SLC25A11

Chr 17AD

solute carrier family 25 member 11

Also known as: OGC, PGL6, PPGL6, SLC20A4

NCBI Gene: 8402ENSG00000108528UniProt: Q02978OMIM: 604165

The oxoglutarate/malate carrier catalyzes the transport of 2-oxoglutarate across the inner mitochondrial membrane in exchange for malate and other dicarboxylic acids, contributing to key metabolic processes including the malate-aspartate shuttle, gluconeogenesis, and nitrogen metabolism. Mutations cause pheochromocytoma/paraganglioma syndrome 6 with autosomal dominant inheritance. The gene shows significant constraint against loss-of-function variants (LOEUF 0.512), indicating intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.511 OMIM phenotype
Clinical Summary— SLC25A11
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 58 VUS of 131 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
0.51LOEUF
pLI 0.535
Z-score 2.89
OE 0.20 (0.09–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.49Z-score
OE missense 0.51 (0.43–0.60)
105 obs / 205.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.20 (0.09–0.51)
0≤0.351.4
Missense OE0.51 (0.43–0.60)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 3 / 15.2Missense obs/exp: 105 / 205.4Syn Z: -0.52
DN
0.7326th %ile
GOF
0.6542th %ile
LOF
0.4234th %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

131 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic2
VUS58
Likely Benign35
Benign3
Conflicting4
27
Pathogenic
2
Likely Pathogenic
58
VUS
35
Likely Benign
3
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
3
22
1
27
Likely Pathogenic
0
0
2
0
2
VUS
1
40
13
4
58
Likely Benign
0
0
19
16
35
Benign
0
0
3
0
3
Conflicting
—4
Total2435921129

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC25A11 · 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 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Neutrophil extracellular trap-induced ferroptosis promotes abdominal aortic aneurysm formation via SLC25A11-mediated depletion of mitochondrial glutathione.
Qi Y et al.·Free Radic Biol Med
2024
An extensive bioinformatics study on the role of mitochondrial solute carrier family 25 in PC and its mechanism behind affecting immune infiltration and tumor energy metabolism.
Zhang Q et al.·J Transl Med
2022Functional
HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Metastatic pheochromocytomas and paragangliomas: proceedings of the MEN2019 workshop.
Dahia PLM et al.·Endocr Relat Cancer
2020Review
Targeting SLC25A10 alleviates improved antioxidant capacity and associated radioresistance of cancer cells induced by chronic-cycling hypoxia.
Hlouschek J et al.·Cancer Lett
2018
Crenolanib-Derived Probes Suitable for Cell- and Tissue-Based Protein Profiling and Single-Cell Imaging.
Chang Y et al.·Chembiochem
2019
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
METTL3-m6A-SLC25A11 Axis Promotes Chronic Hypoxia-Induced Cardiomyocyte Ferroptosis.
Li Y et al.·J Am Heart Assoc
2026Open Access
Deficiency of 2-Oxoglutarate Carrier (Slc25a11) Drives RPE Epithelial-to-Mesenchymal Transition and Exacerbates Subretinal Fibrosis in Neovascular Age-Related Macular Degeneration.
Wang M et al.·Aging Cell
2025Open Access
SLC25A11 Is Associated with KDM2A-Dependent Reduction in rRNA Transcription Induced by Aminooxyacetic Acid.
Tanaka Y et al.·Cells
2025Open Access
Combining decitabine with radiotherapy to enhance nasopharyngeal carcinoma radiosensitivity via the TFAP2C-OTUD1-SLC25A11 axis.
Zhang H et al.·Cell Death Dis
2025Open Access
N-phenylmaleimide induces bioenergetic switch and suppresses tumor growth in glioblastoma tumorspheres by inhibiting SLC25A11.
Cho HJ et al.·Cancer Cell Int
2025Open Access
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