SLC25A22

Chr 11AR

solute carrier family 25 member 22

Also known as: DEE3, EIEE3, GC-1, GC1, NET44

NCBI Gene: 79751ENSG00000177542UniProt: Q9H936OMIM: 609302

This gene encodes a mitochondrial glutamate carrier that transports glutamate across the inner mitochondrial membrane. Mutations cause developmental and epileptic encephalopathy 3, an autosomal recessive early infantile epileptic encephalopathy. The pathogenic mechanism appears to involve loss of glutamate transport function, disrupting mitochondrial metabolism and neurotransmitter homeostasis.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 0.811 OMIM phenotype
Clinical Summary— SLC25A22
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Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 99 VUS of 200 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
0.81LOEUF
pLI 0.007
Z-score 2.09
OE 0.41 (0.22–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.91Z-score
OE missense 0.82 (0.72–0.93)
168 obs / 204.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.22–0.81)
0≤0.351.4
Missense OE0.82 (0.72–0.93)
0≤0.61.4
Synonymous OE1.29
0≤1.21.6
LoF obs/exp: 6 / 14.6Missense obs/exp: 168 / 204.8Syn Z: -2.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSLC25A22-related epileptic encephalopathy, early infantileOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.86top 5%
GOF
0.78top 25%
LOF
0.2484th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
VUS99
Likely Benign82
Benign5
Conflicting3
11
Pathogenic
99
VUS
82
Likely Benign
5
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
7
0
11
Likely Pathogenic
0
0
0
0
0
VUS
2
68
28
1
99
Likely Benign
0
0
44
38
82
Benign
0
0
5
0
5
Conflicting
—3
Total6688439200

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC25A22 · 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
Report on three additional patients and genotype-phenotype correlation in SLC25A22-related disorders group.
Lemattre C et al.·Eur J Hum Genet
2019Cohort
The phenotype caused by recessive variations in SLC25A22: Report of a new case and literature review.
André MV et al.·Arch Pediatr
2021Review
Mutations in SLC25A22: hyperprolinaemia, vacuolated fibroblasts and presentation with developmental delay.
Reid ES et al.·J Inherit Metab Dis
2017
Targeting Glutamine Metabolism Transporter SLC25A22 Enhances CD8+ T-Cell Function and Anti-PD-1 Therapy Efficacy in Cervical Squamous Cell Carcinoma: Integrated Metabolomics, Transcriptomics and T-Cell-Incorporated Tumor Organoid Studies.
Ren T et al.·Adv Sci (Weinh)
2025
Severe early-onset developmental and epileptic encephalopathy (DEE) associated with novel compound heterozygous pathogenic variants in SLC25A22: Case report and literature review.
Giacomini T et al.·Seizure
2019Review
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