MPC1

Chr 6AR

mitochondrial pyruvate carrier 1

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

NCBI Gene: 51660ENSG00000060762UniProt: Q9Y5U8

The protein encoded by this gene is part of an MPC1/MPC2 heterodimer that is responsible for transporting pyruvate into mitochondria. The encoded protein is found in the inner mitochondrial membrane. Defects in this gene are a cause of mitochondrial pyruvate carrier deficiency. Several transcript variants, some protein coding and one non-protein coding, have been found for this gene. [provided by RefSeq, Aug 2012]

Primary Disease Associations & Inheritance

Mitochondrial pyruvate carrier deficiencyMIM #614741
AR
0
Active trials
56
Pathogenic / LP
113
ClinVar variants
29
Pubs (1 yr)
1.1
Missense Z
1.19
LOEUF
Clinical Summary— MPC1
🧬
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.
📋
ClinVar Variants
56 Pathogenic / Likely Pathogenic· 25 VUS of 113 total submissions
📖
GeneReview available — MPC1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.19LOEUF
pLI 0.038
Z-score 1.28
OE 0.46 (0.21–1.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.07Z-score
OE missense 0.62 (0.48–0.81)
40 obs / 64.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.46 (0.21–1.19)
0≤0.351.4
Missense OE0.62 (0.48–0.81)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 3 / 6.5Missense obs/exp: 40 / 64.2Syn Z: -0.09
DNGOF
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

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic7
VUS25
Likely Benign17
Benign15
49
Pathogenic
7
Likely Pathogenic
25
VUS
17
Likely Benign
15
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
47
0
49
Likely Pathogenic
0
4
3
0
7
VUS
1
15
9
0
25
Likely Benign
0
2
8
7
17
Benign
0
1
13
1
15
Total124808113

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

View in ClinVar →

MPC1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients