MPC2

Chr 1

mitochondrial pyruvate carrier 2

Also known as: BRP44, SLC54A2

NCBI Gene: 25874 ENSG00000143158 UniProt: O95563 OMIM: 614737

MPC2 encodes a protein that mediates the uptake of pyruvate into mitochondria to maintain the balance between glycolysis and oxidative phosphorylation. Mutations cause autosomal recessive mitochondrial complex I deficiency, nuclear type 9, which presents with early-onset neurological symptoms including developmental delay, seizures, and movement disorders. The gene shows moderate constraint against loss-of-function variants, consistent with its essential role in cellular metabolism.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Involved in mitochondrial pyruvate transmembrane transport. Located in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.63

Clinical Summary— MPC2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.64) — some intolerance to loss-of-function variants.

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ClinVar Variants

15 VUS of 25 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.63LOEUF

pLI 0.635

Z-score 2.20

OE 0.13 (0.05–0.63)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.99Z-score

OE missense 0.65 (0.51–0.85)

42 obs / 64.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.05–0.63)

0≤0.351.4

Missense OE?0.65 (0.51–0.85)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 1 / 7.5Missense obs/exp: 42 / 64.2Syn Z: -0.71

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedMPC2-related metabolic disorderOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6937th %ile

GOF

0.5465th %ile

LOF

0.4627th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

25 submitted variants in ClinVar

ClinVar

Classification Summary

VUS15

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	15	15
Likely Benign	0	0
Benign	0	0
Total	15	15

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

18 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap MPC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →