GRIA2 (Glutamate receptor 2) variants and mutations
GRIA2 (also known as Glutamate receptor 2) is a human protein-coding gene encoding a glutamate receptor 2 protein. An AMPA-type glutamate receptor subunit that contributes to fast excitatory signaling in the nervous system. Together with other subunits it forms a glutamate-gated cation channel, and its presence helps shape the channel's ion permeability and synaptic behavior. This analysis covers 93 GRIA2 variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes neurodevelopmental disorder with language impairment and behavioral abnormalitie, epilepsy, and migraine disorder. Example GRIA2 variants include Q2*, Q2K, and Q2R.
Variant analysis overview
- Gene: GRIA2
- Protein: Glutamate receptor 2
- UniProt accession: P42262
- Organism: Homo sapiens
- Variants analyzed: 93
- Variant scope: all variants
- Completed: 2026-09-07
Variant and mutation evidence
- Variant composition: 17 natural variant; 6 frameshift variants; 2 stop-gained variants; 49 missense variants; 17 synonymous variants; 1 in-frame deletions; 1 substitution
- Prediction scores: 91 variants have prediction scores (98% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodevelopmental disorder with language impairment and behavioral abnormalitie, epilepsy, migraine disorder, alcohol dependence, Seizure, Lennox-Gastaut syndrome, focal epilepsy, diabetic neuropathy, obesity disorder, Obesity, Focal-onset seizure, Parkinson disease.
Protein structure and variant hotspots
- Protein features: 3 transmembrane segments; 6 binding sites; 10 post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable GRIA2 variants
Examples include Q2*, Q2K, Q2R, Q2L, Q2Q, K3R, K3N, I4T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- Q2* (p.Gln2Ter), gnomAD 4-157221046-C-T, CADD 36.00
- Q2K (p.Gln2Lys), rs993511881, gnomAD 4-157221046-C-A, REVEL 0.14, CADD 19.80
- Q2R (p.Gln2Arg), rs773902923, gnomAD 4-157221047-A-G, REVEL 0.19, CADD 17.00
- Q2L (p.Gln2Leu), gnomAD 4-157221047-A-T, REVEL 0.15, CADD 22.20
- Q2Q (p.Gln2Gln), gnomAD 4-157221048-A-G, CADD 11.10
- K3R (p.Lys3Arg), gnomAD 4-157221046-CA-C, CADD 25.30
- K3N (p.Lys3Asn), gnomAD 4-157221051-G-T, REVEL 0.06, CADD 22.90
- I4T (p.Ile4Thr), gnomAD 4-157221053-T-C, REVEL 0.14, CADD 23.10
- I4I (p.Ile4Ile), gnomAD 4-157221054-T-C, CADD 13.20
- M5C (p.Met5Cys), gnomAD 4-157221052-AT-A, CADD 25.70
- M5V (p.Met5Val), gnomAD 4-157221055-A-G, REVEL 0.15, CADD 19.20
- M5T (p.Met5Thr), rs1368880258, gnomAD 4-157221056-T-C, REVEL 0.17, CADD 21.40
- M5I (p.Met5Ile), rs1729469797, gnomAD 4-157221057-G-A, REVEL 0.20, CADD 22.60
- H6Y (p.His6Tyr), gnomAD 4-157221058-C-T, REVEL 0.07, CADD 21.40
- H6N (p.His6Asn), gnomAD 4-157221058-C-A, REVEL 0.10, CADD 20.20
- H6P (p.His6Pro), gnomAD 4-157221059-A-C, REVEL 0.20, CADD 22.30
- H6R (p.His6Arg), rs1431881361, gnomAD 4-157221059-A-G, REVEL 0.13, CADD 19.80
- H6Q (p.His6Gln), gnomAD 4-157221060-T-A, REVEL 0.06, CADD 18.70
- H6H (p.His6His), rs1309607720, gnomAD 4-157221060-T-C, CADD 10.80
- I7V (p.Ile7Val), gnomAD 4-157221061-A-G, REVEL 0.10, CADD 17.30
- I7T (p.Ile7Thr), gnomAD 4-157221062-T-C, REVEL 0.16, CADD 21.70
- I7I (p.Ile7Ile), gnomAD 4-157221063-T-C, CADD 13.00
- S8F (p.Ser8Phe), gnomAD 4-157221065-C-T, REVEL 0.18, CADD 21.20
- S8Y (p.Ser8Tyr), gnomAD 4-157221065-C-A, REVEL 0.09, CADD 19.30
- S8S (p.Ser8Ser), gnomAD 4-157221066-T-C, CADD 13.70
- V9V (p.Val9Val), gnomAD 4-157221069-C-A, CADD 10.10
- L10I (p.Leu10Ile), gnomAD 4-157221070-C-A, REVEL 0.06, CADD 19.70
- L10V (p.Leu10Val), rs1386115958, gnomAD 4-157221070-C-G, REVEL 0.05, CADD 20.40
- L11del (p.Leu11del), rs1299198234, gnomAD 4-157221067-GTCC-, CADD 18.40
- L11I (p.Leu11Ile), gnomAD 4-157221073-C-A, REVEL 0.08, CADD 20.30
- L11L (p.Leu11Leu), gnomAD 4-157221075-T-C, CADD 11.10
- S12L (p.Ser12Leu), gnomAD 4-157221073-CT-C, CADD 26.80
- S12Y (p.Ser12Tyr), gnomAD 4-157221077-C-A, REVEL 0.20, CADD 17.30
- S12S (p.Ser12Ser), gnomAD 4-157221078-T-A, CADD 12.90
- P13A (p.Pro13Ala), rs144979119, gnomAD 4-157221079-C-G, REVEL 0.08, CADD 15.70
- P13H (p.Pro13His), gnomAD 4-157221080-C-A, REVEL 0.11, CADD 23.20
- P13L (p.Pro13Leu), rs1332790445, gnomAD 4-157221080-C-T, REVEL 0.07, CADD 21.30
- V14I (p.Val14Ile), rs1381634370, gnomAD 4-157221082-G-A, REVEL 0.05, CADD 17.40
- L15L (p.Leu15Leu), gnomAD 4-157221085-T-C, CADD 11.40
- W16G (p.Trp16Gly), rs771354204, gnomAD 4-157221088-T-G, REVEL 0.41, CADD 26.10
- G17D (p.Gly17Asp), gnomAD 4-157221088-TG-T, CADD 29.70
- G17* (p.Gly17Ter), gnomAD 4-157221091-G-T, CADD 36.00
- G17R (p.Gly17Arg), gnomAD 4-157221091-G-A, REVEL 0.37, CADD 24.30
- G17G (p.Gly17Gly), gnomAD 4-157221093-A-T, CADD 14.20
- L18L (p.Leu18Leu), gnomAD 4-157221094-C-T, CADD 11.60
- L18M (p.Leu18Met), gnomAD 4-157221094-C-A, REVEL 0.12, CADD 19.60
- L18V (p.Leu18Val), rs1296243918, gnomAD 4-157221094-C-G, REVEL 0.09, CADD 20.10
- L18P (p.Leu18Pro), gnomAD 4-157221095-T-C, REVEL 0.26, CADD 24.50
- I19V (p.Ile19Val), gnomAD 4-157221097-A-G, REVEL 0.09, CADD 18.60
- I19T (p.Ile19Thr), gnomAD 4-157221098-T-C, REVEL 0.20, CADD 21.10
- I19I (p.Ile19Ile), rs759814002, gnomAD 4-157221099-T-A, CADD 10.80
- F20L (p.Phe20Leu), gnomAD 4-157221097-AT-A, CADD 26.10
- F20S (p.Phe20Ser), gnomAD 4-157221101-T-C, REVEL 0.22, CADD 22.80
- G21W (p.Gly21Trp), gnomAD 4-157221097-A-AT, CADD 26.90
- G21S (p.Gly21Ser), rs767782426, gnomAD 4-157221103-G-A, REVEL 0.28, CADD 23.30
- G21R (p.Gly21Arg), gnomAD 4-157221103-G-C, REVEL 0.45, CADD 26.60
- G21D (p.Gly21Asp), gnomAD 4-157221104-G-A, REVEL 0.47, CADD 24.20
- V22I (p.Val22Ile), gnomAD 4-157221106-G-A, REVEL 0.11, CADD 23.60
- V22V (p.Val22Val), rs775661930, gnomAD 4-157221108-C-T, CADD 10.50
- S23P (p.Ser23Pro), gnomAD 4-157221109-T-C, REVEL 0.12, CADD 21.40
- S23F (p.Ser23Phe), gnomAD 4-157221110-C-T, REVEL 0.12, CADD 20.30
- S23Y (p.Ser23Tyr), gnomAD 4-157221110-C-A, REVEL 0.10, CADD 17.40
- S23S (p.Ser23Ser), gnomAD 4-157221111-T-A, CADD 10.60
- S24P (p.Ser24Pro), gnomAD 4-157221112-T-C, REVEL 0.12, CADD 17.90
- S24Y (p.Ser24Tyr), gnomAD 4-157221113-C-A, REVEL 0.24, CADD 24.20
- S24S (p.Ser24Ser), gnomAD 4-157221114-T-A, CADD 11.00
- N25S (p.Asn25Ser), gnomAD 4-157221116-A-G, REVEL 0.11, CADD 16.40
- N25K (p.Asn25Lys), gnomAD 4-157221117-C-A, REVEL 0.09, CADD 21.40
- N25N (p.Asn25Asn), rs764113259, gnomAD 4-157221117-C-T, CADD 12.70
- S26G (p.Ser26Gly), gnomAD 4-157221118-A-G, REVEL 0.11, CADD 22.80
- S26N (p.Ser26Asn), rs1452701756, gnomAD 4-157221119-G-A, REVEL 0.06, CADD 22.10
- S26S (p.Ser26Ser), gnomAD 4-157221120-C-T, CADD 13.40
- S26R (p.Ser26Arg), gnomAD 4-157221120-C-A, REVEL 0.15, CADD 21.30
- I27V (p.Ile27Val), rs1450023419, gnomAD 4-157221121-A-G, REVEL 0.07, CADD 20.10
- I27T (p.Ile27Thr), gnomAD 4-157221122-T-C, REVEL 0.34, CADD 24.30
- G47E (p.Gly47Glu), rs2126669313, AlphaMissense 0.85, MetaLR 0.12, Uncertain significance, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- D302G (p.Asp302Gly), rs1735116193, AlphaMissense 1.00, MetaLR 0.24, Likely pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- E434G (p.Glu434Gly), rs776108757, []
- P528T (p.Pro528Thr), rs1735294501, AlphaMissense 1.00, MetaLR 0.26, Likely pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- Q607E (p.Gln607Glu), rs2126940512, AlphaMissense 0.82, MetaLR 0.21, Likely pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- Q607R (p.Gln607Arg), rs17850674, REVEL 0.18, CADD 22.40
- Q608R (p.Gln608Arg), rs17850675, AlphaMissense 0.96, MetaLR 0.23
- G609R (p.Gly609Arg), rs1735303754, AlphaMissense 1.00, MetaLR 0.90, Likely pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- D611N (p.Asp611Asn), rs1553956958, AlphaMissense 0.95, MetaLR 0.29, Conflicting interpretations, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- A639S (p.Ala639Ser), rs1579377564, AlphaMissense 0.98, MetaLR 0.66, Likely pathogenic, not provided; Neurodevelopmental disorder with language impairment and behaviora
- F644L (p.Phe644Leu), rs761753966, AlphaMissense 1.00, MetaLR 0.45, Likely pathogenic, not provided
- T646N (p.Thr646Asn), rs761753966, AlphaMissense 1.00, MetaLR 0.45, Pathogenic/Likely pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- V647L (p.Val647Leu), rs765072736, AlphaMissense 0.53, MetaLR 0.27, Pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- W788L (p.Trp788Leu), rs2127000861, AlphaMissense 0.99, MetaLR 0.26, Likely pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- G792V (p.Gly792Val), rs2127000875, AlphaMissense 0.99, MetaLR 0.42, Likely pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- A807V (p.Ala807Val), rs2127004544, AlphaMissense 0.95, MetaLR 0.31, Likely pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- N812S (p.Asn812Ser), rs2127004559, AlphaMissense 0.49, MetaLR 0.26, Likely pathogenic, Neurodevelopmental disorder with language impairment and behavioral abnormalitie
- E776D (p.Glu776Asp)
Public GRIA2 analysis runs
- GRIA2 analysis run — GRIA2 (93 variants) — completed 2026-09-07
- GRIA2 analysis run — GRIA2 (1,323 variants) — completed 2026-07-24
- GRIA2 analysis run — GRIA2 (1,323 variants) — completed 2026-07-24
- GRIA2 analysis run — GRIA2 (1,323 variants) — completed 2026-07-23
- GRIA2 analysis run — GRIA2 (1,323 variants) — completed 2026-07-22