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…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 3MIM #609304

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · genetic developmental and epileptic encephalopathy · AR · ClinGen 2020
Strong · developmental and epileptic encephalopathy, 3 · AR · Labcorp Genetics (formerly Invitae)
Supportive · malignant migrating partial seizures of infancy · AD · Orphanet

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in SLC25A22?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

461 rare PASS variants

Rare truncating (LoF)

1 in 3,300

67 rare PASS variants

Rare synonymous (reference)

1 in 140

266 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC25A22. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 190	1 in 4,000
South Asian	~43k	1 in 110	1 in 3,800
Remaining (unassigned)	~30k	1 in 110	1 in 5,900
European (Finnish)	~26k	1 in 290	≈ 1 in 5,600
Admixed American	~22k	1 in 130	≈ 1 in 11,000
African / African American	~21k	1 in 70	≈ 1 in 6,000
East Asian	~20k	1 in 110	1 in 3,300
Ashkenazi Jewish	~13k	1 in 1,000	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓