SLC1A2

Chr 11AD

solute carrier family 1 member 2

Also known as: DEE41, EAAT2, EIEE41, GLT-1, GLT1, HBGT

NCBI Gene: 6506 ENSG00000110436 UniProt: P43004 OMIM: 600300

This gene encodes the principal transporter that clears glutamate from synapses in the central nervous system, preventing neuronal damage from excessive glutamate receptor activation. Mutations cause developmental and epileptic encephalopathy 41 through an autosomal dominant inheritance pattern. The pathogenic mechanism involves gain-of-function mutations that disrupt normal glutamate clearance regulation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. Alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 41MIM #617105

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · developmental and epileptic encephalopathy, 41 · AD · ClinGen 2020
Supportive · undetermined early-onset epileptic encephalopathy · AD · Orphanet

Interpreting a novel variant

Both gain of function and loss of function mechanisms are described for this gene and which one applies is variant-dependent. Do not assume a null variant is — or isn't — the pathogenic class without checking the specific variant against curated evidence.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

GOF/LOF*

Mechanism· annotated

📖

GeneReview available — SLC1A2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.710

Z-score 3.51

OE 0.19 (0.09–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.28Z-score

OE missense 0.65 (0.58–0.73)

217 obs / 334.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.19 (0.09–0.42)

0≤0.351.4

Missense OE?0.65 (0.58–0.73)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 4 / 21.6Missense obs/exp: 217 / 334.6Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in SLC1A2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 67

707 rare PASS variants

Rare truncating (LoF)

1 in 2,600

62 rare PASS variants

Rare synonymous (reference)

1 in 120

334 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC1A2. 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 130	1 in 2,400
South Asian	~43k	1 in 64	1 in 4,200
Remaining (unassigned)	~30k	1 in 48	1 in 2,200
European (Finnish)	~27k	1 in 340	≈ 1 in 6,700
Admixed American	~22k	1 in 72	1 in 2,200
African / African American	~21k	1 in 82	1 in 2,500
East Asian	~20k	1 in 93	1 in 1,300
Ashkenazi Jewish	~13k	1 in 310	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 170	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 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓