MPC1L

Summary

MPC1L (mitochondrial pyruvate carrier 1 like, HGNC:44205) is a protein-coding gene on chromosome Xp11.4, encoding Mitochondrial pyruvate carrier 1-like protein (P0DKB6). Mediates the uptake of pyruvate into mitochondria.

Predicted to enable pyruvate transmembrane transporter activity. Involved in mitochondrial pyruvate transmembrane transport. Located in mitochondrial inner membrane.

Source: NCBI Gene 347411 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001195522

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44205
Approved symbol	MPC1L
Name	mitochondrial pyruvate carrier 1 like
Location	Xp11.4
Locus type	gene with protein product
Status	Approved
Aliases	SLC54A3
Ensembl gene	ENSG00000238205
Ensembl biotype	protein_coding
OMIM	301103
Entrez	347411

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000423387

RefSeq mRNA: 1 — MANE Select: NM_001195522 NM_001195522

CCDS: CCDS83466

Canonical transcript exons

ENST00000423387 — 1 exons

Exon	Start	End
ENSE00001620310	40623428	40624136

Expression profiles

Bgee: expression breadth broad, 48 present calls, max score 94.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0544 / max 50.1582, expressed in 4 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195997	0.0326	4
195998	0.0129	4
195999	0.0089	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.11	gold quality
left testis	UBERON:0004533	83.73	gold quality
testis	UBERON:0000473	83.13	gold quality
right testis	UBERON:0004534	83.07	gold quality
granulocyte	CL:0000094	56.18	gold quality
stromal cell of endometrium	CL:0002255	41.77	silver quality
right coronary artery	UBERON:0001625	39.63	silver quality
sural nerve	UBERON:0015488	37.26	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	37.12	silver quality
mucosa of stomach	UBERON:0001199	36.49	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
placenta	UBERON:0001987	33.29	gold quality
islet of Langerhans	UBERON:0000006	33.27	gold quality
right uterine tube	UBERON:0001302	32.86	gold quality
lymph node	UBERON:0000029	32.66	silver quality
leukocyte	CL:0000738	32.60	silver quality
blood	UBERON:0000178	32.15	gold quality
monocyte	CL:0000576	31.74	silver quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
kidney	UBERON:0002113	30.74	silver quality
adult mammalian kidney	UBERON:0000082	30.29	silver quality
right lobe of liver	UBERON:0001114	29.92	silver quality
primary visual cortex	UBERON:0002436	29.85	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting MPC1L, 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-548AU-3P	99.70	68.22	1373
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-657	99.48	66.02	848
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-631	97.05	66.93	602
HSA-MIR-106B-3P	82.36	64.48	34

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gm4984	ENSMUSG00000079871
rattus_norvegicus	Mpc1l	ENSRNOG00000023163

Paralogs (2): MPC1 (ENSG00000060762), MPC2 (ENSG00000143158)

Protein

Protein identifiers

Mitochondrial pyruvate carrier 1-like protein — P0DKB6 (reviewed: P0DKB6)

All UniProt accessions (1): P0DKB6

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the uptake of pyruvate into mitochondria.

Subunit / interactions. Heterodimer; dimerises with MPC2 to form a functional mitochondrial pyruvate carrier.

Subcellular location. Mitochondrion inner membrane.

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

RefSeq proteins (1): NP_001182451* (*=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 (8 total): topological domain 3, transmembrane region 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9GIV	ELECTRON MICROSCOPY	3.65
9GIX	ELECTRON MICROSCOPY	3.65
9GIY	ELECTRON MICROSCOPY	3.79
9GIW	ELECTRON MICROSCOPY	3.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DKB6-F1	61.48	0.01

Antibody-complex structures (SAbDab): 1 — 9GIX

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: 26 (showing top): GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSMEMBRANE_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, REACTOME_PYRUVATE_METABOLISM, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_INNER_MITOCHONDRIAL_MEMBRANE_PROTEIN_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_MITOCHONDRIAL_PROTEIN_CONTAINING_COMPLEX, GOMF_MONOCARBOXYLIC_ACID_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, GOCC_ORGANELLE_ENVELOPE

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 (3): mitochondrial inner membrane (GO:0005743), mitochondrion (GO:0005739), 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
import into the mitochondrion	1
monocarboxylic acid transmembrane transporter activity	1
binding	1
organelle inner membrane	1
mitochondrial membrane	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPC1L	MPC2	O95563	711
MPC1L	DRC4	O95995	376
MPC1L	PC	P11498	376
MPC1L	PDHA1	P08559	359
MPC1L	AASDH	Q4L235	348
MPC1L	DNALI1	O14645	329
MPC1L	SPEF2	Q9C093	321
MPC1L	ACLY	P53396	315
MPC1L	SPAG6	O75602	309
MPC1L	LDHA	P00338	300
MPC1L	NDUFB2	O95178	294
MPC1L	PDK1	Q15118	283
MPC1L	DNAI2	Q9GZS0	274
MPC1L	PPARGC1A	Q9UBK2	269
MPC1L	RSPH4A	Q5TD94	261

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MPC2	MPC1L	psi-mi:“MI:0407”(direct interaction)	0.650

ESM2 similar proteins: A5A761, A6QP55, A8E7G5, B2LU20, O01578, O13793, O14949, O74847, P0DKB6, P19783, P38857, P53157, P53311, P63030, P63031, Q09201, Q09896, Q12029, Q21828, Q28852, Q2L897, Q3ZCG2, Q54NQ9, Q54PP1, Q55GU3, Q55GU4, Q5E9M8, Q5EA43, Q5FC79, Q5R597, Q5RD16, Q63965, Q6FJJ0, Q6PDU7, Q759E9, Q7KSC4, Q7TQ16, Q91V61, Q925N2, Q949R9

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MPC1L	“form complex”	“Mitochondrial pyruvate carrier complex, testis variant”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:40623776:T:C	F71L	0.957
X:40623778:C:A	F71L	0.957
X:40623778:C:G	F71L	0.957
X:40623668:A:C	S35R	0.924
X:40623670:C:A	S35R	0.924
X:40623670:C:G	S35R	0.924
X:40623845:A:C	S94R	0.919
X:40623847:T:A	S94R	0.919
X:40623847:T:G	S94R	0.919
X:40623767:T:C	F68L	0.906
X:40623769:C:A	F68L	0.906
X:40623769:C:G	F68L	0.906
X:40623650:T:C	F29L	0.871
X:40623652:C:A	F29L	0.871
X:40623652:C:G	F29L	0.871
X:40623725:A:C	S54R	0.855
X:40623727:T:A	S54R	0.855
X:40623727:T:G	S54R	0.855
X:40623824:T:C	C87R	0.819
X:40623802:C:A	N79K	0.797
X:40623802:C:G	N79K	0.797
X:40623671:T:A	W36R	0.794
X:40623671:T:C	W36R	0.794
X:40623844:G:C	Q93H	0.789
X:40623844:G:T	Q93H	0.789
X:40623832:C:A	N89K	0.788
X:40623832:C:G	N89K	0.788
X:40623623:T:C	F20L	0.780
X:40623625:C:A	F20L	0.780
X:40623625:C:G	F20L	0.780

dbSNP variants (sampled 300 via entrez): RS1000398916 (X:40623025 G>A,C), RS1003794941 (X:40623446 G>A,C), RS1007875655 (X:40622307 T>C), RS1007929629 (X:40622861 A>G), RS1008882109 (X:40624136 A>G), RS1010270905 (X:40622960 C>G), RS1010344536 (X:40622594 A>T), RS1010992590 (X:40624037 G>GA), RS1011398215 (X:40623677 C>T), RS1012512424 (X:40623547 C>A,T), RS1014141818 (X:40623059 C>G,T), RS1014187184 (X:40621517 C>T), RS1015193909 (X:40622354 C>G), RS1016607503 (X:40623448 G>C,T), RS1017289328 (X:40623856 C>G,T)

Disease associations

OMIM: gene MIM:301103 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

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 (6 total), top 6:

Ligand	Action	Affinity	Parameter
UK-5099	Inhibition	7.28	pIC50
zaprinast	Inhibition	6.49	pIC50
entacapone	Inhibition	6.2	pIC50
mitoglitazone	Inhibition	5.57	pIC50
nitrofurantoin	Inhibition	5.48	pIC50
lonidamine	Inhibition	5.34	pIC50

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
butyraldehyde	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation	1
Rotenone	decreases expression	1

Clinical trials (associated diseases)

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