MPC1

mitochondrial pyruvate carrier 1, the group of Solute carrier family 54, mitochondrial pyruvate carriers

Basic information

Region (hg38): 6:166364919-166383013

Previous symbols: [ "BRP44L" ]

Links

ENSG00000060762 ∙ NCBI:51660 ∙ OMIM:614738 ∙ HGNC:21606 ∙ Uniprot:Q9Y5U8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial pyruvate carrier deficiency (Limited), mode of inheritance: AR
• mitochondrial pyruvate carrier deficiency (Strong), mode of inheritance: AR
• mitochondrial pyruvate carrier deficiency (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial pyruvate carrier deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Neurologic	12649063; 22628558

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MPC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MPC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6		6
missense		4	9	1	1	15
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				2	1	3
non coding				5	8	13
Total	0	4	11	12	9

Variants in MPC1

This is a list of pathogenic ClinVar variants found in the MPC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-166365191-T-G			Benign (Jun 23, 2018)
6-166365439-G-A		not specified	Uncertain significance (Jul 15, 2021)
6-166365441-C-T			Likely benign (May 04, 2023)
6-166365442-G-A		not specified	Uncertain significance (Sep 26, 2023)
6-166365447-A-T			Likely benign (May 16, 2018)
6-166365461-G-GA		MPC1-related disorder	Likely benign (Jul 19, 2022)
6-166365546-T-A			Benign (Jul 11, 2018)
6-166365975-C-T		not specified	Uncertain significance (Oct 13, 2022)
6-166365976-G-A		not specified	Benign (Feb 01, 2024)
6-166365978-G-A		Fraser syndrome 3 • not specified	Likely benign (Apr 19, 2023)
6-166365989-C-T		Mitochondrial pyruvate carrier deficiency	Likely pathogenic (Sep 02, 2021)
6-166365990-G-A		Mitochondrial pyruvate carrier deficiency	Pathogenic (Jul 06, 2012)
6-166365997-C-T			Likely benign (Dec 26, 2023)
6-166366005-G-C		Mitochondrial pyruvate carrier deficiency	Uncertain significance (-)
6-166366027-G-A		MPC1-related disorder	Likely benign (Oct 21, 2019)
6-166366043-A-T		Mitochondrial pyruvate carrier deficiency	Pathogenic (Jul 06, 2012)
6-166366052-C-T		not specified	Uncertain significance (Jan 04, 2022)
6-166366059-G-T		Mitochondrial pyruvate carrier deficiency	Uncertain significance (Jun 03, 2020)
6-166366065-T-C		Mitochondrial pyruvate carrier deficiency	Likely pathogenic (Nov 17, 2017)
6-166366071-C-T		Mitochondrial pyruvate carrier deficiency	Likely pathogenic (Sep 02, 2021)
6-166366105-G-A			Likely benign (Nov 07, 2017)
6-166366120-C-T			Likely benign (Aug 19, 2022)
6-166366190-T-C			Benign (Jul 11, 2018)
6-166366786-C-A			Likely benign (Nov 27, 2023)
6-166366807-G-A			Uncertain significance (Dec 27, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MPC1	protein_coding	protein_coding	ENST00000360961	5	18080

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0385	0.848	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	40	64.2	0.623	0.00000346	712
Missense in Polyphen		4	18.034	0.2218		221
Synonymous	-0.0896	22	21.5	1.02	0.00000105	204
Loss of Function	1.27	3	6.51	0.461	2.80e-7	75

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000356	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates the uptake of pyruvate into mitochondria. {ECO:0000269|PubMed:22628558}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:22628558}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Warburg Effect;Transfer of Acetyl Groups into Mitochondria;The oncogenic action of Succinate;The oncogenic action of Fumarate;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Gluconeogenesis;Citric Acid Cycle;Glycogenosis, Type IA. Von gierke disease;Glycogenosis, Type IC;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;Glycolysis and Gluconeogenesis;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;The citric acid (TCA) cycle and respiratory electron transport;Metabolism (Consensus)

Recessive Scores

• pRec: 0.0989

Intolerance Scores

• rvis_EVS: 0.26
• rvis_percentile_EVS: 69.83

Haploinsufficiency Scores

• pHI: 0.175
• hipred: N
• hipred_score: 0.462
• ghis: 0.398

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mpc1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: mitochondrial pyruvate transmembrane transport;biological_process;mitochondrial acetyl-CoA biosynthetic process from pyruvate;cellular response to leukemia inhibitory factor
• Cellular component: cellular_component;mitochondrion;integral component of mitochondrial inner membrane
• Molecular function: molecular_function;pyruvate transmembrane transporter activity