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 pyruvate import into mitochondria. Located in mitochondrial inner membrane. Part of mitochondrial pyruvate carrier complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in MPC2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 680

129 rare PASS variants

Rare truncating (LoF)

1 in 4,700

40 rare PASS variants

Rare synonymous (reference)

1 in 840

67 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MPC2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,000	1 in 5,200
South Asian	~43k	1 in 310	1 in 1,900
Remaining (unassigned)	~30k	1 in 530	1 in 3,700
European (Finnish)	~27k	1 in 3,300	≈ 1 in 13,000
Admixed American	~22k	1 in 440	≈ 1 in 6,200
African / African American	~21k	1 in 500	≈ 1 in 6,300
East Asian	~20k	1 in 1,700	≈ 1 in 9,700
Ashkenazi Jewish	~13k	≈ 1 in 4,300	≈ 1 in 4,100
Middle Eastern	~2,884	≈ 1 in 600	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 5 coding exons well covered in gnomAD exomes; exons 3, 6 marginal. Genomes: all 5.? see exons ↓