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Early onset or syndromic epilepsy v9.81 SLC1A2 Ida Ertmanska Publications for gene: SLC1A2 were set to 27476654; 28777935; 23934111; 9180080; 28915517; 27445142
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska Tag Q3_26_expert_review was removed from gene: SLC1A2.
Tag Q3_26_MOI was removed from gene: SLC1A2.
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska changed review comment from: Comment on mode of inheritance: There are numerous 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 vision loss. A supportive mouse model showed that knockout slc1a2-/- mice develop severe epilepsy. Functional effects of the 2 recessive variants were assessed as LoF in HEK293T and COS-7 cell transfection experiments (PMID: 40174554). Hence, the mode of inheritance should remain as BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: 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 vision loss. A supportive mouse model showed that knockout slc1a2-/- mice develop severe epilepsy. Functional effects of the 2 recessive variants were assessed as LoF in HEK293T and COS-7 cell transfection experiments (PMID: 40174554). Hence, the mode of inheritance should remain as BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska commented on gene: SLC1A2: Comment on mode of inheritance: There are numerous 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 vision loss. A supportive mouse model showed that knockout slc1a2-/- mice develop severe epilepsy. Functional effects of the 2 recessive variants were assessed as LoF in HEK293T and COS-7 cell transfection experiments (PMID: 40174554). Hence, the mode of inheritance should remain as BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska edited their review of gene: SLC1A2: Changed publications to: 9180080, 28915517, 40174554
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska changed review comment from: 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.

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.; to: 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.
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska changed review comment from: 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 "either displayed normal intelligence or mild ID, and both were able to walk independently and to talk in full sentences. However, both had severe vision loss, and one had bilateral hypoplasia of the optic nerves."

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.; to: 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.

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.
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska changed review comment from: 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 "either displayed normal intelligence or mild ID, and both were able to walk independently and to talk in full sentences. However, both had severe vision loss, and one had bilateral hypoplasia of the optic nerves."; to: 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 "either displayed normal intelligence or mild ID, and both were able to walk independently and to talk in full sentences. However, both had severe vision loss, and one had bilateral hypoplasia of the optic nerves."

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.
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska changed review comment from: 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.; to: 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 "either displayed normal intelligence or mild ID, and both were able to walk independently and to talk in full sentences. However, both had severe vision loss, and one had bilateral hypoplasia of the optic nerves."
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska reviewed gene: SLC1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28915517, 40174554; Phenotypes: Developmental and epileptic encephalopathy 41, OMIM:617105, developmental and epileptic encephalopathy, 41, MONDO:0014916; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v9.80 SLC1A2 Ida Ertmanska Tag Q3_26_expert_review tag was added to gene: SLC1A2.
Tag Q3_26_MOI tag was added to gene: SLC1A2.
Early onset or syndromic epilepsy v2.547 SLC1A2 Sarah Leigh Phenotypes for gene: SLC1A2 were changed from Epileptic encephalopathy, early infantile, 41, 617105 to Epileptic encephalopathy, early infantile, 41, OMIM:617105; developmental and epileptic encephalopathy, 41, MONDO:0014916
Early onset or syndromic epilepsy v2.546 SLC1A2 Sarah Leigh Publications for gene: SLC1A2 were set to 27476654; 28777935; 23934111; 9180080; 28915517
Early onset or syndromic epilepsy v2.545 SLC1A2 Sarah Leigh changed review comment from: PMID:28915517 reports one case of homozygous c.1421+1G>C in a case of epileptic seizures with visual impairment. The nonconsanguineous German parents of the case, were heterozygous for c.1421+1G>C. The authors observe that haploinsufficiency is not the underlying genetic mechanism in autosomal dominant SLC1A2-related
epileptic encephalopathy, they suggest the autosomal dominant variants, which are in between the first two transmembrane domains of the SLC1A2 protein, result in a gain-of-function. In contrast, loss-of-function appears to the mechanism in the homozygous patient; RT-PCR of the patients' fibroblasts revealed two abarrant SLC1A2 products, with deletion of the highly conserverd exon 9 in one and a cryptic splicing product, with termination at p.Leu474 in the other.; to: PMID:28915517 reports one case of homozygous c.1421+1G>C in a case of epileptic seizures with visual impairment. The nonconsanguineous German parents of the case, were heterozygous for c.1421+1G>C. The authors observe that haploinsufficiency is not the underlying genetic mechanism in autosomal dominant SLC1A2-related
epileptic encephalopathy, they suggest the autosomal dominant variants, which are in between the first two transmembrane domains of the SLC1A2 protein, result in a gain-of-function, possibly by abnormal channel conductance (PMID: 27445142). In contrast, loss-of-function appears to the mechanism in the homozygous patient; RT-PCR of the patients' fibroblasts revealed two abarrant SLC1A2 products, with deletion of the highly conserverd exon 9 in one and a cryptic splicing product, with termination at p.Leu474 in the other. Clearly further functional studies will be required to clafiry the mechanisms by which SLC1A2 variants result in epilepsy and other phenotypic features.
Early onset or syndromic epilepsy v2.517 SLC1A2 Sarah Leigh changed review comment from: PMID 28915517 reports one case of hmz c.1421+1G>C in a case of epileptic seizures and visual impairment. The authors observe that haploinsufficiency is not the underlying genetic mechanism in autosomal dominant SLC1A2-related
epileptic encephalopathy, they suggest the autosomal dominant variants, which are in between the first two transmembrane domains of the SLC1A2 protein, result in a gain-of-function. In contrast, loss-of-function appears to the mechanism in the homozygous patient; RT-PCR of the patients' fibroblasts revealed two abarrant SLC1A2 products, with deletion of the highly conserverd exon 9 in one and a cryptic splicing product, with termination at p.Leu474 in the other.; to: PMID:28915517 reports one case of homozygous c.1421+1G>C in a case of epileptic seizures with visual impairment. The nonconsanguineous German parents of the case, were heterozygous for c.1421+1G>C. The authors observe that haploinsufficiency is not the underlying genetic mechanism in autosomal dominant SLC1A2-related
epileptic encephalopathy, they suggest the autosomal dominant variants, which are in between the first two transmembrane domains of the SLC1A2 protein, result in a gain-of-function. In contrast, loss-of-function appears to the mechanism in the homozygous patient; RT-PCR of the patients' fibroblasts revealed two abarrant SLC1A2 products, with deletion of the highly conserverd exon 9 in one and a cryptic splicing product, with termination at p.Leu474 in the other.
Early onset or syndromic epilepsy v2.517 SLC1A2 Sarah Leigh reviewed gene: SLC1A2: Rating: ; Mode of pathogenicity: None; Publications: 23934111, 27476654; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.297 SLC1A2 Rebecca Foulger Marked gene: SLC1A2 as ready
Early onset or syndromic epilepsy v1.297 SLC1A2 Rebecca Foulger Gene: slc1a2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.297 SLC1A2 Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex review by Helen Lord.
Early onset or syndromic epilepsy v1.297 SLC1A2 Rebecca Foulger Mode of inheritance for gene: SLC1A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.262 SLC1A2 Rebecca Foulger commented on gene: SLC1A2: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
Early onset or syndromic epilepsy v1.261 SLC1A2 Helen Lord reviewed gene: SLC1A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.191 SLC1A2 Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC1A2.
Early onset or syndromic epilepsy v1.190 SLC1A2 Rebecca Foulger Source NHS GMS was added to SLC1A2.
Early onset or syndromic epilepsy v1.189 SLC1A2 Rebecca Foulger reviewed gene: SLC1A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v1.188 SLC1A2 Tracy Lester reviewed gene: SLC1A2: Rating: GREEN; Mode of pathogenicity: ; Publications: 27476654, 28777935 ; Phenotypes: Epileptic encephalopathy, early infantile, 617105; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy SLC1A2 Sarah Leigh Added gene to panel