletion is associated with temozolomide resistance in glioblastoma. (PMID:31236818)
• A novel KDM5A/MPC-1 signaling pathway promotes pancreatic cancer progression via redirecting mitochondrial pyruvate metabolism. (PMID:31641207)
• 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)
• MPC1 Deficiency Promotes CRC Liver Metastasis via Facilitating Nuclear Translocation of beta-Catenin. (PMID:32851100)
• Structural Insights into the Human Mitochondrial Pyruvate Carrier Complexes. (PMID:34664967)
• Identification and characterization of novel MPC1 gene variants causing mitochondrial pyruvate carrier deficiency. (PMID:34873722)
• Mitochondrial pyruvate carrier 1 regulates fatty acid synthase lactylation and mediates treatment of nonalcoholic fatty liver disease. (PMID:36651176)
• Inactivation of mitochondrial pyruvate carrier promotes NLRP3 inflammasome activation and gout development via metabolic reprogramming. (PMID:36708143)
• Loss of mitochondrial pyruvate carrier 1 supports proline-dependent proliferation and collagen biosynthesis in ovarian cancer. (PMID:38354856)
• Metabolism-focused CRISPR screen unveils mitochondrial pyruvate carrier 1 as a critical driver for PARP inhibitor resistance in lung cancer. (PMID:38411275)
• Exploring MPC1 as a potential ferroptosis-linked biomarker in the cervical cancer tumor microenvironment: a comprehensive analysis. (PMID:39390460)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpc1	ENSDARG00000093448
mus_musculus	Mpc1	ENSMUSG00000023861
rattus_norvegicus	Mpc1	ENSRNOG00000012415
drosophila_melanogaster	Mpc1	FBGN0038662

Paralogs (2): MPC2 (ENSG00000143158), MPC1L (ENSG00000238205)

Protein

Protein identifiers

Mitochondrial pyruvate carrier 1 — Q9Y5U8 (reviewed: Q9Y5U8)

Alternative names: Brain protein 44-like protein

All UniProt accessions (2): Q9Y5U8, A0A087WVZ0

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 MPC2 to form a functional mitochondrial pyruvate carrier. May form a homodimer.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Mitochondrial pyruvate carrier deficiency (MPYCD) [MIM:614741] An autosomal recessive metabolic disorder characterized by severely delayed psychomotor development, mild dysmorphic features, hepatomegaly, marked metabolic acidosis, hyperlactacidemia with normal lactate/pyruvate, and encephalopathy. Some patients have epilepsy and peripheral neuropathy. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (6): NP_001257808, NP_001363495, NP_001363496, NP_001363497, NP_001363498, NP_057182* (*=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 (29 total): helix 8, topological domain 4, binding site 3, sequence variant 3, transmembrane region 3, modified residue 2, initiator methionine 1, chain 1, mutagenesis site 1, sequence conflict 1, strand 1, turn 1

Structure

Experimental structures (PDB)

13 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
9KNX	ELECTRON MICROSCOPY	3.72

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5U8-F1	92.85	0.85

Antibody-complex structures (SAbDab): 9 — 8YW6, 8YW8, 8YW9, 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 (3): 69; 80; 66

Post-translational modifications (2): 2, 72

Mutagenesis-validated functional residues (1):

Position	Phenotype
52	impairs 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: 215 (showing top): TAATAAT_MIR126, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, SCIBETTA_KDM5B_TARGETS_UP, GOBP_MITOCHONDRIAL_TRANSPORT, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSMEMBRANE_TRANSPORT, ONKEN_UVEAL_MELANOMA_UP, CAIRO_HEPATOBLASTOMA_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOBP_ORGANIC_ANION_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, chr6q27

GO Biological Process (1): pyruvate import into mitochondria (GO:0006850)

GO Molecular Function (2): pyruvate transmembrane transporter activity (GO:0050833), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), sperm principal piece (GO:0097228), inner mitochondrial membrane protein complex (GO:0098800), 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
cellular anatomical structure	2
import into the mitochondrion	1
monocarboxylic acid transmembrane transporter activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
sperm flagellum	1
mitochondrial inner membrane	1
membrane protein complex	1
mitochondrial protein-containing complex	1

Protein interactions and networks

STRING

606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPC1	MPC2	O95563	997
MPC1	IL6	P05231	523
MPC1	IL1B	P01584	482
MPC1	CCL8	P78388	475
MPC1	PDHA1	P08559	457
MPC1	IL1A	P01583	447
MPC1	CD44	P16070	444
MPC1	PC	P11498	429
MPC1	CXCL8	P10145	418
MPC1	LDHA	P00338	408
MPC1	AASDH	Q4L235	399
MPC1	PRR18	Q8N4B5	399
MPC1	ITGA5	P08648	397
MPC1	CS	O75390	388
MPC1	PDK1	Q15118	377

IntAct

14 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
MPC1	MGST3	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
MPC1	MPC2	psi-mi:“MI:0915”(physical association)	0.000
MAGED1	MPC1	psi-mi:“MI:0915”(physical association)	0.000
MPC1	ACTC1	psi-mi:“MI:0915”(physical association)	0.000
MPC1	GABARAP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): MPC1 (Two-hybrid), MPC2 (Two-hybrid), MPC1 (Negative Genetic), MPC1 (Negative Genetic), MPC2 (Affinity Capture-MS), ASS1 (Affinity Capture-MS), MPC1 (Affinity Capture-MS), MPC1 (Reconstituted Complex), MGST3 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), RAB35 (Affinity Capture-MS), RAB8B (Affinity Capture-MS), TFAM (Affinity Capture-MS)

ESM2 similar proteins: A0A1D8PI78, A1XQR6, A2RVP7, A4QNF3, B2RYW8, O44477, O48528, P0CR88, P0CR89, P25710, P32897, P60602, P60603, P63030, P63031, P79082, P87130, P87146, Q02889, Q12328, Q3SZV8, Q3ZCG2, Q4V7T9, Q54K35, Q54QM0, Q55GU4, Q5NVQ1, Q5TGZ0, Q6BT35, Q6BZY4, Q6CRJ6, Q6FT37, Q6NYD1, Q751T2, Q75E80, Q7KSC4, Q7TNS2, Q80W89, Q8HXG6, Q8IN78

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MPC1	“form complex”	“Mitochondrial pyruvate carrier complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	18
Likely benign	15
Benign	11

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
35561	NM_016098.4(MPC1):c.289C>T (p.Arg97Trp)	Pathogenic
35562	NM_016098.4(MPC1):c.236T>A (p.Leu79His)	Pathogenic
1236162	NM_016098.4(MPC1):c.208G>A (p.Ala70Thr)	Likely pathogenic
1236163	NM_016098.4(MPC1):c.290G>A (p.Arg97Gln)	Likely pathogenic
1299296	NM_016098.4(MPC1):c.109C>T (p.Pro37Ser)	Likely pathogenic
488547	NM_016098.4(MPC1):c.214A>G (p.Lys72Glu)	Likely pathogenic

SpliceAI

836 predictions. Top by Δscore:

Variant	Effect	Δscore
6:166365449:TCATC:T	acceptor_gain	1.0000
6:166365450:CATC:C	acceptor_gain	1.0000
6:166365450:CATCC:C	acceptor_gain	1.0000
6:166365451:ATC:A	acceptor_gain	1.0000
6:166365452:TC:T	acceptor_gain	1.0000
6:166365453:CC:C	acceptor_gain	1.0000
6:166365453:CCTG:C	acceptor_loss	1.0000
6:166365454:C:CA	acceptor_loss	1.0000
6:166365454:C:CC	acceptor_gain	1.0000
6:166365455:T:A	acceptor_loss	1.0000
6:166365972:A:AC	donor_gain	1.0000
6:166365973:C:CC	donor_gain	1.0000
6:166365973:CT:C	donor_gain	1.0000
6:166366789:TCTTA:T	donor_loss	1.0000
6:166366790:CTTA:C	donor_loss	1.0000
6:166366791:TTAC:T	donor_loss	1.0000
6:166366792:TACC:T	donor_loss	1.0000
6:166366793:A:AC	donor_gain	1.0000
6:166366793:ACCAA:A	donor_loss	1.0000
6:166366794:C:A	donor_loss	1.0000
6:166366794:C:CC	donor_gain	1.0000
6:166366887:AAGTG:A	acceptor_gain	1.0000
6:166366888:AGTG:A	acceptor_gain	1.0000
6:166366889:GTG:G	acceptor_gain	1.0000
6:166366890:TG:T	acceptor_gain	1.0000
6:166366891:GCTA:G	acceptor_loss	1.0000
6:166366892:C:CC	acceptor_gain	1.0000
6:166366892:C:T	acceptor_loss	1.0000
6:166370261:C:CT	acceptor_gain	1.0000
6:166370262:A:AC	acceptor_gain	1.0000

AlphaMissense

719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:166366018:A:C	N87K	0.999
6:166366018:A:T	N87K	0.999
6:166366072:A:C	F69L	0.999
6:166366072:A:T	F69L	0.999
6:166366074:A:G	F69L	0.999
6:166366081:G:C	F66L	0.999
6:166366081:G:T	F66L	0.999
6:166366083:A:G	F66L	0.999
6:166366091:G:A	S63F	0.999
6:166366867:A:G	W34R	0.999
6:166366867:A:T	W34R	0.999
6:166366872:G:T	A32D	0.999
6:166366886:G:C	F27L	0.999
6:166366886:G:T	F27L	0.999
6:166366888:A:G	F27L	0.999
6:166366029:G:C	H84D	0.998
6:166366030:G:C	C83W	0.998
6:166366031:C:T	C83Y	0.998
6:166366040:A:T	L80Q	0.998
6:166366073:A:C	F69C	0.998
6:166366073:A:G	F69S	0.998
6:166366091:G:T	S63Y	0.998
6:166366851:G:T	A39D	0.998
6:166366857:G:T	P37H	0.998
6:166366860:A:T	L36H	0.998
6:166366863:C:T	G35D	0.998
6:166366864:C:G	G35R	0.998
6:166366882:C:G	G29R	0.998
6:166366885:A:G	W28R	0.998
6:166366885:A:T	W28R	0.998

dbSNP variants (sampled 300 via entrez): RS1000043522 (6:166384377 G>A,C,T), RS1000081289 (6:166368366 G>A), RS1000104386 (6:166383917 C>T), RS1000161305 (6:166365806 TC>T), RS1000347797 (6:166381955 C>T), RS1000433327 (6:166368671 T>C), RS1000849726 (6:166376793 T>A,C), RS1000880644 (6:166377087 G>C), RS1001033730 (6:166370524 T>C), RS1001312474 (6:166374865 T>G), RS1001446539 (6:166374501 A>G), RS1001613673 (6:166381712 G>A,C,T), RS1002321177 (6:166382510 C>A), RS1002452430 (6:166376147 T>C), RS1002593456 (6:166382643 C>T)

Disease associations

OMIM: gene MIM:614738 | disease phenotypes: MIM:614741, MIM:617667

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial pyruvate carrier deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (2): mitochondrial pyruvate carrier deficiency (MONDO:0013877), Fraser syndrome 3 (MONDO:0054739)

Orphanet (1): Mitochondrial pyruvate carrier deficiency (Orphanet:447784)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000219	Thin upper lip vermilion
HP:0000253	Progressive microcephaly
HP:0000286	Epicanthus
HP:0000343	Long philtrum
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001583	Rotary nystagmus
HP:0001943	Hypoglycemia
HP:0001992	Organic aciduria
HP:0002098	Respiratory distress
HP:0002151	Increased circulating lactate concentration
HP:0002240	Hepatomegaly
HP:0003128	Lactic acidosis
HP:0003542	Increased circulating pyruvate concentration
HP:0003577	Congenital onset
HP:0003828	Variable expressivity
HP:0009830	Peripheral neuropathy

GWAS associations

0 associations (top):

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 — SLC54 Mitochondrial pyruvate carriers

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
UK-5099	Inhibition	7.3	pIC50
α-cyanocinnamate	Inhibition	6.7	pIC50
α-Cyano-5-phenyl-2,4-pentadienic acid	Inhibition	6.7	pIC50
mitoglitazone	Inhibition	5.89	pIC50
α-cyano-4-hydroxycinnamate	Inhibition	5.82	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
sodium arsenite	increases abundance, increases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
ciglitazone	affects binding, increases expression	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, decreases reaction, affects reaction, increases expression	1
4-phenylbutyric acid	decreases expression, decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	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
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine	decreases expression, decreases reaction, increases expression	1
bisphenol AF	increases expression	1
Sevoflurane	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	affects expression	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, increases expression	1
Dexamethasone	increases expression	1
Diethylhexyl Phthalate	increases expression	1

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D0VM	BCHNCi003-A	Induced pluripotent stem cell	Male
CVCL_D4GY	HCT116-MPC1-KO-c2	Cancer cell line	Male
CVCL_D4GZ	HCT116-MPC1-KO-c7	Cancer cell line	Male
CVCL_E2CN	HAP1 MPC1 (-) 2	Cancer cell line	Male
CVCL_E2CP	HAP1 MPC1 (-) 3	Cancer cell line	Male
CVCL_XQ59	HAP1 MPC1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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