SLC25A51

Chr 9

solute carrier family 25 member 51

Also known as: CG7943, MCART1

NCBI Gene: 92014ENSG00000122696UniProt: Q9H1U9OMIM: 619153

The protein functions as a mitochondrial membrane carrier that mediates the essential import of NAD(+) into mitochondria, which is required for glycolysis and mitochondrial respiration. Mutations cause mitochondrial complex I deficiency with severe early-onset encephalomyopathy, typically presenting in infancy with neurological and metabolic dysfunction. The condition follows an autosomal recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.20
Clinical Summary— SLC25A51
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
70 unique Pathogenic / Likely Pathogenic· 30 VUS of 112 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.20LOEUF
pLI 0.003
Z-score 1.18
OE 0.57 (0.30–1.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
2.00Z-score
OE missense 0.56 (0.47–0.67)
93 obs / 165.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.30–1.20)
0≤0.351.4
Missense OE0.56 (0.47–0.67)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 5 / 8.8Missense obs/exp: 93 / 165.3Syn Z: 0.48
DN
0.87top 5%
GOF
0.83top 10%
LOF
0.2190th %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

112 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic9
VUS30
Likely Benign1
61
Pathogenic
9
Likely Pathogenic
30
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
61
0
61
Likely Pathogenic
0
0
9
0
9
VUS
0
27
3
0
30
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total028730101

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC25A51 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 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