Table 2.
Genes involved in epileptic encephalopathy and DEE pathogenesis
| Approved Symbol | Gene/Locus Name |
|---|---|
| Ion channels | |
| KCNA2 | Potassium channel, voltage-gated, Shaker-related subfamily, member 2 |
| CACNA1E | Calcium channel, voltage-dependent, alpha 1E subunit |
| KCNT2 | Potassium channel, subfamily T, member 2 |
| SCN3A | Sodium channel, voltage-gated, type III, alpha polypeptide |
| SCN2A | Sodium channel, voltage-gated, type II, alpha subunit |
| SCN1A | Sodium channel, voltage-gated, type I, alpha polypeptide |
| SCN9A | Sodium channel, voltage-gated, type IX, alpha subunit |
| CACNA2D2 | Calcium channel, voltage-dependent, alpha-2/delta subunit 2 |
| HCN1 | Hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 |
| KCNQ5 | Potassium channel, voltage-gated, KQT-like subfamily, member 5 |
| KCNT1 | Potassium channel, subfamily T, member 1 |
| CACNA1B | Calcium channel, voltage-dependent, L type, alpha 1B subunit |
| SCN8A | Sodium channel, voltage gated, type VIII, alpha polypeptide |
| CACNA1G | Calcium channel, voltage-dependent, T type, alpha-1G subunit |
| CACNA1A | Calcium channel, voltage-dependent, P/Q type, alpha 1A subunit |
| SCN1B | Sodium channel, voltage-gated, type I, beta polypeptide |
| KCNB1 | Potassium voltage-gated channel, Shab-related subfamily, member 1 |
| KCNQ2 | Potassium voltage-gated channel, KQT-like subfamily, member 2 |
| CLCN4 | Chloride channel-4 |
| Receptors | |
| GABRA2 | Gamma-aminobutyric acid (GABA) A receptor, alpha-2 |
| GABRB1 | Gamma-aminobutyric acid (GABA) A receptor, beta-1 |
| GABRB2 | Gamma-aminobutyric acid (GABA) A receptor, beta-2 |
| GABRA1 | Gamma-aminobutyric acid (GABA) A receptor, alpha-1 |
| GABRG2 | Gamma-aminobutyric acid (GABA) A receptor, gamma-2 |
| NTRK2 | Neurotrophic tyrosine kinase, receptor, type 2 |
| GABBR2 | Gamma-aminobutyric acid B receptor 2 |
| GRIN1 | Glutamate receptor, ionotropic, N-methyl d-aspartate 1 |
| GABRB3 | Gamma-aminobutyric acid (GABA) A receptor, beta-3 |
| GABRA5 | Gamma-aminobutyric acid (GABA) A receptor, alpha-5 |
| GRIN2A | Glutamate receptor, ionotropic, N-methyl d-aspartate 2A |
| GRIN2D | Glutamate receptor, ionotropic, N-methyl d-aspartate 2D |
| Transporters | |
| ATP1A2 | ATPase, Na+-K+ transporting, alpha-2 polypeptide |
| SLC2A1 | Solute carrier family 2 (facilitated glucose transporter), member 1 |
| ARV1 | ARV1 homolog, fatty acid homeostasis modulator |
| SLC1A4 | Solute carrier family 1 (glutamate/neutral amino acid transporter), member 4 |
| SLC25A12 | Solute carrier family 25 (mitochondrial carrier, Aralar), member 12 |
| SLC6A1 | Solute carrier family 6 (neurotransmitter transporter, GABA), member 1 |
| SLC25A22 | Solute carrier family 25 (mitochondrial carrier, glutamate), member 22 |
| SLC1A2 | Solute carrier family 1 (glial high affinity glutamate transporter), member 2 |
| SLC13A5 | Solute carrier family 13 (sodium-dependent citrate transporter), member 5 |
| SLC25A10 | Solute carrier family 25 (mitochondrial carrier), member 10 (dicarboxylate ion carrier) |
| SLC25A42 | Solute carrier family 25, member 42 |
| ATP1A3 | ATPase, Na+-K+ transporting, alpha-3 polypeptide |
| SLC12A5 | Solute carrier family 12, (potassium-chloride transporter) member 5 |
| SLC35A2 | Solute carrier family 35 (UDP-galactose transporter), member 2 |
| SLC9A6 | Solute carrier family 9 (sodium/hydrogen exchanger), member 6 |
| Synapse related | |
| CPLX1 | Complexin 1 |
| PPP3CA | Protein phosphatase 3, catalytic subunit, alpha isoform (calcineurin A alpha) |
| SYNGAP1 | Synaptic Ras GTPase activating protein 1 |
| ADAM22 | ADAM metallopeptidase domain 22 |
| STXBP1 | Syntaxin-binding protein 1 |
| DNM1 | Dynamin-1 |
| NECAP1 | NECAP endocytosis-associated protein 1 |
| DMXL2 | DMX-like 2 |
| AP3B2 | Adaptor-related protein complex 3, beta2 subunit |
| STX1B | Syntaxin 1B |
| SYNJ1 | Synaptojanin 1 |
| NRXN1 | Neurexin 1 |
| Cell growth, division, and proliferation related | |
| MTOR | Mechanistic target of rapamycin |
| AKT3 | AKT serine/threonine kinase 3 |
| NPRL2 | NPR2-like protein, GATOR1 complex subunit |
| STAG1 | Stromal antigen 1 |
| RNF13 | RING finger protein 13 |
| PIK3CA | Phosphatidylinositol 3-kinase, catalytic, alpha |
| PPP2CA | Protein phosphatase-2 (formerly 2A), catalytic subunit, alpha isoform |
| ACTL6B | Actin-like 6B |
| RHOBTB2 | Rho-related BTB domain-containing protein 2 |
| TSC1 | Hamartin |
| AKT1 | AKT serine/threonine kinase 1 |
| NPRL3 | Nitrogen permease regulator-like 3 |
| TSC2 | Tuberin |
| PIK3R2 | Phosphatidylinositol 3-kinase, regulatory subunit 2 |
| DEPDC5 | DEP domain-containing protein 5 |
| Cell metabolism related | |
| MTHFR | Methylenetetrahydrofolate reductase |
| ST3GAL3 | ST3 beta-galactoside alpha-2,3-sialyltransferase 3 |
| PARS2 | Prolyl-tRNA synthetase 2 |
| HNRNPU | Heterogeneous nuclear ribonucleoprotein U |
| CAD | CAD trifunctional protein of pyrimidine biosynthesis |
| MDH1 | Malate dehydrogenase, soluble |
| UGP2 | Uridyl diphosphate glucose pyrophosphorylase-2 |
| BOLA3 | bolA family member 3 |
| ST3GAL5 | Sialyltransferase 9 |
| GAD1 | Glutamate decarboxylase-1, brain, 67 kDa |
| GLS | Glutaminase |
| D2HGDH | D-2-hydroxyglutarate dehydrogenase |
| UGDH | UDP-glucose dehydrogenase |
| MANBA | Mannosidase, beta A, lysosomal |
| NUS1 | NUS1 dehydrodolichyl diphosphate synthase subunit |
| MDH2 | Malate dehydrogenase, mitochondrial |
| DENND5A | DENN domain-containing protein 5A |
| NARS2 | Asparaginyl-tRNA synthetase 2 |
| ALG9 | ALG9 alpha-1,2-mannosyltransferase |
| FCSK | Fucose kinase |
| PNPO | Pyridoxamine 5′-phosphate oxidase |
| ITPA | Inosine triphosphatase-A |
| ALG13 | ALG13 UDP-N-acetylglucosaminyltransferase subunit |
| Intracellular trafficking related | |
| TRAK1 | Trafficking protein, kinesin-binding 1 |
| AP2M1 | Adaptor-related protein complex 2, mu 1 subunit |
| CAMK2G | Calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma |
| TBC1D24 | TBC1 domain family, member 24 |
| NSF | N-ethylmaleimide-sensitive factor |
| CLTC | Clathrin, heavy polypeptide (Hc) |
| ARX | Aristaless-related homeobox, X-linked |
| Intracellular signaling related | |
| SZT2 | SZT2 subunit of KICSTOR complex |
| DOCK7 | Dedicator of cytokinesis 7 |
| YWHAG | Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma isoform |
| GNAO1 | Guanine nucleotide-binding protein (G protein), alpha-activating activity |
| PLCB1 | Phospholipase C, beta-1 |
| SIK1 | Salt-inducible kinase 1 |
| Transcription and gene expression related | |
| PUM1 | Pumilio RNA binding family member 1 |
| TSEN2 | tRNA splicing endonuclease, subunit 2 |
| PURA | Purine-rich element binding protein A |
| MEF2C | MADS box transcription enhancer factor 2, polypeptide C (myocyte enhancer factor 2C) |
| KMT2E | Lysine (K)-specific methyltransferase 2E |
| CELF2 | CUGbp- and ELAV-like family, member 2 |
| CUX2 | Cut-like homeobox 2 |
| FOXG1 | Forkhead box G1B |
| IRF2BPL | Interferon regulatory factor 2-binding protein like |
| CHD2 | Chromodomain helicase DNA binding protein-2 |
| NEUROD2 | Neurogenic differentiation 2 |
| MECP2 | Methyl-CpG-binding protein-2 |
| Protein biosynthesis/degradation related | |
| DHDDS | Dehydrodolichyl diphosphate synthase |
| ATP6V1A | ATPase, H+ transporting, V1 subunit A |
| UBA5 | Ubiquitin-like modifier activating enzyme 5 |
| GUF1 | GUF1 homolog, GTPase |
| VARS1 | Valyl-tRNA synthetase 1 |
| PLAA | Phospholipase A2-activating protein |
| CARS2 | Cysteinyl-tRNA synthetase 2 |
| AARS1 | Alanyl-tRNA synthetase 1 |
| EEF1A2 | Eukaryotic translation elongation factor-1, alpha-2 |
| PIGP | Phosphatidylinositol glycan, class P |
| PIGA | Phosphatidylinositol glycan, class A |
| Cytoskeletal proteins | |
| CYFIP2 | Cytoplasmic FMRP interacting protein 2 |
| PHACTR1 | Phosphatase and actin regulator 1 |
| SPTAN1 | Spectrin, alpha, nonerythrocytic-1 (alpha-fodrin) |
| Mitochondria proteins | |
| MFF | Mitochondrial fission factor |
| FARS2 | Phenylalanyl-tRNA synthetase 2, mitochondrial |
| RMND1 | Required for meiotic nuclear division 1 homolog |
| BRAT1 | BRCA1-associated ATM activator 1 |
| PMPCB | Peptidase, mitochondrial processing, beta |
| TWNK | Twinkle mtDNA helicase |
| DNM1L | Dynamin 1-like |
| POLG | Polymerase (DNA directed), gamma |
| GOT2 | Glutamic-oxaloacetic transaminase 2, mitochondrial |
| TIMM50 | Translocase of inner mitochondrial membrane 50 |
| Other/multiple-function proteins | |
| FBXO11 | F-box only protein 11 |
| MBD5 | Methyl-CpG-binding domain protein 5 |
| PTPN23 | Protein-tyrosine phosphatase, nonreceptor-type, 23 |
| DALRD3 | DALR anticodon-binding domain-containing protein 3 |
| SERPINI1 | Protease inhibitor 12 |
| FGF12 | Fibroblast growth factor-12 |
| CSNK2B | Casein kinase-2, beta polypeptide |
| CNPY3 | Canopy 3, zebrafish, homolog of |
| CDK19 | Cyclin-dependent kinase 19 |
| TRRAP | Transformation/transcription domain-associated protein |
| FRRS1L | Ferric-chelate reductase 1-like |
| COQ4 | Coenzyme Q4, S. cerevisiae, homolog of |
| ATN1 | Atrophin 1 |
| PACS2 | Phosphofurin acidic cluster sorting protein 2 |
| PIGB | Phosphatidylinositol glycan, class B |
| PIGQ | Phosphatidylinositol glycan anchor biosynthesis class Q protein |
| ROGDI | Rogdi atypical leucine zipper |
| WWOX | WW domain-containing oxidoreductase |
| PIGS | Phosphatidylinositol glycan, class S |
| TCF4 | Transcription factor-4 (immunoglobulin transcription factor-2) |
| PNKP | Polynucleotide kinase 3′ phosphatase |
| CDKL5 | Cyclin-dependent kinase-like 5 (serine/threonine protein kinase 9) |
| CASK | Calcium/calmodulin-dependent serine protein kinase |
| SMC1A | Segregation of mitotic chromosomes 1 (SMC1, yeast, homolog of; DXS423E; SB1.8) |
| FGF13 | Fibroblast growth factor-13 |
| ARHGEF9 | Rho guanine nucleotide exchange factor 9 |
| PCDH19 | Protocadherin 19 |
Genes gathered from OMIM (https://www.omim.org/) interrogated on October 27, 2021, with the keywords “epileptic encephalopathy” and “developmental and epileptic encephalopathy.” See SUPPLEMENTAL TABLE S1 for more details. DEE, developmental and epileptic encephalopathy.