KCNMA1

Summary

KCNMA1 (potassium calcium-activated channel subfamily M alpha 1, HGNC:6284) is a protein-coding gene on chromosome 10q22.3, encoding Calcium-activated potassium channel subunit alpha-1 (Q12791). Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+).

This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome.

Source: NCBI Gene 3778 — RefSeq curated summary.

At a glance

• Gene–disease (curated): generalized epilepsy-paroxysmal dyskinesia syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 31
• Clinical variants (ClinVar): 1,385 total — 16 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001161352

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6284
Approved symbol	KCNMA1
Name	potassium calcium-activated channel subfamily M alpha 1
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KCa1.1, mSLO1
Ensembl gene	ENSG00000156113
Ensembl biotype	protein_coding
OMIM	600150
Entrez	3778

Gene structure

Transcript identifiers

Ensembl transcripts: 96 — 69 protein_coding, 13 protein_coding_CDS_not_defined, 9 nonsense_mediated_decay, 5 retained_intron

ENST00000286627, ENST00000286628, ENST00000354353, ENST00000372403, ENST00000372408, ENST00000372421, ENST00000372437, ENST00000372440, ENST00000372443, ENST00000404771, ENST00000404857, ENST00000406533, ENST00000428546, ENST00000434208, ENST00000450795, ENST00000457953, ENST00000468471, ENST00000475352, ENST00000480683, ENST00000481070, ENST00000484343, ENST00000484507, ENST00000604624, ENST00000618048, ENST00000626620, ENST00000637862, ENST00000638203, ENST00000638223, ENST00000638249, ENST00000638252, ENST00000638283, ENST00000638306, ENST00000638351, ENST00000638361, ENST00000638370, ENST00000638506, ENST00000638512, ENST00000638514, ENST00000638531, ENST00000638575, ENST00000638606, ENST00000638632, ENST00000638751, ENST00000638754, ENST00000638759, ENST00000638848, ENST00000638895, ENST00000638991, ENST00000638999, ENST00000639069, ENST00000639090, ENST00000639120, ENST00000639204, ENST00000639205, ENST00000639282, ENST00000639321, ENST00000639344, ENST00000639370, ENST00000639406, ENST00000639483, ENST00000639486, ENST00000639489, ENST00000639498, ENST00000639544, ENST00000639591, ENST00000639601, ENST00000639657, ENST00000639691, ENST00000639716, ENST00000639730, ENST00000639823, ENST00000639851, ENST00000639913, ENST00000639968, ENST00000639995, ENST00000640029, ENST00000640093, ENST00000640141, ENST00000640182, ENST00000640311, ENST00000640353, ENST00000640386, ENST00000640523, ENST00000640570, ENST00000640605, ENST00000640626, ENST00000640632, ENST00000640773, ENST00000640807, ENST00000640824, ENST00000640834, ENST00000640934, ENST00000640969, ENST00000674918, ENST00000707137, ENST00000707138

RefSeq mRNA: 18 — MANE Select: NM_001161352 NM_001014797, NM_001161352, NM_001161353, NM_001271518, NM_001271519, NM_001271520, NM_001271521, NM_001271522, NM_001322829, NM_001322830, NM_001322832, NM_001322835, NM_001322836, NM_001322837, NM_001322838, NM_001322839, NM_001410940, NM_002247

CCDS: CCDS53545, CCDS60569, CCDS60571, CCDS60572, CCDS73156, CCDS7352, CCDS81481, CCDS86106, CCDS86115, CCDS86116, CCDS86121, CCDS91276

Canonical transcript exons

ENST00000286628 — 28 exons

Exon	Start	End
ENSE00000000028	77403862	77404023
ENSE00001024623	76949142	76949366
ENSE00001024627	76909966	76910096
ENSE00001024628	77039528	77039637
ENSE00001024637	76944773	76944965
ENSE00001024644	76914936	76915049
ENSE00001024655	76889451	76889569
ENSE00001024657	76891525	76891719
ENSE00001242343	76969974	76970067
ENSE00001299773	77019013	77019099
ENSE00001318295	77027823	77027891
ENSE00001327323	76953801	76953924
ENSE00001432087	77001407	77001580
ENSE00001601911	77090400	77090510
ENSE00001608791	77108481	77108572
ENSE00001649548	77084637	77084719
ENSE00001697851	77086488	77086593
ENSE00001726209	77110173	77110343
ENSE00001748461	77120973	77121048
ENSE00001786421	77112367	77112442
ENSE00001789484	77183421	77183532
ENSE00002432021	77184823	77184916
ENSE00002443151	77251195	77251256
ENSE00003539675	77079481	77079550
ENSE00003659617	77073097	77073252
ENSE00003694651	77011967	77012043
ENSE00003740232	76884882	76887515
ENSE00003847750	77637265	77637808

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.8288 / max 396.6505, expressed in 1426 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110174	9.9376	1069
110173	5.2853	1131
110170	3.3280	1031
110179	2.7027	774
110172	0.9246	445
110180	0.6283	307
110175	0.5116	339
110171	0.3028	163
110176	0.2362	117
110157	0.2204	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.25	gold quality
saphenous vein	UBERON:0007318	99.14	gold quality
tibia	UBERON:0000979	98.58	gold quality
calcaneal tendon	UBERON:0003701	98.52	gold quality
blood vessel layer	UBERON:0004797	98.52	gold quality
myometrium	UBERON:0001296	98.38	gold quality
urethra	UBERON:0000057	98.35	gold quality
mucosa of stomach	UBERON:0001199	98.30	gold quality
cauda epididymis	UBERON:0004360	98.21	gold quality
seminal vesicle	UBERON:0000998	98.11	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.87	gold quality
body of uterus	UBERON:0009853	97.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.40	gold quality
middle temporal gyrus	UBERON:0002771	97.28	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.23	gold quality
lower esophagus	UBERON:0013473	97.17	gold quality
superficial temporal artery	UBERON:0001614	97.01	gold quality
popliteal artery	UBERON:0002250	96.94	gold quality
descending thoracic aorta	UBERON:0002345	96.93	gold quality
tibial artery	UBERON:0007610	96.93	gold quality
aorta	UBERON:0000947	96.83	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.76	gold quality
thoracic aorta	UBERON:0001515	96.66	gold quality
ascending aorta	UBERON:0001496	96.63	gold quality
right coronary artery	UBERON:0001625	96.30	gold quality
cartilage tissue	UBERON:0002418	96.24	gold quality
vena cava	UBERON:0004087	96.14	gold quality
cranial nerve II	UBERON:0000941	95.76	gold quality
sigmoid colon	UBERON:0001159	95.63	gold quality
tendon	UBERON:0000043	95.60	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1198.09
E-MTAB-7316	yes	41.48
E-MTAB-10287	yes	38.39
E-CURD-114	yes	10.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CREB1, MITF, SPI1, THRB

miRNA regulators (miRDB)

82 targeting KCNMA1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-607	99.97	73.62	5593
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-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-5580-3P	99.70	69.41	2052

Literature-anchored findings (GeneRIF, showing 40)

• The targets of H2O2 action are located in the intracellular aspect of the channel and the H2O2 effect on channel activity is mediated by hydroxyl radical (PMID:11832330)
• Inhibited by hypoxia by a mechanism which is membrane delimited and Ca(2+) sensitive. (PMID:11986367)
• besides its conductance function, hSlo channel can behave in bone cells, as a true transduction protein intervening in the bone remodeling induced by PGE2 (PMID:12009018)
• N-terminal variation and strex exon splicing in rSlo interact to produce BK(Ca) channels with a physiologically relevant phenotype. (PMID:12016222)
• Stepwise contribution of each subunit to the cooperative activation of channels by calcium (PMID:12161564)
• pore-forming alpha subunit of the hSlo channel promotes N-linked glycosylation of its auxiliary beta4 subunit, and this in turn influences the modulation of the channel by the beta4 subunit (PMID:12223479)
• propose that MaxiK channels via direct c-Src-dependent phosphorylation play a significant role supporting vasoconstriction after activation of G protein-coupled receptors by vasoactive substances and neurotransmitters (PMID:12391293)
• the cytoplasmic tail of rbslo1 is important for the cell surface expression of MaxiK channels (PMID:12438308)
• Chronic hypoxia caused no change in alpha-subunit but evoked a 3-fold increase in beta-subunit expression, and augmented alpha/beta-subunit co-localization at the plasma membrane; maxiK channel function is modulated via post-transcriptional mechanisms. (PMID:14522958)
• electrophysiological and structural evidence showing that haem directly regulates cloned human Slo1 channels and wild-type BK channels in rat brain (PMID:14523450)
• pp125FAK interacts with the large conductance calcium-activated hSlo potassium channel in human osteoblasts: potential role in mechanotransduction (PMID:14584897)
• cAMP-dependent protein kinase (PKA) phosphorylation of the conserved C-terminal PKA consensus site (S899) in all four BKCa alpha-subunits is required for channel activation (PMID:15280542)
• Hemoxygenase-2 is part of the BK channel complex and enhances channel activity in normoxia (PMID:15528406)
• Actin cytoskeleton is involved as part of a caveolar complex in the regulation of myometrial maxi-K channel function. (PMID:15703204)
• Present findings suggest that hslo gating structures targeted by ethanol are accessible to sense changes in bilayer stress. (PMID:15849354)
• mutated in generalized epilepsy and paroxysmal dyskinesia and have implications for the pathogenesis of human epilepsy, the neurophysiology of paroxysmal movement disorders and the role of BK channels in neurological disease (PMID:15937479)
• The Maxi-K channel domain ranging from the N-terminus through the S6 linker region contains the determinants necessary for formation and surface expression of tetramers, while the C-terminus is needed for normal channel gating and surface expression. (PMID:16042390)
• analysis of C-terminal residues that contribute to the Ca2+ sensitivity of a BKCa channel (PMID:16100257)
• Oxidation of M536, M712 or M739 may enhance the Slo1 BK activity during conditions of oxidative stress, such as those associated with ischaemia-reperfusion and neurodegenerative disease, or in response to metabolic cues. (PMID:16396928)
• Evidence is provided for functional association of the MaxiK channel and toll-like receptor signaling complexes in human macrophages. (PMID:16790810)
• Results describe the conformational changes that the large conductance voltage- and Ca(2+)-activated K(+) channel undergoes during activation. (PMID:16895996)
• Appears to be a central molecule in the NF-kappa B-dependent inflammatory response of macrophages to bacterial lipopolysaccharides. (PMID:16951373)
• Amplification of chromosomal region 10q22 drives KCNMA1 expression and cell proliferation in prostate cancer. (PMID:17146446)
• Alternative splicing of this protein may represent a mechanism with which relaxation of corporal tissue may be triggered as a result of a diabetes-related decline in erectile capacity. (PMID:17150299)
• RACK1 binds to the BK(Ca) channel and it may form part of a BK(Ca)-channel regulatory complex in vascular smooth muscle. (PMID:17166942)
• both the inner and outer domains of the KCNMA1 channel where these two channel functions are localized respond to deformation and that a fixed amount of distortion results in reciprocal changes in protein function. (PMID:17468961)
• The activity of BK(Ca) channels present in human cardiac fibroblasts may contribute to the functional activities of heart cells through transfer of electrical signals between these two cell types. (PMID:17483867)
• reports that coexpression of beta2 subunit (KCNMB2) with hSlo can also modulate hSlo surface expression levels in HEK293T cells (PMID:17521822)
• Interactions with filamin A stimulate surface expression of KCNMA1 in the absence of direct actin binding. (PMID:17586600)
• A study evaluating the mechanism of gating of MaxiK is reported. (PMID:17591987)
• the beta(2) subunit of BK(Ca) channels facilitates channel activation by changing the voltage sensor equilibrium and that the beta(2)-induced inactivation process does not follow a typical N-type mechanism (PMID:17591990)
• data suggest sensory nerves and BKCa channels play major roles in the EDHF component of reactive hyperaemia and appear to work partly independent of each other (PMID:17901123)
• Slo1-actin interactions are necessary for normal trafficking of calcium channels to the plasma membrane. (PMID:17989352)
• Acute alcohol tolerance is intrinsic to the BKCa protein, but is modulated by the lipid environment (PMID:18084004)
• analysis of how the RCK2 domain of the human BKCa channel is a calcium sensor (PMID:18162557)
• Show that a motif in the S9-S10 part of the C-terminal of KCNMA1 is essential for carbon monoxide activation. CO may activate KCNMA1 by redox-independent changes in gating. (PMID:18180950)
• The influence of the intrinsic electrostatic potential on the channel conductance of KCNMA1 was studied experimentally and theoretically by amino acid substitution. (PMID:18227273)
• Carbon monoxide acts as a partial agonist for the high-affinity divalent cation sensor in the RCK1 domain of the Slo1 BK channel. (PMID:18316727)
• common motif in the RCK1 domain of SLO1 mediates the stimulatory effects of both H+ and Ca2+, and provides a basis for the bidirectional coupling of cell metabolism and membrane electrical excitability (PMID:18345016)
• insulin activates BK in the plasma membrane of mesangial cells and stimulates, via MAPK, an increase in cellular and plasma membrane BK-alpha (PMID:18367663)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnma1a	ENSDARG00000079840
danio_rerio	kcnma1b	ENSDARG00000110727
mus_musculus	Kcnma1	ENSMUSG00000063142
rattus_norvegicus	Kcnma1	ENSRNOG00000005985
drosophila_melanogaster	SLO2	FBGN0261698
caenorhabditis_elegans		WBGENE00004831

Paralogs (3): KCNT1 (ENSG00000107147), KCNT2 (ENSG00000162687), KCNU1 (ENSG00000215262)

Protein

Protein identifiers

Calcium-activated potassium channel subunit alpha-1 — Q12791 (reviewed: Q12791)

Alternative names: BK channel, BKCA alpha, Calcium-activated potassium channel, subfamily M subunit alpha-1, K(VCA)alpha, KCa1.1, Maxi K channel, Slo-alpha, Slo1, Slowpoke homolog

All UniProt accessions (71): Q12791, A0A087WZL8, A0A0A0MRC3, A0A0A0MRR0, A0A0A0MSE6, A0A1B0GWD4, A0A1W2PNG1, A0A1W2PNH9, A0A1W2PNN5, A0A1W2PNN6, A0A1W2PNQ3, A0A1W2PNW6, A0A1W2PNX9, A0A1W2PNY7, A0A1W2PNY8, A0A1W2PNY9, A0A1W2PP06, A0A1W2PP26, A0A1W2PP37, A0A1W2PP76, A0A1W2PP94, A0A1W2PPH9, A0A1W2PPQ3, A0A1W2PPS2, A0A1W2PPT7, A0A1W2PPX7, A0A1W2PPY5, A0A1W2PPZ1, A0A1W2PQ39, A0A1W2PQ53, A0A1W2PQ61, A0A1W2PQ93, A0A1W2PQA0, A0A1W2PQJ9, A0A1W2PQK5, A0A1W2PQR1, A0A1W2PQU4, A0A1W2PQZ4, A0A1W2PQZ8, A0A1W2PR56, A0A1W2PR62, A0A1W2PRA7, A0A1W2PRB0, A0A1W2PRC3, A0A1W2PRE5, A0A1W2PRF1, A0A1W2PRG5, A0A1W2PRJ1, A0A1W2PRN5, A0A1W2PRT6, A0A1W2PRV4, A0A1W2PRX6, A0A1W2PS54, A0A1W2PS97, A0A1W2PSA7, A0A1W2PSD3, A0A9L9PXP1, A0A9L9PYL6, B7ZMF5, D5MRH1, H0Y379, H0Y382, H0Y406, J3KQ16, Q5SVJ7, Q5SVJ8, Q5SVJ9, Q5SVK0, Q5SVK5, S4R2X4, S4R453

UniProt curated annotations — full annotation on UniProt →

Function. Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX). Possibly induces sleep when activated by melatonin and through melatonin receptor MTNR1A-dependent dissociation of G-beta and G-gamma subunits, leading to increased sensitivity to Ca(2+) and reduced synaptic transmission. Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+).

Subunit / interactions. Homotetramer; which constitutes the calcium-activated potassium channel. Interacts with RAB11B. Interacts with beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. Interacts with gamma subunits LRRC26, LRRC38, LRRC52 and LRRC55. Beta and gamma subunits are accessory, and modulate its activity.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed. Except in myocytes, it is almost ubiquitously expressed.

Post-translational modifications. Phosphorylated. Phosphorylation by kinases such as PKA and/or PKG. In smooth muscles, phosphorylation affects its activity. Palmitoylation by ZDHHC22 and ZDHHC23 within the intracellular linker between the S0 and S1 transmembrane domains regulates localization to the plasma membrane. Depalmitoylated by LYPLA1 and LYPLAL1, leading to retard exit from the trans-Golgi network.

Disease relevance. Paroxysmal non-kinesigenic dyskinesia 3 with or without generalized epilepsy (PNKD3) [MIM:609446] An autosomal dominant neurologic disorder characterized by absence seizures, generalized tonic-clonic seizures, paroxysmal nonkinesigenic dyskinesia and involuntary dystonic or choreiform movements. Onset is usually in childhood. Patients may have seizures only, dyskinesia only, or both. The disease is caused by variants affecting the gene represented in this entry. Epilepsy, idiopathic generalized 16 (EIG16) [MIM:618596] An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. EIG16 is characterized by onset of seizures soon after birth or in the first years of life. Disease susceptibility is associated with variants affecting the gene represented in this entry. Cerebellar atrophy, developmental delay, and seizures (CADEDS) [MIM:617643] An autosomal recessive disease characterized by epilepsy, developmental delay and severe cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry. Liang-Wang syndrome (LIWAS) [MIM:618729] An autosomal dominant syndrome characterized by a highly variable phenotype and severity. The broad spectrum of clinical features includes developmental delay, intellectual disability, ataxia, axial hypotonia, and poor or absent speech, visceral and cardiac malformations, connective tissue presentations with arterial involvement, bone dysplasia and characteristic craniofacial dysmorphism. About half of patients have cerebral and cerebellar atrophy, and thin corpus callosum. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation.

Domain organisation. The S0 segment is essential for the modulation by the accessory beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor. The pore-forming domain (also referred as P region) is imbedded into the membrane, and forms the selectivity filter of the pore. It contains the signature sequence of potassium channels that displays selectivity to potassium. The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel. It includes binding sites for Ca(2+) and Mg(2+). The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site. There are however other Ca(2+) sensors region required for activation of the channel. The heme-binding motif mediates inhibition of channel activation by heme. Carbon monoxide-bound heme leads to increased channel activation.

Miscellaneous. The protein was initially thought to contain two functionally distinct parts: The core channel (from the N-terminus to the S9 segment) that mediates the channel activity, and the cytoplasmic tail (from the S9 segment to the C-terminus) that mediates the calcium sensing. The situation is however more complex, since the core channel also contains binding sites for Ca(2+) and Mg(2+).

Similarity. Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa1.1/KCNMA1 sub-subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
Q12791-1	1, SAKCA	yes
Q12791-2	2, BKTM
Q12791-3	3
Q12791-4	4, hbr5
Q12791-5	5
Q12791-6	6
Q12791-7	7, gBK

RefSeq proteins (18): NP_001014797, NP_001154824, NP_001154825, NP_001258447, NP_001258448, NP_001258449, NP_001258450, NP_001258451, NP_001309758, NP_001309759, NP_001309761, NP_001309764, NP_001309765, NP_001309766, NP_001309767, NP_001309768, NP_001397869, NP_002238 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003148	RCK_N	Domain
IPR003929	K_chnl_BK_asu	Domain
IPR005821	Ion_trans_dom	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR047871	K_chnl_Slo-like	Family
IPR048735	Slowpoke-like_C	Domain

Pfam: PF00520, PF03493, PF21014, PF22614

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (189 total): helix 54, strand 38, mutagenesis site 16, topological domain 9, modified residue 9, region of interest 8, sequence variant 8, transmembrane region 7, sequence conflict 7, binding site 7, splice variant 7, turn 6, compositionally biased region 4, lipid moiety-binding region 3, domain 2, short sequence motif 2, chain 1, intramembrane region 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6V5A	X-RAY DIFFRACTION	2
8V60	ELECTRON MICROSCOPY	2.43
9CZM	ELECTRON MICROSCOPY	2.57
8V64	ELECTRON MICROSCOPY	2.6
8GHF	ELECTRON MICROSCOPY	2.7
8V63	ELECTRON MICROSCOPY	2.72
9JO3	ELECTRON MICROSCOPY	2.8
8VAZ	ELECTRON MICROSCOPY	2.82
9CZO	ELECTRON MICROSCOPY	2.87
9CZQ	ELECTRON MICROSCOPY	2.88
9D18	ELECTRON MICROSCOPY	2.88
9D19	ELECTRON MICROSCOPY	2.88
9CZH	ELECTRON MICROSCOPY	2.9
3MT5	X-RAY DIFFRACTION	3
3NAF	X-RAY DIFFRACTION	3.1
7YO3	ELECTRON MICROSCOPY	3.1
8VAV	ELECTRON MICROSCOPY	3.13
6V22	ELECTRON MICROSCOPY	3.2
7YO2	ELECTRON MICROSCOPY	3.3
8GHG	ELECTRON MICROSCOPY	3.3
9JO4	ELECTRON MICROSCOPY	3.4
10AD	ELECTRON MICROSCOPY	3.44
6ND0	ELECTRON MICROSCOPY	3.5
6V35	ELECTRON MICROSCOPY	3.5
7YNZ	ELECTRON MICROSCOPY	3.5
9CZK	ELECTRON MICROSCOPY	3.5
9CZJ	ELECTRON MICROSCOPY	3.54
7YO0	ELECTRON MICROSCOPY	3.6
7YO1	ELECTRON MICROSCOPY	3.6
6V38	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12791-F1	76.94	0.48

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 (7): 439; 462; 464; 1012; 1015; 1018; 1020

Post-translational modifications (12): 763, 765, 778, 782, 970, 978, 982, 1221, 1224, 118, 119, 121

Mutagenesis-validated functional residues (16):

Position	Phenotype
118	decreased localization to the plasma membrane. abolishes localization to the plasma membrane; when associated with a-119
119	decreased localization to the plasma membrane. abolishes localization to the plasma membrane; when associated with a-118
121	decreased localization to the plasma membrane. abolishes localization to the plasma membrane; when associated with a-119
269	no effect in the coupling between calcium and channel opening.
272	induces reduction in the coupling between calcium and channel opening.
275	induces reduction in the coupling between calcium and channel opening.
278	induces reduction in the coupling between calcium and channel opening.
281	no effect in the coupling between calcium and channel opening.
284	no effect in the coupling between calcium and channel opening.
352	activated at more negative voltages. slower rate of inactivation. impaired inhibition by hmimp. no effect on channel inh
354–356	loss of function.
380	loss of function.
381	activated at more negative voltages. no effect on inhibition by hmimp.
384	no effect on activation voltage. no effect on inhibition by hmimp.
680	loss of heme-induced channel inhibition.
681	loss of heme-induced channel inhibition.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1296052	Ca2+ activated K+ channels
R-HSA-418457	cGMP effects
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-9667769	Acetylcholine inhibits contraction of outer hair cells
R-HSA-109582	Hemostasis
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels
R-HSA-392154	Nitric oxide stimulates guanylate cyclase
R-HSA-418346	Platelet homeostasis
R-HSA-9659379	Sensory processing of sound
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 449 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_EXCRETION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MODY_HIPPOCAMPUS_POSTNATAL, BENPORATH_ES_WITH_H3K27ME3, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_POTASSIUM_CHANNELS, TTTGTAG_MIR520D, AAGCCAT_MIR135A_MIR135B, GOBP_POTASSIUM_ION_HOMEOSTASIS, GTTAAAG_MIR302B, AP4_Q6, LHX3_01, CACCAGC_MIR138

GO Biological Process (16): response to hypoxia (GO:0001666), potassium ion transport (GO:0006813), response to osmotic stress (GO:0006970), intracellular potassium ion homeostasis (GO:0030007), response to carbon monoxide (GO:0034465), vasodilation (GO:0042311), regulation of membrane potential (GO:0042391), positive regulation of apoptotic process (GO:0043065), negative regulation of cell volume (GO:0045794), response to calcium ion (GO:0051592), micturition (GO:0060073), smooth muscle contraction involved in micturition (GO:0060083), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (9): actin binding (GO:0003779), voltage-gated potassium channel activity (GO:0005249), calcium-activated potassium channel activity (GO:0015269), identical protein binding (GO:0042802), metal ion binding (GO:0046872), large conductance calcium-activated potassium channel activity (GO:0060072), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), caveola (GO:0005901), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), apical plasma membrane (GO:0016324), postsynaptic membrane (GO:0045211), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Sensory processing of sound	2
Potassium Channels	1
Nitric oxide stimulates guanylate cyclase	1
Sensory processing of sound by outer hair cells of the cochlea	1
Neuronal System	1
Platelet homeostasis	1
Hemostasis	1
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	2
transport	2
potassium channel activity	2
response to decreased oxygen levels	1
metal ion transport	1
response to abiotic stimulus	1
intracellular monoatomic cation homeostasis	1
potassium ion homeostasis	1
response to oxygen-containing compound	1
blood vessel diameter maintenance	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
cell volume homeostasis	1
response to metal ion	1
renal system process	1
excretion	1
urinary bladder smooth muscle contraction	1
micturition	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
cytoskeletal protein binding	1
voltage-gated monoatomic cation channel activity	1
calcium-activated cation channel activity	1
protein binding	1
cation binding	1
calcium-activated potassium channel activity	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
plasma membrane raft	1

Protein interactions and networks

STRING

2552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNMA1	KCNMB1	P78475	990
KCNMA1	LRRC26	Q2I0M4	960
KCNMA1	KCNMB3	Q9NPA1	955
KCNMA1	KCNMB4	Q86W47	954
KCNMA1	CRBN	Q96SW2	888
KCNMA1	KCNN4	O15554	827
KCNMA1	KCNN1	Q92952	809
KCNMA1	KCNJ1	P48048	803
KCNMA1	PXK	Q7Z7A4	747
KCNMA1	CACNA1C	Q13936	737
KCNMA1	CSN3	P07498	720
KCNMA1	KCNN2	Q9H2S1	709
KCNMA1	STK39	Q9UEW8	704
KCNMA1	WNK4	Q96J92	685
KCNMA1	KCNA2	P16389	682

IntAct

10 interactions, top by confidence:

A	B	Type	Score
PTPRA	PTPRE	psi-mi:“MI:0914”(association)	0.420
Asic1	KCNMA1	psi-mi:“MI:0915”(physical association)	0.400
KCNMA1	Asic1	psi-mi:“MI:0915”(physical association)	0.400
LRRC26	KCNMA1	psi-mi:“MI:0915”(physical association)	0.400
TBXA2R	KCNMA1	psi-mi:“MI:0915”(physical association)	0.400
KCNMA1	KCNMB2	psi-mi:“MI:0915”(physical association)	0.400
ALB	CDC45	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): KCNMA1 (Affinity Capture-MS), KCNMA1 (Affinity Capture-MS), KCNMA1 (Affinity Capture-RNA), CRBN (Affinity Capture-Western), DDB1 (Affinity Capture-Western), FBXO7 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), MAGI1 (Reconstituted Complex), MAGI1 (Affinity Capture-Western), KCNMA1 (Affinity Capture-Western), KCNMA1 (Affinity Capture-MS), TNPO1 (Affinity Capture-MS), LAMP1 (Affinity Capture-MS), PRKDC (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3R8G1, A0A0M4FLW6, A9YWR6, B8ALI0, B8BDK8, B9FMX4, D3GE74, D3ZCM3, D4AYW0, O18866, O18867, O80946, P45843, P45844, P93025, Q00195, Q03041, Q03720, Q08460, Q12791, Q16280, Q28204, Q28718, Q5W274, Q62398, Q62976, Q64343, Q7XA72, Q84K47, Q8GU83, Q8H8V7, Q8RWI9, Q8RXN0, Q90ZC7, Q91WA9, Q93YS4, Q96290, Q9BG98, Q9C8J8, Q9C8K2

Diamond homologs: A5LFX5, A8MYU2, B7ZC96, D4A6Z8, O18866, O18867, O54982, Q03720, Q08460, Q12791, Q28204, Q28265, Q57603, Q62976, Q8AYS8, Q90ZC7, Q95V25, Q9BG98, O43526, O88943, Q8I5E6

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PRKCA	up-regulates	KCNMA1	phosphorylation
KCNMA1	“down-regulates quantity”	potassium(1+)	relocalization
calcium(2+)	“up-regulates activity”	KCNMA1	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1385 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	26
Uncertain significance	643
Likely benign	505
Benign	78

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072449	NM_001161352.2(KCNMA1):c.302dup (p.Leu102fs)	Pathogenic
1414943	NM_001161352.2(KCNMA1):c.1284del (p.Leu429fs)	Pathogenic
1458025	NC_000010.10:g.(?78998319)(79163801_?)del	Pathogenic
1685896	NM_001161352.2(KCNMA1):c.1437del (p.Lys480fs)	Pathogenic
265313	NM_001161352.2(KCNMA1):c.3158A>G (p.Asn1053Ser)	Pathogenic
2704729	NM_001161352.2(KCNMA1):c.1869del (p.Phe623fs)	Pathogenic
3342855	NM_001161352.2(KCNMA1):c.940G>A (p.Ala314Thr)	Pathogenic
3638934	NM_001161352.2(KCNMA1):c.1123G>T (p.Gly375Trp)	Pathogenic
3728777	NM_001161352.2(KCNMA1):c.297del (p.Phe99fs)	Pathogenic
4071955	NM_001161352.2(KCNMA1):c.2899C>T (p.Gln967Ter)	Pathogenic
4082457	NM_001161352.2(KCNMA1):c.1051T>A (p.Ser351Thr)	Pathogenic
437872	NM_001161352.2(KCNMA1):c.2026dup (p.Tyr676fs)	Pathogenic
691495	NM_001161352.2(KCNMA1):c.1372C>T (p.Arg458Ter)	Pathogenic
804292	NM_001161352.2(KCNMA1):c.1052C>A (p.Ser351Tyr)	Pathogenic
859287	NM_001161352.2(KCNMA1):c.2786del (p.Asn929fs)	Pathogenic
9427	NM_001161352.2(KCNMA1):c.1301A>G (p.Asp434Gly)	Pathogenic
1004014	NM_001161352.2(KCNMA1):c.1807A>G (p.Thr603Ala)	Likely pathogenic
1203674	NM_001161352.2(KCNMA1):c.540+1G>A	Likely pathogenic
1479179	NM_001161352.2(KCNMA1):c.574C>A (p.Leu192Ile)	Likely pathogenic
1506973	NM_001161352.2(KCNMA1):c.2092+1G>A	Likely pathogenic
1519204	NC_000010.10:g.(?78998319)(79163801_?)dup	Likely pathogenic
1526134	NM_001161352.2(KCNMA1):c.1334+1G>T	Likely pathogenic
216948	NM_001161352.2(KCNMA1):c.1054A>G (p.Thr352Ala)	Likely pathogenic
2424381	NC_000010.10:g.(?78943159)(78944694_?)dup	Likely pathogenic
2429851	NM_001161352.2(KCNMA1):c.1845C>G (p.Phe615Leu)	Likely pathogenic
2629023	NM_001161352.2(KCNMA1):c.2837del (p.Ala946fs)	Likely pathogenic
2633700	NM_001161352.2(KCNMA1):c.771del (p.Val258fs)	Likely pathogenic
2866161	NM_001161352.2(KCNMA1):c.1749+2T>C	Likely pathogenic
3068628	NM_001161352.2(KCNMA1):c.2173del (p.Ser725fs)	Likely pathogenic
3338089	NM_001161352.2(KCNMA1):c.33_34del (p.Ser11fs)	Likely pathogenic

SpliceAI

6339 predictions. Top by Δscore:

Variant	Effect	Δscore
10:76887511:CATAC:C	acceptor_gain	1.0000
10:76887513:TAC:T	acceptor_gain	1.0000
10:76887514:ACC:A	acceptor_loss	1.0000
10:76887516:C:CA	acceptor_loss	1.0000
10:76887517:T:A	acceptor_loss	1.0000
10:76889579:A:T	acceptor_gain	1.0000
10:76891441:G:C	donor_gain	1.0000
10:76891523:ACC:A	donor_gain	1.0000
10:76891524:CCC:C	donor_gain	1.0000
10:76891717:CGT:C	acceptor_gain	1.0000
10:76909959:AACTC:A	donor_loss	1.0000
10:76909960:ACT:A	donor_loss	1.0000
10:76909961:CTCAC:C	donor_loss	1.0000
10:76909962:TCA:T	donor_loss	1.0000
10:76909963:CACC:C	donor_loss	1.0000
10:76909964:A:AC	donor_gain	1.0000
10:76909964:ACC:A	donor_loss	1.0000
10:76909965:C:CC	donor_gain	1.0000
10:76909965:CCG:C	donor_gain	1.0000
10:76909965:CCGCG:C	donor_gain	1.0000
10:76910092:GTTCA:G	acceptor_gain	1.0000
10:76910093:TTCA:T	acceptor_gain	1.0000
10:76910094:TCA:T	acceptor_gain	1.0000
10:76910095:CA:C	acceptor_gain	1.0000
10:76910095:CAC:C	acceptor_gain	1.0000
10:76910096:ACTA:A	acceptor_loss	1.0000
10:76910097:C:CC	acceptor_gain	1.0000
10:76910097:CTAG:C	acceptor_loss	1.0000
10:76910098:T:G	acceptor_loss	1.0000
10:76914930:CCCTA:C	donor_loss	1.0000

AlphaMissense

8191 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:76889505:C:T	G1136E	1.000
10:76889506:C:G	G1136R	1.000
10:76889506:C:T	G1136R	1.000
10:76889510:A:C	C1134W	1.000
10:76889512:A:G	C1134R	1.000
10:76891711:G:C	F1052L	1.000
10:76891711:G:T	F1052L	1.000
10:76891713:A:G	F1052L	1.000
10:76910010:C:A	G1035W	1.000
10:76944832:A:G	L948P	1.000
10:76944904:A:T	V924D	1.000
10:76949210:C:G	G881R	1.000
10:76949316:G:C	C845W	1.000
10:76949318:A:G	C845R	1.000
10:76949320:A:T	V844D	1.000
10:76953840:A:C	F815L	1.000
10:76953840:A:T	F815L	1.000
10:76953841:A:G	F815S	1.000
10:76953842:A:G	F815L	1.000
10:77012030:A:G	C677R	1.000
10:77039622:A:G	W589R	1.000
10:77039622:A:T	W589R	1.000
10:77073122:A:G	L575P	1.000
10:77073228:A:G	W540R	1.000
10:77073228:A:T	W540R	1.000
10:77073245:A:G	L534P	1.000
10:77079535:C:A	K513N	1.000
10:77079535:C:G	K513N	1.000
10:77079537:T:C	K513E	1.000
10:77079539:A:C	I512R	1.000

dbSNP variants (sampled 300 via entrez): RS1000009547 (10:77520983 T>C), RS1000010452 (10:77337234 T>C), RS1000011032 (10:77120006 T>C), RS1000016726 (10:77003111 C>G,T), RS1000019121 (10:77420157 G>C), RS1000022089 (10:77089743 T>C), RS1000022149 (10:77632472 G>A), RS1000032138 (10:77089556 C>T), RS1000037409 (10:77298263 A>G), RS1000038200 (10:76955917 T>C), RS1000038475 (10:77203934 T>C,G), RS1000041528 (10:77408223 G>A), RS1000044269 (10:76901623 A>C,G), RS1000052670 (10:77133386 T>G), RS1000054025 (10:77542062 T>C)

Disease associations

OMIM: gene MIM:600150 | disease phenotypes: MIM:609446, MIM:617643, MIM:618596, MIM:618729, MIM:108600

GenCC curated gene-disease

Disease	Classification	Inheritance
generalized epilepsy-paroxysmal dyskinesia syndrome	Definitive	Autosomal dominant
cerebellar atrophy, developmental delay, and seizures	Strong	Autosomal recessive
Liang-Wang syndrome	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
generalized epilepsy-paroxysmal dyskinesia syndrome	Definitive	AD
generalized epilepsy-paroxysmal dyskinesia syndrome	Moderate	AR

Mondo (8): generalized epilepsy-paroxysmal dyskinesia syndrome (MONDO:0012276), cerebellar atrophy, developmental delay, and seizures (MONDO:0060551), epilepsy, idiopathic generalized, susceptibility to, 16 (MONDO:0032827), Liang-Wang syndrome (MONDO:0032886), intellectual disability (MONDO:0001071), infantile epileptic-dyskinetic encephalopathy (MONDO:0018226), autism spectrum disorder (MONDO:0005258), spastic ataxia (MONDO:0017845)

Orphanet (6): Generalized epilepsy-paroxysmal dyskinesia syndrome (Orphanet:79137), Gingival fibromatosis-aortic root dilatation-facial dysmorphism-intellectual disability syndrome (Orphanet:664438), Infantile epileptic-dyskinetic encephalopathy (Orphanet:364063), Spastic ataxia (Orphanet:316226), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000212	Gingival overgrowth
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000431	Wide nasal bridge
HP:0000485	Megalocornea
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000675	Macrodontia of permanent maxillary central incisor
HP:0000699	Diastema
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001332	Dystonia
HP:0001348	Brisk reflexes
HP:0001601	Laryngomalacia
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000661_1	Mortality in heart failure	7.000000e-06
GCST001130_2	Obesity	3.000000e-10
GCST001482_22	Lumbar spine bone mineral density	5.000000e-19
GCST002497_8	Blood pressure	9.000000e-07
GCST002497_9	Blood pressure	9.000000e-07
GCST002563_14	Hypospadias	2.000000e-10
GCST002598_9	Educational attainment	6.000000e-06
GCST003084_9	Glucocorticoid-induced osteonecrosis	9.000000e-06
GCST003380_6	Bone mineral density (spine)	4.000000e-07
GCST003997_28	Myopia	3.000000e-22
GCST005023_27	Initial pursuit acceleration	8.000000e-06
GCST005796_17	Lumbar spine bone mineral density	5.000000e-09
GCST005918_2	Smoking cessation in chronic obstructive pulmonary disease	6.000000e-08
GCST006277_2	Response to ranibizumab in age-related macular degeneration (exudative)	2.000000e-06
GCST006288_109	Heel bone mineral density	4.000000e-08
GCST006288_636	Heel bone mineral density	2.000000e-15
GCST006288_720	Heel bone mineral density	1.000000e-08
GCST006291_104	Spherical equivalent or myopia (age of diagnosis)	8.000000e-19
GCST006661_248	Male-pattern baldness	2.000000e-24
GCST006979_593	Heel bone mineral density	3.000000e-29
GCST007676_14	3-month functional outcome in ischaemic stroke (modified Rankin score)	4.000000e-06
GCST007876_114	Estimated glomerular filtration rate	3.000000e-08
GCST008058_302	Estimated glomerular filtration rate	3.000000e-11
GCST008059_256	Estimated glomerular filtration rate	2.000000e-10
GCST008153_22	Lean body mass	5.000000e-06
GCST009725_45	Intraocular pressure	9.000000e-06
GCST010002_292	Refractive error	3.000000e-69
GCST011354_48	Bell’s palsy	2.000000e-06
GCST011769_19	Schizophrenia	1.000000e-07
GCST012490_134	Femur bone mineral density x serum urate levels interaction	2.000000e-08

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0004784	self reported educational attainment
EFO:0007701	spine bone mineral density
EFO:0008434	initial pursuit acceleration
EFO:0004319	smoking cessation
EFO:0008348	response to ranibizumab
EFO:0009270	heel bone mineral density
EFO:0004847	age at onset
EFO:0009603	stroke outcome severity measurement
EFO:0004995	lean body mass
EFO:0004695	intraocular pressure measurement
EFO:0004531	urate measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C563719	Generalized Epilepsy and Paroxysmal Dyskinesia (supp.)
C567924	Infantile Epileptic-Dyskinetic Encephalopathy (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL3038495 (PROTEIN COMPLEX), CHEMBL4304 (SINGLE PROTEIN), CHEMBL4523613 (PROTEIN COMPLEX), CHEMBL4524132 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 26,453 (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
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL266510	FLINDOKALNER	3	74

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2253201	Toxicity	3	Ace Inhibitors;Plain	Angioedema

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs35793	KCNMA1		0.00	0
rs2253201	KCNMA1	3	3.00	1	Ace Inhibitors;Plain
rs16934182	KCNMA1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Calcium- and sodium-activated potassium channels (K_Ca, K_Na)

Most potent curated ligand interactions (32 total), top 25:

Ligand	Action	Affinity	Parameter
BmTx2	Channel blocker	9.52	pIC50
BmTx1	Channel blocker	9.19	pIC50
slotoxin	Channel blocker	8.82	pIC50
paxilline	Channel blocker	8.72	pKi
Penitrem A	Channel blocker	8.19	pIC50
kaliotoxin	Channel blocker	7.7	pIC50
toxin BmP09	Channel blocker	7.6	pEC50
BmP09	Channel blocker	7.57	pIC50
natrin	Channel blocker	7.47	pIC50
ChTX-Lq2	Channel blocker	7.37	pIC50
butantoxin	Channel blocker	7.3	pIC50
Lqh Tx 15-1	Channel blocker	7.3	pIC50
martentoxin	Channel blocker	7.11	pIC50
dehydrosoyasaponin I	Activator	7.0	pEC50
verruculogen	Channel blocker	7.0	pIC50
16,17-EpDPE	Activator	6.64	pEC50
GoSlo-SR-5-69	Activator	6.6	pEC50
charybdotoxin	Channel blocker	6.6	pIC50
iberiotoxin	Channel blocker	6.6	pIC50
flindokalner	Activator	6.5	pEC50
magnolol	Activator	6.0	pEC50
NS1643	Agonist	5.68	pEC50
17β-estradiol	Activator	5.6	pEC50
BMS-191011	Activator	5.6	pEC50
BC5	Activator	5.6	pEC50

ChEMBL bioactivities

64 potent at pChembl≥5 of 100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.49	IC50	3.236	nM	CHEMBL445346
7.56	IC50	27.54	nM	CHEMBL448335
7.56	IC50	27.54	nM	CHEMBL465922
6.92	EC50	120	nM	CHEMBL6173629
6.87	IC50	134.9	nM	CHEMBL524902
6.84	IC50	144.5	nM	CHEMBL504160
6.75	IC50	177.8	nM	CHEMBL511200
6.72	IC50	190.6	nM	CHEMBL506373
6.60	IC50	251.2	nM	CHEMBL464057
6.55	IC50	281.8	nM	CHEMBL517012
6.55	IC50	280	nM	CANNABIDIOL
6.46	EC50	350	nM	FLINDOKALNER
6.45	EC50	352	nM	FLINDOKALNER
6.43	IC50	371.5	nM	CHEMBL455306
6.40	EC50	400	nM	CHEMBL4303589
6.38	EC50	420	nM	CHEMBL6166658
6.35	IC50	446.7	nM	CHEMBL453712
6.22	IC50	602	nM	CHEMBL4516172
6.19	IC50	645.6	nM	CHEMBL465950
6.17	EC50	680	nM	CHEMBL6176092
6.16	IC50	691.8	nM	CHEMBL464249
5.92	EC50	1210	nM	CHEMBL6166315
5.86	EC50	1370	nM	CHEMBL6169698
5.84	IC50	1445	nM	CHEMBL465109
5.82	EC50	1500	nM	CHEMBL444449
5.81	IC50	1549	nM	CHEMBL465454
5.80	EC50	1580	nM	CHEMBL6177233
5.67	IC50	2138	nM	CHEMBL512408
5.61	IC50	2455	nM	CHEMBL465455
5.60	IC50	2512	nM	CHEMBL499800
5.58	IC50	2630	nM	CHEMBL465456
5.57	EC50	2700	nM	CHEMBL5187254
5.55	EC50	2820	nM	CHEMBL6177852
5.52	IC50	3020	nM	CHEMBL526140
5.51	IC50	3090	nM	CHEMBL481576
5.51	IC50	3090	nM	CHEMBL481577
5.48	EC50	3340	nM	CHEMBL61989
5.48	IC50	3311	nM	CHEMBL481578
5.46	IC50	3467	nM	CHEMBL519785
5.41	EC50	3860	nM	CHEMBL60343
5.41	EC50	3900	nM	CHEMBL6145166
5.39	IC50	4074	nM	CHEMBL480795
5.35	EC50	4430	nM	CHEMBL303805
5.29	EC50	5130	nM	CHEMBL303056
5.29	EC50	5070	nM	CHEMBL59388
5.28	IC50	5248	nM	CHEMBL297914
5.27	EC50	5400	nM	CHEMBL4859302
5.23	EC50	5860	nM	CHEMBL294334
5.23	IC50	5888	nM	CHEMBL482376
5.23	IC50	5888	nM	CHEMBL384903

PubChem BioAssay actives

45 with measured affinity, of 503 total; 45 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
5-chloro-N-(5-chloro-2-hydroxyphenyl)-2-methoxybenzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.0032	uM
2-[(4-benzyltriazol-1-yl)methyl]phenol	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.0275	uM
5-chloro-N-(2-hydroxy-5-methylphenyl)-2-methoxybenzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.0275	uM
N-(5-chloro-2-hydroxyphenyl)-2-hydroxybenzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.1349	uM
(2-hydroxyphenyl)-(5-methylbenzotriazol-1-yl)methanone	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.1445	uM
2-(4-benzyltriazol-1-yl)-4-chlorophenol	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.1778	uM
2-hydroxy-N-(2-methoxy-4-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.1905	uM
2-hydroxy-N-(2-methyl-6-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.2512	uM
Cannabidiol	2144300: Inhibition of human KCNMA1 expressed in HEK293 cells assessed as reduction in 100+ mV pulse elicited current by inside-out configuration based patch clamp method	ic50	0.2800	uM
ethyl 1-(4-chloro-2-nitrophenyl)-5-(4-nitrophenyl)triazole-4-carboxylate	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.2818	uM
(3S)-3-(5-chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1H-indol-2-one	726264: Positive modulation of Kca 1.1 (unknown origin)	ec50	0.3520	uM
5-chloro-N-(5-chloro-2-hydroxyphenyl)-2-hydroxybenzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.3715	uM
2-hydroxy-N-(2-methoxy-5-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.4467	uM
(3S)-3-[[(2S,3S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-[[(2S)-1-[[(2S)-6-amino-1-oxo-1-[[(1R,3S,5R,10R,13S,16S,19S,22S,28S,34S,40S,43R,48R,51S,54S,57S,60S,63S,66R,72S,76S,79S,82S,87S,90S,93S)-13,16,40-tris(4-aminobutyl)-76,79-bis(2-amino-2-oxoethyl)-34,72,82-tris(3-amino-3-oxopropyl)-51-benzyl-3-(3-carbamimidamidopropyl)-63-(2-carboxyethyl)-5-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]carbamoyl]-22,90-bis[(1R)-1-hydroxyethyl]-28,57,60-tris(hydroxymethyl)-87-(1H-indol-3-ylmethyl)-54,93-dimethyl-2,11,14,17,20,23,26,29,32,35,38,41,49,52,55,58,61,64,73,75,78,81,84,85,88,91,94-heptacosaoxo-19-propan-2-yl-7,8,45,46,68,69-hexathia-4,12,15,18,21,24,27,30,33,36,39,42,50,53,56,59,62,65,71,74,77,80,83,86,89,92,95-heptacosazatricyclo[41.27.14.1110,66]pentanonacontan-48-yl]amino]hexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	1559761: Inhibition of human BK alpha/beta4 channel expressed in HEK293T cells assessed as inhibition of K+ outward current fraction at -80 mV holding potential by whole cell patch clamp technique	ic50	0.6020	uM
[1-(5-chloro-2-hydroxyphenyl)triazol-4-yl]-phenylmethanone	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.6456	uM
5-chloro-2-hydroxy-N-(2-methoxy-4-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	0.6918	uM
2-hydroxy-N-(2-hydroxy-4-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	1.4454	uM
benzotriazol-1-yl-(2-hydroxyphenyl)methanone	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	1.5488	uM
(2-hydroxyphenyl)-[5-(trifluoromethyl)benzotriazol-1-yl]methanone	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	2.1380	uM
(5-chlorobenzotriazol-1-yl)-(2-hydroxyphenyl)methanone	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	2.4547	uM
2-hydroxy-N-(4-methyl-2-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	2.5119	uM
4-nitro-2-(5-phenyltriazol-1-yl)phenol	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	2.6303	uM
(5-fluorobenzotriazol-1-yl)-(2-hydroxyphenyl)methanone	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	3.0200	uM
2-hydroxy-N-(2-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	3.0903	uM
N-(5-chloro-2-hydroxyphenyl)-2-ethoxybenzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	3.0903	uM
(2-hydroxyphenyl)-(5-phenylbenzotriazol-1-yl)methanone	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	3.3113	uM
2-(azepan-1-yl)-1H-pyrrolo[3,2-b]pyridine-3-carbonitrile	41964: [86Rb+] efflux induced by BKca alpha subunits expressed in HEK293 cells at 10 uM	ec50	3.3400	uM
2-hydroxy-N-[2-nitro-4-(trifluoromethyl)phenyl]benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	3.4674	uM
2-morpholin-4-yl-1H-pyrrolo[3,2-b]pyridine-3-carbonitrile	41964: [86Rb+] efflux induced by BKca alpha subunits expressed in HEK293 cells at 10 uM	ec50	3.8600	uM
5-chloro-2-hydroxy-N-(4-methyl-2-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	4.0738	uM
2-(3-azabicyclo[3.2.2]nonan-3-yl)-1H-pyrrolo[3,2-b]pyridine-3-carbonitrile	41964: [86Rb+] efflux induced by BKca alpha subunits expressed in HEK293 cells at 10 uM	ec50	4.4300	uM
2-[(3S)-3-hydroxypiperidin-1-yl]-1H-pyrrolo[3,2-b]pyridine-3-carbonitrile	41964: [86Rb+] efflux induced by BKca alpha subunits expressed in HEK293 cells at 10 uM	ec50	5.0700	uM
2-(dimethylamino)-1H-pyrrolo[3,2-b]pyridine-3-carbonitrile	41964: [86Rb+] efflux induced by BKca alpha subunits expressed in HEK293 cells at 10 uM	ec50	5.1300	uM
5-chloro-2-hydroxy-N-(4-hydroxy-2-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	5.2481	uM
2-imidazol-1-yl-1H-pyrrolo[3,2-b]pyridine-3-carbonitrile	41964: [86Rb+] efflux induced by BKca alpha subunits expressed in HEK293 cells at 10 uM	ec50	5.8600	uM
2-hydroxy-N-(2-nitro-4-phenylphenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	5.8884	uM
3-[2-hydroxy-5-(trifluoromethyl)phenyl]-6-(trifluoromethyl)-1H-benzimidazol-2-one	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	5.8884	uM
2-[2-(dimethylamino)ethyl-methylamino]-1H-pyrrolo[3,2-b]pyridine-3-carbonitrile	41964: [86Rb+] efflux induced by BKca alpha subunits expressed in HEK293 cells at 10 uM	ec50	6.7500	uM
N-(4-chloro-2-nitrophenyl)-2-hydroxybenzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	6.9183	uM
2-(diethylamino)-1H-pyrrolo[3,2-b]pyridine-3-carbonitrile	41964: [86Rb+] efflux induced by BKca alpha subunits expressed in HEK293 cells at 10 uM	ec50	6.9400	uM
2-[(4-benzyltriazol-1-yl)methyl]-4-chlorophenol	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	7.7625	uM
2-pyrrolidin-1-yl-1H-pyrrolo[3,2-b]pyridine-3-carbonitrile	41964: [86Rb+] efflux induced by BKca alpha subunits expressed in HEK293 cells at 10 uM	ec50	8.1200	uM
2-hydroxy-N-(2-hydroxy-5-nitrophenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	8.1283	uM
5-(5-phenylbenzotriazol-1-yl)-2H-triazole-4-carboxamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	8.7096	uM
N-(2-hydroxy-5-methylphenyl)benzamide	410706: Activation of BK channel-mediated vasorelaxation activity assessed as reduction in KCl-induced contractile tone	ic50	9.3325	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	7
Aflatoxin B1	decreases methylation, affects methylation, decreases expression	4
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	4
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance	3
Cisplatin	decreases expression, increases reaction, affects cotreatment, increases expression	3
Estradiol	affects cotreatment, increases expression, increases activity, decreases reaction	3
Methapyrilene	increases expression, affects methylation, decreases expression	3
Nickel	affects expression, decreases expression, decreases reaction	3
Progesterone	affects cotreatment, increases expression, decreases reaction, increases activity, decreases activity	3
Tobacco Smoke Pollution	decreases expression, increases expression	3
lasiocarpine	decreases expression	2
methyleugenol	decreases expression	2
bisphenol A	decreases methylation, affects cotreatment, affects methylation, decreases expression	2
trichostatin A	affects expression, decreases reaction, decreases expression	2
iberiotoxin	increases activity, decreases activity, decreases reaction	2
clothianidin	decreases expression	2
Arsenic	increases abundance, affects methylation, affects cotreatment, decreases expression	2
Cadmium	increases abundance, increases palmitoylation, increases expression, decreases reaction	2
Calcium	increases transport, increases reaction, increases response to substance, affects cotreatment	2
Endosulfan	decreases expression	2
Lithocholic Acid	increases transport, increases activity, increases response to substance, affects cotreatment, increases reaction	2
N-Nitrosopyrrolidine	decreases expression	2
Tetraethylammonium	increases activity, affects binding, decreases activity, increases reaction, decreases reaction	2
aristolochic acid I	decreases expression	1
propionaldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1

ChEMBL screening assays

94 unique, capped per target: 91 binding, 2 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2399498	Binding	Activation of human BKCA alpha/beta1 channel expressed in HEK293 cells assessed as increase of rubidium efflux after 10 mins in presence paxilline	Large conductance Ca(2+)-activated K(+) channel (BKCa) activating properties of a series of novel N-arylbenzamides: Channel subunit dependent effects. — Bioorg Med Chem
CHEMBL5519517	Toxicity	Inhibition of BK channel (unknown origin) at 10 uM relative to control	Discovery and development of BI 1265162, an ENaC inhibitor for the treatment of cystic fibrosis. — Eur J Med Chem
CHEMBL702912	Functional	Maxi-K opening activity on cloned human (hSlo) large- conductance (BK) Ca(2+)-activated K+ channel expressed in Xenopus laevis oocytes at concentration of 20 uM	Novel openers of Ca2+-dependent large-conductance potassium channels: symmetrical pharmacophore and electrophysiological evaluation of bisphenols. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7T4	Ubigene A-549 KCNMA1 KO	Cancer cell line	Male
CVCL_D9HV	Ubigene HEK293 KCNMA1 KO	Transformed cell line	Female
CVCL_E0G0	Ubigene HeLa KCNMA1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)