ANK2 pathway in epilepsy development (WP5557)

Homo sapiens

Open in new tab Open in Newt (SBGN)
Download PNG Download SVG Download JSON Download GPML Learn more about Downloads

This pathway describes the molecular pathway around the protein ANK2. Mutations in ANK2 can cause a severe genetic disorder with epilepsy.

For a description of pathway objects, see the WikiPathways Legend.

Authors

Sanauwbar Mohammad , Friederike Ehrhart , and Egon Willighagen

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Rare Diseases

Annotations

Pathway Ontology

disease pathway

Disease Ontology

epilepsy

Participants
Query Drugst.One

Label Type Compact URI Comment
SCN5A GeneProduct ensembl:ENSG00000183873
CSNK2A2 GeneProduct ensembl:ENSG00000070770
KCNQ2 GeneProduct ensembl:ENSG00000075043
SPTAN1 GeneProduct ensembl:ENSG00000197694 Pathogenic SPTAN1 (human gene encoding spectrin) variants cause early infantile epileptic encephalopathy type 5, an infantile epileptic encephalopathy with diffuse hypomyelination, brain atrophy and developmental retardation. Subsequent studies of these human variants, as well as studies using mice with conditional knockout of spectrin all show disruptions in AIS structure and neuronal excitability so, SPTAN1 maintains AIS integrity and supports Na-channel organization and neuronal excitability in normal states.
DNM1L GeneProduct ensembl:ENSG00000087470 DLP1
PRICKLE1 GeneProduct ensembl:ENSG00000139174
EIF2AK3 GeneProduct ensembl:ENSG00000172071 Also known as PERK
SPTBN4 GeneProduct ensembl:ENSG00000160460 SPTBN4 dysfunction causes disrupted KCNQ2 clustering, which normally regulates potassium currents and controls neuronal excitability. this therefore leads to epileptic dischanrges and seizures
ANK3 GeneProduct ensembl:ENSG00000151150
BRSK2 GeneProduct ensembl:ENSG00000174672 AKA SadB kinase
EIF2A GeneProduct ensembl:ENSG00000144895 p-eIF2alpha
BRSK1 GeneProduct ensembl:ENSG00000160469 AKA SadA kinase
ATF6 GeneProduct ensembl:ENSG00000118217
ANK2 GeneProduct ensembl:ENSG00000145362
CSNK2A1 GeneProduct ensembl:ENSG00000101266
L1CAM GeneProduct ensembl:ENSG00000198910
CSNK2B GeneProduct ensembl:ENSG00000204435
SNAP25 GeneProduct ensembl:ENSG00000132639
PRRT2 GeneProduct ensembl:ENSG00000167371
SCN2A GeneProduct ensembl:ENSG00000136531 if you have a LoF of scn2a-> dendritic excitability decreases due to impaired sodium influx. If yu have a GoF, dendritic excitability increases
DDIT3 Protein ensembl:ENSG00000175197 Also known as CHOP
ATF4 Protein ensembl:ENSG00000128272
SEMA3A Protein ensembl:ENSG00000075213
ANKB220 Protein uniprot:Q01484
MAPT Protein ensembl:ENSG00000186868 Tau
MAPT Protein ensembl:ENSG00000186868 MAPT (microtubule associated protein Tau)
ANKB440 Protein uniprot:Q01484 Giant ankyrin-B (gAnkB)

References

  1. Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Mohler PJ, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori SG, et al. Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17533–8. PubMed Europe PMC Scholia
  2. PRRT2: a major cause of infantile epilepsy and other paroxysmal disorders of childhood. Nobile C, Striano P. Prog Brain Res. 2014;213:141–58. PubMed Europe PMC Scholia
  3. Axon initial segments: structure, function, and disease. Huang CYM, Rasband MN. Ann N Y Acad Sci. 2018 May;1420(1):46–61. PubMed Europe PMC Scholia
  4. Giant ankyrin-B suppresses stochastic collateral axon branching through direct interaction with microtubules. Chen K, Yang R, Li Y, Zhou JC, Zhang M. J Cell Biol. 2020 Aug 3;219(8):e201910053. PubMed Europe PMC Scholia
  5. The roles of ER stress in epilepsy: Molecular mechanisms and therapeutic implications. Fu J, Tao T, Li Z, Chen Y, Li J, Peng L. Biomed Pharmacother. 2020 Nov;131:110658. PubMed Europe PMC Scholia
  6. Novel bi-allelic variants expand the SPTBN4-related genetic and phenotypic spectrum. Buelow M, Süßmuth D, Smith LD, Aryani O, Castiglioni C, Stenzel W, et al. Eur J Hum Genet. 2021 Jul;29(7):1121–8. PubMed Europe PMC Scholia
  7. The balance of mitochondrial fission and fusion in cortical axons depends on the kinases SadA and SadB. Di Meo D, Ravindran P, Sadhanasatish T, Dhumale P, Püschel AW. Cell Rep. 2021 Dec 21;37(12):110141. PubMed Europe PMC Scholia
  8. Epilepsy gene prickle ensures neuropil glial ensheathment through regulating cell adhesion molecules. Chen Y, Liu TT, Niu M, Li X, Wang X, Liu T, et al. iScience. 2022 Dec 5;26(1):105731. PubMed Europe PMC Scholia
  9. ANK2 loss-of-function variants are associated with epilepsy, and lead to impaired axon initial segment plasticity and hyperactive network activity in hiPSC-derived neuronal networks. Teunissen MWA, Lewerissa E, van Hugte EJH, Wang S, Ockeloen CW, Koolen DA, et al. Hum Mol Genet. 2023 Jul 4;32(14):2373–85. PubMed Europe PMC Scholia
  10. Early developmental deletion of forebrain Ank2 causes seizure-related phenotypes by reshaping the synaptic proteome. Yoon S, Santos MD, Forrest MP, Pratt CP, Khalatyan N, Mohler PJ, et al. Cell Rep. 2023 Jul 25;42(7):112784. PubMed Europe PMC Scholia
  11. Epilepsy-associated SCN2A (NaV1.2) variants exhibit diverse and complex functional properties. Thompson CH, Potet F, Abramova TV, DeKeyser JM, Ghabra NF, Vanoye CG, et al. J Gen Physiol. 2023 Oct 2;155(10):e202313375. PubMed Europe PMC Scholia
  12. Unraveling the nexus of age, epilepsy, and mitochondria: exploring the dynamics of cellular energy and excitability. Xie W, Koppula S, Kale MB, Ali LS, Wankhede NL, Umare MD, et al. Front Pharmacol. 2024 Sep 5;15:1469053. PubMed Europe PMC Scholia
  13. Roles of ANK2/ankyrin-B in neurodevelopmental disorders: Isoform functions and implications for autism spectrum disorder and epilepsy. Yoon S, Penzes P. Curr Opin Neurobiol. 2025 Feb;90:102938. PubMed Europe PMC Scholia