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Intellectual disability

Gene: SLC1A2

Green List (high evidence)
SLC1A2 (solute carrier family 1 member 2)
EnsemblGeneIds (GRCh38): ENSG00000110436
EnsemblGeneIds (GRCh37): ENSG00000110436
OMIM: 600300, Gene2Phenotype
SLC1A2 is in 4 panels

4 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on mode of inheritance: There are at least 16 individuals reported in literature with heterozygous missense varinats in SLC1A2 and a DEE. There are also 2 unrelated patients reported with biallelic SLC1A2 variants and syndromic early-onset epilepsy with normal intelligence / mild ID. Hence, the mode of inheritance should remain as MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown.
Created: 10 Sep 2026, 10:15 a.m. | Last Modified: 10 Sep 2026, 10:15 a.m.
Panel Version: 11.29
PMID: 40174554 Kovermann et al., 2025
Report of 18 individuals harbouring 13 different SLC1A2 variants (7 cases previously published, including the homozygous splice variant case in PMID:28915517).
Based on functional studies, variants were categorised as: overall loss-of-function (F249Sfs∗17, A432D, A439V, c.1421+1G>C), mild gain-of-anion-channel function (I276S, G360A), and mixed loss-of-transport/gain-of-anion-channel function (G82R, L85R, L85P, P289R). In contrast, L37P, H542R and I546T did not mediate significant changes to EAAT2 expression or function.
1 newly reported biallelic case: patient homozygous for SLC1A2 c.1316C>T, p.Ala439Val - variant is rare in gnomAD v4, no homz, categorised as LoF in the study. The two individuals with the homozygous variants had neurodevelopmental impairment and epilepsy with seizure onset between 2 and 4 years of age, had normal intelligence or mild ID, and both were able to walk independently and to talk in full sentences. Both had severe vision loss, and one had bilateral hypoplasia of the optic nerves.
In contrast, 2 individuals heterozygous for F249Sfs∗17 and A432D variants (also in the LoF category) had a more severe NDD phenotype without vision loss.

Functional: PMID: 9180080 Tanaka et al., 1997 - homozygous Slc1a2−/− mice have severe epilepsy with neurodegeneration resulting from reduced glial L-Glu uptake.

SLC1A2 is only associated with AD Developmental and epileptic encephalopathy 41, MIM:617105 in OMIM, and Definitive for association with AD developmental and epileptic encephalopathy, 41 in ClinGen (Oct 2020, Aminoacidopathy GCEP) - resources accessed 10th Sept 2026.
Created: 10 Sep 2026, 10:14 a.m. | Last Modified: 10 Sep 2026, 10:14 a.m.
Panel Version: 11.29

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental and epileptic encephalopathy 41, OMIM:617105; developmental and epileptic encephalopathy, 41, MONDO:0014916

Publications

Created: 10 Sep 2026, 10:14 a.m.
Last Modified: 10 Sep 2026, 10:14 a.m.
Panel version: 11.29

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Green. Added to panel and reviewed Green by Konstantinos Varvagiannis. As noted by Konstantinos Varvagiannis, 4 unrelated individuals reported (PMIDs:27476654, 28777935) all with profound/severe ID as a feature. Therefore sufficient cases to support a Green (diagnostic-grade) rating.
Created: 14 Feb 2019, 2 p.m.
PMID:27476654 (Epi4K Consortium) identified 2 individuals with de novo variants in SLC1A2, both with profound ID amongst their phenotypes (Table 3).

PMID:28777935 (Guella et al, 2017) report 2 individuals with de novo variants in SLC1A2. Both had ID (profound in Subject A, and severe in Subject C).
Created: 14 Feb 2019, 1:56 p.m.
Created: 14 Feb 2019, 1:56 p.m.

Panel version: 2.641

Louise Daugherty (Genomics England Curator)

Comment on phenotypes: amended formatting of MIM phenotype
Created: 19 Jan 2019, 6:41 p.m.
Created: 19 Jan 2019, 6:41 p.m.

Panel version: 2.597

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Pathogenic variants in SLC1A2 cause Epileptic encephalopathy, early infantile, 41 (EIEE41 - MIM 617105).

At least 4 unrelated patients each with (private) de novo variants have been reported (PMIDs: 27476654, 28777935). ID is a universal feature.

This gene is included in gene panels for ID offered by diagnostic laboratories (incl. Radboudumc).

SLC1A2 is a probable DD gene in G2P associated with Epileptic encephalopathy.

As a result this gene could possibly be included in this panel as green if the phenotype is thought to be relevant.

Note: According to the Genetic epilepsy syndromes panel this gene was first added in the ID panel but appears to have been removed subsequently (phenotype thought to fit better the other panel). However several other "pure" EIEE genes (probably more than 20) have been included here, most rated green.

Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 14 Dec 2018, 8:08 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Epileptic encephalopathy, early infantile, 41 (MIM 617105)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 14 Dec 2018, 8:08 a.m.

Panel version: 2.584

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • Epileptic encephalopathy, early infantile, 41, OMIM:617105
  • developmental and epileptic encephalopathy, 41, MONDO:0014916
OMIM
600300
Clinvar variants
Variants in SLC1A2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

14 Jul 2022, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SLC1A2 were changed from Epileptic encephalopathy, early infantile, 41, 617105; Intellectual disability to Epileptic encephalopathy, early infantile, 41, OMIM:617105; developmental and epileptic encephalopathy, 41, MONDO:0014916

14 Feb 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: slc1a2 has been classified as Green List (High Evidence).

14 Feb 2019, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: SLC1A2 were changed from Epileptic encephalopathy, early infantile, 41, 617105 to Epileptic encephalopathy, early infantile, 41, 617105; Intellectual disability

19 Jan 2019, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: SLC1A2 were changed from Epileptic encephalopathy, early infantile, 41 (MIM 617105) to Epileptic encephalopathy, early infantile, 41, 617105

12 Dec 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: SLC1A2 was added gene: SLC1A2 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: SLC1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SLC1A2 were set to 27476654; 28777935 Phenotypes for gene: SLC1A2 were set to Epileptic encephalopathy, early infantile, 41 (MIM 617105) Penetrance for gene: SLC1A2 were set to Complete Review for gene: SLC1A2 was set to AMBER gene: SLC1A2 was marked as current diagnostic