CACNA1E (Q15878) variants and mutations
CACNA1E (also known as Q15878) is a human protein-coding gene encoding a voltage-dependent R-type calcium channel subunit alpha-1E protein. It contributes R-type calcium current at neuronal membranes and presynaptic terminals, shaping neurotransmitter release and neuronal firing. De novo pathogenic variants can cause severe developmental and epileptic encephalopathy with movement abnormalities. This analysis covers 2,854 CACNA1E variants and mutations. Of these, 64% have computational variant effect predictions. Disease context includes Seizure, genetic developmental and epileptic encephalopathy, and epilepsy. Example CACNA1E variants include M1I, A2T, and R3C.
Variant analysis overview
- Gene: CACNA1E
- Protein: Q15878
- UniProt accession: Q15878
- Organism: Homo sapiens
- Variants analyzed: 2854
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 2,580 unspecified-consequence records; 186 missense variants; 59 synonymous variants; 13 stop-gained variants; 8 frameshift variants; 4 in-frame deletions; 1 in-frame insertions; 3 substitution
- Prediction scores: 1,817 variants have prediction scores (64% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Seizure, genetic developmental and epileptic encephalopathy, epilepsy, neuropathic pain, fibromyalgia, restless legs syndrome, postherpetic neuralgia, anxiety disorder, neuralgia, Focal-onset seizure, hereditary disease, spinal cord injury.
Protein structure and variant hotspots
- Protein features: 24 transmembrane segments; 1 domains; 7 binding sites; 16 post-translational modification sites.
- Structural context: 467 variants have structural context.
- PTM context: 21 variants overlap post-translational modification sites.
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 CACNA1E variants
Examples include M1I, A2T, R3C, R3H, R3L, R3S, R3P, R3R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs994486607, gnomAD 1-181413161-G-A, CADD 22.90
- A2T (p.Ala2Thr), NCI-TCGA TCGA novel, REVEL 0.72, CADD 28.70, Variant assessed as somatic; moderate impact.
- R3C (p.Arg3Cys), rs769614151, ClinGen CA1274807, NCI-TCGA Cosmic COSV6241, cosmic curated COSV62412, REVEL 0.75, CADD 31.00, Uncertain significance, not provided
- R3H (p.Arg3His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R3L (p.Arg3Leu), ExAC rs775240148, gnomAD rs775240148, REVEL 0.79, CADD 31.00, Uncertain significance, not specified
- R3S (p.Arg3Ser), gnomAD 1-181413162-C-A, CADD 22.70
- R3P (p.Arg3Pro), rs929731901, gnomAD 1-181413163-G-C, CADD 19.70
- R3R (p.Arg3Arg), rs1407353759, gnomAD 1-181413164-T-G, CADD 7.82
- F4L (p.Phe4Leu), rs1228809248, ClinGen CA343844156, ClinVar RCV003015632, REVEL 0.53, CADD 25.60, Uncertain significance, not provided
- F4F (p.Phe4Phe), rs1228809248, gnomAD 1-181483756-C-T, CADD 13.40
- G5E (p.Gly5Glu), rs1663514169, ClinGen CA343844161, ClinVar RCV003676692, Ensembl rs1663514169, REVEL 0.69, CADD 25.20, Uncertain significance, not provided
- G5R (p.Gly5Arg), NCI-TCGA Cosmic COSV6242, cosmic curated COSV62426, Variant assessed as somatic; moderate impact.
- G5* (p.Gly5Ter), gnomAD 1-181413165-G-T, CADD 37.00
- G5V (p.Gly5Val), gnomAD 1-181413166-G-T, CADD 25.30
- E6K (p.Glu6Lys), rs1484737332, gnomAD 1-181413156-G-A, CADD 23.20
- E6G (p.Glu6Gly), gnomAD 1-181413157-A-G, CADD 23.40
- E6D (p.Glu6Asp), gnomAD 1-181413158-G-T, CADD 17.20
- E6* (p.Glu6Ter), gnomAD 1-181413192-G-T, CADD 37.00
- E6E (p.Glu6Glu), rs1657993669, gnomAD 1-181413194-G-A, CADD 8.94
- E6del (p.Glu6del), gnomAD 1-181483758-GGGA-, CADD 22.50
- A7T (p.Ala7Thr), gnomAD 1-181483763-G-A, REVEL 0.37, CADD 25.00
- A7P (p.Ala7Pro), gnomAD 1-181483763-G-C, REVEL 0.43, CADD 25.20
- A7V (p.Ala7Val), gnomAD 1-181483764-C-T, REVEL 0.39, CADD 23.90
- A7A (p.Ala7Ala), gnomAD 1-181483765-G-A, CADD 9.19
- V8A (p.Val8Ala), ExAC rs763180598, gnomAD rs763180598, REVEL 0.30, CADD 20.50
- V8L (p.Val8Leu), gnomAD 1-181413150-G-T, CADD 22.60
- V8M (p.Val8Met), gnomAD 1-181413150-G-A, CADD 24.20
- V8V (p.Val8Val), gnomAD 1-181413152-G-A, CADD 7.97
- V9D (p.Val9Asp), Ensembl rs1571980351
- V9G (p.Val9Gly), Ensembl rs1571980351
- V9V (p.Val9Val), gnomAD 1-181483771-C-A, CADD 10.80
- A10D (p.Ala10Asp), ExAC rs761740155, TOPMed rs761740155, gnomAD rs761740155, REVEL 0.25, CADD 21.00
- A10S (p.Ala10Ser), rs751662861, ClinGen CA1274811, ClinVar RCV002160299, ClinVar RCV006357329, REVEL 0.27, CADD 21.10, Benign/Likely benign, not provided; Inborn genetic diseases
- A10T (p.Ala10Thr), ExAC rs751662861, TOPMed rs751662861, gnomAD rs751662861, REVEL 0.33, CADD 22.00, Uncertain significance, Inborn genetic diseases
- A10P (p.Ala10Pro), gnomAD 1-181413197-CG-C, CADD 19.30
- A10V (p.Ala10Val), gnomAD 1-181413199-C-T, CADD 9.96
- R11K (p.Arg11Lys), ExAC rs767620162, TOPMed rs767620162, gnomAD rs767620162, REVEL 0.49, CADD 21.50, Uncertain significance
- R11M (p.Arg11Met), rs767620162, ClinGen CA1274813, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10070, REVEL 0.56, CADD 22.50, Uncertain significance, Developmental and epileptic encephalopathy, 69
- R11S (p.Arg11Ser), gnomAD 1-181413180-C-A, CADD 19.50
- R11C (p.Arg11Cys), rs1335031644, gnomAD 1-181413180-C-T, CADD 23.30
- R11L (p.Arg11Leu), gnomAD 1-181413181-G-T, CADD 19.90
- R11H (p.Arg11His), rs1657992369, gnomAD 1-181413181-G-A, CADD 20.50
- R11R (p.Arg11Arg), gnomAD 1-181413182-C-A, CADD 9.70
- R11W (p.Arg11Trp), gnomAD 1-181413183-A-T, CADD 24.10
- R11G (p.Arg11Gly), gnomAD 1-181413183-A-G, CADD 22.40
- P12S (p.Pro12Ser), NCI-TCGA TCGA novel, REVEL 0.26, CADD 19.40, Uncertain significance, Inborn genetic diseases
- P12T (p.Pro12Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P12L (p.Pro12Leu), gnomAD 1-181413154-C-T, CADD 23.90
- P12P (p.Pro12Pro), rs1162824139, gnomAD 1-181413155-C-G, CADD 4.36
- P12Q (p.Pro12Gln), gnomAD 1-181413175-C-A, CADD 24.20
- P12A (p.Pro12Ala), rs1657993059, gnomAD 1-181413189-C-G, CADD 22.20
- P12H (p.Pro12His), gnomAD 1-181413190-C-A, CADD 22.50
- S14A (p.Ser14Ala), Ensembl rs1571980472
- S14C (p.Ser14Cys), gnomAD rs1422179994, REVEL 0.42, CADD 25.20
- S14G (p.Ser14Gly), gnomAD 1-181413171-A-G, CADD 22.60
- S14I (p.Ser14Ile), gnomAD 1-181413172-G-T, CADD 25.60
- S14R (p.Ser14Arg), gnomAD 1-181413173-C-A, CADD 23.60
- S14S (p.Ser14Ser), rs950634485, gnomAD 1-181413173-C-T, CADD 10.30
- G15C (p.Gly15Cys), NCI-TCGA Cosmic COSV6241, cosmic curated COSV62417, Variant assessed as somatic; moderate impact.
- G15S (p.Gly15Ser), rs376471584, ClinGen CA34178243, cosmic curated COSV62389, ClinVar RCV001913076, REVEL 0.53, CADD 23.30, Uncertain significance, not provided
- D16G (p.Asp16Gly), gnomAD rs903283906, REVEL 0.36, CADD 22.80
- D16V (p.Asp16Val), gnomAD rs903283906
- D16Y (p.Asp16Tyr), gnomAD 1-181413177-G-T, CADD 20.20
- D16E (p.Asp16Glu), gnomAD 1-181413179-C-A, CADD 14.00
- G17E (p.Gly17Glu), rs780589733, ClinGen CA1274816, ClinVar RCV002288141, ClinVar RCV003355846, REVEL 0.55, CADD 26.90, Conflicting interpretations, not provided; Inborn genetic diseases
- D18G (p.Asp18Gly), rs1379505181, ClinGen CA343844238, ClinVar RCV002298291, Uncertain significance, not provided
- D18V (p.Asp18Val), gnomAD rs1379505181, REVEL 0.50, CADD 23.70
- D18Y (p.Asp18Tyr), NCI-TCGA TCGA novel, Ensembl rs1663519914, Variant assessed as somatic; moderate impact.
- S19L (p.Ser19Leu), rs758128368, ClinGen CA1274818, cosmic curated COSV62398, ClinVar RCV002090431, REVEL 0.45, CADD 22.50, Conflicting interpretations, Inborn genetic diseases; not provided; Developmental and epileptic encephalopath
- S19W (p.Ser19Trp), rs758128368, ClinGen CA343844246, ClinVar RCV001767099, ExAC rs758128368, REVEL 0.53, CADD 26.10, Uncertain significance, not provided
- D20E (p.Asp20Glu), rs2526274758, ClinGen CA343844253, ClinVar RCV003557343, Uncertain significance, not provided
- S22C (p.Ser22Cys), NCI-TCGA Cosmic COSV6240, cosmic curated COSV62401, Variant assessed as somatic; moderate impact.
- S22E (p.Ser22Glu), gnomAD 1-181413214-C-CG, CADD 17.30
- S22A (p.Ser22Ala), gnomAD 1-181413214-CG-C, CADD 15.50
- S22G (p.Ser22Gly), gnomAD 1-181413219-A-G, CADD 19.90
- S22N (p.Ser22Asn), gnomAD 1-181413220-G-A, CADD 21.70
- S22S (p.Ser22Ser), rs1657997667, gnomAD 1-181413221-C-T, CADD 9.86
- N24K (p.Asn24Lys), gnomAD rs1290397583, REVEL 0.31, CADD 19.70
- R25P (p.Arg25Pro), TOPMed rs1227533595, gnomAD rs1227533595
- R25Q (p.Arg25Gln), rs1227533595, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10070, TOPMed rs1227533595, REVEL 0.50, CADD 22.70, Variant assessed as somatic; moderate impact.
- R29del (p.Arg29del), gnomAD 1-181413230-CAGG-, CADD 7.40
- R25G (p.Arg25Gly), rs1657999033, gnomAD 1-181413231-A-G, CADD 4.51
- R25K (p.Arg25Lys), gnomAD 1-181413232-G-A, CADD 3.92
- R25M (p.Arg25Met), gnomAD 1-181413232-G-T, CADD 10.50
- R25R (p.Arg25Arg), gnomAD 1-181413233-G-A, CADD 4.83
- R25S (p.Arg25Ser), gnomAD 1-181413233-G-T, CADD 10.70
- R25C (p.Arg25Cys), rs922015029, gnomAD 1-181413243-C-T, CADD 23.30
- R25H (p.Arg25His), rs1215271452, gnomAD 1-181413244-G-A, CADD 22.20
- G27R (p.Gly27Arg), rs965834191, gnomAD 1-181413216-G-C, CADD 23.10
- G27W (p.Gly27Trp), gnomAD 1-181413216-G-T, CADD 23.60
- G27E (p.Gly27Glu), gnomAD 1-181413217-G-A, CADD 24.80
- G27G (p.Gly27Gly), gnomAD 1-181413218-G-A, CADD 9.35
- T28I (p.Thr28Ile), rs1405275408, ClinGen CA343844310, ClinVar RCV003830492, TOPMed rs1405275408, Uncertain significance, not provided
- T28N (p.Thr28Asn), TOPMed rs1405275408, gnomAD rs1405275408, REVEL 0.32, CADD 19.20, Uncertain significance
- P29S (p.Pro29Ser), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- P29T (p.Pro29Thr), gnomAD 1-181413207-C-A, CADD 16.50
- P29Q (p.Pro29Gln), gnomAD 1-181413208-C-A, CADD 16.50
- P29L (p.Pro29Leu), rs1657995505, gnomAD 1-181413208-C-T, CADD 12.40
- P29P (p.Pro29Pro), gnomAD 1-181413209-G-T, CADD 2.61
- P29H (p.Pro29His), gnomAD 1-181413223-C-A, CADD 24.10
- V30L (p.Val30Leu), rs1013161252, ClinGen CA343844318, ClinVar RCV002305114, TOPMed rs1013161252, REVEL 0.40, CADD 21.30, Uncertain significance, not provided
- V30M (p.Val30Met), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10070, REVEL 0.38, CADD 22.70, Variant assessed as somatic; moderate impact.
- V30I (p.Val30Ile), rs1270306626, gnomAD 1-181413258-G-A, CADD 13.30
- P31L (p.Pro31Leu), rs780719691, ClinGen CA1274822, cosmic curated COSV62398, ClinVar RCV001955826, REVEL 0.29, CADD 22.60, Benign/Likely benign, not provided; Inborn genetic diseases
- P31S (p.Pro31Ser), TOPMed rs1663527927
- P31T (p.Pro31Thr), rs1658003584, gnomAD 1-181413270-C-A, CADD 22.00
- P31Q (p.Pro31Gln), rs1266912038, gnomAD 1-181413271-C-A, CADD 22.80
- P31P (p.Pro31Pro), rs1326484143, gnomAD 1-181413272-G-T, CADD 0.22
- A32T (p.Ala32Thr), gnomAD 1-181413210-G-A, CADD 12.30
- A32D (p.Ala32Asp), rs1571805950, gnomAD 1-181413211-C-A, CADD 19.80
- A32S (p.Ala32Ser), gnomAD 1-181413213-G-T, CADD 4.04
- A32V (p.Ala32Val), rs1018822636, gnomAD 1-181413214-C-T, CADD 5.50
- A32E (p.Ala32Glu), gnomAD 1-181413214-C-A, CADD 4.95
- A32A (p.Ala32Ala), rs892257205, gnomAD 1-181413215-G-A, CADD 2.89
- A32P (p.Ala32Pro), rs904882375, gnomAD 1-181413237-G-C, CADD 6.48
- S33L (p.Ser33Leu), rs1663529063, ClinGen CA343844338, cosmic curated COSV10818, ClinVar RCV003673006, Likely benign, not provided
- S33W (p.Ser33Trp), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10070, Variant assessed as somatic; moderate impact.
- S33P (p.Ser33Pro), gnomAD 1-181413234-T-C, CADD 3.81
- S33F (p.Ser33Phe), gnomAD 1-181413235-C-T, CADD 16.80
- S33Y (p.Ser33Tyr), gnomAD 1-181413235-C-A, CADD 15.80
- S33S (p.Ser33Ser), gnomAD 1-181413236-C-A, CADD 3.48
- G34A (p.Gly34Ala), rs2102468518, ClinGen CA343844343, ClinVar RCV001771438, Ensembl rs2102468518, Uncertain significance, not provided
- G34R (p.Gly34Arg), TOPMed rs1482505711, REVEL 0.69, CADD 26.60
- G34S (p.Gly34Ser), gnomAD 1-181413240-G-A, CADD 21.10
- G34C (p.Gly34Cys), gnomAD 1-181413240-G-T, CADD 22.80
- G34D (p.Gly34Asp), gnomAD 1-181413241-G-A, CADD 22.50
- G34G (p.Gly34Gly), gnomAD 1-181413242-C-T, CADD 7.48
- Q35H (p.Gln35His), ExAC rs768935172, gnomAD rs768935172, REVEL 0.29, CADD 5.42
- Q35K (p.Gln35Lys), cosmic curated COSV10888, gnomAD rs1244349881, CADD 8.85
- Q35R (p.Gln35Arg), rs2526275809, ClinGen CA343844349, ClinVar RCV003676450, Uncertain significance, not provided
- Q35Q (p.Gln35Gln), rs536181446, gnomAD 1-181413251-A-G, CADD 0.66
- A36G (p.Ala36Gly), Ensembl rs1262899211, REVEL 0.29, CADD 21.20
- A36V (p.Ala36Val), NCI-TCGA Cosmic COSV6238, cosmic curated COSV62385, Variant assessed as somatic; moderate impact.
- A37G (p.Ala37Gly), Ensembl rs1571981013, Uncertain significance, Developmental and epileptic encephalopathy, 69
- A38S (p.Ala38Ser), NCI-TCGA Cosmic COSV6238, cosmic curated COSV62387, REVEL 0.29, CADD 16.50, Variant assessed as somatic; moderate impact.
- A38T (p.Ala38Thr), rs1299132420, ClinGen CA343844364, NCI-TCGA Cosmic COSV6238, cosmic curated COSV62383, REVEL 0.34, CADD 19.10, Uncertain significance, Inborn genetic diseases
- A38V (p.Ala38Val), rs971589755, ClinGen CA34178246, ClinVar RCV002000828, TOPMed rs971589755, REVEL 0.34, CADD 20.40, Likely benign, not provided
- A38D (p.Ala38Asp), gnomAD 1-181413265-C-A, CADD 23.90
- A38A (p.Ala38Ala), gnomAD 1-181413266-C-A, CADD 4.47
- Y39C (p.Tyr39Cys), Ensembl rs1663532372, REVEL 0.75, CADD 25.90
- Y39N (p.Tyr39Asn), ExAC rs762088533, gnomAD rs762088533, REVEL 0.80, CADD 24.30
- Q41P (p.Gln41Pro), rs773295315, ClinGen CA1274831, ClinVar RCV002024698, ClinVar RCV005535261, REVEL 0.90, CADD 27.70, Benign/Likely benign, Inborn genetic diseases; not provided
- Q41R (p.Gln41Arg), ExAC rs773295315, TOPMed rs773295315, gnomAD rs773295315, REVEL 0.81, CADD 27.00, Uncertain significance
- T42M (p.Thr42Met), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10070, Uncertain significance, not provided
- T42R (p.Thr42Arg), TOPMed rs1284141306, gnomAD rs1284141306, REVEL 0.49, CADD 23.60
- Q45H (p.Gln45His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q45R (p.Gln45Arg), Ensembl rs1558040990
- Q45* (p.Gln45Ter), gnomAD 1-181413294-C-T, CADD 37.00
- Q45Q (p.Gln45Gln), gnomAD 1-181413296-G-A, CADD 6.39
- R46M (p.Arg46Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R46W (p.Arg46Trp), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10070, Variant assessed as somatic; moderate impact.
- R46S (p.Arg46Ser), gnomAD 1-181413252-C-A, CADD 21.40
- R46C (p.Arg46Cys), rs1658002237, gnomAD 1-181413252-C-T, CADD 24.00
- R46L (p.Arg46Leu), gnomAD 1-181413253-G-T, CADD 22.70
- R46H (p.Arg46His), rs1358018967, gnomAD 1-181413253-G-A, CADD 22.50
- R46R (p.Arg46Arg), gnomAD 1-181413254-C-A, CADD 7.96
- A47T (p.Ala47Thr), rs1161110769, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10070, gnomAD rs1161110769, REVEL 0.77, CADD 29.30, Variant assessed as somatic; moderate impact.
- A47V (p.Ala47Val), rs1383093652, ClinGen CA343844431, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10070, Uncertain significance, not provided
- A47S (p.Ala47Ser), gnomAD 1-181413282-G-T, CADD 16.50
- A47G (p.Ala47Gly), gnomAD 1-181413283-C-G, CADD 22.80
- A47A (p.Ala47Ala), gnomAD 1-181413284-A-G, CADD 12.60
- R48Q (p.Arg48Gln), rs1446954006, ClinGen CA343844436, ClinVar RCV003014187, TOPMed rs1446954006, CADD 23.70, Benign, not provided
- R48G (p.Arg48Gly), rs1443484500, gnomAD 1-181413288-C-G, CADD 24.00
- R48W (p.Arg48Trp), gnomAD 1-181413288-C-T, CADD 24.90
- R48R (p.Arg48Arg), gnomAD 1-181413288-C-A, CADD 8.82
- R48L (p.Arg48Leu), rs1001802936, gnomAD 1-181413289-G-T, CADD 25.20
- T49I (p.Thr49Ile), gnomAD rs1303263206
- M50I (p.Met50Ile), gnomAD rs1663536362, REVEL 0.87, CADD 27.30
- M50V (p.Met50Val), rs1663536108, ClinGen CA343844445, ClinVar RCV003315041, TOPMed rs1663536108, REVEL 0.87, CADD 25.60, Uncertain significance, not provided
- M50C (p.Met50Cys), gnomAD 1-181413338-CA-C, CADD 25.20
- M50T (p.Met50Thr), gnomAD 1-181413340-T-C, CADD 17.70
- A51T (p.Ala51Thr), rs539853027, gnomAD 1-181413303-G-A, CADD 16.70
- A51S (p.Ala51Ser), gnomAD 1-181413303-G-T, CADD 8.91
- A51A (p.Ala51Ala), gnomAD 1-181413305-T-A, CADD 3.46
- A51V (p.Ala51Val), gnomAD 1-181413316-C-T, CADD 20.50
- A51D (p.Ala51Asp), gnomAD 1-181413316-C-A, CADD 22.70
- L52F (p.Leu52Phe), rs766926616, ClinGen CA343844462, ClinVar RCV002223676, ClinVar RCV003458849, Uncertain significance, Developmental and epileptic encephalopathy, 69; not provided
- L52S (p.Leu52Ser), cosmic curated COSV10442, TOPMed rs972657966, gnomAD rs972657966, REVEL 0.89, CADD 29.20
- L52M (p.Leu52Met), gnomAD 1-181413168-C-A, CADD 22.40
- L52L (p.Leu52Leu), gnomAD 1-181413168-C-T, CADD 9.37
Public CACNA1E analysis runs
- CACNA1E analysis run — CACNA1E (2,854 variants) — completed 2026-08-20