SLC25A22

Chr 11AR

solute carrier family 25 member 22

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

NCBI Gene: 79751 ENSG00000177542 UniProt: Q9H936 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a mitochondrial glutamate carrier. Mutations in this gene are associated with early infantile epileptic encephalopathy. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jul 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.811 OMIM phenotype

Clinical Summary— SLC25A22

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Gene-Disease Validity (ClinGen)

genetic 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

23 unique Pathogenic / Likely Pathogenic· 251 VUS of 619 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 OE?0.41 (0.22–0.81)

0≤0.351.4

Missense OE?0.82 (0.72–0.93)

0≤0.61.4

Synonymous OE?1.29

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

This gene — mechanism propensity

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

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

619 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16

Likely Pathogenic7

VUS251

Likely Benign259

Benign32

Conflicting40

Pathogenic

Likely Pathogenic

251

VUS

259

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	3	1	0	16
Likely Pathogenic	6	1	0	0	7
VUS	6	181	62	2	251
Likely Benign	0	3	132	124	259
Benign	0	1	28	3	32
Conflicting	—				40
Total	24	189	223	129	605

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap SLC25A22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →