EAST syndrome

Summary

EAST syndrome (MONDO:0013005) is a disease caused by KCNJ10 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: KCNJ10 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 392
• Phenotypes (HPO): 26

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		26	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0002197	Generalized-onset seizure	Very frequent (80-99%)
HP:0002900	Hypokalemia	Very frequent (80-99%)
HP:0002917	Hypomagnesemia	Very frequent (80-99%)
HP:0005567	Renal magnesium wasting	Very frequent (80-99%)
HP:0012591	Abnormal urinary electrolyte concentration	Very frequent (80-99%)
HP:0012606	Renal sodium wasting	Very frequent (80-99%)
HP:0030083	Salt craving	Very frequent (80-99%)
HP:0200114	Metabolic alkalosis	Very frequent (80-99%)
HP:0000127	Renal salt wasting	Very frequent (80-99%)
HP:0000407	Sensorineural hearing impairment	Very frequent (80-99%)
HP:0000848	Increased circulating renin level	Very frequent (80-99%)
HP:0000859	Hyperaldosteronism	Very frequent (80-99%)
HP:0000805	Enuresis	Frequent (30-79%)
HP:0001959	Polydipsia	Frequent (30-79%)
HP:0002345	Action tremor	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001344	Absent speech	Occasional (5-29%)
HP:0002540	Inability to walk	Occasional (5-29%)
HP:0003477	Peripheral axonal neuropathy	Occasional (5-29%)
HP:0007182	Peripheral hypomyelination	Occasional (5-29%)
HP:0007340	Lower limb muscle weakness	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	EAST syndrome
Mondo ID	MONDO:0013005
MeSH	C557674
OMIM	612780
Orphanet	199343
DOID	DOID:0060484
SNOMED CT	721207002
UMLS	C2748572
MedGen	411243
GARD	0010514
Is cancer (heuristic)	no

Also known as: EAST syndrome · seizures - sensorineural deafness - ataxia - intellectual disability - electrolyte imbalance · seizures, sensorineural deafness, ataxia, intellectual disability and electrolyte imbalance · seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance · seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance · seizures-sensorineural deafness-ataxia-intellectual disability-electrolyte imbalance syndrome · sesame syndrome · SESAMES

Data availability: 392 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › renal tubule disorder › inherited renal tubular disease › EAST syndrome

Related subtypes (27): cranioectodermal dysplasia, cystinuria, hereditary renal hypouricemia, nephrogenic diabetes insipidus-intracranial calcification syndrome, Gitelman syndrome, nephrogenic syndrome of inappropriate antidiuresis, oculocerebrorenal syndrome, RHYNS syndrome, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, autosomal recessive proximal renal tubular acidosis, familial juvenile hyperuricemic nephropathy type 2, hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome, Bartter syndrome, Dent disease, nephrogenic diabetes insipidus, autosomal dominant proximal renal tubular acidosis, Senior-Loken syndrome, familial primary hypomagnesemia, mitochondrial DNA depletion syndrome, hepatocerebrorenal form, Jeune syndrome, nephronophthisis, pseudohypoaldosteronism type 1, Senior-Boichis syndrome, pseudohypoparathyroidism, psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome, HELIX syndrome, inherited Fanconi renotubular syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

392 retrieved; paginated sample, class counts are floors:

219 uncertain significance, 84 likely benign, 46 conflicting classifications of pathogenicity, 16 pathogenic, 14 benign/likely benign, 8 likely pathogenic, 3 benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1382196	NM_002241.5(KCNJ10):c.305del (p.Pro102fs)	KCNJ10	Pathogenic	criteria provided, single submitter
2813485	NM_002241.5(KCNJ10):c.798dup (p.Asp267fs)	KCNJ10	Pathogenic	criteria provided, single submitter
2813570	NM_002241.5(KCNJ10):c.19_20insC (p.Val7fs)	KCNJ10	Pathogenic	criteria provided, single submitter
2817984	NM_002241.5(KCNJ10):c.211_212del (p.Phe71fs)	KCNJ10	Pathogenic	criteria provided, single submitter
2898358	NM_002241.5(KCNJ10):c.236G>A (p.Trp79Ter)	KCNJ10	Pathogenic	criteria provided, single submitter
30252	NM_002241.5(KCNJ10):c.225T>G (p.Phe75Leu)	KCNJ10	Pathogenic	no assertion criteria provided
30253	NM_002241.5(KCNJ10):c.775del (p.Val258_Val259insTer)	KCNJ10	Pathogenic	no assertion criteria provided
3654768	NM_002241.5(KCNJ10):c.331C>T (p.Gln111Ter)	KCNJ10	Pathogenic	criteria provided, single submitter
3660708	NM_002241.5(KCNJ10):c.198C>G (p.Tyr66Ter)	KCNJ10	Pathogenic	criteria provided, single submitter
3667559	NM_002241.5(KCNJ10):c.68del (p.Pro23fs)	KCNJ10	Pathogenic	criteria provided, single submitter
7462	NM_002241.5(KCNJ10):c.194G>C (p.Arg65Pro)	KCNJ10	Pathogenic	no assertion criteria provided
7463	NM_002241.5(KCNJ10):c.595C>T (p.Arg199Ter)	KCNJ10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7464	NM_002241.5(KCNJ10):c.418T>C (p.Cys140Arg)	KCNJ10	Pathogenic	no assertion criteria provided
7465	NM_002241.5(KCNJ10):c.491C>T (p.Thr164Ile)	KCNJ10	Pathogenic	no assertion criteria provided
7466	NM_002241.5(KCNJ10):c.500C>T (p.Ala167Val)	KCNJ10	Pathogenic	criteria provided, multiple submitters, no conflicts
7467	NM_002241.5(KCNJ10):c.889C>T (p.Arg297Cys)	KCNJ10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7468	NM_002241.5(KCNJ10):c.229G>C (p.Gly77Arg)	KCNJ10	Pathogenic	criteria provided, single submitter
841424	NM_002241.5(KCNJ10):c.321_322del (p.Val109fs)	KCNJ10	Pathogenic	criteria provided, single submitter
1299582	NM_002241.5(KCNJ10):c.400C>A (p.Arg134Ser)	KCNJ10	Likely pathogenic	criteria provided, single submitter
205825	NM_002241.5(KCNJ10):c.-1+1G>T	KCNJ10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2573206	NM_002241.5(KCNJ10):c.305dup (p.Ala103fs)	KCNJ10	Likely pathogenic	criteria provided, single submitter
30251	NM_002241.5(KCNJ10):c.193C>T (p.Arg65Cys)	KCNJ10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3061960	NM_002241.5(KCNJ10):c.170C>T (p.Thr57Ile)	KCNJ10	Likely pathogenic	criteria provided, single submitter
4747222	NM_002241.5(KCNJ10):c.890G>T (p.Arg297Leu)	KCNJ10	Likely pathogenic	criteria provided, single submitter
4845855	NM_002241.5(KCNJ10):c.579_585del (p.Lys193fs)	KCNJ10	Likely pathogenic	criteria provided, single submitter
7469	NM_002241.5(KCNJ10):c.581C>A (p.Pro194His)	KCNJ10	Likely pathogenic	criteria provided, single submitter
1035800	NM_002241.5(KCNJ10):c.769C>G (p.His257Asp)	KCNJ10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1152240	NM_002241.5(KCNJ10):c.117G>A (p.Val39=)	KCNJ10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129316	NM_002241.5(KCNJ10):c.53G>A (p.Arg18Gln)	KCNJ10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129318	NM_002241.5(KCNJ10):c.812G>A (p.Arg271His)	KCNJ10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
KCNJ10	Definitive	Autosomal recessive	EAST syndrome	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNJ10	Orphanet:199343	EAST syndrome
KCNJ10	Orphanet:705	Pendred syndrome
KCNJ10	Orphanet:98809	Paroxysmal kinesigenic dyskinesia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNJ10	HGNC:6256	ENSG00000177807	P78508	ATP-sensitive inward rectifier potassium channel 10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNJ10	ATP-sensitive inward rectifier potassium channel 10	May be responsible for potassium buffering action of glial cells in the brain.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNJ10	Ion channel	yes		K_chnl_inward-rec_Kir1.2, K_chnl_inward-rec_Kir_cyto, Ig_E-set

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	1
globus pallidus	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNJ10	185	tissue_specific	marker	C1 segment of cervical spinal cord, medial globus pallidus, globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNJ10	1,862

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNJ10	P78508	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Potassium transport channels	1	3806.7×	0.003	KCNJ10
G protein gated Potassium channels	1	1142.0×	0.004	KCNJ10
Inwardly rectifying K+ channels	1	713.8×	0.004	KCNJ10
Activation of GABAB receptors	1	601.0×	0.004	KCNJ10
GABA B receptor activation	1	543.8×	0.004	KCNJ10
Activation of G protein gated Potassium channels	1	393.8×	0.004	KCNJ10
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	1	393.8×	0.004	KCNJ10
GABA receptor activation	1	317.2×	0.005	KCNJ10
Potassium Channels	1	134.3×	0.010	KCNJ10
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.012	KCNJ10
Transmission across Chemical Synapses	1	76.1×	0.014	KCNJ10
Neuronal System	1	44.3×	0.023	KCNJ10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glutamate reuptake	1	8426.0×	0.002	KCNJ10
regulation of resting membrane potential	1	1296.3×	0.003	KCNJ10
cellular response to potassium ion	1	1053.2×	0.003	KCNJ10
central nervous system myelination	1	991.3×	0.003	KCNJ10
regulation of long-term neuronal synaptic plasticity	1	991.3×	0.003	KCNJ10
potassium ion homeostasis	1	766.0×	0.003	KCNJ10
regulation of monoatomic ion transmembrane transport	1	732.7×	0.003	KCNJ10
adult walking behavior	1	495.6×	0.003	KCNJ10
potassium ion import across plasma membrane	1	366.4×	0.004	KCNJ10
non-motile cilium assembly	1	290.6×	0.004	KCNJ10
potassium ion transport	1	191.5×	0.006	KCNJ10
potassium ion transmembrane transport	1	135.9×	0.008	KCNJ10
visual perception	1	79.5×	0.013	KCNJ10

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNJ10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KCNJ10	10	Binding:10

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	KCNJ10
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
KCNJ10	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.