MPC1

Chr 6AR

mitochondrial pyruvate carrier 1

Also known as: BRP44L, CGI-129, MPYCD, SLC54A1

The encoded protein forms a heterodimer with MPC2 in the inner mitochondrial membrane to transport pyruvate into mitochondria, maintaining the balance between glycolysis and oxidative phosphorylation. Mutations cause mitochondrial pyruvate carrier deficiency, an autosomal recessive disorder affecting cellular metabolism. The gene shows tolerance to loss-of-function variants (pLI 0.04, LOEUF 1.19), consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.191 OMIM phenotype
Clinical SummaryMPC1
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.19LOEUF
pLI 0.038
Z-score 1.28
OE 0.46 (0.211.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.07Z-score
OE missense 0.62 (0.480.81)
40 obs / 64.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.46 (0.211.19)
00.351.4
Missense OE0.62 (0.480.81)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 3 / 6.5Missense obs/exp: 40 / 64.2Syn Z: -0.09
DN
0.85top 10%
GOF
0.73top 25%
LOF
0.2580th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MPC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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