KCNJ10

Summary

KCNJ10 (potassium inwardly rectifying channel subfamily J member 10, HGNC:6256) is a protein-coding gene on chromosome 1q23.2, encoding ATP-sensitive inward rectifier potassium channel 10 (P78508). May be responsible for potassium buffering action of glial cells in the brain.

This gene 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.

Source: NCBI Gene 3766 — RefSeq curated summary.

At a glance

• Gene–disease (curated): EAST syndrome (Definitive, ClinGen) — +3 more curated relationships
• Clinical variants (ClinVar): 453 total — 18 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 68
• Druggable target: yes
• MANE Select transcript: NM_002241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6256
Approved symbol	KCNJ10
Name	potassium inwardly rectifying channel subfamily J member 10
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	Kir4.1, Kir1.2
Ensembl gene	ENSG00000177807
Ensembl biotype	protein_coding
OMIM	602208
Entrez	3766

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000509700, ENST00000636689, ENST00000637644, ENST00000638728, ENST00000638840, ENST00000638868, ENST00000639408, ENST00000640017, ENST00000640914, ENST00000644903, ENST00000869143

RefSeq mRNA: 1 — MANE Select: NM_002241 NM_002241

CCDS: CCDS1193

Canonical transcript exons

ENST00000644903 — 2 exons

Exon	Start	End
ENSE00001446297	160037467	160042532
ENSE00003829729	160070022	160070160

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 98.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.1906 / max 365.8507, expressed in 144 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15463	1.6336	105
15462	1.3951	101
15465	1.2707	126
15461	0.6695	92
15464	0.1075	59
15460	0.0585	34
15459	0.0557	14

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	98.74	gold quality
medial globus pallidus	UBERON:0002477	98.47	gold quality
globus pallidus	UBERON:0001875	98.26	gold quality
inferior vagus X ganglion	UBERON:0005363	98.14	gold quality
lateral globus pallidus	UBERON:0002476	97.65	gold quality
spinal cord	UBERON:0002240	97.60	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.47	gold quality
subthalamic nucleus	UBERON:0001906	97.20	gold quality
nucleus accumbens	UBERON:0001882	96.93	gold quality
endothelial cell	CL:0000115	96.80	gold quality
caudate nucleus	UBERON:0001873	96.72	gold quality
substantia nigra pars compacta	UBERON:0001965	96.69	gold quality
ventricular zone	UBERON:0003053	96.69	gold quality
amygdala	UBERON:0001876	96.44	gold quality
right frontal lobe	UBERON:0002810	96.13	gold quality
putamen	UBERON:0001874	96.08	gold quality
ventral tegmental area	UBERON:0002691	95.96	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.70	gold quality
superior vestibular nucleus	UBERON:0007227	95.02	gold quality
corpus callosum	UBERON:0002336	94.28	gold quality
Ammon’s horn	UBERON:0001954	94.17	gold quality
temporal lobe	UBERON:0001871	93.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.36	gold quality
midbrain	UBERON:0001891	93.22	gold quality
substantia nigra	UBERON:0002038	92.92	gold quality
hypothalamus	UBERON:0001898	92.73	gold quality
telencephalon	UBERON:0001893	92.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.39	gold quality
prefrontal cortex	UBERON:0000451	92.32	gold quality
cingulate cortex	UBERON:0003027	92.29	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	24.62
E-ANND-3	yes	4.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

194 targeting KCNJ10, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-329-3P	99.91	66.56	1234

Literature-anchored findings (GeneRIF, showing 40)

• molecular analysis on chromosome 1q as a candidate gene for Type 2 diabetes in Pima Indians (PMID:12401729)
• Arg271Cys missense variation in KCNJ10 (or a nearby variation) is related to general seizure susceptibility in humans. (PMID:15120748)
• Our results support previous evidence that the common KCNJ10 Arg271Cys missense variation influences seizure susceptibility of common IGE syndromes. (PMID:15725393)
• Calcium-sensing receptor interacts directly with Kir4.1 and Kir4.2 and can decrease their currents. (PMID:17122384)
• The results showed that the expression of Kir 4.1 mRNA and protein, as well as the Kir 4.1 immunoreactivity score (IRS), increased markedly with increasing pathologic grade. (PMID:18191638)
• identifY previously unidentified KCNJ10 missense or nonsense mutations on both alleles in all subjects affected by a unique human syndrome, and establish the essential role of basolateral K(+) channels in renal electrolyte homeostasis. (PMID:19289823)
• Mutations in KCNJ10 cause a specific disorder. Our findings indicate that KCNJ10 plays a major role in renal salt handling and possibly also in blood-pressure maintenance and its regulation. (PMID:19420365)
• mutations in the inwardly rectifying K(+) channel gene KCNJ10 are associated with nonsyndromic hearing loss in carriers of SLC26A4 mutations with an EVA/PS phenotype. (PMID:19426954)
• Variations in the AQP4 and the KCNJ10/KCNJ9 region are likely to be associated with temporal lobe epilepsy. (PMID:19864112)
• SLC26A4, FOXI1 and KCNJ10 are not major determinants in unilateral deafness and enlarged vestibular aqueduct (PMID:20621367)
• When expressed in CHO and HEK293 cells, the KCNJ10 mutations R65P, G77R, and R175Q caused a marked impairment of channel function (PMID:20651251)
• This study suggests that the SNPs within the kcnj10 genes we examined do not play a major role in schizophrenia in the Han Chinese population. (PMID:20933057)
• CaR decreases cell surface expression of Kir4.1 channels via a mechanism that involves Galpha(q) and caveolin. (PMID:21084311)
• Perturbed pH gating may underlie the loss of channel function for the disease-associated mutant Kir4.1 channels and may have important physiologic consequences. [review] (PMID:21088294)
• The Kir4.1 channel transgene plays a role in setting the membrane potential of glial cells and in maintaining potassium permeability in glial-conditioned Kir4.1 knock-out mice. (PMID:21106816)
• Mutations in the K+ channel gene KCNJ10 (Kir4.1) cause the autosomal recessive EAST syndrome which is characterized by epilepsy, ataxia, sensorineural deafness, and a salt-wasting tubulopathy. (PMID:21221631)
• Role of KCNJ10 function in the physiology of proximal and possibly also the distal retina. Impact of KCNJ10 mutations on the electroretinogram in four unrelated patients with EAST syndrome. (PMID:21300747)
• Gain-of-function defects in Kir4.1 causes dysfunction in astrocytic-dependent potassium buffering and contributes to autism/epilepsy phenotype by altering neuronal excitability and synaptic function. (PMID:21458570)
• extracellular volume recordings indicate that compromised K(+) spatial buffering in brain underlies the epilepsy phenotype associated with human KCNJ10 mutations (PMID:21748805)
• Study confirms that EAST syndrome can be caused by many different mutations in KCNJ10 that significantly reduce K+ conductance. (PMID:21849804)
• Downregulation of Kir4.1 channels aggravates the visual impairment caused by the initial photoreceptor degeneration. (PMID:22055109)
• No KCNJ10 mutations were present in bilateral deafness patients with inner ear malformation. (PMID:22412181)
• The subcellular co-localisation of K(ir)4.1 and AQP4 in the supporting cells of the cochlea described in this study resembles that of the astroglia of the central nervous system and the glial Mueller cells in the retina. (PMID:22802001)
• This study demonistrated that Loss of perivascular Kir4.1 potassium channels in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy. (PMID:22878665)
• The results of this study indicated that alterations in expression of Kir4.1 occurring in epilepsy-associated lesions are possibly influenced by the local inflammatory environment and in particular by the inflammatory cytokine IL-1beta. (PMID:23270518)
• Oligodendrocyte precursor cells establish themselves progressively through postnatal upregulation of Kir4.1 potassium channels. (PMID:23392672)
• the modulation of tyrosine phosphorylation of KCNJ10 should play a role in regulating membrane transport function in DCT1. (PMID:23873931)
• We found no evidence for a significant association between mutations of KCNJ10 and FOXI1 with SLC26A4 in Pendred syndrome/enlarged vestibular aqueducts. (PMID:23965030)
• Ordered disorder of the astrocytic dystrophin-associated protein complex in the norm and pathology. (PMID:24014171)
• study provides an explanation for the pathophysiology of the p.A167V KCNJ10 mutation, which had not been considered pathogenic on its own; findings provide evidence for functional cooperation of KCNJ10 and KCNJ16; in vitro ascertainment of KCNJ10 function may necessitate co-expression with KCNJ16 (PMID:24193250)
• KCNJ10rs1130183 did not contribute to risk of seizure susceptibility. (PMID:24378235)
• Serum antibodies to KIR4.1 are found in the majority of children with acquired demylinating disease but not in children with other diseases or in healthy controls. (PMID:24415573)
• Mislocalization of the Kir4.1 channels contributes to renal salt wasting. (PMID:24561201)
• we confirmed the presence of anti-Kir4.1 antibodies in multiple sclerosis patients, but at a much lower prevalence than previously reported. (PMID:24756568)
• This study observed a decrease of astroglial KIR4.1 but not glial fibrillary acidic protein IR. In chronic inactive and remyelinating MS lesions, KIR4.1 IR was restored on astrocytes and found in a subset of presumably new myelinating oligodendrocytes. (PMID:24777949)
• No KIR4.1-specific antigen is detected in serum or cerebrospinal fluid of multiple sclerosis (MS) patients; the target antigen of MS remains elusive. (PMID:25008548)
• This study showed that rs2486253, but not rs61822012, polymorphism of KCNJ10 gene was associated with childhood idiopathic generalized epilepsy. (PMID:25008907)
• KCNJ10 SNP is not associated with nonsyndromic enlargement of vestibular aqueduct in Chinese patients. (PMID:25372295)
• anti-KIR4.1 antibody levels differed in multiple sclerosis patients during relapse and remission; as such, they may represent a marker of disease exacerbation (PMID:25392324)
• disruption of cav-1 decreases basolateral K(+) channel activity and depolarizes the cell membrane potential in the DCT1 at least in part by suppressing the stimulatory effect of c-Src on Kcnj10 (PMID:25848073)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnj10a	ENSDARG00000090815
danio_rerio	kcnj10b	ENSDARG00000105022
mus_musculus	Kcnj10	ENSMUSG00000044708
rattus_norvegicus	Kcnj10	ENSRNOG00000068444
drosophila_melanogaster	Irk3	FBGN0032706
drosophila_melanogaster	Irk2	FBGN0039081
drosophila_melanogaster	Irk1	FBGN0265042
caenorhabditis_elegans		WBGENE00002149
caenorhabditis_elegans		WBGENE00002150
caenorhabditis_elegans		WBGENE00002151

Paralogs (15): KCNJ13 (ENSG00000115474), KCNJ5 (ENSG00000120457), KCNJ8 (ENSG00000121361), KCNJ2 (ENSG00000123700), KCNJ1 (ENSG00000151704), KCNJ16 (ENSG00000153822), KCNJ6 (ENSG00000157542), KCNJ15 (ENSG00000157551), KCNJ9 (ENSG00000162728), KCNJ3 (ENSG00000162989), KCNJ4 (ENSG00000168135), KCNJ14 (ENSG00000182324), KCNJ12 (ENSG00000184185), KCNJ11 (ENSG00000187486), KCNJ18 (ENSG00000260458)

Protein

Protein identifiers

ATP-sensitive inward rectifier potassium channel 10 — P78508 (reviewed: P78508)

Alternative names: ATP-dependent inwardly rectifying potassium channel Kir4.1, Inward rectifier K(+) channel Kir1.2, Potassium channel, inwardly rectifying subfamily J member 10

All UniProt accessions (7): A0A1B0GUX2, A0A1W2PP51, A0A1W2PP61, A0A1W2PPI0, A0A1W2PQC0, A0A1W2PQP0, P78508

UniProt curated annotations — full annotation on UniProt →

Function. May be responsible for potassium buffering action of glial cells in the brain. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium. In the kidney, together with KCNJ16, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules.

Subunit / interactions. Homotetramer. In kidney cells, it forms heteromeric channels with Kir5.1/KCNJ16; this interaction is required for KCNJ16 localization to the basolateral membrane. Interacts with MAGI1, alone and possibly as a heteromer with KCNJ16; this interaction may facilitate KCNJ10/KCNJ16 potassium channel expression at the basolateral membrane in kidney cells. Interacts with PATJ.

Subcellular location. Membrane. Basolateral cell membrane.

Tissue specificity. Expressed in kidney (at protein level). In the nephron, expressed in the distal convoluted tubule, the connecting tubule, the collecting duct and cortical thick ascending limbs.

Disease relevance. Seizures, sensorineural deafness, ataxia, impaired intellectual development, and electrolyte imbalance (SESAMES) [MIM:612780] A complex disorder characterized by generalized seizures with onset in infancy, delayed psychomotor development, ataxia, sensorineural hearing loss, hypokalemia, metabolic alkalosis, and hypomagnesemia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Channel activity is strongly regulated by variations of cytosolic pH; channels are activated by alkaline and inhibited by acidic pH values. Inhibited by Ba(2+) and Cs(+). Activated by phosphatidylinositol 4,5 biphosphate (PtdIns(4,5)P2).

Similarity. Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ10 subfamily.

RefSeq proteins (1): NP_002232* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003269	K_chnl_inward-rec_Kir1.2	Family
IPR013518	K_chnl_inward-rec_Kir_cyto	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR016449	K_chnl_inward-rec_Kir	Family
IPR040445	Kir_TM	Domain
IPR041647	IRK_C	Domain

Pfam: PF01007, PF17655

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (33 total): sequence variant 14, binding site 5, topological domain 4, sequence conflict 3, transmembrane region 2, chain 1, site 1, disulfide bond 1, intramembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9MAE	ELECTRON MICROSCOPY	3.13
9MA5	ELECTRON MICROSCOPY	3.18
9MAI	ELECTRON MICROSCOPY	3.35
9MAG	ELECTRON MICROSCOPY	3.37

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78508-F1	82.66	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 158 (role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium)

Ligand- & substrate-binding residues (5): 168; 171; 173; 210–217; 36

Disulfide bonds (1): 108–140

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1296041	Activation of G protein gated Potassium channels
R-HSA-1296067	Potassium transport channels
R-HSA-997272	Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1296059	G protein gated Potassium channels
R-HSA-1296065	Inwardly rectifying K+ channels
R-HSA-1296071	Potassium Channels
R-HSA-977443	GABA receptor activation
R-HSA-977444	GABA B receptor activation
R-HSA-991365	Activation of GABAB receptors

MSigDB gene sets: 351 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_NEUROTRANSMITTER_UPTAKE, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, GOBP_ADULT_BEHAVIOR, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_RESPONSE_TO_POTASSIUM_ION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_POTASSIUM_ION_HOMEOSTASIS, GOBP_NEUROGENESIS, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT

GO Biological Process (20): potassium ion transport (GO:0006813), visual perception (GO:0007601), adult walking behavior (GO:0007628), central nervous system myelination (GO:0022010), regulation of monoatomic ion transmembrane transport (GO:0034765), cellular response to potassium ion (GO:0035865), regulation of long-term neuronal synaptic plasticity (GO:0048169), glutamate reuptake (GO:0051935), potassium ion homeostasis (GO:0055075), regulation of resting membrane potential (GO:0060075), potassium ion transmembrane transport (GO:0071805), non-motile cilium assembly (GO:1905515), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), oligodendrocyte development (GO:0014003), metal ion transport (GO:0030001), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), establishment of localization in cell (GO:0051649), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (6): inward rectifier potassium channel activity (GO:0005242), ATP binding (GO:0005524), ATP-activated inward rectifier potassium channel activity (GO:0015272), nucleotide binding (GO:0000166), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (8): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), monoatomic ion channel complex (GO:0034702), cell body (GO:0044297), astrocyte projection (GO:0097449), ciliary base (GO:0097546), presynapse (GO:0098793), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Inwardly rectifying K+ channels	2
Neuronal System	2
G protein gated Potassium channels	1
Activation of GABAB receptors	1
Transmission across Chemical Synapses	1
Potassium Channels	1
Neurotransmitter receptors and postsynaptic signal transmission	1
GABA receptor activation	1
GABA B receptor activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
monoatomic ion transmembrane transport	3
monoatomic cation transport	2
metal ion transport	1
sensory perception of light stimulus	1
adult locomotory behavior	1
walking behavior	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
myelination	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
response to potassium ion	1
cellular response to metal ion	1
regulation of neuronal synaptic plasticity	1
amino acid neurotransmitter reuptake	1
L-glutamate import across plasma membrane	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
regulation of membrane potential	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
cilium assembly	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
transport	1
glial cell development	1
oligodendrocyte differentiation	1
monoatomic ion transport	1
transmembrane transport	1
regulation of biological quality	1
establishment of localization	1
cellular localization	1
voltage-gated potassium channel activity	1
ligand-gated monoatomic cation channel activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
inward rectifier potassium channel activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

1800 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNJ10	KCNJ16	Q9NPI9	983
KCNJ10	SLC26A4	O43511	927
KCNJ10	DMD	P11532	907
KCNJ10	CAV1	Q03135	869
KCNJ10	FOXI1	Q12951	847
KCNJ10	DAG1	Q14118	744
KCNJ10	GJB2	P29033	738
KCNJ10	SLC1A2	P43004	713
KCNJ10	HEPACAM	Q14CZ8	706
KCNJ10	GJA1	P17302	672
KCNJ10	LRRC8A	Q8IWT6	670
KCNJ10	DLG1	Q12959	667
KCNJ10	SLC1A3	P43003	664
KCNJ10	KCNQ1	P51787	650
KCNJ10	TRPV4	Q9HBA0	649

IntAct

17 interactions, top by confidence:

A	B	Type	Score
SIAH1	KCNJ10	psi-mi:“MI:0915”(physical association)	0.560
KCNJ10	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
KCNJ16	KCNJ10	psi-mi:“MI:0403”(colocalization)	0.460
KCNJ10	KCNJ16	psi-mi:“MI:0915”(physical association)	0.460
MAGI1	KCNJ10	psi-mi:“MI:0915”(physical association)	0.400
Magi1	KCNJ10	psi-mi:“MI:0915”(physical association)	0.400
TRPV2	KCNJ10	psi-mi:“MI:0915”(physical association)	0.370
	ATP1B1	psi-mi:“MI:0914”(association)	0.350
KCNJ10	HSPA8	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
GPATCH2	LRP5	psi-mi:“MI:0914”(association)	0.350
KCNJ10	COPA	psi-mi:“MI:0914”(association)	0.350
KCNJ10	KCNJ12	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): SIAH1 (Two-hybrid), HSPA8 (Affinity Capture-MS), COPB2 (Affinity Capture-MS), SEC24B (Affinity Capture-MS), COPG1 (Affinity Capture-MS), SEC23B (Affinity Capture-MS), TTC1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), TMED8 (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS), SEC24A (Affinity Capture-MS), BAG1 (Affinity Capture-MS), ADO (Affinity Capture-MS), TMED8 (Affinity Capture-MS), COPG1 (Affinity Capture-MS)

ESM2 similar proteins: B7U540, E1BNE9, F1MYR9, F1NHE9, O02670, O18839, O19182, O70339, O88335, O88932, P35560, P35561, P48048, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49655, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P63250, P63251, P63252, P63253, P70673, P78508, Q14500, Q4TZY1

Diamond homologs: B7U540, E1BN00, E1BNE9, F1MYR9, F1NHE9, O02670, O02822, O18839, O19182, O60928, O70339, O70596, O70617, O88335, O88932, P35560, P35561, P48048, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49655, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P52192, P63250, P63251

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
KCNJ10	“up-regulates quantity”	potassium(1+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

453 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	11
Uncertain significance	253
Likely benign	94
Benign	15

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1382196	NM_002241.5(KCNJ10):c.305del (p.Pro102fs)	Pathogenic
2664662	NM_002241.5(KCNJ10):c.376C>T (p.Gln126Ter)	Pathogenic
2813485	NM_002241.5(KCNJ10):c.798dup (p.Asp267fs)	Pathogenic
2813570	NM_002241.5(KCNJ10):c.19_20insC (p.Val7fs)	Pathogenic
2817984	NM_002241.5(KCNJ10):c.211_212del (p.Phe71fs)	Pathogenic
2898358	NM_002241.5(KCNJ10):c.236G>A (p.Trp79Ter)	Pathogenic
30252	NM_002241.5(KCNJ10):c.225T>G (p.Phe75Leu)	Pathogenic
30253	NM_002241.5(KCNJ10):c.775del (p.Val258_Val259insTer)	Pathogenic
3654768	NM_002241.5(KCNJ10):c.331C>T (p.Gln111Ter)	Pathogenic
3660708	NM_002241.5(KCNJ10):c.198C>G (p.Tyr66Ter)	Pathogenic
3667559	NM_002241.5(KCNJ10):c.68del (p.Pro23fs)	Pathogenic
692217	NM_002241.5(KCNJ10):c.601G>A (p.Ala201Thr)	Pathogenic
7462	NM_002241.5(KCNJ10):c.194G>C (p.Arg65Pro)	Pathogenic
7464	NM_002241.5(KCNJ10):c.418T>C (p.Cys140Arg)	Pathogenic
7465	NM_002241.5(KCNJ10):c.491C>T (p.Thr164Ile)	Pathogenic
7466	NM_002241.5(KCNJ10):c.500C>T (p.Ala167Val)	Pathogenic
7468	NM_002241.5(KCNJ10):c.229G>C (p.Gly77Arg)	Pathogenic
841424	NM_002241.5(KCNJ10):c.321_322del (p.Val109fs)	Pathogenic
1299582	NM_002241.5(KCNJ10):c.400C>A (p.Arg134Ser)	Likely pathogenic
1879103	NM_002241.5(KCNJ10):c.487G>T (p.Gly163Cys)	Likely pathogenic
205825	NM_002241.5(KCNJ10):c.-1+1G>T	Likely pathogenic
2573206	NM_002241.5(KCNJ10):c.305dup (p.Ala103fs)	Likely pathogenic
30251	NM_002241.5(KCNJ10):c.193C>T (p.Arg65Cys)	Likely pathogenic
3061960	NM_002241.5(KCNJ10):c.170C>T (p.Thr57Ile)	Likely pathogenic
4747222	NM_002241.5(KCNJ10):c.890G>T (p.Arg297Leu)	Likely pathogenic
4845855	NM_002241.5(KCNJ10):c.579_585del (p.Lys193fs)	Likely pathogenic
692216	NM_002241.5(KCNJ10):c.626T>C (p.Ile209Thr)	Likely pathogenic
694648	NM_002241.5(KCNJ10):c.755C>G (p.Pro252Arg)	Likely pathogenic
7469	NM_002241.5(KCNJ10):c.581C>A (p.Pro194His)	Likely pathogenic

SpliceAI

674 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160031455:T:A	donor_gain	1.0000
1:160042532:TC:T	acceptor_loss	0.9900
1:160042533:C:A	acceptor_loss	0.9900
1:160042533:C:CC	acceptor_gain	0.9900
1:160042534:T:A	acceptor_loss	0.9900
1:160070016:TCTTA:T	donor_loss	0.9900
1:160070017:CTTAC:C	donor_loss	0.9900
1:160070018:TTACC:T	donor_loss	0.9900
1:160070019:TA:T	donor_loss	0.9900
1:160042529:TCAT:T	acceptor_gain	0.9800
1:160042530:CAT:C	acceptor_gain	0.9800
1:160042530:CATC:C	acceptor_gain	0.9800
1:160042531:AT:A	acceptor_gain	0.9800
1:160070020:A:AC	donor_gain	0.9800
1:160070021:C:CC	donor_gain	0.9800
1:160042528:GTCAT:G	acceptor_gain	0.9600
1:160045836:A:AC	donor_gain	0.9500
1:160041859:T:TA	donor_gain	0.9400
1:160070020:AC:A	donor_gain	0.9400
1:160070021:CC:C	donor_gain	0.9400
1:160042543:C:CT	acceptor_gain	0.9300
1:160031437:G:C	donor_gain	0.9200
1:160031098:ACAAG:A	donor_gain	0.9100
1:160031099:CAAGC:C	donor_gain	0.9100
1:160041446:C:CA	donor_gain	0.8800
1:160042544:A:T	acceptor_gain	0.8800
1:160046860:T:A	donor_gain	0.8800
1:160041567:T:C	donor_gain	0.8700
1:160041829:TTG:T	donor_gain	0.8700
1:160041830:TG:T	donor_gain	0.8600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000100515 (1:160039361 TAGGA>T), RS1000257039 (1:160037784 G>C), RS1000334703 (1:160068060 A>G), RS1000356337 (1:160058212 G>A,C), RS1000403551 (1:160046131 T>C), RS1000595958 (1:160039392 A>G), RS1000625095 (1:160044717 C>T), RS1000756625 (1:160051472 T>C), RS1001027292 (1:160057988 T>C), RS1001043907 (1:160063720 T>A,C), RS1001074859 (1:160069304 G>C), RS1001126870 (1:160063817 C>T), RS1001387846 (1:160058157 C>T), RS1001418409 (1:160054881 C>T), RS1001512424 (1:160061124 A>C,G)

Disease associations

OMIM: gene MIM:602208 | disease phenotypes: MIM:612780, MIM:600791, MIM:274600, MIM:209850, MIM:220290, MIM:607197, MIM:128200, MIM:141500

GenCC curated gene-disease

Disease	Classification	Inheritance
EAST syndrome	Definitive	Autosomal recessive
paroxysmal dyskinesia	Strong	Autosomal dominant
Pendred syndrome	Supportive	Autosomal recessive
enlarged vestibular aqueduct syndrome	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
enlarged vestibular aqueduct syndrome	Disputed	AD
EAST syndrome	Definitive	AR

Mondo (16): EAST syndrome (MONDO:0013005), autosomal recessive nonsyndromic hearing loss 4 (MONDO:0010933), Pendred syndrome (MONDO:0010134), intellectual disability (MONDO:0001071), autism (MONDO:0005260), myoepithelial tumor (MONDO:0002380), hearing loss, autosomal recessive (MONDO:0019588), episodic kinesigenic dyskinesia (MONDO:0044202), familial hemiplegic migraine (MONDO:0000700), congenital nervous system disorder (MONDO:0002320), cerebellar ataxia (MONDO:0000437), microcephaly (MONDO:0001149), renal tubule disorder (MONDO:0021568), peripheral neuropathy (MONDO:0005244), enlarged vestibular aqueduct syndrome (MONDO:0023069)

Orphanet (8): EAST syndrome (Orphanet:199343), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Pendred syndrome (Orphanet:705), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Paroxysmal kinesigenic dyskinesia (Orphanet:98809), Rare ataxia (Orphanet:102002), Rare renal tubular disease (Orphanet:93603), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000103	Polyuria
HP:0000112	Nephropathy
HP:0000127	Renal salt wasting
HP:0000128	Renal potassium wasting
HP:0000359	Abnormality of the inner ear
HP:0000376	Incomplete partition of the cochlea type II
HP:0000407	Sensorineural hearing impairment
HP:0000750	Delayed speech and language development
HP:0000805	Enuresis
HP:0000821	Hypothyroidism
HP:0000822	Hypertension
HP:0000843	Hyperparathyroidism
HP:0000848	Increased circulating renin concentration
HP:0000853	Goiter
HP:0000859	Increased circulating aldosterone concentration
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001751	Abnormal vestibular function
HP:0001959	Polydipsia
HP:0001960	Hypokalemic metabolic alkalosis
HP:0002072	Chorea

GWAS associations

0 associations (top):

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009208	Myoepithelioma	C04.557.435.585
C564609	Deafness, Autosomal Recessive (supp.)
C566366	Deafness, Autosomal Recessive 4 (supp.)
C536648	Pendred syndrome (supp.)
C557674	SeSAME syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2146348 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Inwardly rectifying potassium channels (K_IR)

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
H+	Antagonist	6.1	pEC50
VU0134992	Antagonist	6.01	pIC50
nortriptyline	Antagonist	4.8	pKd

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	4
Valproic Acid	affects expression, increases expression	3
Tetrachlorodibenzodioxin	decreases expression	2
lly-283	increases expression	1
dicrotophos	increases expression	1
perfluorooctanoic acid	increases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluorohexanesulfonic acid	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Dronabinol	increases expression	1
Urethane	decreases expression	1
Sodium Selenite	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2148631	Binding	Inhibition of Kir4.1 expressed in HEK293 cells assessed as inhibition of thallium efflux up to 100 uM by fluorescence assay	Discovery of Selective Small Molecule ROMK Inhibitors as Potential New Mechanism Diuretics. — ACS Med Chem Lett

Clinical trials (associated diseases)

303 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder