SLC25A11

Chr 17AD

solute carrier family 25 member 11

Also known as: OGC, PGL6, PPGL6, SLC20A4

NCBI Gene: 8402ENSG00000108528UniProt: Q02978

The oxoglutarate/malate carrier transports 2-oxoglutarate across the inner membranes of mitochondria in an electroneutral exchange for malate or other dicarboxylic acids (summary by Iacobazzi et al., 1992 [PubMed 1457818]).[supplied by OMIM, Jan 2011]

Primary Disease Associations & Inheritance

Pheochromocytoma/paraganglioma syndrome 6MIM #618464
AD
129
ClinVar variants
29
Pathogenic / LP
0.53
pLI score
0
Active trials
Clinical Summary— SLC25A11
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 58 VUS of 129 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.09–0.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.43–0.60)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 3 / 15.2Missense obs/exp: 105 / 205.4Syn Z: -0.52

ClinVar Variant Classifications

129 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
0
40
14
4
58
Likely Benign
0
0
19
16
35
Benign
0
0
3
0
3
Conflicting
—4
Total1436021129

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Pheochromocytoma/paraganglioma syndrome 6

MIM #618464

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
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
SLC25A11 serves as a novel prognostic biomarker in liver cancer.
Pan G et al.·Sci Rep
2020
Genetics of urinary bladder paragangliomas: a multi-center study of a Chinese cohort.
Jiang J et al.·J Endocrinol Invest
2025Cohort
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
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
Crenolanib-Derived Probes Suitable for Cell- and Tissue-Based Protein Profiling and Single-Cell Imaging.
Chang Y et al.·Chembiochem
2019
Targeting SLC25A10 alleviates improved antioxidant capacity and associated radioresistance of cancer cells induced by chronic-cycling hypoxia.
Hlouschek J et al.·Cancer Lett
2018
Quantitative clinical proteomic study of autopsied human infarcted brain specimens to elucidate the deregulated pathways in ischemic stroke pathology.
Datta A et al.·J Proteomics
2013
A candidate region for Asperger syndrome defined by two 17p breakpoints.
Tentler D et al.·Eur J Hum Genet
2003
A mitochondrial carrier transports glycolytic intermediates to link cytosolic and mitochondrial glycolysis in the human gut parasite Blastocystis.
Pyrihová E et al.·Elife
2024
Top 10 resultsSearch 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
2026🔓 Open 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
2025🔓 Open Access
SLC25A11 Is Associated with KDM2A-Dependent Reduction in rRNA Transcription Induced by Aminooxyacetic Acid.
Tanaka Y et al.·Cells
2025🔓 Open Access
Combining decitabine with radiotherapy to enhance nasopharyngeal carcinoma radiosensitivity via the TFAP2C-OTUD1-SLC25A11 axis.
Zhang H et al.·Cell Death Dis
2025🔓 Open Access
N-phenylmaleimide induces bioenergetic switch and suppresses tumor growth in glioblastoma tumorspheres by inhibiting SLC25A11.
Cho HJ et al.·Cancer Cell Int
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools