KCNC3

Summary

KCNC3 (potassium voltage-gated channel subfamily C member 3, HGNC:6235) is a protein-coding gene on chromosome 19q13.33, encoding Voltage-gated potassium channel KCNC3 (Q14003). Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons.

The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to one of these subfamilies, namely the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. Alternate splicing results in several transcript variants.

Source: NCBI Gene 3748 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 13 (Definitive, ClinGen)
• Clinical variants (ClinVar): 505 total — 6 pathogenic, 5 likely-pathogenic (top 7% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 7 regions constrained (≈9% of expected missense variation)
• GTEx eGene: eQTL in 26 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 44
• Constraint (gnomAD): pLI 0.30 (intermediate), LOEUF 0.65 (unconstrained)
• MANE Select transcript: NM_004977

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6235
Approved symbol	KCNC3
Name	potassium voltage-gated channel subfamily C member 3
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	Kv3.3
Ensembl gene	ENSG00000131398
Ensembl biotype	protein_coding
OMIM	176264
Entrez	3748

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

MANE Select: ENST00000477616

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 5: 1

ENST00000477616, ENST00000376959, ENST00000474951, ENST00000670667

RefSeq mRNA: 2 — MANE Select: NM_004977 NM_001372305, NM_004977

CCDS: CCDS12793

Canonical transcript exons

ENST00000477616 — 5 exons

Exon	Start	End
ENSE00001937373	50320223	50320349
ENSE00002233598	50322975	50324082
ENSE00002529285	50311937	50316091
ENSE00003471278	50320593	50320784
ENSE00004802921	50328213	50329377

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 95.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3837 / max 166.7517, expressed in 922 samples.

Highest expression (Bgee): kidney epithelium, uterine tube, cerebellar vermis, hemisphere of cerebellum, cerebellar cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

KCNC3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 29 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.6e-55	-0.54	19:50349019:A:G
Spleen	eqtl	1.6e-52	+0.81	19:50342447:G:A
Skin Not Sun Exposed Suprapubic	eqtl	5.8e-48	-0.55	19:50347277:C:T
Adipose Subcutaneous	eqtl	5.3e-37	-0.44	19:50349019:A:G
Nerve Tibial	eqtl	2.0e-18	+0.34	19:50345954:G:A
Esophagus Muscularis	eqtl	1.2e-12	-0.38	19:50349019:A:G
Artery Tibial	eqtl	6.9e-11	-0.27	19:50352678:G:A
Adipose Visceral Omentum	eqtl	7.6e-08	-0.26	19:50349019:A:G
Esophagus Mucosa	eqtl	1.8e-06	-0.26	19:50353078:A:G
Thyroid	sqtl	8.4e-06	-0.47	19:50333427:C:G
Muscle Skeletal	eqtl	1.7e-05	-0.19	19:50349019:A:G
Esophagus Gastroesophageal Junction	eqtl	1.8e-05	-0.33	19:50349019:A:G
Cells EBV-transformed lymphocytes	eqtl	1.7e-04	+0.27	19:50348677:C:T
Artery Aorta	eqtl	2.6e-04	-0.21	19:50349019:A:G
Brain Cerebellar Hemisphere	eqtl	2.9e-03	+0.30	19:49902030:C:T
Stomach	eqtl	3.7e-03	+0.20	19:50411493:C:CT
Breast Mammary Tissue	eqtl	3.9e-03	-0.14	19:50349019:A:G
Thyroid	eqtl	4.2e-03	-0.18	19:50334189:C:T
Testis	eqtl	4.4e-03	+0.29	19:50269877:C:T
Colon Sigmoid	eqtl	6.5e-03	+0.23	19:50354128:T:C

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
182149	4.5644	828
182151	0.8434	315
182152	0.4188	230
182155	0.3788	216
182153	0.2768	188
182148	0.2595	141
182146	0.2040	104
182147	0.1700	73
182154	0.1678	76
182150	0.1002	57

Top tissues by expression

showing 100 of 238 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	95.92	silver quality
right uterine tube	UBERON:0001302	95.51	gold quality
cerebellar vermis	UBERON:0004720	94.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.96	gold quality
cerebellar cortex	UBERON:0002129	93.02	gold quality
cerebellar hemisphere	UBERON:0002245	92.95	gold quality
cerebellum	UBERON:0002037	92.46	gold quality
left lobe of thyroid gland	UBERON:0001120	91.69	gold quality
right lobe of thyroid gland	UBERON:0001119	91.53	gold quality
vena cava	UBERON:0004087	90.39	silver quality
lateral nuclear group of thalamus	UBERON:0002736	90.18	gold quality
thyroid gland	UBERON:0002046	90.08	gold quality
pons	UBERON:0000988	89.93	gold quality
left ventricle myocardium	UBERON:0006566	89.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.57	gold quality
inferior vagus X ganglion	UBERON:0005363	88.42	gold quality
lateral globus pallidus	UBERON:0002476	87.82	gold quality
right frontal lobe	UBERON:0002810	87.63	gold quality
parietal lobe	UBERON:0001872	87.25	gold quality
epithelial cell of pancreas	CL:0000083	87.03	silver quality
dorsal plus ventral thalamus	UBERON:0001897	86.96	gold quality
ventral tegmental area	UBERON:0002691	86.80	gold quality
body of tongue	UBERON:0011876	86.60	silver quality
medulla oblongata	UBERON:0001896	86.36	gold quality
postcentral gyrus	UBERON:0002581	86.19	gold quality
superior vestibular nucleus	UBERON:0007227	86.04	gold quality
frontal cortex	UBERON:0001870	85.62	gold quality
prefrontal cortex	UBERON:0000451	85.45	gold quality
myocardium	UBERON:0002349	85.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.02	silver quality
Brodmann (1909) area 9	UBERON:0013540	85.01	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.87	gold quality
subthalamic nucleus	UBERON:0001906	84.78	gold quality
upper arm skin	UBERON:0004263	84.54	gold quality
metanephros cortex	UBERON:0010533	84.31	gold quality
superior frontal gyrus	UBERON:0002661	84.20	gold quality
pharyngeal mucosa	UBERON:0000355	84.16	silver quality
neocortex	UBERON:0001950	84.14	gold quality
tongue	UBERON:0001723	84.02	silver quality
occipital lobe	UBERON:0002021	83.94	gold quality
cortex of kidney	UBERON:0001225	83.93	gold quality
renal medulla	UBERON:0000362	83.72	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.66	gold quality
pituitary gland	UBERON:0000007	83.23	gold quality
cerebral cortex	UBERON:0000956	82.90	gold quality
adenohypophysis	UBERON:0002196	82.67	gold quality
parotid gland	UBERON:0001831	82.65	gold quality
substantia nigra pars compacta	UBERON:0001965	82.62	silver quality
superior surface of tongue	UBERON:0007371	82.48	gold quality
pericardium	UBERON:0002407	82.34	silver quality
anterior cingulate cortex	UBERON:0009835	82.27	gold quality
brain	UBERON:0000955	82.21	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.14	silver quality
pylorus	UBERON:0001166	81.88	silver quality
primary visual cortex	UBERON:0002436	81.57	gold quality
forebrain	UBERON:0001890	81.21	gold quality
vastus lateralis	UBERON:0001379	80.83	gold quality
metanephros	UBERON:0000081	80.69	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	80.29	gold quality
trigeminal ganglion	UBERON:0001675	80.01	silver quality
Ammon’s horn	UBERON:0001954	79.85	gold quality
granulocyte	CL:0000094	79.59	gold quality
nucleus accumbens	UBERON:0001882	79.48	gold quality
entorhinal cortex	UBERON:0002728	79.44	gold quality
putamen	UBERON:0001874	79.31	gold quality
biceps brachii	UBERON:0001507	79.04	gold quality
temporal lobe	UBERON:0001871	78.90	gold quality
kidney	UBERON:0002113	78.34	gold quality
caudate nucleus	UBERON:0001873	78.27	gold quality
amygdala	UBERON:0001876	78.10	gold quality
dorsal root ganglion	UBERON:0000044	77.95	silver quality
adult mammalian kidney	UBERON:0000082	77.94	gold quality
midbrain	UBERON:0001891	77.04	gold quality
fallopian tube	UBERON:0003889	76.79	gold quality
synovial joint	UBERON:0002217	76.54	silver quality
left uterine tube	UBERON:0001303	76.44	gold quality
monocyte	CL:0000576	76.35	gold quality
leukocyte	CL:0000738	76.20	gold quality
hypothalamus	UBERON:0001898	76.15	gold quality
substantia nigra	UBERON:0002038	75.58	gold quality
mammary duct	UBERON:0001765	75.16	silver quality
cortical plate	UBERON:0005343	75.14	gold quality
epithelium of mammary gland	UBERON:0003244	75.13	silver quality
spinal cord	UBERON:0002240	75.08	gold quality
thymus	UBERON:0002370	74.87	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	74.23	gold quality
muscle tissue	UBERON:0002385	73.68	gold quality
skeletal muscle tissue	UBERON:0001134	73.40	silver quality
penis	UBERON:0000989	73.10	gold quality
globus pallidus	UBERON:0001875	73.09	silver quality
caecum	UBERON:0001153	72.74	gold quality
urethra	UBERON:0000057	72.43	silver quality
oviduct epithelium	UBERON:0004804	72.26	silver quality
secondary oocyte	CL:0000655	71.93	gold quality
trabecular bone tissue	UBERON:0002483	71.86	gold quality
decidua	UBERON:0002450	71.55	gold quality
spleen	UBERON:0002106	70.97	gold quality
endometrium	UBERON:0001295	70.93	gold quality
superficial temporal artery	UBERON:0001614	70.67	gold quality
esophagus squamous epithelium	UBERON:0006920	70.24	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.37

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Postcentral gyrus	tissue	147.8
Cerebellum	tissue	70.8	medium
Cerebral cortex	tissue	70.5	medium
Somatosensory cortex	tissue	70.5
Occipital cortex	tissue	63.7
Superior colliculi	tissue	48.1
Hippocampus	tissue	45.2	low
Motor cortex	tissue	38.8
Temporal cortex	tissue	37.2
Thalamus	tissue	36.8
Retrosplenial and cingulate cortex	tissue	35.0
Prefrontal cortex	tissue	33.9
Hippocampal formation	tissue	32.1
Entorhinal cortex	tissue	32.1
Insular cortex	tissue	30.3
Spinal cord	tissue	29.8
Medulla oblongata	tissue	27.9
Retrosplenial cortex	tissue	27.4
Midbrain	tissue	26.7
Pons	tissue	24.8
Frontal cortex	tissue	24.4
Nucleus accumbens	tissue	20.8
Olfactory bulb	tissue	19.9
Putamen	tissue	18.1
Amygdala	tissue	17.1
Pituitary gland	tissue	16.9
Basal ganglia	tissue	14.8	low
Locus coeruleus	tissue	14.5
Ventral forebrain	tissue	13.9
Parathyroid gland	tissue	13.3	not detected
Caudate putamen	tissue	12.7
Substantia nigra	tissue	10.3
Periaqueductal gray	tissue	10.0
Septum	tissue	8.8
Seminal vesicle	tissue	7.7	low
Hypothalamus	tissue	7.7
Retina	tissue	7.4
Fallopian tube	tissue	6.9	not detected
Thyroid gland	tissue	4.8	low
Choroid plexus	tissue	4.3
Corpus callosum	tissue	4.2
Kidney	tissue	3.8	not detected
Spleen	tissue	3.5	low
Appendix	tissue	2.6	not detected
Lymph node	tissue	2.5	not detected
Epididymis	tissue	2.5	low
Endometrium 1	tissue	2.3	not detected
Thymus	tissue	2.3
Lung	tissue	2.2	low
Pancreas	tissue	1.9	low
Tonsil	tissue	1.8	low
Cervix	tissue	1.5	not detected
Liver	tissue	1.3	low
Breast	tissue	1.1	not detected
Vagina	tissue	1.1	not detected
Salivary gland	tissue	1.1	not detected
Placenta	tissue	1.1	low
Prostate	tissue	1.1	not detected
Skin 1	tissue	1.0	not detected
Testis	tissue	1.0	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Precentral gyrus (195.2), Supplementary motor cortex (101.1), Postcentral gyrus, middle (91.3), Precentral gyrus, middle (88.5), Somatomor cortex, precentral gyrus (white matter) (78.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

miRNA regulators (miRDB)

Targeting KCNC3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 40 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548

Functional genomics

gnomAD constraint: pLI 0.296, LOEUF 0.654, missense Z 3.04 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000477616 splits into 7 regions with different missense tolerance; 1 is missense-constrained (≈9% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:50,320,249–50,323,287	308 / 276.2	1.11	no
19:50,323,288–50,323,498	33 / 96.0	0.34	yes (p 1.3e-10)
19:50,323,499–50,323,539	21 / 21.0	1.00	no
19:50,323,540–50,328,294	157 / 293.5	0.53	no
19:50,328,295–50,328,405	60 / 56.0	1.07	no
19:50,328,406–50,328,877	121 / 247.4	0.49	no
19:50,328,878–50,329,082	129 / 83.6	1.54	no

Literature-anchored findings (GeneRIF, showing 19)

• results establish a role for KCNC3 in phenotypes ranging from developmental disorders to adult-onset neurodegeneration and suggest voltage-gated K+ channels as candidates for additional neurodegenerative diseases (PMID:16501573)
• Mutations in the voltage-gated potassium channel KCNC3 are causative for spinocerebellar ataxia 13. (PMID:18592334)
• The p.Arg420His mutation, which results in a nonfunctional channel subunit, was recurrent and associated with late-onset progressive ataxia. (PMID:19953606)
• Mutations in KCNC3 are a rare cause of spinocerebellar ataxia with a frequency of less than 1%. (PMID:21479265)
• The spinocerebellar ataxia type 13 mutation of the KV3.3 gene specifically suppresses the excitability of Kv3.3-expressing, fast-spiking neurons in zebrafish (PMID:21543613)
• The KCNC3 mutation casued Spinocerebellar ataxia 13. (PMID:21827913)
• Kv3.3 gating contributes significantly to an early age of onset in spinocerebellar ataxia type 13 (PMID:22289912)
• no disease-related KCNC3 mutation was identified, suggesting that spinocerebellar ataxia type 13 is a rare form of SCA in mainland China (PMID:23293936)
• Data suggest that mutant forms of Kv3.3 (as seem in subjects with spinocerebellar ataxia-13) are unstable, are degraded through proteasomes at faster rates, and can be stabilized by a chemical chaperone. (PMID:23734863)
• This study presented the results of a detailed neurological clinical and diagnostic testing on 21 mutation-positive members of a four-generation Filipino family to further define this disease, aiding diagnosis and prognosis. (PMID:23912307)
• Data indicate that an autosomal dominant mutation in the gene encoding Kv3.3 has been identified in a large Filipino kindred manifesting as spinocerebellar ataxia type 13 (SCA13). (PMID:24116147)
• These results are specific to the KCNC3(R420H) allele and provide new insight into the molecular basis of disease manifestation in SCA13. (PMID:25152487)
• Functional and in silico analysis identified at least one novel pathogenic mutation in KCNC3 that cause Spinocerebellar ataxia type 13 (SCA13) and two additionally potential ones. (PMID:25756792)
• investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2 (PMID:25981959)
• This review covers the localization and physiological function of Kv3.3 in the central nervous system and how the normal function of the channel is altered by the disease-causing mutations (PMID:26442672)
• The Kv channels, or at least Kv3.3, appear to be associated with cell differentiation (PMID:26849432)
• Kv3.3 regulates Arp2/3-dependent cortical actin nucleation mediated by Hax-1; resulting cortical actin structures interact with the channel’s gating machinery to slow its inactivation rate during sustained membrane depolarizations; a mutation that leads to late-onset spinocerebellar ataxia type 13. (PMID:26997484)
• results therefore confirm the KCNC3R423H allele as causative for SCA13, through a dominant negative effect on KCNC3WT and links with EGFR that account for dominant inheritance, congenital onset, and disease pathology (PMID:28467418)
• Study expanded the genotype-phenotype-pathophysiology repertoire of SCA13 by addition of a causative KCNC3 mutation, p.Pro583_Pro585del, its associated phenotype of profound spasticity, and the decreased inactivation rate of the mutant channel. (PMID:29949095)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kcnc3	ENSMUSG00000062785
rattus_norvegicus	Kcnc3	ENSRNOG00000019959

Paralogs (31): KCNG1 (ENSG00000026559), KCNQ1 (ENSG00000053918), KCNQ2 (ENSG00000075043), KCND1 (ENSG00000102057), KCNA7 (ENSG00000104848), KCNA1 (ENSG00000111262), KCNC4 (ENSG00000116396), KCNQ4 (ENSG00000117013), KCNS1 (ENSG00000124134), KCNC1 (ENSG00000129159), KCNA5 (ENSG00000130037), 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), KCND2 (ENSG00000184408), KCNQ5 (ENSG00000185760)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96669) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	1
hyperactivity	1
increased vertical activity	1
increased grip strength	1
decreased grip strength	1
decreased bone mineral content	1
abnormal sleep behavior	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RC10	100.0%	Diamond
Macaca fascicularis	Q9GKU7	100.0%	Diamond
Macaca mulatta	A4K2T1	99.8%	Diamond
Chlorocebus aethiops	A4K2Y2	99.8%	Diamond
Pan troglodytes	A4K2N8	99.4%	Diamond
Oryctolagus cuniculus	P59995	99.4%	Diamond
Mustela putorius furo	Q8HYZ1	99.4%	Diamond
Papio anubis	A4K2M4	99.2%	Diamond
Gorilla gorilla gorilla	A4K2R3	99.2%	Diamond
Colobus guereza	A4K2P6	98.9%	Diamond
Canis lupus familiaris	Q28293	98.8%	Diamond
Aotus nancymaae	A4K2W6	98.1%	Diamond
Saimiri boliviensis boliviensis	A4K2X4	98.1%	Diamond
Sus scrofa	O18868	97.3%	Diamond
Bos taurus	Q0P583	96.8%	Diamond
Otolemur garnettii	A4K2Q6	93.4%	Diamond
Lemur catta	A4K2S2	93.4%	Diamond
Xenopus laevis	P22739	91.4%	Diamond
Danio rerio	Q6DG99	90.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
IZUMO2	protein-coding	126123
POLD1	protein-coding	5424
NR1H2	protein-coding	7376
MYH14	protein-coding	79784
NAPSA	protein-coding	9476
SNAR-D	snRNA	100170227
SNAR-B2	snRNA	100170217

Protein

Protein identifiers

Voltage-gated potassium channel KCNC3 — Q14003 (reviewed: Q14003)

Alternative names: KSHIIID, Potassium voltage-gated channel subfamily C member 3, Voltage-gated potassium channel subunit Kv3.3

All UniProt accessions (4): A0A590UJ62, E7ETH1, E9PQY4, Q14003

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics. It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells. Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis. Required for normal motor function. Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex.

Subunit / interactions. Homotetramer. Heterotetramer with KCNC1. Interacts (via C-terminus) with HAX1; this interaction modulates channel gating. Identified in a complex with ACTR3, a subunit of the Arp2/3 complex; this interaction is indirect and depends on the presence of HAX1.

Subcellular location. Cell membrane. Presynaptic cell membrane. Perikaryon. Cell projection. Axon. Dendrite. Dendritic spine membrane. Cytoplasm. Cell cortex. Cytoskeleton.

Post-translational modifications. N-glycosylated.

Disease relevance. Spinocerebellar ataxia 13 (SCA13) [MIM:605259] Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA13 is an autosomal dominant cerebellar ataxia (ADCA) characterized by slow progression and variable age at onset, ranging from childhood to late adulthood. Intellectual disability can be present in some patients. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. The cytoplasmic N-terminus mediates N-type inactivation. The C-terminal cytoplasmic tail contributes to the regulation of channel inactivation and to the interaction with HAX1 and the Arp2/3 complex.

Similarity. Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.3/KCNC3 sub-subfamily.

RefSeq proteins (2): NP_001359234, NP_004968* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR003968	K_chnl_volt-dep_Kv	Family
IPR003974	K_chnl_volt-dep_Kv3	Family
IPR005404	K_chnl_volt-dep_Kv3.3	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)

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (54 total): sequence variant 14, binding site 8, transmembrane region 6, region of interest 5, mutagenesis site 5, topological domain 4, compositionally biased region 4, modified residue 3, glycosylation site 3, chain 1, short sequence motif 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14003-F1	66.01	0.27

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Voltage-gated ion channels, Voltage-Gated Potassium Channels, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

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)

Position	Role
157	Zn(2+)
163	Zn(2+)
184	Zn(2+)
185	Zn(2+)
503	K(+)
504	K(+)
505	K(+)
506	K(+)

Post-translational modifications (3)

Type	Positions
Omega-n-methylarginine	625
Phosphoserine	686, 691

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	320, 336, 483

Mutagenesis-validated functional residues (5)

Position	Phenotype
1–78	loss of n-type inactivation.
366	decreases protein abundance.
420	decreases protein abundance.
423	decreases protein abundance.
592	loss of interaction with actr3. no effect on voltage-dependent channel opening or current amplitude, but decreased rate of inactivation …

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

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

MSigDB gene sets: 208 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, MODULE_64, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOCC_NEURON_PROJECTION, GOBP_PROTEIN_TETRAMERIZATION, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_CORTICAL_CYTOSKELETON_ORGANIZATION, GOCC_NEURON_PROJECTION_TERMINUS, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_POSTSYNAPSE, GOCC_POTASSIUM_CHANNEL_COMPLEX, GOCC_NEURON_SPINE

GO Biological Process (9): action potential (GO:0001508), potassium ion transport (GO:0006813), cortical actin cytoskeleton organization (GO:0030866), protein homooligomerization (GO:0051260), protein tetramerization (GO:0051262), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (6): voltage-gated potassium channel activity (GO:0005249), delayed rectifier potassium channel activity (GO:0005251), metal ion binding (GO:0046872), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (15): cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell cortex (GO:0005938), voltage-gated potassium channel complex (GO:0008076), dendrite (GO:0030425), dendrite membrane (GO:0032590), dendritic spine membrane (GO:0032591), neuronal cell body membrane (GO:0032809), presynaptic membrane (GO:0042734), perikaryon (GO:0043204), axon terminus (GO:0043679), postsynaptic membrane (GO:0045211), membrane (GO:0016020), axon (GO:0030424), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Potassium Channels	1
Neuronal System	1

GO top-level categories

41 GO namespaces:

Category	Terms
synaptic membrane	3
protein complex oligomerization	2
transport	2
cell periphery	2
neuron projection	2
neuron projection membrane	2
neuronal cell body	2
presynapse	2
cellular anatomical structure	2
regulation of membrane potential	1
metal ion transport	1
actin cytoskeleton organization	1
cortical cytoskeleton organization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
voltage-gated potassium channel activity	1
cation binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
binding	1
intracellular membraneless organelle	1
membrane	1
cytoplasm	1
potassium channel complex	1
plasma membrane protein complex	1
dendritic tree	1
dendrite	1
dendrite membrane	1
dendritic spine	1
cell body membrane	1
neuron projection terminus	1
distal axon	1
postsynapse	1
transmembrane transporter complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
cortical actin cytoskeleton organization	BP	direct assay
potassium ion transmembrane transport	BP	mutant phenotype
potassium ion transport	BP	direct assay
protein tetramerization	BP	direct assay
cell cortex	CC	direct assay
dendrite	CC	direct assay
plasma membrane	CC	direct assay
voltage-gated potassium channel complex	CC	direct assay
voltage-gated potassium channel activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,270 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNC3	SLC17A7	Q9P2U7	780
KCNC3	SCN1B	Q07699	746
KCNC3	SPTBN2	O15020	718
KCNC3	CACNA1A	P78510	678
KCNC3	ATXN10	Q9UBB4	675
KCNC3	ATXN7	O15265	654
KCNC3	TTBK2	Q6IQ55	621
KCNC3	PRKCG	P05129	606
KCNC3	FGF14	Q92915	593
KCNC3	SCN1A	P35498	590
KCNC3	SCN3A	Q9NY46	586
KCNC3	PPP2R2B	Q00005	571
KCNC3	AFG3L2	Q9Y4W6	570
KCNC3	SCN3B	Q9NY72	523
KCNC3	SCN2A	Q99250	523

IntAct

Human interaction partners of KCNC3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
ATF6	association	0.350	1
FYN	association	0.350	1

BioGRID (30 interactions; top human partners by supporting records): KCNC4 (Affinity Capture-MS; 3 records), ATF6 (Affinity Capture-MS), ATF6B (Affinity Capture-MS), AXL (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), CSNK1G2 (Affinity Capture-MS), DDR1 (Affinity Capture-MS), EPHX1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FYN (Affinity Capture-MS), JAK1 (Affinity Capture-MS), KCNC1 (Affinity Capture-MS), KDELR1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
KCNC3	“down-regulates quantity”	potassium(1+)	relocalization

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ KCNC1-KCNG3 complex	2	KCNC3, KCNG3

Disease & clinical

Genetic variants

Variant evidence for KCNC3: 505 ClinVar records (11 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	5
Uncertain significance	275
Likely benign	145
Benign	12

Top pathogenic / likely-pathogenic (11)

Showing all 11 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
208671	NM_004977.3(KCNC3):c.1268G>A (p.Arg423His)	Pathogenic	criteria provided, multiple submitters, no conflicts	23
13473	NM_004977.3(KCNC3):c.1259G>A (p.Arg420His)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
522615	NM_004977.3(KCNC3):c.11_12del (p.Ser4fs)	Pathogenic	criteria provided, single submitter	1
422460	NM_004977.3(KCNC3):c.2079C>G (p.Ile693Met)	Likely pathogenic	criteria provided, single submitter	1
808628	NM_004977.3(KCNC3):c.2113C>T (p.Arg705Ter)	Likely pathogenic	criteria provided, single submitter	1
976029	NM_004977.3(KCNC3):c.1223A>G (p.Asp408Gly)	Likely pathogenic	criteria provided, single submitter	1
3251038	NM_004977.3(KCNC3):c.1267C>T (p.Arg423Cys)	Likely pathogenic	criteria provided, single submitter	1
13474	NM_004977.3(KCNC3):c.1344C>A (p.Phe448Leu)	Pathogenic	no assertion criteria provided	1
245604	NM_004977.3(KCNC3):c.1283C>T (p.Thr428Ile)	Pathogenic	no assertion criteria provided	1
545048	NM_004977.3(KCNC3):c.1344C>G (p.Phe448Leu)	Pathogenic	no assertion criteria provided	1
1679940	NM_004977.3(KCNC3):c.2077A>C (p.Ile693Leu)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore KCNC3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 21 predictions of 396):

Position(s)	Effect	Δscore	Sites
19:50320592	donor_loss	1.0000
19:50320786	acceptor_loss	1.0000	3
19:50320793–50320794	acceptor_gain	1.0000	2
19:50320803	acceptor_gain	1.0000
19:50320591–50320592	donor_loss	0.9900	2
19:50320785	acceptor_loss	0.9900	3
19:50320807	acceptor_gain	0.9900
19:50324083–50324084	acceptor_loss	0.9900	6
19:50324092	acceptor_gain	0.9900
19:50320592	donor_loss	0.9800

AlphaMissense

2,576 missense substitutions predicted likely pathogenic (of 4,891 scored), across 478 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M501	9	0.996	1.000
M550	9	0.982	0.999
M509	9	0.974	0.997
M544	9	0.965	0.999
M533	9	0.954	1.000
M465	9	0.950	1.000
M517	9	0.950	0.998
M187	9	0.914	0.989
D385	8	1.000	1.000
F542	8	1.000	1.000
D138	8	0.999	1.000
F144	8	0.999	1.000
F307	8	0.999	1.000
F359	8	0.999	1.000
F454	8	0.999	1.000
F462	8	0.999	1.000
F487	8	0.999	1.000
D508	8	0.999	1.000
H157	8	0.998	1.000
H192	8	0.998	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (validation)	favorable	0.000167
Prostate Adenocarcinoma (TCGA)	unfavorable	0.000345

Disease associations

OMIM: gene MIM:176264 | disease phenotypes: MIM:605259

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
spinocerebellar ataxia type 13	Strong	Autosomal dominant	5

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
spinocerebellar ataxia type 13	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (14 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

14 panels:

Panel	Rating
Adult-onset neurological disorders	green
Ataxia and cerebellar anomalies - childhood onset	green
Cerebellar hypoplasia	green
DDG2P	green
Fetal anomalies	green
Hereditary ataxia	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hereditary ataxia, adult onset	green
Neurodegenerative disorders, adult onset	green
Dystonia, chorea or related movement disorder, childhood onset	amber
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber

Mondo (2): spinocerebellar ataxia type 13 (MONDO:0011529), hereditary ataxia (MONDO:0100309)

Orphanet (2): Hereditary ataxia (Orphanet:183518), Spinocerebellar ataxia type 13 (Orphanet:98768)

HPO phenotypes

44 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000365	Hearing impairment
HP:0000473	Torticollis
HP:0000543	Optic disc pallor
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001999	Abnormal facial shape
HP:0002015	Dysphagia
HP:0002062	Abnormal pyramidal tract morphology
HP:0002066	Gait ataxia
HP:0002067	Bradykinesia
HP:0002070	Limb ataxia
HP:0002073	Progressive cerebellar ataxia
HP:0002172	Postural instability
HP:0002312	Clumsiness
HP:0002406	Limb dysmetria
HP:0003596	Middle age onset
HP:0003677	Slowly progressive
HP:0004322	Short stature
HP:0006801	Hyperactive deep tendon reflexes
HP:0006886	Impaired distal vibration sensation
HP:0007256	Abnormal pyramidal sign
HP:0008003	Jerky ocular pursuit movements
HP:0009046	Difficulty running
HP:0010794	Impaired visuospatial constructive cognition
HP:0011462	Young adult onset
HP:0025331	Upgaze palsy
HP:0030187	Titubation
HP:0100543	Cognitive impairment

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
C531684	Hereditary spinal ataxia *(supp.)*
C537195	Spinocerebellar ataxia 13 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362996 (PROTEIN FAMILY)

PharmGKB: 1 entry (CPIC guideline: no)

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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
tetraethylammonium	Channel blocker	3.9	pIC50
fampridine	Channel blocker	2.9	pIC50

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 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 34 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

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	2
Valproic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
OTX015	increases expression	1
mivebresib	increases expression	1
dicrotophos	increases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases expression	1
jinfukang	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
T-2 Toxin	increases expression	1
Theophylline	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

21 unique, capped per target: 20 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 induced pluripotent stem cell, 1 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1K6	PrecisION hKv3.3-CHO	Spontaneously immortalized cell line	Female
CVCL_E4WA	KOLF2.1J KCNC3 8.9kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_E7LD	KOLF2.1J KCNC3 R420H SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7LE	KOLF2.1J KCNC3 R420H SNV/WT	Induced pluripotent stem cell	Male
CVCL_XP94	HAP1 KCNC3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 95 trials:

NCT	Phase	Status	Title
NCT02422056	Phase 4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	Phase 4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	Phase 4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT03632044	Phase 4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	Phase 4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT00098319	Phase 3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	Phase 3	COMPLETED	Oral Cleft Prevention Program
NCT04928352	Phase 3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT04928391	Phase 3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT00202397	Phase 2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00004639	Phase 2	COMPLETED	Cleft Palate Surgery and Speech Development
NCT00760006	Phase 2	COMPLETED	Preventing Complications in Cleft Palate Repair With Antibiotics
NCT01760330	Phase 2	WITHDRAWN	IV Acetaminophen in Children Undergoing Palatoplasty
NCT02350803	Phase 2	COMPLETED	Does Use of Rigid Fixation After Removing Distraction Osteogenesis Device Reduce the Relapse?
NCT03412474	Phase 2	COMPLETED	Suprazygomatic Block in Cleft Palate Surgery in Children
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01360164	Phase 1/2	UNKNOWN	Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Hereditary Ataxia
NCT00004306	Not specified	COMPLETED	Clinical and Molecular Correlations in Spinocerebellar Ataxia Type 10 (SCA10)
NCT04750850	Not specified	COMPLETED	Core Stability Exercises and Hereditary Ataxia
NCT05160870	Not specified	UNKNOWN	Genotype-phenotype Correlation and Pathogenic Mechanism in Hereditary Ataxia
NCT05160883	Not specified	UNKNOWN	Neuroimaging Changes in Hereditary Ataxia
NCT06034886	Not specified	AVAILABLE	Expanded Access Protocol of Troriluzole in Patients With Spinocerebellar Ataxia (SCA)
NCT06152133	Not specified	COMPLETED	Telerehabilitation, Core Stability Exercises and Hereditary Ataxia (TRCore-ataxia)
NCT06267222	Not specified	UNKNOWN	Trans-spinal Electrical Stimulation in Individuals With Spinocerebellar Ataxia
NCT07092358	Not specified	RECRUITING	Hereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta
NCT07200505	Not specified	NOT_YET_RECRUITING	Telerehabilitation for Core Stability and Strength in Hereditary Ataxia
NCT01616953	Phase 1/2	COMPLETED	Cell Therapy for Craniofacial Bone Defects
NCT02247193	Phase 1/2	COMPLETED	Botulinum Toxin to Improve Cosmesis of Primary Cleft Lip Repair
NCT07734974	Phase 1/2	COMPLETED	Description of Pain in Pediatric Patients With Cleft Lip and Palate Undergoing Alveolar Grafting Using Two Surgical Strategies: Stem Cells and Autogenous Iliac Crest Bone (Pain Evaluation in Children Undergoing Alveolar Grafting: Stem Cells vs. Iliac Crest Bone)
NCT00097149	Not specified	COMPLETED	Systematic Pediatric Care for Oral Clefts - South America
NCT00285714	Not specified	UNKNOWN	3D Imaging of Hard and Soft Tissue in Orthognathic Surgery
NCT00340977	Not specified	COMPLETED	Svangerskap, Arv, Og Miljo (Pregnancy, Heredity and Environment)
NCT00423072	Not specified	COMPLETED	Middle Ear Pressure Disregulation in Cleft Palate Patients
NCT00584272	Not specified	COMPLETED	Retrospective Study on the Outcome of Cleft Palate Repair: Comparing US Surgical and Ethicon Suture Materials
NCT00773994	Not specified	COMPLETED	Pilot Study Evaluating Characteristic Closure Patterns of the Normal Velopharyngeal Portal
NCT00779961	Not specified	UNKNOWN	An Investigation for the Optimal Timing of a Cleft Palate Repair
NCT00829101	Not specified	COMPLETED	Articulation and Phonology in Children With Unilateral Cleft Lip and Palate
NCT00993551	Not specified	COMPLETED	Timing of Primary Surgery for Cleft Palate
NCT00993993	Not specified	COMPLETED	Relational Development in Children With Cleft Lips and Palates: Influence of the Waiting Period Prior to the First Surgical Intervention and the Parents’ Psychological Perception of the Abnormality
NCT01046591	Not specified	COMPLETED	Sleep and Behavior in Children With Cleft Palate
NCT01252264	Not specified	COMPLETED	FaceBase Biorepository
NCT01380171	Not specified	COMPLETED	Primary Palatoplasty in Pediatric Patients - A Retrospective Review of Surgical Outcomes
NCT01500109	Not specified	COMPLETED	Efficacy of Oral Versus Intravenous Acetaminophen for Primary Pediatric Cleft Palate Repair
NCT01535131	Not specified	COMPLETED	Furlow Palatoplasty With Tensor Tenopexy
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01867632	Not specified	COMPLETED	Acellular Dermal Matrix in Primary Palatoplasty
NCT02329509	Not specified	COMPLETED	Evaluation of Facial Growth in Two Primary Protocols Used in the Surgical Treatment of Unilateral Cleft Lip and Palate Patients
NCT02415361	Not specified	COMPLETED	Follow Ups of Parents With Infants With Cleft Lip and Palate
NCT02583100	Not specified	COMPLETED	Improving Outcomes in Cleft Palate Surgery
NCT02595307	Not specified	UNKNOWN	Improving Informed Consent for Cleft Palate Repair
NCT02658318	Not specified	COMPLETED	Postoperative Complications After Cleft Palate Closure in Patients With Pierre Robin Sequence: Operative Considerations
NCT02688634	Not specified	WITHDRAWN	The Role of Antibiotic Prophylaxis in Cleft Palate and Velopharyngeal Insufficiency Repair
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)
NCT02900014	Not specified	COMPLETED	Validation of a Production Method of Stem Cell Isolated From the Nasal Cavity for an Innovative Cell Therapy of Cleft Palate
NCT03170505	Not specified	COMPLETED	Using of Acellular Dermal Matrix in Cleft Palatal Fistula and Compare With Use of Conchal Cartolage
NCT03537976	Not specified	UNKNOWN	Targeting Surgeons’ Decision-Making for Cleft Lip Surgery
NCT03572907	Not specified	WITHDRAWN	Use of Titanium Plate in Rhinoplasty in Patients With Cleft Lip and Palate : Aesthetic and Functional Impact.
NCT03585608	Not specified	COMPLETED	Optic Nerve Sheath Diameter in Patients Undergoing Palatoplasty
NCT03837652	Not specified	UNKNOWN	Bone-borne Palatal Expander With Corticotomy for Cleft Palate Patients
NCT03839290	Not specified	UNKNOWN	Development of the Palate in Bilateral Orofacial Cleft Newborns One Year After Early Neonatal Cheiloplasty