KCND2

Summary

KCND2 (potassium voltage-gated channel subfamily D member 2, HGNC:6238) is a protein-coding gene on chromosome 7q31.31, encoding A-type voltage-gated potassium channel KCND2 (Q9NZV8). Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain.

Voltage-gated potassium (Kv) 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, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels.

Source: NCBI Gene 3751 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 493 total — 3 pathogenic, 3 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_012281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6238
Approved symbol	KCND2
Name	potassium voltage-gated channel subfamily D member 2
Location	7q31.31
Locus type	gene with protein product
Status	Approved
Aliases	Kv4.2, RK5, KIAA1044
Ensembl gene	ENSG00000184408
Ensembl biotype	protein_coding
OMIM	605410
Entrez	3751

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000331113, ENST00000425288, ENST00000473190

RefSeq mRNA: 1 — MANE Select: NM_012281 NM_012281

CCDS: CCDS5776

Canonical transcript exons

ENST00000331113 — 6 exons

Exon	Start	End
ENSE00001295053	120741534	120741629
ENSE00001300279	120273175	120275747
ENSE00001312622	120742510	120742602
ENSE00001316360	120747681	120750337
ENSE00001325824	120732903	120733065
ENSE00003468812	120745780	120746027

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 94.71.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0730 / max 157.5708, expressed in 413 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80749	0.8514	297
80748	0.6099	142
80752	0.3056	117
80751	0.1177	60
80750	0.0813	39
80753	0.0521	20
204670	0.0293	10
80754	0.0257	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	94.71	gold quality
paraflocculus	UBERON:0005351	89.85	gold quality
cerebellum	UBERON:0002037	89.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.23	gold quality
cerebellar cortex	UBERON:0002129	89.19	gold quality
cerebellar hemisphere	UBERON:0002245	88.93	gold quality
pons	UBERON:0000988	88.39	gold quality
stromal cell of endometrium	CL:0002255	86.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.91	gold quality
prefrontal cortex	UBERON:0000451	81.68	gold quality
primary visual cortex	UBERON:0002436	80.89	gold quality
ganglionic eminence	UBERON:0004023	80.12	gold quality
CA1 field of hippocampus	UBERON:0003881	79.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.58	gold quality
endothelial cell	CL:0000115	79.26	gold quality
caudate nucleus	UBERON:0001873	78.02	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.61	gold quality
superior frontal gyrus	UBERON:0002661	77.43	gold quality
middle temporal gyrus	UBERON:0002771	77.40	gold quality
frontal cortex	UBERON:0001870	77.18	gold quality
occipital lobe	UBERON:0002021	76.84	gold quality
decidua	UBERON:0002450	76.68	gold quality
neocortex	UBERON:0001950	76.66	gold quality
nucleus accumbens	UBERON:0001882	76.39	gold quality
right uterine tube	UBERON:0001302	76.38	gold quality
brain	UBERON:0000955	76.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.06	gold quality
cerebral cortex	UBERON:0000956	76.03	gold quality
putamen	UBERON:0001874	75.96	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	89.00
E-HCAD-25	yes	24.19
E-ANND-3	no	3.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRX3, IRX4, IRX5, ZFPM2

miRNA regulators (miRDB)

176 targeting KCND2, 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-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 40)

• PSD-95 increased the amount of Kv1.4, but not Kv4.2, in lipid rafts. (PMID:14559911)
• Kv4.2 and K+ channel-interacting protein 2 make up a complex of Ito channels (PMID:14623880)
• Data show that KChIP1, KChIP2.1, and KChIP2.2 could form homo- as well as hetero-oligomers, and that this oligomerization did not perturb their interaction with Kv4.2 potassium channel. (PMID:15358149)
• mutations in KCND2 and KCND3 are not a frequent cause of long QT syndrome (PMID:15563876)
• Data show that the Kv4.2 voltage-dependent potassium channel acts as a fast-responding steroid sensor in human granulosa cells. (PMID:15991246)
• Traffic of Kv4.2 is coat protein complex I (COPI)-dependent. (PMID:16260497)
• the C-terminal domain of Kv4.2 plays a critical role in voltage-dependent activation and functional expression that is mediated by direct interaction between the Kv4.2 C terminus and KChIP2 (PMID:16820361)
• Electrophysiological analysis indicates attenuated K+ current density in cells expressing this Kv4.2-N587fsX1 mutant channel, which is consistent with a model of aberrant neuronal excitability characteristic of TLE. (PMID:16934482)
• two Ca2+-dependent posttranslational events regulate the activity of DREAM on Kv4.2 channel function (PMID:17102134)
• Our results further suggest distinct mechanisms for Kv4.2 gating modulation by KChIPs and DPPs. (PMID:17981906)
• biophysical and biochemical methods indicate that I(SA) channels carry four subunits each of Kv4.2 and DPP6. (PMID:18364354)
• rodent and human Abeta are effective in modulating K currents (PMID:18463498)
• An ALA-scanning mutagenesis in the S4-S5 linker region, the initial part of S5, and the distal part of S6, in X. laevis oocytes showed that temporary uncoupling at the interface between V sensor and cytoplasmic gate may underlie closed-state inactivation. (PMID:19171772)
• SAP97 is a major partner for surface expression and CaMKII-dependent regulation of cardiac Kv4.2 and kv4.3 channels. (PMID:19213956)
• the inhibition of maximal amplitude of Kv4.2 channels by arachidonic acid can explain the inhibition of somatodendritic I(A) in hippocampal neurons (PMID:19453640)
• This study indicated that Kv4.2 is expressed in both neuronal and glial cells and its regulation may involve potassium channel interacting proteins, alterations in the subcellular localization of the channel. (PMID:19596445)
• MiRP3 modulates Kv4.2 current activation, inactivation and recovery from inactivation. MiRP3 shifts the half-maximal voltage for activation and slows time to peak ~ 100%. (PMID:20498229)
• KChIP2 differentially regulates total and cell surface Kv4.2 protein expression and Kv4 current densities. (PMID:20709747)
• Seizures in Kv4.2 transgenic mice rapidly redistribute K+ channel subunit Kv4.2 to the neuronal surface, implicating a molecular substrate for the increased K+ current. (PMID:22122031)
• Autoantibodies from patients with encephalitis are specific for DPPX (a subunit of Kv4.2) without reacting to Kv4.2. (PMID:23225603)
• Our results support the hypothesis that KChIPs enhances Kv4.2 functional expression by a 1 : 1 suppression of the N-terminal FERN domain and by producing additional positive regulatory effects on functional channel expression. (PMID:23692269)
• KCND2 is expressed in human skin, but has not been associated with aging. (PMID:24037343)
• WT PrP(C), in a DPP6-dependent manner, modulated Kv4.2 channel properties, causing an increase in peak amplitude (PMID:24225951)
• study identified a de novo variant p.Val404Met in KCND2 in a family with identical twins affected with autism and severe seizures; findings suggest KCND2 is the causal gene for epilepsy in this family and has a role in the etiology of autism (PMID:24501278)
• S-glutathionylation of an auxiliary subunit confers redox sensitivity to Kv4 channel inactivation. (PMID:24675763)
• Subunit counting by single-molecule imaging revealed that the bound number of KChIP4 in each Kv4.2.KChIP4 complex was dependent on the expression level of KChIP4. (PMID:24811166)
• reflected in the immunoblotting data KV4.2 receptors were detected at higher levels of expression in patient with cortical dysplasia with intractable epilepsy. (PMID:25003238)
• A rare genetic mutation of the KCND2 gene, p.D612N, was identified in a single patient. Co-expression of mutant and wild-type KCND2 with KChIP2 demonstrated a gain-of-function phenotype. (PMID:25214526)
• The findings of this study suggest that variations in KCND2 genes are associated with both mild and severe persistent breast pain after breast cancer surgery. (PMID:25599232)
• The study provides the first piece of evidence for the role of H2S in regulating Ito potassium channels and also the specific motif in an ion channel labile for H2S regulation. (PMID:25756524)
• The stoichiometry of the Kv4.2-DPP10 complex was variable depending on the relative expression level of each subunit, with a preference for 4:2 stoichiometry (PMID:26209633)
• closed-state inactivation in Kv4.2 channels is a multistep process (PMID:26745419)
• Ca(2+)/calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) c4 axis is required for neuritin-induced Kv4.2 transcriptional expression and potentiation of IA densities in cerebellum granule neurons. (PMID:27307045)
• Our results do not support the notion that accessory KChIP2 binding is a prerequisite for dendritic trafficking and functional surface expression of Kv4.2 channels, however, accessory KChIP2 binding may play a potential role in Kv4.2 modulation during intrinsic plasticity processes. (PMID:29385176)
• A mutation, V404M, in the Kv4.2 channel subunit is associated with infant-onset epilepsy and autism. V404M enhances inactivation of channels that have not opened but dramatically impairs inactivation after opening. Authors show that increased side-chain volume is largely responsible for these seemingly paradoxical effects. (PMID:29581270)
• KCND2 upregulation is a valuable prognostic biomarker in gastric cancer patients, in terms of overall survival and recurrence-free survival. (PMID:30051729)
• The atrial-specific phenotype suggests that targeting Kv4.2 might be effective in the treatment of nocturnal paroxysmal atrial fibrillation, avoiding adverse ventricular effects. (PMID:30571183)
• Modulation of Kv4.2/KChIP3 interaction by the ceroid lipofuscinosis neuronal 3 protein CLN3. (PMID:32641494)
• Potassium voltage-gated channel subfamily D member 2 induces an aggressive phenotype in lung adenocarcinoma. (PMID:32977724)
• KCND2 variants associated with global developmental delay differentially impair Kv4.2 channel gating. (PMID:34245260)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnd2	ENSDARG00000032799
mus_musculus	Kcnd2	ENSMUSG00000060882
rattus_norvegicus	Kcnd2	ENSRNOG00000067416

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), KCNA2 (ENSG00000177301), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNB2 (ENSG00000182674), KCNQ3 (ENSG00000184156), KCNQ5 (ENSG00000185760)

Protein

Protein identifiers

A-type voltage-gated potassium channel KCND2 — Q9NZV8 (reviewed: Q9NZV8)

Alternative names: Potassium voltage-gated channel subfamily D member 2, Voltage-gated potassium channel subunit Kv4.2

All UniProt accessions (3): A4D0V9, Q9NZV8, H7C445

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons. This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity. Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5. Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. 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 KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation. Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity. Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state).

Subunit / interactions. Homotetramer or heterotetramer with KCND1 or KCND3. Associates with the regulatory subunits KCNIP2, KCNIP3 and KCNIP4. Interacts with the regulatory subunit KCNIP1; this interaction mediates the capture of both the N- and C-terminus of KCND2, preventing N-type inactivation and stabilizing the S6 conformation, thereby accelerating closed state inactivation and recovery. In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10. The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4. Interaction with four KCNIP4 chains does not reduce interaction with DPP10. Interacts with DLG4 and NCS1/FREQ. Interacts with DLG1. Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. Interacts with FLNA, FLNC and DPP10. Interacts (via S1 and S2 helices) with DPP6; this interaction stabilizes the conformation of the S1-S2 helices and facilitates S4 conformational change, including S4 sliding up and down, thereby accelerating activation, inactivation, and recovery.

Subcellular location. Cell membrane. Cell projection. Dendrite. Synapse. Perikaryon. Postsynaptic cell membrane. Dendritic spine. Cell junction.

Tissue specificity. Detected in ovary, in corpus luteum and in granulosa and theca cells in the follicle (at protein level). Highly expressed throughout the brain. Detected in amygdala, caudate nucleus, cerebellum, hippocampus, substantia nigra and thalamus. Expression is not detectable or very low in heart, kidney, liver, lung, pancreas and skeletal muscle. Not detectable in human heart atrium.

Post-translational modifications. Phosphorylation at Ser-438 in response to MAPK activation is increased in stimulated dendrites. Interaction with KCNIP2 and DPP6 propomtes phosphorylation by PKA at Ser-552. Phosphorylation at Ser-552 has no effect on interaction with KCNIP3, but is required for the regulation of channel activity by KCNIP3. Phosphorylation at Ser-552 leads to KCND2 internalization. Phosphorylated by MAPK in response to signaling via the metabotropic glutamate receptor GRM5. Phosphorylation at Ser-616 is required for the down-regulation of neuronal A-type currents in response to signaling via GRM5.

Disease relevance. KNCD2 mutations have been found in a family with autism and epilepsy and may play a role in disease pathogenesis. Autism is a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system. A KCND2 mutation leading to the production of a C-terminally truncated protein has been identified in a patient with epilepsy. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.

Domain organisation. 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. The N-terminal cytoplasmic region can mediate N-type inactivation by physically blocking the channel. This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2. The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex. The channel undergoes closed-state inactivation, where conformation changes lead to inactivation through an intermediate state involving breakdown of its 4-fold symmetry. that governs the distinct transient, fast-inactivating currents. The C-terminal cytoplasmic region is important for normal expression at the cell membrane and modulates the voltage-dependence of channel activation and inactivation. It is required for interaction with KCNIP2, and probably other family members as well.

Miscellaneous. The transient neuronal A-type potassium current called I(SA) is triggered at membrane potentials that are below the threshold for action potentials. It inactivates rapidly and recovers rapidly from inactivation. It regulates the firing of action potentials and plays a role in synaptic integration and plasticity. Potassium channels containing KCND2 account for about 80% of the neuronal A-type potassium current. In contrast, the potassium channel responsible for the cardiac I(to) current differs between species; it is mediated by KCND2 in rodents. In human and other non-rodents KCND3 may play an equivalent role. Is specifically and reversibly inhibited by the scorpion toxin Ts8 (AC P69940).

Similarity. Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily.

RefSeq proteins (1): NP_036413* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR003968	K_chnl_volt-dep_Kv	Family
IPR003975	K_chnl_volt-dep_Kv4	Family
IPR004055	K_chnl_volt-dep_Kv4.2	Family
IPR005821	Ion_trans_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR021645	Shal-type_N	Domain
IPR024587	K_chnl_volt-dep_Kv4_C	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR028325	VG_K_chnl	Family

Pfam: PF00520, PF02214, PF11601, PF11879

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (116 total): mutagenesis site 30, helix 26, strand 9, modified residue 9, topological domain 8, binding site 8, transmembrane region 6, region of interest 6, sequence conflict 4, turn 4, intramembrane region 2, short sequence motif 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
7UKG	ELECTRON MICROSCOPY	2.24
7UKH	ELECTRON MICROSCOPY	2.33
7UK5	ELECTRON MICROSCOPY	2.76
7UKD	ELECTRON MICROSCOPY	2.88
7F0J	ELECTRON MICROSCOPY	2.9
7UKC	ELECTRON MICROSCOPY	3
7UKE	ELECTRON MICROSCOPY	3.01
7UKF	ELECTRON MICROSCOPY	3.02
7E83	ELECTRON MICROSCOPY	3.1
7E84	ELECTRON MICROSCOPY	3.1
7F3F	ELECTRON MICROSCOPY	3.1
7E7Z	ELECTRON MICROSCOPY	3.2
7E87	ELECTRON MICROSCOPY	3.4
7E8E	ELECTRON MICROSCOPY	3.9
7E8B	ELECTRON MICROSCOPY	4.2
7E8H	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZV8-F1	72.28	0.40

Functional residue map

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

Ligand- & substrate-binding residues (8): 105 (in chain a); 111 (in chain b); 132 (in chain a); 133 (in chain a); 370; 371; 372; 373

Post-translational modifications (9): 38, 438, 548, 552, 572, 575, 602, 607, 616

Mutagenesis-validated functional residues (30):

Position	Phenotype
309	increases peak current amplitude and causes a negative shift in the voltage-dependence of activation.
311	no effect on peak current amplitude, but causes a positive shift in the voltage-dependence of activation. may increase t
312	increases peak current amplitude and causes a positive shift in the voltage-dependence of activation.
313	causes a positive shift in the voltage-dependence of activation. may decrease the affinity for the closed-inactivated st
314	loss of channel activity.
315	increases peak current amplitude but has a minor effect on the voltage-dependence of activation.
316	increases peak current amplitude and causes a positive shift in the voltage-dependence of activation.
317	increases peak current amplitude and causes a positive shift in the voltage-dependence of activation.
318	increases peak current amplitude and causes a positive shift in the voltage-dependence of activation.
319	may impair protein folding.
320	increases peak current amplitude and causes a positive shift in the voltage-dependence of activation.
320	increases peak current amplitude and slows the onset of inactivation at low voltage, but has no effect on the voltage-de
322	increases peak current amplitude and causes a positive shift in the voltage-dependence of activation. may increase the a
323	slightly increases peak current amplitude and causes a negative shift in the voltage-dependence of activation. may decre
324	may impair protein folding.
327	loss of channel activity.
328	may impair protein folding.
329	loss of channel activity.
397	may impair protein folding.
398	loss of channel activity.
399	may impair protein folding.
401	may impair protein folding.
402–404	increases pak current amplitude and causes a positive shift in the voltage-dependence of activation and steady-state ina
403	loss of channel activity.
405	loss of channel activity.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1296072	Voltage gated Potassium channels
R-HSA-5576894	Phase 1 - inactivation of fast Na+ channels
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 262 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_POTASSIUM_ION_TRANSPORT, E2F_Q4, E2F_Q4_01, RRAGTTGT_UNKNOWN, TAATAAT_MIR126, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, TGCACTT_MIR519C_MIR519B_MIR519A, REACTOME_POTASSIUM_CHANNELS, GCANCTGNY_MYOD_Q6, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_SENSORY_PERCEPTION_OF_PAIN

GO Biological Process (16): action potential (GO:0001508), muscle contraction (GO:0006936), chemical synaptic transmission (GO:0007268), regulation of heart contraction (GO:0008016), neuronal action potential (GO:0019228), sensory perception of pain (GO:0019233), locomotor rhythm (GO:0045475), protein homooligomerization (GO:0051260), cellular response to hypoxia (GO:0071456), potassium ion transmembrane transport (GO:0071805), membrane repolarization (GO:0086009), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (7): voltage-gated potassium channel activity (GO:0005249), A-type (transient outward) potassium channel activity (GO:0005250), metal ion binding (GO:0046872), voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1905030), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (18): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), neuronal cell body membrane (GO:0032809), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), perikaryon (GO:0043204), plasma membrane raft (GO:0044853), postsynaptic membrane (GO:0045211), anchoring junction (GO:0070161), Kv4.2-KChIP2 channel complex (GO:0071193), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), postsynaptic specialization membrane (GO:0099634), membrane (GO:0016020), dendrite (GO:0030425), monoatomic ion channel complex (GO:0034702), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Potassium Channels	1
Cardiac conduction	1
Neuronal System	1
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of membrane potential	3
cellular anatomical structure	3
transport	2
neuronal cell body	2
postsynapse	2
synaptic membrane	2
cell junction	2
synapse	2
muscle system process	1
anterograde trans-synaptic signaling	1
heart contraction	1
regulation of blood circulation	1
action potential	1
transmission of nerve impulse	1
sensory perception	1
locomotory behavior	1
circadian behavior	1
protein complex oligomerization	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
outward rectifier potassium channel activity	1
cation binding	1
voltage-gated monoatomic ion channel activity	1
regulation of postsynaptic membrane potential	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCND2	KCNIP2	Q9NS61	991
KCND2	KCNIP1	Q9NZI2	981
KCND2	DPP10	Q8N608	969
KCND2	KCNIP3	Q9Y2W7	941
KCND2	DPP6	P42658	888
KCND2	IRX5	P78411	884
KCND2	KCND3	Q9UK17	882
KCND2	KCNIP4	Q6PIL6	860
KCND2	KCNE2	Q9Y6J6	839
KCND2	IRX1	P78414	839
KCND2	DLG4	P78352	826
KCND2	NCS1	P36610	797
KCND2	KCNH2	Q12809	791
KCND2	KCNE1	P15382	760
KCND2	KCNAB2	Q13303	744

IntAct

13 interactions, top by confidence:

A	B	Type	Score
KCND2	KCNIP2	psi-mi:“MI:0915”(physical association)	0.550
KCNIP2	KCND2	psi-mi:“MI:0915”(physical association)	0.550
KCND2	BAG3	psi-mi:“MI:0914”(association)	0.530
KCND2	KCNIP2	psi-mi:“MI:0407”(direct interaction)	0.520
KCND2	KCNIP2	psi-mi:“MI:0914”(association)	0.520
KCNIP1	KCND2	psi-mi:“MI:0407”(direct interaction)	0.520
KCNIP1	KCNIP2	psi-mi:“MI:0914”(association)	0.520
KCND2	USP20	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (46): KCTD17 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), BAG1 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), BAG3 (Affinity Capture-MS), GNB4 (Affinity Capture-MS), KCTD5 (Affinity Capture-MS), STUB1 (Affinity Capture-MS), KCND2 (Affinity Capture-Western), NCS1 (Affinity Capture-Western), FLNC (Two-hybrid), FLNC (Reconstituted Complex), KCNIP3 (Affinity Capture-Western), KCTD17 (Affinity Capture-MS), BAG1 (Affinity Capture-MS)

ESM2 similar proteins: A0JPH4, A1DWM3, A4QN56, A6H8H5, B0UYT5, B3MG58, B3NSE1, B4GAP7, B4KR05, B4LPX5, B4QBN2, O18868, O60741, P08911, P11483, P15387, P20309, P41984, P59995, Q03717, Q0P5V9, Q14721, Q1LUC3, Q1LUQ4, Q291H8, Q4V887, Q4ZHA6, Q5BKX6, Q5VW38, Q62897, Q63099, Q63881, Q6ZSS7, Q8C145, Q8CBH5, Q8HYZ1, Q91WD0, Q92953, Q95167, Q95L11

Diamond homologs: A2BDX4, A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, A6H8H5, D4AD53, D4ADX7, G5EFC3, O18868, O35173, O35174, O73606, O88758, O88759, P10499, P15384, P15385, P15387, P15388, P16388, P16390, P17970, P17971, P17972, P22001, P22459, P22739, P25122, P48547, P59053, P59994, P59995

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
IRX5	“down-regulates quantity by repression”	KCND2	“transcriptional regulation”
MAPK1	“up-regulates activity”	KCND2	phosphorylation
FLNA	“up-regulates activity”	KCND2	binding
KCNIP4	“up-regulates activity”	KCND2	relocalization
DPP6	“up-regulates activity”	KCND2	relocalization
DPP10	“up-regulates activity”	KCND2	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	282
Likely benign	170
Benign	20

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
144007	NM_012281.3(KCND2):c.1210G>A (p.Val404Met)	Pathogenic
1457866	NM_012281.3(KCND2):c.913C>T (p.Arg305Cys)	Pathogenic
2007789	NM_012281.3(KCND2):c.1096G>T (p.Val366Phe)	Pathogenic
1297091	NM_012281.3(KCND2):c.1204G>C (p.Val402Leu)	Likely pathogenic
1308937	NM_012281.3(KCND2):c.1184T>C (p.Val395Ala)	Likely pathogenic
1473173	NM_012281.3(KCND2):c.1215T>G (p.Ile405Met)	Likely pathogenic

SpliceAI

3879 predictions. Top by Δscore:

Variant	Effect	Δscore
7:120540726:GGA:G	donor_gain	1.0000
7:120540727:GA:G	donor_gain	1.0000
7:120570988:T:G	acceptor_gain	1.0000
7:120647027:TTGA:T	donor_gain	1.0000
7:120732902:GGT:G	acceptor_gain	1.0000
7:120732902:GGTAT:G	acceptor_gain	1.0000
7:120733062:AAAGG:A	donor_loss	1.0000
7:120733063:AAGGT:A	donor_loss	1.0000
7:120733064:AGG:A	donor_loss	1.0000
7:120733065:GGT:G	donor_loss	1.0000
7:120733066:GTG:G	donor_loss	1.0000
7:120733067:T:A	donor_loss	1.0000
7:120741531:T:G	acceptor_gain	1.0000
7:120741531:TA:T	acceptor_loss	1.0000
7:120741532:A:AG	acceptor_gain	1.0000
7:120741532:A:G	acceptor_loss	1.0000
7:120741533:G:GG	acceptor_gain	1.0000
7:120741533:GA:G	acceptor_gain	1.0000
7:120741533:GAA:G	acceptor_gain	1.0000
7:120741533:GAAA:G	acceptor_gain	1.0000
7:120741625:TGCAG:T	donor_loss	1.0000
7:120741627:CAG:C	donor_loss	1.0000
7:120741628:AG:A	donor_loss	1.0000
7:120741629:GG:G	donor_loss	1.0000
7:120741630:G:T	donor_loss	1.0000
7:120741631:T:G	donor_loss	1.0000
7:120741771:A:AG	acceptor_gain	1.0000
7:120742505:A:AG	acceptor_gain	1.0000
7:120742507:CAGTC:C	acceptor_loss	1.0000
7:120742508:A:AG	acceptor_gain	1.0000

AlphaMissense

4144 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:120274775:G:T	S48I	1.000
7:120274778:G:T	G49V	1.000
7:120274786:T:C	F52L	1.000
7:120274787:T:C	F52S	1.000
7:120274788:C:A	F52L	1.000
7:120274788:C:G	F52L	1.000
7:120274826:C:T	T65I	1.000
7:120274832:T:A	L67Q	1.000
7:120274834:G:C	G68R	1.000
7:120274835:G:A	G68D	1.000
7:120274835:G:T	G68V	1.000
7:120274855:T:C	F75L	1.000
7:120274857:C:A	F75L	1.000
7:120274857:C:G	F75L	1.000
7:120274886:T:C	F85S	1.000
7:120274891:C:A	R87S	1.000
7:120274892:G:C	R87P	1.000
7:120274919:T:C	L96P	1.000
7:120274927:T:G	Y99D	1.000
7:120274931:G:C	R100P	1.000
7:120274963:T:C	C111R	1.000
7:120274988:T:C	L119P	1.000
7:120274993:T:C	F121L	1.000
7:120274995:C:A	F121L	1.000
7:120274995:C:G	F121L	1.000
7:120274996:T:A	F122I	1.000
7:120274996:T:C	F122L	1.000
7:120274998:T:A	F122L	1.000
7:120274998:T:G	F122L	1.000
7:120275026:T:C	C132R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000702 (7:120373820 C>A), RS1000001241 (7:120457349 C>T), RS1000005787 (7:120286768 A>G), RS1000012482 (7:120509351 T>C), RS1000017738 (7:120277414 T>C), RS1000025559 (7:120327101 T>A,C), RS1000026182 (7:120280120 A>G), RS1000026858 (7:120688862 A>G), RS1000034075 (7:120637157 G>A,C), RS1000035829 (7:120506777 T>C), RS1000040078 (7:120567458 G>A,T), RS1000048147 (7:120702661 G>A,T), RS1000051162 (7:120479383 A>G), RS1000061299 (7:120560527 G>A), RS1000063029 (7:120740198 T>C)

Disease associations

OMIM: gene MIM:605410 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
KCND2-related neurodevelopmental disorder with or without seizures	Moderate	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
KCND2-related neurodevelopmental disorder with or without seizures	Moderate	AD

Mondo (3): neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038), KCND2-related neurodevelopmental disorder with or without seizures (MONDO:1040003)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001471_7	Alcohol and nicotine co-dependence	4.000000e-06
GCST001537_10	Immune reponse to smallpox (secreted IL-12p40)	3.000000e-09
GCST006979_147	Heel bone mineral density	2.000000e-15
GCST006979_149	Heel bone mineral density	4.000000e-09
GCST006979_845	Heel bone mineral density	3.000000e-10
GCST009439_21	Age-related cognitive decline (language) (slope of z-scores)	4.000000e-06
GCST010540_3	Mean degree of stenosis	2.000000e-07
GCST010541_7	Maximum stenosis	9.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0009270	heel bone mineral density
EFO:0007710	cognitive decline measurement
EFO:0006501	carotid plaque build

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2362996 (PROTEIN FAMILY), CHEMBL5885 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 115 (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
CHEMBL2107383	VERNAKALANT HYDROCHLORIDE	4	115

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 (8 total), top 8:

Ligand	Action	Affinity	Parameter
phrixotoxin 1	Channel blocker	8.3	pIC50
phrixotoxin 2	Channel blocker	8.3	pIC50
heteropodatoxin-2	Channel blocker	6.5	pIC50
sBmTX 3	Channel blocker	6.0	pIC50
arachidonic acid	Channel blocker	5.7	pIC50
quinidine	Channel blocker	4.9	pIC50
riluzole	Channel blocker	3.89	pIC50
fampridine	Channel blocker	2.3	pIC50

ChEMBL bioactivities

2 potent at pChembl≥5 of 7 total, top 2 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

PubChem BioAssay actives

2 with measured affinity, of 41 total; 1 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

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	5
trichostatin A	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
MRK 003	increases expression	1
incobotulinumtoxinA	increases expression	1
Decitabine	affects expression	1
Vorinostat	decreases expression	1
Adenosine Triphosphate	affects binding, decreases expression, increases abundance, increases expression, decreases abundance	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects expression	1
Dexamethasone	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Formaldehyde	increases expression	1
Glucose	affects binding, decreases expression, increases expression, increases import, decreases import	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Ouabain	increases expression	1
Phthalic Acids	increases methylation	1
Progesterone	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Testosterone	affects cotreatment, increases expression, decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1

ChEMBL screening assays

23 unique, capped per target: 22 binding, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1787442	Binding	Inhibition of human recombinant Kv channel at 10 uM by radioligand binding assay	Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. — Bioorg Med Chem Lett
CHEMBL5522525	Toxicity	Inhibition of human K+ channel by automated electrophysiology	Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. — J Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1K7	PrecisION hKv4.2/KCHiP2-CHO	Spontaneously immortalized cell line	Female
CVCL_D1TA	Abcam U-87MG KCND2 KO	Cancer cell line	Male
CVCL_H518	HEK293/hKv4.2	Transformed cell line	Female
CVCL_ST97	HAP1 KCND2 (-) 1	Cancer cell line	Male
CVCL_ST98	HAP1 KCND2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

204 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
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
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
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