GRIN1 (Q05586) variants and mutations
GRIN1 (also known as Q05586) is a human protein-coding gene encoding a glutamate receptor ionotropic, NMDA 1 protein. It provides an obligatory subunit of NMDA receptors and is essential for glutamate-dependent synaptic transmission, calcium signaling, and plasticity. Pathogenic variants can cause GRIN1-related neurodevelopmental disorder with intellectual disability, movement abnormalities, epilepsy, and cortical visual impairment. This analysis covers 193 GRIN1 variants and mutations. Of these, 91% have computational variant effect predictions. Disease context includes neurodevelopmental disorder with or without hyperkinetic movements and seizures, Alzheimer disease, and Parkinson disease. Example GRIN1 variants include S2R, S2I, and S2N.
Variant analysis overview
- Gene: GRIN1
- Protein: Q05586
- UniProt accession: Q05586
- Organism: Homo sapiens
- Variants analyzed: 193
- Variant scope: all variants
- Completed: 2026-09-07
Variant and mutation evidence
- Variant composition: 36 natural variant; 94 missense variants; 49 synonymous variants; 1 in-frame deletions; 1 frameshift variants; 3 stop-gained variants; 9 substitution
- Prediction scores: 176 variants have prediction scores (91% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodevelopmental disorder with or without hyperkinetic movements and seizures, Alzheimer disease, Parkinson disease, developmental and epileptic encephalopathy 101, infection, influenza, depressive disorder, major depressive disorder, alcohol dependence, dementia, secondary Parkinson disease, postencephalitic Parkinson disease.
Protein structure and variant hotspots
- Protein features: 3 transmembrane segments; 5 binding sites; 16 post-translational modification sites.
- Structural context: 16 variants have structural context.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable GRIN1 variants
Examples include S2R, S2I, S2N, T3A, T3T, M4T, M4I, R5C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2R (p.Ser2Arg), rs745492450, gnomAD 9-137139490-A-C, REVEL 0.05, CADD 23.80
- S2I (p.Ser2Ile), gnomAD 9-137139491-G-T, REVEL 0.08, CADD 24.40
- S2N (p.Ser2Asn), rs1832047745, gnomAD 9-137139491-G-A, REVEL 0.10, CADD 23.80
- T3A (p.Thr3Ala), rs1284901632, gnomAD 9-137139493-A-G, REVEL 0.10, CADD 19.60
- T3T (p.Thr3Thr), gnomAD 9-137139495-C-G, CADD 12.20
- M4T (p.Met4Thr), gnomAD 9-137139497-T-C, REVEL 0.37, CADD 23.90
- M4I (p.Met4Ile), gnomAD 9-137139498-G-T, REVEL 0.23, CADD 23.40
- R5C (p.Arg5Cys), rs755880462, gnomAD 9-137139499-C-T, REVEL 0.18, CADD 24.60
- R5S (p.Arg5Ser), rs755880462, gnomAD 9-137139499-C-A, REVEL 0.07, CADD 22.50
- R5L (p.Arg5Leu), gnomAD 9-137139500-G-T, REVEL 0.12, CADD 22.50
- R5H (p.Arg5His), rs779872478, gnomAD 9-137139500-G-A, REVEL 0.18, CADD 22.60
- L6M (p.Leu6Met), gnomAD 9-137139502-C-A, REVEL 0.14, CADD 22.60
- L6L (p.Leu6Leu), rs749261070, gnomAD 9-137139502-C-T, CADD 14.40
- L7L (p.Leu7Leu), rs1832048430, gnomAD 9-137139505-C-T, CADD 14.80
- L7P (p.Leu7Pro), gnomAD 9-137139506-T-C, REVEL 0.65, CADD 24.80
- T8P (p.Thr8Pro), rs768572879, gnomAD 9-137139508-A-C, REVEL 0.07, CADD 22.60
- T8K (p.Thr8Lys), rs1324864352, gnomAD 9-137139509-C-A, REVEL 0.20, CADD 22.80
- T8M (p.Thr8Met), rs1324864352, gnomAD 9-137139509-C-T, REVEL 0.07, CADD 22.90
- T8T (p.Thr8Thr), gnomAD 9-137139510-G-A, CADD 8.93
- L9I (p.Leu9Ile), gnomAD 9-137139511-C-A, REVEL 0.07, CADD 22.70
- L9P (p.Leu9Pro), gnomAD 9-137139512-T-C, REVEL 0.63, CADD 28.70
- L9L (p.Leu9Leu), gnomAD 9-137139513-C-A, CADD 12.70
- A10S (p.Ala10Ser), gnomAD 9-137139514-G-T, REVEL 0.28, CADD 24.60
- A10T (p.Ala10Thr), gnomAD 9-137139514-G-A, REVEL 0.32, CADD 24.90
- A10D (p.Ala10Asp), gnomAD 9-137139515-C-A, REVEL 0.63, CADD 27.10
- L11L (p.Leu11Leu), gnomAD 9-137139517-C-T, CADD 13.40
- L11M (p.Leu11Met), gnomAD 9-137139517-C-A, REVEL 0.14, CADD 22.50
- L12L (p.Leu12Leu), gnomAD 9-137139520-C-T, CADD 14.10
- F13V (p.Phe13Val), gnomAD 9-137139523-T-G, REVEL 0.08, CADD 18.60
- F13F (p.Phe13Phe), gnomAD 9-137139525-C-T, CADD 13.80
- S14del (p.Ser14del), rs778242525, gnomAD 9-137139524-TCTC-, CADD 19.40
- S14F (p.Ser14Phe), gnomAD 9-137139527-C-T, REVEL 0.25, CADD 23.80
- C15C (p.Cys15Cys), gnomAD 9-137139531-C-T, CADD 11.90
- S16S (p.Ser16Ser), rs201816843, gnomAD 9-137139534-C-T, CADD 10.90
- V17I (p.Val17Ile), gnomAD 9-137139535-G-A, REVEL 0.06, CADD 12.60
- V17V (p.Val17Val), gnomAD 9-137139537-C-T, CADD 8.72
- A18S (p.Ala18Ser), gnomAD 9-137139538-G-T, REVEL 0.17, CADD 21.50
- A18G (p.Ala18Gly), rs1478687903, gnomAD 9-137139539-C-G, REVEL 0.19, CADD 22.80
- A18V (p.Ala18Val), gnomAD 9-137139539-C-T, REVEL 0.17, CADD 20.40
- R19V (p.Arg19Val), gnomAD 9-137139538-GC-G, CADD 24.80
- R19S (p.Arg19Ser), gnomAD 9-137139541-C-A, REVEL 0.32, CADD 19.30
- R19H (p.Arg19His), gnomAD 9-137139542-G-A, REVEL 0.28, CADD 22.80
- A20S (p.Ala20Ser), gnomAD 9-137139544-G-T, REVEL 0.16, CADD 17.80
- A20T (p.Ala20Thr), rs770981821, gnomAD 9-137139544-G-A, REVEL 0.20, CADD 20.60
- A20V (p.Ala20Val), gnomAD 9-137139545-C-T, REVEL 0.10, CADD 17.30
- A20A (p.Ala20Ala), gnomAD 9-137139546-C-A, CADD 5.43
- A21S (p.Ala21Ser), gnomAD 9-137139547-G-T, REVEL 0.05, CADD 14.20
- A21E (p.Ala21Glu), gnomAD 9-137139548-C-A, REVEL 0.04, CADD 18.00
- A21V (p.Ala21Val), gnomAD 9-137139548-C-T, REVEL 0.06, CADD 18.60
- A21A (p.Ala21Ala), gnomAD 9-137139549-G-T, CADD 7.34
- C22W (p.Cys22Trp), gnomAD 9-137139552-C-G, REVEL 0.30, CADD 25.20
- C22C (p.Cys22Cys), rs148688400, gnomAD 9-137139552-C-T, CADD 13.00
- D23N (p.Asp23Asn), rs1832050674, gnomAD 9-137139553-G-A, REVEL 0.20, CADD 21.90
- P24S (p.Pro24Ser), rs1453332629, gnomAD 9-137139556-C-T, REVEL 0.14, CADD 23.80
- P24R (p.Pro24Arg), rs1832050918, gnomAD 9-137139557-C-G, REVEL 0.15, CADD 23.30
- P24P (p.Pro24Pro), rs1336084238, gnomAD 9-137139558-C-T, CADD 15.40
- K25Q (p.Lys25Gln), gnomAD 9-137139559-A-C, REVEL 0.07, CADD 22.50
- K25K (p.Lys25Lys), rs1832051310, gnomAD 9-137139561-G-A, CADD 14.60
- K25N (p.Lys25Asn), gnomAD 9-137139561-G-T, REVEL 0.11, CADD 24.50
- I26I (p.Ile26Ile), rs2131186471, gnomAD 9-137139564-C-T, CADD 13.80
- V27I (p.Val27Ile), rs775967941, gnomAD 9-137139565-G-A, REVEL 0.10, CADD 21.90
- N28I (p.Asn28Ile), rs974103165, gnomAD 9-137139569-A-T, REVEL 0.29, CADD 24.40
- N28N (p.Asn28Asn), rs1440128775, gnomAD 9-137139570-C-T, CADD 13.80
- I29T (p.Ile29Thr), gnomAD 9-137139572-T-C, REVEL 0.23, CADD 23.90
- G30G (p.Gly30Gly), rs1239167934, gnomAD 9-137139576-C-T, CADD 13.40
- A31P (p.Ala31Pro), gnomAD 9-137139577-G-C, REVEL 0.31, CADD 27.70
- A31V (p.Ala31Val), rs1832052066, gnomAD 9-137139578-C-T, REVEL 0.14, CADD 24.50
- V32A (p.Val32Ala), gnomAD 9-137139581-T-C, REVEL 0.29, CADD 25.10
- V32V (p.Val32Val), rs1832052266, gnomAD 9-137139582-G-A, CADD 12.90
- L33V (p.Leu33Val), rs1278963684, gnomAD 9-137139583-C-G, REVEL 0.19, CADD 24.00
- L33L (p.Leu33Leu), gnomAD 9-137139583-C-T, CADD 13.90
- S34T (p.Ser34Thr), gnomAD 9-137139587-G-C, REVEL 0.18, CADD 24.50
- T35A (p.Thr35Ala), rs2131186563, gnomAD 9-137139589-A-G, REVEL 0.04, CADD 23.00
- T35T (p.Thr35Thr), rs144566508, gnomAD 9-137139591-G-A, CADD 14.60
- R36R (p.Arg36Arg), rs1230411550, gnomAD 9-137139592-C-A, CADD 14.70
- R36Q (p.Arg36Gln), rs1261706375, gnomAD 9-137139593-G-A, REVEL 0.08, CADD 23.60
- K37K (p.Lys37Lys), rs1323269371, gnomAD 9-137139597-G-A, CADD 13.80
- H38Y (p.His38Tyr), rs1201591275, gnomAD 9-137139598-C-T, REVEL 0.07, CADD 19.40
- H38H (p.His38His), rs1241572680, gnomAD 9-137139600-C-T, CADD 11.50
- E39* (p.Glu39Ter), gnomAD 9-137139601-G-T, CADD 38.00
- Q40K (p.Gln40Lys), gnomAD 9-137139604-C-A, REVEL 0.15, CADD 21.50
- Q40H (p.Gln40His), rs764709864, gnomAD 9-137139606-G-C, REVEL 0.17, CADD 24.00
- M41I (p.Met41Ile), rs1832053827, gnomAD 9-137139609-G-A, REVEL 0.05, CADD 22.30
- F42F (p.Phe42Phe), rs1366155237, gnomAD 9-137139612-C-T, CADD 14.60
- R43H (p.Arg43His), gnomAD 9-137139614-G-A, REVEL 0.38, CADD 23.60
- R43L (p.Arg43Leu), gnomAD 9-137139614-G-T, REVEL 0.47, CADD 23.30
- R43R (p.Arg43Arg), gnomAD 9-137139615-C-T, CADD 12.60
- A45S (p.Ala45Ser), gnomAD 9-137139619-G-T, REVEL 0.75, CADD 24.50
- A45A (p.Ala45Ala), gnomAD 9-137139621-C-G, CADD 9.56
- V46L (p.Val46Leu), gnomAD 9-137139622-G-T, REVEL 0.55, CADD 24.30
- V46M (p.Val46Met), rs200747846, gnomAD 9-137139622-G-A, REVEL 0.71, CADD 28.80
- V46V (p.Val46Val), gnomAD 9-137139624-G-C, CADD 12.80
- N47Y (p.Asn47Tyr), rs1347150317, gnomAD 9-137139625-A-T, REVEL 0.18, CADD 25.00
- N47N (p.Asn47Asn), rs1473399287, gnomAD 9-137139627-C-T, CADD 12.40
- A49T (p.Ala49Thr), gnomAD 9-137139631-G-A, REVEL 0.61, CADD 24.20
- A49V (p.Ala49Val), gnomAD 9-137139632-C-T, REVEL 0.49, CADD 19.40
- A49G (p.Ala49Gly), rs756747799, gnomAD 9-137139632-C-G, REVEL 0.70, CADD 23.60
- A49A (p.Ala49Ala), gnomAD 9-137139633-C-T, CADD 15.50
- N50N (p.Asn50Asn), rs1428415601, gnomAD 9-137139636-C-T, CADD 13.30
- K51R (p.Lys51Arg), rs767000671, gnomAD 9-137139638-A-G, REVEL 0.06, CADD 22.70
- K51K (p.Lys51Lys), rs894474650, gnomAD 9-137139639-G-A, CADD 13.50
- R52G (p.Arg52Gly), rs950054021, gnomAD 9-137139640-C-G, REVEL 0.26, CADD 21.30
- R52R (p.Arg52Arg), rs950054021, gnomAD 9-137139640-C-A, CADD 13.70
- R52P (p.Arg52Pro), rs1045827866, gnomAD 9-137139641-G-C, REVEL 0.62, CADD 23.50
- H53D (p.His53Asp), gnomAD 9-137139643-C-G, REVEL 0.10, CADD 22.50
- H53H (p.His53His), rs147818786, gnomAD 9-137139645-C-T, CADD 4.96
- G54S (p.Gly54Ser), gnomAD 9-137139646-G-A, REVEL 0.16, CADD 22.40
- G54V (p.Gly54Val), gnomAD 9-137139647-G-T, REVEL 0.31, CADD 21.90
- G54G (p.Gly54Gly), rs1328297732, gnomAD 9-137139648-C-T, CADD 11.50
- W56* (p.Trp56Ter), rs755757497, gnomAD 9-137139653-G-A, CADD 37.00
- K57T (p.Lys57Thr), rs1832057244, gnomAD 9-137139656-A-C, REVEL 0.19, CADD 22.90
- I58F (p.Ile58Phe), rs1377456941, gnomAD 9-137139658-A-T, REVEL 0.19, CADD 21.00
- I58T (p.Ile58Thr), gnomAD 9-137139659-T-C, REVEL 0.32, CADD 22.20
- Q59R (p.Gln59Arg), gnomAD 9-137139662-A-G, REVEL 0.27, CADD 20.40
- L60F (p.Leu60Phe), gnomAD 9-137139664-C-T, REVEL 0.21, CADD 20.10
- L60L (p.Leu60Leu), rs1411983565, gnomAD 9-137139666-C-G, CADD 9.06
- A62T (p.Ala62Thr), gnomAD 9-137139670-G-A, REVEL 0.50, CADD 24.20
- A62V (p.Ala62Val), gnomAD 9-137139671-C-T, REVEL 0.52, CADD 21.60
- S64S (p.Ser64Ser), gnomAD 9-137139678-C-A, CADD 6.96
- V65I (p.Val65Ile), gnomAD 9-137139679-G-A, REVEL 0.31, CADD 20.20
- V65V (p.Val65Val), gnomAD 9-137139681-C-A, CADD 11.60
- T66T (p.Thr66Thr), rs1450115619, gnomAD 9-137139684-G-T, CADD 9.11
- H67Q (p.His67Gln), gnomAD 9-137139687-C-A, REVEL 0.40, CADD 21.90
- K68N (p.Lys68Asn), rs753619855, gnomAD 9-137139690-G-T, REVEL 0.20, CADD 20.50
- N70S (p.Asn70Ser), rs1276935687, gnomAD 9-137139695-A-G, REVEL 0.26, CADD 26.20
- N70K (p.Asn70Lys), rs1338045893, gnomAD 9-137139696-C-A, REVEL 0.29, CADD 24.60
- N70N (p.Asn70Asn), rs1338045893, gnomAD 9-137139696-C-T, CADD 12.70
- A71T (p.Ala71Thr), rs754711981, gnomAD 9-137139697-G-A, REVEL 0.60, CADD 29.60
- A71P (p.Ala71Pro), gnomAD 9-137139697-G-C, REVEL 0.56, CADD 22.60
- Q73Q (p.Gln73Gln), gnomAD 9-137139705-G-A, CADD 12.30
- M74V (p.Met74Val), gnomAD 9-137139706-A-G, REVEL 0.58, CADD 23.00
- A75G (p.Ala75Gly), rs1274780996, gnomAD 9-137139710-C-G, REVEL 0.27, CADD 28.20
- L76L (p.Leu76Leu), rs1483746045, gnomAD 9-137139714-G-A, CADD 12.80
- S77L (p.Ser77Leu), rs2131187092, gnomAD 9-137139716-C-T, REVEL 0.50, CADD 23.70
- S77S (p.Ser77Ser), rs1219867246, gnomAD 9-137139717-G-T, CADD 8.18
- V78A (p.Val78Ala), gnomAD 9-137139719-T-C, REVEL 0.69, CADD 26.80
- C79C (p.Cys79Cys), rs200529044, gnomAD 9-137139723-C-T, CADD 16.40
- E80K (p.Glu80Lys), rs748041860, gnomAD 9-137139724-G-A, REVEL 0.18, CADD 23.40
- E80* (p.Glu80Ter), gnomAD 9-137139724-G-T, CADD 38.00
- E80E (p.Glu80Glu), rs879189605, gnomAD 9-137139726-G-A, CADD 10.40
- D81N (p.Asp81Asn), gnomAD 9-137139727-G-A, REVEL 0.11, CADD 23.70
- D81E (p.Asp81Glu), rs1200771297, gnomAD 9-137139729-C-A, REVEL 0.06, CADD 21.40
- L82V (p.Leu82Val), gnomAD 9-137139730-C-G, REVEL 0.19, CADD 23.90
- L82L (p.Leu82Leu), rs192006771, gnomAD 9-137139732-C-T, CADD 14.10
- I83L (p.Ile83Leu), gnomAD 9-137139733-A-C, REVEL 0.13, CADD 22.90
- I83I (p.Ile83Ile), rs781310102, gnomAD 9-137139735-C-A, CADD 13.60
- S84F (p.Ser84Phe), rs201419574, gnomAD 9-137139737-C-T, REVEL 0.22, CADD 26.10
- S85S (p.Ser85Ser), rs797045605, gnomAD 9-137139741-C-T, CADD 14.80
- R217W (p.Arg217Trp), rs200777850, REVEL 0.52, CADD 26.70, Uncertain significance, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- D227H (p.Asp227His), rs869312865, REVEL 0.75, CADD 27.10, Likely pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- Y261F (p.Tyr261Phe), rs893141433, Uncertain significance
- Q290H (p.Gln290His), rs781512304, []
- R306Q (p.Arg306Gln), REVEL 0.34, CADD 24.20, Uncertain significance, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- A349S (p.Ala349Ser), rs148008303, REVEL 0.59, CADD 22.90, Conflicting interpretations, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- T419A (p.Thr419Ala), rs763133592, REVEL 0.16, CADD 22.90, Conflicting interpretations, not specified; Inborn genetic diseases; Neurodevelopmental disorder with or with
- D461G (p.Asp461Gly), rs955781126, Uncertain significance
- I540M (p.Ile540Met), rs3181457, AlphaMissense 0.98, MetaLR 0.18
- D552E (p.Asp552Glu), rs1554770054, REVEL 0.21, CADD 21.80, Pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- F554S (p.Phe554Ser), rs867175190, []
- P557R (p.Pro557Arg), rs878853143, AlphaMissense 1.00, MetaLR 0.22, Pathogenic, Intellectual disability; not provided
- G618R (p.Gly618Arg), rs1833614590, AlphaMissense 0.99, MetaLR 0.81, Pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- G620R (p.Gly620Arg), rs797045047, REVEL 0.91, CADD 32.00, Pathogenic, Inborn genetic diseases; not provided; Neurodevelopmental disorder with or witho
- A637S (p.Ala637Ser), Uncertain significance, in NDHMSD
- A637V (p.Ala637Val), rs1554770221, AlphaMissense 1.00, MetaLR 0.33, Uncertain significance, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- G638A (p.Gly638Ala), rs1393555703, AlphaMissense 1.00, MetaLR 0.27, Pathogenic/Likely pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- M641I (p.Met641Ile), rs1060500046, AlphaMissense 1.00, MetaLR 0.30, Likely pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- M641L (p.Met641Leu), rs2131299136, AlphaMissense 0.96, MetaLR 0.16, Likely pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- M641V (p.Met641Val), rs2131299136, AlphaMissense 0.96, MetaLR 0.16, Likely pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- I642T (p.Ile642Thr), Likely pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- I643V (p.Ile643Val), rs1554770243, AlphaMissense 0.31, MetaLR 0.19, Pathogenic/Likely pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- A645S (p.Ala645Ser), rs1833621434, AlphaMissense 0.89, MetaLR 0.19, Likely pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- Y647C (p.Tyr647Cys), Pathogenic, not provided
- N650I (p.Asn650Ile), rs1131691590, AlphaMissense 1.00, MetaLR 0.49, Pathogenic, not provided
- N650K (p.Asn650Lys), rs771610568, AlphaMissense 1.00, MetaLR 0.47, Pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- A652T (p.Ala652Thr), Uncertain significance, in NDHMSD
- F654C (p.Phe654Cys), rs1554770262, AlphaMissense 1.00, MetaLR 0.44, Pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- L655Q (p.Leu655Gln), rs1564363923, AlphaMissense 1.00, MetaLR 0.54, Uncertain significance, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- E662K (p.Glu662Lys), rs387906635, AlphaMissense 0.94, MetaLR 0.09, Pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
- A682S (p.Ala682Ser), rs1126448, AlphaMissense 0.78, MetaLR 0.33
- S688Y (p.Ser688Tyr), rs1833635820, REVEL 0.47, CADD 28.30, Pathogenic/Likely pathogenic, Neurodevelopmental disorder with or without hyperkinetic movements and seizures
Public GRIN1 analysis runs
- GRIN1 analysis run — GRIN1 (193 variants) — completed 2026-09-07
- GRIN1 analysis run — GRIN1 (1,184 variants) — completed 2026-08-19