- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_01
,
released March 12, 2026
This report describes EAST syndrome, a genetic disease characterized by the association of epilepsy, ataxia, sensorineural hearing impairment, and renal tubulopathy. The human gene implicated is KCNJ10, which encodes Kir4.1, a member of the inward rectifier-type potassium channel family. KCNJ10 is also associated with autosomal recessive deafness-4 with enlarged vestibular aqueduct (MIM:600791). There are three low-scoring fly ortholog, Dmel\Irk2, Dmel\Irk3, and Dmel\Irk1; only Dmel\Irk2 is highly expressed in the adult head. Human disease modeling has made use of Dmel\Irk2, for which multiple genetic reagents, including loss of function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Additionally, variants orthologous to those associated with disease in KCNJ10 have been constructed in Dmel\Irk2; see the 'Disease-Implicated Variants' table below.
Wild-type Hsap\KCNJ10 has been introduced into flies. Functional complementation of mutations in DmelIrk2 has been demonstration.
Flies bearing homozygous or heterozygous Dmel\Irk2 loss of function mutations exhibit paralysis after heat shock, with homozygotes having a longer recovery time than heterozygotes. Both homozygotes and heterozygotes exhibit alterations to neuronal excitability. Glial-specific expression of Hsap\KCNJ10 rescues both of these phenotypes. Flies bearing disease-implicated variants exhibit hyperexcitability phenotypes.
[updated Dec. 2024 by FlyBase; FBrf0222196]
[SEIZURES, SENSORINEURAL DEAFNESS, ATAXIA, IMPAIRED INTELLECTUAL DEVELOPMENT, AND ELECTROLYTE IMBALANCE; SESAMES](https://omim.org/entry/612780)
[POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 10; KCNJ10](https://omim.org/entry/602208)
EAST syndrome is rare genetic disease characterized by the association of epilepsy, ataxia, sensorineural hearing impairment, and renal tubulopathy. Patients present in infancy with generalized seizures, cerebellar dysfunction (including gait ataxia, intention tremor, and dysdiadochokinesis), and variable developmental delay and sensorineural hearing loss. Laboratory studies show persistent hypokalemic metabolic acidosis with hypomagnesemia. Additional reported neurologic features include brisk deep tendon reflexes, ankle clonus, extensor plantar responses, or nystagmus. [from Genetic and Rare Diseases (GARD) Information Center https://rarediseases.info.nih.gov/diseases/10514/index 2024.12.13]
SeSAME syndrome is characterized by seizures, sensorineural deafness, ataxia, intellectual deficit, and electrolyte imbalance (hypokalemia, metabolic alkalosis, and hypomagnesemia). [from National Organization for Rare Diseases (NORD) https://rarediseases.org/mondo-disease/east-syndrome/ 2024.12.16]
Seizures, sensorineural deafness, ataxia, impaired intellectual development, and electrolyte imbalance (SESAMES), is caused by homozygous or compound heterozygous mutation in the KCNJ10 gene on chromosome 1q23.. [from MIM:612780; 2024.12.13]
KCNJ10 encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]
The KCNJ10 gene encodes an inwardly rectifying potassium channel that is expressed in renal epithelial cells, inner ear cells, and glial cells in the central nervous system (Scholl et al., 2009, pubmed:19289823). [from MIM:602208; 2024.12.16]
High-scoring ortholog of human KCNJ5, KCNJ6, KCNJ9, and KCNJ12; moderate-scoring ortholog of KCNJ18, KCNJ2, KCNJ4, KCNJ3, KCNJ14; low-scoring ortholog of human KCNJ6, KCNJ1, KCNJ11, KCNJ15, KCNJ8, KCNJ10, KCNJ13 (many Drosophila to many human).
Low-scoring ortholog of human KCNJ10,KCNJ1, KCNJ11, KCNJ13, KCNJ15, KCNJ8, KCNJ12, KCNJ14, KCNJ16, KCNJ18, KCNJ2, KCNJ3, KCNJ4, KCNJ5, KCNJ6, KCNJ9 (many Drosophila to many human).
Moderate-scoring ortholog of human KCNJ5, KCNJ6, KCNJ9, KCNJ2, KCNJ12, KCNJ18; low-scoring ortholog of KCNJ4, KCNJ14, KCNJ3, 16, KCNJ1, KCNJ10, KCNJ11, KCNJ13, KCNJ15, KCNJ8 (many Drosophila to many human).