KCNA2

Summary

KCNA2 (potassium voltage-gated channel subfamily A member 2, HGNC:6220) is a protein-coding gene on chromosome 1p13.3, encoding Potassium voltage-gated channel subfamily A member 2 (P16389). Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system.

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1.

Source: NCBI Gene 3737 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 578 total — 26 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 57
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004974

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6220
Approved symbol	KCNA2
Name	potassium voltage-gated channel subfamily A member 2
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Kv1.2, HK4
Ensembl gene	ENSG00000177301
Ensembl biotype	protein_coding
OMIM	176262
Entrez	3737

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000316361, ENST00000369770, ENST00000485317, ENST00000525120, ENST00000633222, ENST00000638477, ENST00000638532, ENST00000638616, ENST00000639048, ENST00000639227, ENST00000639233, ENST00000640450, ENST00000640680, ENST00000640774, ENST00000640956, ENST00000674674, ENST00000675391, ENST00000851652, ENST00000851653, ENST00000851654, ENST00000851655

RefSeq mRNA: 2 — MANE Select: NM_004974 NM_001204269, NM_004974

CCDS: CCDS55625, CCDS827

Canonical transcript exons

ENST00000316361 — 3 exons

Exon	Start	End
ENSE00001303222	110605391	110605722
ENSE00002164055	110606228	110606358
ENSE00003776617	110593580	110604945

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 96.83.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8971 / max 138.0457, expressed in 199 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13765	1.2635	115
13760	0.5376	123
13761	0.2480	101
13767	0.2039	74
13762	0.1630	73
13763	0.1340	74
13768	0.1033	50
13766	0.0718	45
13758	0.0675	39
13764	0.0286	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	96.83	gold quality
middle temporal gyrus	UBERON:0002771	96.58	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.64	gold quality
postcentral gyrus	UBERON:0002581	95.47	gold quality
primary visual cortex	UBERON:0002436	95.40	gold quality
cerebellar vermis	UBERON:0004720	95.29	gold quality
parietal lobe	UBERON:0001872	95.01	gold quality
superior frontal gyrus	UBERON:0002661	94.90	gold quality
occipital lobe	UBERON:0002021	94.58	gold quality
pons	UBERON:0000988	94.30	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.55	gold quality
endothelial cell	CL:0000115	91.76	gold quality
trigeminal ganglion	UBERON:0001675	91.00	gold quality
entorhinal cortex	UBERON:0002728	90.80	gold quality
dorsal root ganglion	UBERON:0000044	90.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.15	gold quality
right frontal lobe	UBERON:0002810	89.07	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.95	gold quality
frontal cortex	UBERON:0001870	88.94	gold quality
lateral globus pallidus	UBERON:0002476	88.92	gold quality
superior vestibular nucleus	UBERON:0007227	88.80	gold quality
cerebellum	UBERON:0002037	88.71	gold quality
cerebellar cortex	UBERON:0002129	88.67	gold quality
cerebellar hemisphere	UBERON:0002245	88.55	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.08	gold quality
neocortex	UBERON:0001950	87.64	gold quality
prefrontal cortex	UBERON:0000451	87.53	gold quality
cerebral cortex	UBERON:0000956	87.01	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.68	gold quality
substantia nigra pars compacta	UBERON:0001965	86.44	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting KCNA2, 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-137-3P	99.87	74.74	2401
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-6872-3P	97.08	66.99	750

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 37)

• endocytosis of Kv1.2 from the cell surface is a key mechanism for channel suppression by tyrosine kinases (PMID:15215309)
• our results demonstrate the multiplicity of gating inhibition of different K(v) channels by Syn-1A and is compatible with versatility of Syntaxin-1A modulation of repolarization in various secretory and nonsecretory (smooth muscle) cell types. (PMID:17234891)
• MK2-HSP27 pathway regulates the NF-kappaB transcriptional output by switching the activation pattern from high level to low level. (PMID:17576778)
• Kv1.2 and cortactin interact in vivo (PMID:17959782)
• Kv1.2 levels at the cell surface are kept in dynamic balance by opposing effects of cAMP (PMID:18003609)
• Replacement of the N-terminal domain of maurotoxin by the one of the Agitoxin 2 chimera results in reorganization of disulfide bridge arrangements and increase of affinity to the Kv1.2 channel. (PMID:18042681)
• the numbers of Kv1.2 channels are higher in DRs than VRs. (PMID:18053989)
• The spectrum of neurologic manifestations and neoplasms associated with voltage-gated potassium channel (VGKC) autoimmunity is broader than previously recognized (PMID:18474843)
• Both receptor-stimulated and steady-state Kv1.2 trafficking modulated by RhoA/ROCK required the activation of dynamin as well as the ROCK effector Lim-kinase, indicating a key role for actin remodeling in RhoA-dependent Kv1.2 regulation. (PMID:19403695)
• Data show that multivalent calix[4]arene ligands bind to the surface of voltage-dependent potassium channels (K(v)1.2 in a reversible manner. (PMID:19435843)
• analysis of molecular basis for the actions of KVbeta1.2 on the opening and closing of the KV1.2 delayed rectifier channel (PMID:19713757)
• molecular model for how the pre-gating process occurs in sequential steps: Gating charge response, movement and stabilization of the S4 voltage sensor domain, and movement near the base of the S5 region to close the pore domain. (PMID:19883299)
• Using fluorimetry and gating currents, study of the Kv1.2 voltage sensor domain revealed at least two independent conformational changes in this region in response to depolarization. (PMID:20584892)
• in addition to its known effect on pore stability, V370 of Kv1.2 is also crucial in controlling ion selectivity. (PMID:20842544)
• observe for both the open and closed conformations of the Kv1.2 that specific mutations of S4 gating-charge residues destabilize the electrostatic network between helices of the voltage sensor domain (PMID:21044565)
• The immunoreactivity of potassium channels (Kv1.2) was markedly reduced in the ventral roots, but normal in the dorsal roots of all the amyotrophic lateral sclerosis patients. (PMID:21906595)
• This study indicated that the T2DM condition leads to potassium channel-mediated peripheral nerve hyperexcitability , thus identifying them as a potential drug target to treat some of the DPN related symptoms. (PMID:22649228)
• isoform betaII plays a central role in the PKC-dependent regulation of Kv1.5/Kvbeta1.2 channels. (PMID:24682423)
• Using mutagenesis and analysis of gating currents from gating pore mutations in the Shaker Kv channel, we identified statistically highly significant correlations between VSD function and physicochemical properties of gating pore residues. (PMID:24782544)
• the inhibition of two K(+) channel isoforms, Kv1.2 and KCa3.1, by two drug molecules, lidocaine and TRAM-34, is examined in atomic detail using molecular dynamics simulations. (PMID:25300013)
• This gene has not been previously described as a cause of disease in humans, but mutations of the orthologous gene in mice (Kcna2) are known to cause both ataxia and convulsions (PMID:25477152)
• KCNA2 is a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons. (PMID:25751627)
• Use-dependent activation of Kv1.2 channels is mediated by an extrinsic regulator that binds preferentially to the channel closed state, with Thr252 being necessary but not sufficient for this interaction to alter channel function. (PMID:26646078)
• In the asymptomatic mother, the mutated copy of the CDKL5 gene was inactivated in 90% of blood cells. We also identified a premature stop codon (p.Arg926*) in IQSEC2 in a patient with a Rett-like phenotype. Finally, exome sequencing enabled us to characterize a heterozygous de novo missense (p.Val408Ala) in KCNA2 in a girl with infantile-onset seizures variant of Rett syndrome (RTT) (PMID:27062609)
• Novel recurrent missense mutation within the Kv1.2 voltage sensor associated with variable phenotypes, including hereditary spastic paraplegia, ataxia, and intellectual disability. (PMID:27543892)
• This study demonstrated that KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy. (PMID:27733563)
• Pharmacogenetic and case-control study evaluated the role of the variants of KCNA1, KCNA2, and KCNV2 in the susceptibility and drug resistance of genetic generalized epilepsies and revealed no significant association between 8 variants of KCNA1, KCNA2, and KCNV2 genes and risk or drug resistance of genetic generalized epilepsies after a Bonferroni correction for multiple comparisons. (PMID:28658141)
• We identified 3 patients with KCNA2 mutations with novel characteristics (PMID:28806589)
• study indicates well represented genotype-phenotype associations between three subgroups of patients with KCNA2 encephalopathy according to the electrophysiological features of the mutations. (PMID:29050392)
• recurrent de novo variants in the paralogous PVP motif of KCNA2 have previously been shown to abolish channel function and also cause early-onset epileptic encephalopathy. Importantly, this report extends the range of phenotypes associated with KCNA1 variants to include epileptic encephalopathy when the PVP motif is involved. (PMID:30055040)
• these results suggest that Notch activation enhances CaSR-mediated increases in [Ca(2+)]cyt by enhancing store-operated Ca(2+) entry and inhibits KCNA5/KV1.5 and KCNA2/KV1.2, ultimately leading to voltage-activated Ca(2+) entry. (PMID:32186932)
• Deep phenotyping unstructured data mining in an extensive pediatric database to unravel a common KCNA2 variant in neurodevelopmental syndromes. (PMID:33500571)
• Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders. (PMID:33802230)
• An epilepsy-associated KV1.2 charge-transfer-center mutation impairs KV1.2 and KV1.4 trafficking. (PMID:35439054)
• Two epilepsy-associated variants in KCNA2 (KV 1.2) at position H310 oppositely affect channel functional expression. (PMID:37883018)
• KCNA2 IgG autoimmunity in neuropsychiatric diseases. (PMID:38309639)
• Roles of KCNA2 in Neurological Diseases: from Physiology to Pathology. (PMID:38517617)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcna2a	ENSDARG00000002241
danio_rerio	kcna2b	ENSDARG00000102064
mus_musculus	Kcna2	ENSMUSG00000040724
rattus_norvegicus	Kcna2	ENSRNOG00000018285

Paralogs (31): KCNG1 (ENSG00000026559), KCNQ1 (ENSG00000053918), KCNQ2 (ENSG00000075043), KCND1 (ENSG00000102057), KCNA7 (ENSG00000104848), KCNA1 (ENSG00000111262), KCNC4 (ENSG00000116396), KCNQ4 (ENSG00000117013), KCNS1 (ENSG00000124134), KCNC1 (ENSG00000129159), KCNA5 (ENSG00000130037), KCNC3 (ENSG00000131398), KCNA10 (ENSG00000143105), KCNA6 (ENSG00000151079), KCNS2 (ENSG00000156486), KCNB1 (ENSG00000158445), KCNF1 (ENSG00000162975), KCNV1 (ENSG00000164794), KCNC2 (ENSG00000166006), KCNV2 (ENSG00000168263), KCNG4 (ENSG00000168418), KCNS3 (ENSG00000170745), KCNG3 (ENSG00000171126), KCND3 (ENSG00000171385), KCNA3 (ENSG00000177272), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNB2 (ENSG00000182674), KCNQ3 (ENSG00000184156), KCND2 (ENSG00000184408), KCNQ5 (ENSG00000185760)

Protein

Protein identifiers

Potassium voltage-gated channel subfamily A member 2 — P16389 (reviewed: P16389)

Alternative names: NGK1, Voltage-gated K(+) channel HuKIV, Voltage-gated potassium channel HBK5, Voltage-gated potassium channel subunit Kv1.2

All UniProt accessions (6): A0A1W2PP65, A0A1W2PPM7, A0A1W2PPN8, A0A1W2PR01, A0A1W2PRY2, P16389

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure. In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation. Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials. KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing. Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination. Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus. May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons. May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA). Contributes to the regulation of the axonal release of the neurotransmitter dopamine. Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain. Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep.

Subunit / interactions. Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7. Channel activity is regulated by interaction with the beta subunits, including KCNAB1 and KCNAB2. Identified in a complex with KCNA1 and KCNAB2. Identified in a complex with KCNA5 and KCNAB1. Identified in a complex with KCNA4 and FYN. Interacts with the beta subunit KCNAB1. Interacts with PTK2B. Interacts (via C-terminus) with CTTN. Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation. Interacts with DRD2. Interacts with SIGMAR1; cocaine consumption leads to increased interaction. Interacts with ADAM22. Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4. Interacts with CNTNAP2. Interacts with ADAM11. Interacts with LYNX1.

Subcellular location. Cell membrane. Membrane. Cell projection. Axon. Synapse. Endoplasmic reticulum membrane. Lamellipodium membrane. Synaptosome. Presynaptic cell membrane. Dendrite. Cell junction. Paranodal septate junction.

Tissue specificity. Detected in brain cortex. Detected in peroneal nerve in the juxtaparanodal regions of the node of Ranvier; expression is decreased in patients with diabetes mellitus that suffer from axonal neuropathy. Detected in paranodal and juxtanodal zones in myelinated spinal cord (at protein level).

Post-translational modifications. Phosphorylated on tyrosine residues; phosphorylation increases in response to ischemia. Phosphorylated on tyrosine residues by activated PTK2B/PYK2. Phosphorylation on tyrosine residues suppresses ion channel activity. Phosphorylated on tyrosine residues in response to CHRM1 activation; this abolishes interaction with CTTN. This is probably due to endocytosis of the phosphorylated channel subunits. Phosphorylated on serine residues in response to increased cAMP levels; phosphorylation is apparently not catalyzed by PKA. N-glycosylated, with complex, sialylated N-glycans.

Disease relevance. Developmental and epileptic encephalopathy 32 (DEE32) [MIM:616366] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE32 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Nizon-Isidor syndrome (NIZIDS) [MIM:618872] An autosomal dominant neurodevelopmental disorder characterized by intellectual disability, global developmental delay, speech impairment, and behavioral abnormalities including autism spectrum disorder and aggressive behavior. Other features include a thin corpus callosum, and mild facial dysmorphism. Disease onset is in infancy or early childhood. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by 4-aminopyridine (4-AP) and charybdotoxin (CTX), but not by tetraethylammonium (TEA). Inhibited by dendrotoxin (DTX). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2. Inhibited by maurotoxin. Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK; kappaM-RIIIJ has much higher affinity for channels containing KCNA2 than kappaM-RIIIK, with the exception of heterodimers formed by KCNA2 and KCNA7 where the opposite is true.

Domain organisation. The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics. Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA-mediated endocytosis. The transmembrane segment S4 functions as a voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.

Miscellaneous. The delay or D-type current observed in hippocampus pyramidal neurons is probably mediated by potassium channels containing KCNA2 plus KCNA1 or other family members. It is activated at about -50 mV, i.e. below the action potential threshold, and is characterized by slow inactivation, extremely slow recovery from inactivation, sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP).

Similarity. Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P16389-1	1	yes
P16389-2	2

RefSeq proteins (2): NP_001191198, NP_004965* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR003968	K_chnl_volt-dep_Kv	Family
IPR003972	K_chnl_volt-dep_Kv1	Family
IPR004049	K_chnl_volt-dep_Kv1.2	Family
IPR005821	Ion_trans_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR028325	VG_K_chnl	Family

Pfam: PF00520, PF02214

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (45 total): sequence variant 10, topological domain 8, modified residue 7, transmembrane region 6, region of interest 3, intramembrane region 2, short sequence motif 2, site 2, chain 1, lipid moiety-binding region 1, glycosylation site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16389-F1	78.01	0.57

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 (2): 252 (important for normal, slow channel gating); 381 (important for binding with the scorpion mesomartoxin; when the scorpion mesomartoxin-rkv1.2/kcna2 interaction is modeled, this residue is close to the ‘y-57’ residue of the toxin)

Post-translational modifications (8): 429, 434, 440, 441, 449, 458, 468, 244

Glycosylation sites (1): 207

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1296072	Voltage gated Potassium channels
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels

MSigDB gene sets: 300 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_POTASSIUM_ION_TRANSPORT, AP1_01, AAGCAAT_MIR137, MYOGENIN_Q6, GOBP_BEHAVIOR, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, BIOCARTA_BARRESTIN_SRC_PATHWAY, GOBP_CRANIAL_NERVE_MORPHOGENESIS, GOBP_CRANIAL_NERVE_DEVELOPMENT, CAGCTG_AP4_Q5, GOBP_ANATOMICAL_STRUCTURE_ARRANGEMENT, EFC_Q6, GOBP_FOREBRAIN_DEVELOPMENT

GO Biological Process (18): action potential (GO:0001508), potassium ion transport (GO:0006813), regulation of dopamine secretion (GO:0014059), neuronal action potential (GO:0019228), sensory perception of pain (GO:0019233), optic nerve structural organization (GO:0021633), cerebral cortex development (GO:0021987), corpus callosum development (GO:0022038), regulation of circadian sleep/wake cycle, non-REM sleep (GO:0045188), protein homooligomerization (GO:0051260), potassium ion transmembrane transport (GO:0071805), potassium ion export across plasma membrane (GO:0097623), monoatomic ion transport (GO:0006811), optic nerve development (GO:0021554), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), regulation of postsynaptic membrane potential (GO:0060078), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (10): voltage-gated potassium channel activity (GO:0005249), delayed rectifier potassium channel activity (GO:0005251), potassium channel activity (GO:0005267), outward rectifier potassium channel activity (GO:0015271), kinesin binding (GO:0019894), voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099508), voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1905030), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), voltage-gated monoatomic cation channel activity (GO:0022843)

GO Cellular Component (25): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), lamellipodium (GO:0030027), axon (GO:0030424), dendrite (GO:0030425), lamellipodium membrane (GO:0031258), neuronal cell body membrane (GO:0032809), paranodal junction (GO:0033010), presynaptic membrane (GO:0042734), axon initial segment (GO:0043194), perikaryon (GO:0043204), axon terminus (GO:0043679), juxtaparanode region of axon (GO:0044224), calyx of Held (GO:0044305), postsynaptic membrane (GO:0045211), glutamatergic synapse (GO:0098978), endoplasmic reticulum (GO:0005783), monoatomic ion channel complex (GO:0034702), potassium channel complex (GO:0034705), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Potassium Channels	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of membrane potential	3
voltage-gated monoatomic ion channel activity	3
anatomical structure development	2
transport	2
voltage-gated potassium channel activity	2
monoatomic cation channel activity	2
neuron projection	2
neuronal cell body	2
synaptic membrane	2
presynapse	2
main axon	2
metal ion transport	1
dopamine secretion	1
regulation of catecholamine secretion	1
action potential	1
transmission of nerve impulse	1
sensory perception	1
cranial nerve structural organization	1
optic nerve morphogenesis	1
pallium development	1
telencephalon development	1
circadian sleep/wake cycle, non-REM sleep	1
regulation of circadian sleep/wake cycle, sleep	1
protein complex oligomerization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
potassium ion transmembrane transport	1
export across plasma membrane	1
cranial nerve development	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
cytoskeletal protein binding	1
presynaptic membrane	1
regulation of presynaptic membrane potential	1
regulation of postsynaptic membrane potential	1

Protein interactions and networks

STRING

2666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNA2	KCNAB2	Q13303	994
KCNA2	KCNA1	Q09470	982
KCNA2	KCNA6	P17658	978
KCNA2	CNTNAP2	Q9UHC6	976
KCNA2	CTTN	Q14247	962
KCNA2	KCNA4	P22459	960
KCNA2	KCNA5	P22460	942
KCNA2	KCNAB1	Q14722	923
KCNA2	KCNB1	Q14721	903
KCNA2	HCLS1	P14317	902
KCNA2	CNTN2	P78432	866
KCNA2	CNTNAP1	P78357	854
KCNA2	GJC3	Q8NFK1	827
KCNA2	KCNA3	P22001	819
KCNA2	KCNH2	Q12809	810

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CAMLG	KCNA2	psi-mi:“MI:0915”(physical association)	0.670
KCNA2	CAMLG	psi-mi:“MI:0915”(physical association)	0.670
KCNA2	KCNAB2	psi-mi:“MI:0915”(physical association)	0.670
KCNA2	KCNA3	psi-mi:“MI:0914”(association)	0.530
KCNA2	FADS1	psi-mi:“MI:0914”(association)	0.530
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): KCNA2 (Two-hybrid), KCNA2 (Affinity Capture-Western), KCNA2 (Affinity Capture-Western), KCNA2 (Affinity Capture-Western), DLG4 (Affinity Capture-Western), KCNA2 (Co-localization), CNTNAP2 (Affinity Capture-Western), KCNA2 (Two-hybrid), FAM3C (Two-hybrid), KCNA2 (Affinity Capture-Western), KCNA2 (Affinity Capture-Western), KCNA1 (Affinity Capture-Western), KCNA4 (Affinity Capture-Western), KCNA2 (Affinity Capture-Western), KCNA2 (Affinity Capture-Western)

ESM2 similar proteins: B2RQA1, D4ADX7, G5EFC3, O35119, O35174, O88759, P08510, P10499, P15384, P15385, P16388, P16389, P16390, P17658, P17659, P19024, P22001, P22459, P22462, P22739, P25122, P34586, P48994, P63141, P63142, P79100, Q05037, Q09081, Q09470, Q14B80, Q16322, Q25452, Q28293, Q28527, Q61423, Q61762, Q61923, Q7T199, Q7TSH7, Q8BQZ8

Diamond homologs: A0A509AVL8, O27564, P16389, Q28293, Q795M8, Q8I5E6, Q9YDF8, A2BDX4, A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, A6H8H5, D4AD53, D4ADX7, O18868, O35173, O35174, O73606, O88758, O88759, P10499, P15384, P15385, P15387, P15388, P16388, P16390, P17970, P19024, P22001, P22459, P22460

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	26
Uncertain significance	303
Likely benign	157
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1060438	NM_004974.4(KCNA2):c.1175C>T (p.Ser392Phe)	Pathogenic
1067683	NM_004974.4(KCNA2):c.1220C>G (p.Pro407Arg)	Pathogenic
1070041	NM_004974.4(KCNA2):c.765_773del (p.Met255_Ile257del)	Pathogenic
1196932	NM_004974.4(KCNA2):c.640C>T (p.Gln214Ter)	Pathogenic
1721403	NM_004974.4(KCNA2):c.773T>A (p.Ile258Asn)	Pathogenic
190326	NM_004974.4(KCNA2):c.788T>C (p.Ile263Thr)	Pathogenic
190327	NM_004974.4(KCNA2):c.894G>T (p.Leu298Phe)	Pathogenic
190328	NM_004974.4(KCNA2):c.890G>A (p.Arg297Gln)	Pathogenic
2015540	NM_004974.4(KCNA2):c.181del (p.Asp61fs)	Pathogenic
2091004	NM_004974.4(KCNA2):c.730T>C (p.Cys244Arg)	Pathogenic
2118816	NM_004974.4(KCNA2):c.900A>C (p.Arg300Ser)	Pathogenic
2151893	NM_004974.4(KCNA2):c.637C>T (p.Gln213Ter)	Pathogenic
2664659	NM_004974.4(KCNA2):c.*1150del	Pathogenic
2757952	NM_004974.4(KCNA2):c.1193G>A (p.Gly398Asp)	Pathogenic
2760866	NM_004974.4(KCNA2):c.494T>A (p.Ile165Lys)	Pathogenic
2822519	NM_004974.4(KCNA2):c.1015G>T (p.Val339Phe)	Pathogenic
2825567	NM_004974.4(KCNA2):c.919T>G (p.Leu307Val)	Pathogenic
3061873	NM_004974.4(KCNA2):c.636C>G (p.Tyr212Ter)	Pathogenic
4073679	NM_004974.4(KCNA2):c.1193G>T (p.Gly398Val)	Pathogenic
426735	NM_004974.4(KCNA2):c.869T>C (p.Leu290Pro)	Pathogenic
430391	NM_004974.4(KCNA2):c.1202C>T (p.Thr401Ile)	Pathogenic
559647	NM_004974.4(KCNA2):c.1120A>G (p.Thr374Ala)	Pathogenic
666316	NM_004974.4(KCNA2):c.1223T>C (p.Val408Ala)	Pathogenic
816892	NM_004974.4(KCNA2):c.590del (p.Gly197fs)	Pathogenic
830850	NC_000001.11:g.(?110593873)(110604802_?)del	Pathogenic
986989	NM_004974.4(KCNA2):c.889C>T (p.Arg297Trp)	Pathogenic
1066046	NM_004974.4(KCNA2):c.900A>T (p.Arg300Ser)	Likely pathogenic
1068304	NM_004974.4(KCNA2):c.1210T>A (p.Leu404Ile)	Likely pathogenic
1174095	NM_004974.4(KCNA2):c.906T>G (p.Phe302Leu)	Likely pathogenic
1196855	NM_004974.4(KCNA2):c.1135G>C (p.Asp379His)	Likely pathogenic

SpliceAI

938 predictions. Top by Δscore:

Variant	Effect	Δscore
1:110607254:T:TA	donor_gain	0.9900
1:110605386:TTTAC:T	donor_loss	0.9800
1:110605387:TTA:T	donor_loss	0.9800
1:110605389:A:AG	donor_loss	0.9800
1:110605390:C:A	donor_loss	0.9800
1:110605415:T:TA	donor_gain	0.9800
1:110606226:ACTCT:A	donor_gain	0.9800
1:110606227:CT:C	donor_gain	0.9800
1:110606227:CTCTC:C	donor_gain	0.9800
1:110607043:T:TA	donor_gain	0.9800
1:110607249:AC:A	donor_gain	0.9800
1:110607250:CC:C	donor_gain	0.9800
1:110606226:A:AC	donor_gain	0.9700
1:110606227:C:CC	donor_gain	0.9700
1:110606227:CTCT:C	donor_gain	0.9700
1:110607090:G:A	donor_gain	0.9700
1:110607122:G:A	donor_gain	0.9700
1:110607136:AG:A	donor_gain	0.9700
1:110607136:AGC:A	donor_gain	0.9700
1:110607137:G:C	donor_gain	0.9700
1:110606600:AACCC:A	donor_gain	0.9600
1:110607039:CT:C	donor_gain	0.9600
1:110606230:T:A	donor_gain	0.9500
1:110607006:AAACC:A	donor_gain	0.9500
1:110607074:C:CA	donor_gain	0.9500
1:110607274:T:TA	donor_gain	0.9500
1:110602032:G:A	donor_gain	0.9400
1:110606777:T:TA	donor_gain	0.9400
1:110607038:A:AC	donor_gain	0.9400
1:110607039:C:CC	donor_gain	0.9400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000077912 (1:110622819 G>A), RS1000104049 (1:110599293 G>T), RS1000132864 (1:110622475 T>C), RS1000171614 (1:110597495 G>C), RS1000183341 (1:110617660 G>A), RS1000342794 (1:110624276 C>G), RS1000397534 (1:110631246 G>A), RS1000514368 (1:110618908 G>A), RS1000571044 (1:110618668 T>A), RS1000642697 (1:110629716 A>G,T), RS1000711542 (1:110605744 G>A), RS1000726414 (1:110625697 C>T), RS1000797195 (1:110623876 C>T), RS1000817210 (1:110611240 C>A), RS1000972955 (1:110617309 T>C)

Disease associations

OMIM: gene MIM:176262 | disease phenotypes: MIM:616366, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 32	Definitive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	AD

Mondo (7): developmental and epileptic encephalopathy, 32 (MONDO:0014607), developmental and epileptic encephalopathy, 1 (MONDO:0010632), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), complex neurodevelopmental disorder (MONDO:0100038), intellectual disability (MONDO:0001071), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (4): Non-specific early-onset epileptic encephalopathy (Orphanet:442835), Non-specific syndromic intellectual disability (Orphanet:528084), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Reduced tendon reflexes
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001508	Failure to thrive

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010796_384	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2086 (SINGLE PROTEIN), CHEMBL2362996 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,967 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL24171	BERGAPTEN	3	3,967

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Voltage-gated potassium channels (K_v)

Most potent curated ligand interactions (18 total), top 18:

Ligand	Action	Affinity	Parameter
hongotoxin-1	Channel blocker	13.0	pKd
margatoxin	Inhibition	11.2	pIC50
pandinotoxin-K α	Channel blocker	10.5	pIC50
α-dendrotoxin	Channel blocker	9.4	pIC50
noxiustoxin	Channel blocker	8.7	pKd
charybdotoxin	Channel blocker	7.9	pKd
dendrotoxin-I	Channel blocker	7.8	pKd
BgK	Channel blocker	7.6	pIC50
α-KTx 13.2	Channel blocker	7.0	pKd
κM-conotoxin RIIIK	Channel blocker	6.55	pIC50
mast cell degranulating peptide	Channel blocker	6.4	pIC50
anandamide	Pore blocker	5.6	pIC50
nifedipine	Pore blocker	4.7	pKd
resiniferatoxin	Pore blocker	4.5	pKd
capsaicin	Pore blocker	4.4	pKd
diltiazem	Pore blocker	3.7	pKd
flecainide	Pore blocker	3.7	pKd
fampridine	Pore blocker	3.2	pKd

ChEMBL bioactivities

8 potent at pChembl≥5 of 12 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	Ki	0.15	nM	CHEMBL5722941
9.74	IC50	0.18	nM	CHEMBL5722941
6.60	EC50	250	nM	CHEMBL444449
6.51	IC50	308	nM	CHEMBL5631442
6.35	IC50	450	nM	CHEMBL444449
5.85	EC50	1400	nM	CHEMBL426482
5.60	EC50	2500	nM	CHEMBL382154
5.00	EC50	1e+04	nM	CHEMBL203909

PubChem BioAssay actives

7 with measured affinity, of 62 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(1R,2aS,4S,5aS,8aS,10S,11aR,14aS,16S,17aS,19S,20aS,22S,23aS,25S,26aS,28S,29aS,31R,32aS,35aS,36R,38aS,39S,41aS,42S,44aS,45S,48R,50aS,51S,53aS,54S,56aS,57S,59aS,60S,63S,66S,69S,72S,75S,78S,87R,93S,96S,99S)-17a,20a,23a,53a,63-pentakis(4-aminobutyl)-31-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-16,29a,72,78-tetrakis(2-amino-2-oxoethyl)-14a,26a-bis(3-amino-3-oxopropyl)-2a,38a,66-tribenzyl-28,50a,57-tris[(2S)-butan-2-yl]-4,5a,19,42,45,69-hexakis(3-carbamimidamidopropyl)-51,54-bis(2-carboxyethyl)-56a,99-bis(carboxymethyl)-36-[[(2S,3S)-1-(carboxymethylamino)-3-methyl-1-oxopentan-2-yl]carbamoyl]-39,60-bis[(1R)-1-hydroxyethyl]-75,93-bis(hydroxymethyl)-32a,35a,59a-tris[(4-hydroxyphenyl)methyl]-22-(1H-imidazol-4-ylmethyl)-96-(1H-indol-3-ylmethyl)-41a-methyl-25-(2-methylpropyl)-1a,3,4a,6,7a,9,10a,13a,15,16a,18,19a,21,22a,24,25a,27,28a,30,31a,34a,37a,38,40a,41,43a,44,47,49a,50,52a,53,55a,56,58a,59,61a,62,65,68,71,74,77,80,83,86,89,92,95,98-pentacontaoxo-33,34,63a,64a,67a,68a-hexathia-a,2,3a,5,6a,8,9a,12a,14,15a,17,18a,20,21a,23,24a,26,27a,29,30a,33a,36a,37,39a,40,42a,43,46,48a,49,51a,52,54a,55,57a,58,60a,61,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazapentacyclo[85.74.4.448,111.010,14.0144,148]nonahexacontahectan-8a-yl]propanoic acid	2198828: Binding affinity to KV channel (unknown origin) assessed as inhibition constant	ki	0.0001	uM
[4-[[(2-methoxybenzoyl)amino]methyl]-4-thiophen-3-ylcyclohexyl] N-propylcarbamate	2136220: Inhibition of Kv1.2 (unknown origin) expressed in Xenopus laevis Oocyte cells by electrophysiological recording	ic50	0.3080	uM
4-(4-phenoxybutoxy)furo[3,2-g]chromen-7-one	1379136: Inhibition of human Kv1.2 expressed in CHO cells at -80 mV holding potential by whole cell automated patch clamp method	ic50	0.4500	uM
1-[7-[(4-bromophenyl)methoxy]-6-hydroxy-4-methoxy-1-benzofuran-5-yl]ethanone	261019: Effect on blockade of Kv1.2 channel	ec50	1.4000	uM
1-[4-[(4-chlorophenyl)methoxy]-6-hydroxy-7-methoxy-1-benzofuran-5-yl]ethanone	261019: Effect on blockade of Kv1.2 channel	ec50	2.5000	uM
1-[6-hydroxy-4,7-bis(phenylmethoxy)-1-benzofuran-5-yl]ethanone	261019: Effect on blockade of Kv1.2 channel	ec50	10.0000	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
Nickel	decreases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Aflatoxin B1	increases methylation	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diazinon	increases methylation	1
Methapyrilene	increases methylation	1
Dronabinol	increases expression	1
Tretinoin	increases expression	1
Sodium Selenite	decreases expression	1

ChEMBL screening assays

36 unique, capped per target: 31 binding, 3 functional, 1 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1052983	Binding	Inhibition of Kv1.2 channel expressed in -70 mV-activated HEK293 cells followed by further 10 mV pulse stimulation assessed as slope factor (RVb= 16.3 +/- 1.8 no_unit)	Rhynchophylline from Uncaria rhynchophylla functionally turns delayed rectifiers into A-Type K+ channels. — J Nat Prod
CHEMBL4407436	ADMET	Inhibition of Kv1.2 (unknown origin) at 3 uM relative to control	Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design. — J Med Chem
CHEMBL702904	Functional	Blockade of peak K+ currents against Kv1.2 gene; Not determined	Alkoxypsoralens, novel nonpeptide blockers of Shaker-type K+ channels: synthesis and photoreactivity. — J Med Chem

Cellosaurus cell lines

10 cell lines: 8 induced pluripotent stem cell, 2 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2XY	PUFHi001-A	Induced pluripotent stem cell	Female
CVCL_C0XY	B’SYS CHO Kv1.2	Spontaneously immortalized cell line	Female
CVCL_C1SQ	BJTTHi001-A-3	Induced pluripotent stem cell	Male
CVCL_D1JV	PrecisION hKv1.2-CHO	Spontaneously immortalized cell line	Female
CVCL_UD88	HIHDNEi001-A	Induced pluripotent stem cell	Male
CVCL_WN13	HIHDNEi002-A	Induced pluripotent stem cell	Male
CVCL_WN14	HIHDNEi003-A	Induced pluripotent stem cell	Male
CVCL_YQ75	NUIGi052-A	Induced pluripotent stem cell	Female
CVCL_YQ76	NUIGi052-B	Induced pluripotent stem cell	Female
CVCL_YQ77	NUIGi052-C	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
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