SLC1A7

Chr 1

solute carrier family 1 member 7

Also known as: AAAT, EAAT5

NCBI Gene: 6512 ENSG00000162383 UniProt: O00341 OMIM: 604471

SLC1A7 encodes a sodium-dependent glutamate transporter that mediates high-affinity uptake of glutamate and aspartate, and also functions as an inhibitory glutamate-gated chloride channel at rod bipolar cell terminals in the retina. Mutations cause autosomal recessive episodic ataxia with retinal dysfunction, affecting both neurological and visual systems. The gene shows minimal constraint against loss-of-function variants (very low pLI score), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

Enables glutamate:sodium symporter activity. Involved in neurotransmitter uptake. Predicted to be located in photoreceptor cell terminal bouton. Predicted to be active in glutamatergic synapse; postsynaptic membrane; and presynaptic membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.31

Clinical Summary— SLC1A7

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

112 VUS of 128 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?

1.31LOEUF

pLI 0.000

Z-score 0.52

OE 0.87 (0.60–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.07Z-score

OE missense 0.99 (0.91–1.08)

358 obs / 362.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.60–1.31)

0≤0.351.4

Missense OE?0.99 (0.91–1.08)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 17 / 19.5Missense obs/exp: 358 / 362.0Syn Z: -0.24

This gene — mechanism propensity

0.76top 25%

GOF

0.80top 10%

LOF

0.2678th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

128 submitted variants in ClinVar

ClinVar

Classification Summary

VUS112

Likely Benign7

Benign1

112

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	112	0	112
Likely Benign	5	2	7
Benign	0	1	1
Total	117	3	120

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap SLC1A7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →