KCNMB4

Summary

KCNMB4 (potassium calcium-activated channel subfamily M regulatory beta subunit 4, HGNC:6289) is a protein-coding gene on chromosome 12q15, encoding Calcium-activated potassium channel subunit beta-4 (Q86W47). Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel.

MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. The protein encoded by this gene is an auxiliary beta subunit which slows activation kinetics, leads to steeper calcium sensitivity, and shifts the voltage range of current activation to more negative potentials than does the beta 1 subunit.

Source: NCBI Gene 27345 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 23 total
• Druggable target: yes
• MANE Select transcript: NM_014505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6289
Approved symbol	KCNMB4
Name	potassium calcium-activated channel subfamily M regulatory beta subunit 4
Location	12q15
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135643
Ensembl biotype	protein_coding
OMIM	605223
Entrez	27345

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000258111, ENST00000531884

RefSeq mRNA: 1 — MANE Select: NM_014505 NM_014505

CCDS: CCDS8997

Canonical transcript exons

ENST00000258111 — 3 exons

Exon	Start	End
ENSE00000920736	70430485	70434292
ENSE00000920737	70400209	70400336
ENSE00001195318	70366290	70367070

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 95.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1377 / max 358.1876, expressed in 1148 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126795	3.7373	777
126797	2.3639	627
126794	0.9388	396
126799	0.9019	337
126796	0.4893	216
126798	0.4712	221
126800	0.2041	101
126801	0.0312	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	95.79	gold quality
postcentral gyrus	UBERON:0002581	94.99	gold quality
parietal lobe	UBERON:0001872	94.65	gold quality
entorhinal cortex	UBERON:0002728	94.52	gold quality
Ammon’s horn	UBERON:0001954	94.08	gold quality
corpus callosum	UBERON:0002336	93.89	gold quality
superior frontal gyrus	UBERON:0002661	93.61	gold quality
middle temporal gyrus	UBERON:0002771	93.44	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.31	gold quality
temporal lobe	UBERON:0001871	92.92	gold quality
lateral globus pallidus	UBERON:0002476	92.91	gold quality
globus pallidus	UBERON:0001875	92.64	gold quality
prefrontal cortex	UBERON:0000451	92.62	gold quality
medial globus pallidus	UBERON:0002477	92.13	gold quality
frontal cortex	UBERON:0001870	92.02	gold quality
frontal lobe	UBERON:0016525	92.02	gold quality
cortical plate	UBERON:0005343	91.99	gold quality
amygdala	UBERON:0001876	91.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.82	gold quality
cerebral cortex	UBERON:0000956	91.77	gold quality
pons	UBERON:0000988	91.65	gold quality
neocortex	UBERON:0001950	91.42	gold quality
anterior cingulate cortex	UBERON:0009835	91.28	gold quality
cingulate cortex	UBERON:0003027	91.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.20	gold quality
telencephalon	UBERON:0001893	91.15	gold quality
right frontal lobe	UBERON:0002810	91.03	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.92	gold quality
tibial nerve	UBERON:0001323	90.78	gold quality
inferior vagus X ganglion	UBERON:0005363	90.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	26.18
E-ANND-3	yes	5.63
E-CURD-10	no	58.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

119 targeting KCNMB4, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776

Literature-anchored findings (GeneRIF, showing 13)

• Structural basis for toxin resistance of beta4-associated calcium-activated potassium (BK) channels (PMID:18559348)
• The beta4 subunit controls ethanol tolerance at the molecular, cellular, and behavioral levels, and could determine individual differences in alcohol abuse and alcoholism, as well as represent a therapeutic target for alcoholism. (PMID:18981408)
• Report beta subunit (KNMB1-4)-specific modulations of BK channel function by a Slo1 mutation associated with epilepsy and dyskinesia. (PMID:19204046)
• results argue that, for native mouse Slo3 channels, the beta4 subunit must be considered as a potential interaction partner and, furthermore, that KCNMB subunits may have functions unrelated to regulation of the Slo1 alpha subunit (PMID:19578543)
• These results suggest that fast-gating, type I BK channels lacking beta4 can increase neuronal excitability in response to reduced phosphatase activity and activation of calcium channels. (PMID:21848922)
• our data suggest that the rs398702 variant in the KCNMB4 gene is unlikely to influence significantly the risk of developing mesial temporal lobe epilepsy or its severity (PMID:23623847)
• IFN-gamma changed mRNA levels of the BK beta-modulatory proteins KCNMB2 (increased) and KCNMB4 (decreased) as well as leucine-rich repeat-containing protein (LRRC)26 (decreased). (PMID:24414257)
• Study shows that beta4 subunit of the MaxiK channel has no potential endocytic signal and 2 specific amino acids in the functional basic motif retention/retrieval trafficking signal at the C-terminus may play a role in controlling cellular excitability (PMID:24486049)
• Recombinant martentoxin selectively blocks KCNMA1/KCNMB4 channels. (PMID:24759175)
• BK channel beta4 subunit influences sensitivity and tolerance to alcohol by altering its response to kinases (PMID:25190810)
• Two recurrent fusion genes associated with the 12q locus, LRP1-SNRNP25 and KCNMB4-CCND3, were by RT-PCR, Sanger sequencing and FISH, and were found to be osteosarcoma specific in a validation cohort of 240 other sarcomas. (PMID:25300797)
• This study presents cryo-EM structures of Slo1 in complex with the auxiliary protein, beta4. Four beta4, each containing two transmembrane helices, encircle Slo1, contacting it through helical interactions inside the membrane. (PMID:31815672)
• Family-Based Cohort Association Study of PRKCB1, CBLN1 and KCNMB4 Gene Polymorphisms and Autism in Polish Population. (PMID:34562210)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kcnmb4	ENSMUSG00000054934
rattus_norvegicus	Kcnmb4	ENSRNOG00000054458

Paralogs (3): KCNMB1 (ENSG00000145936), KCNMB3 (ENSG00000171121), KCNMB2 (ENSG00000197584)

Protein

Protein identifiers

Calcium-activated potassium channel subunit beta-4 — Q86W47 (reviewed: Q86W47)

Alternative names: BK channel subunit beta-4, Calcium-activated potassium channel, subfamily M subunit beta-4, Charybdotoxin receptor subunit beta-4, K(VCA)beta-4, Maxi K channel subunit beta-4, Slo-beta-4

All UniProt accessions (2): Q86W47, H0YC85

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations.

Subunit / interactions. Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB4 per KCNMA1 tetramer. Interacts with FMR1 (via N-terminus).

Subcellular location. Membrane.

Tissue specificity. Predominantly expressed in brain. In brain, it is expressed in the cerebellum, cerebral cortex, medulla, spinal cord, occipital pole, frontal lobe, temporal lobe, putamen, amygdala, caudate nucleus, corpus callosum, hippocampus, substantia nigra and thalamus. Weakly or not expressed in other tissues.

Post-translational modifications. Phosphorylated. Phosphorylation modulates its effect on KCNMA1 activation kinetics. N-glycosylated. A highly glycosylated form is promoted by KCNMA1. Glycosylation, which is not required for the interaction with KCNMA1 and subcellular location, increases protection against charybdotoxin.

Domain organisation. Resistance to charybdotoxin (CTX) toxin is mediated by the extracellular domain.

Miscellaneous. Treatment with okadaic acid reduces its effect on KCNMA1.

Similarity. Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB4 subfamily.

RefSeq proteins (1): NP_055320* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003930	K_chnl_Ca-activ_BK_bsu	Family

Pfam: PF03185

UniProt features (32 total): strand 9, mutagenesis site 8, helix 5, topological domain 3, transmembrane region 2, glycosylation site 2, chain 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
9CZM	ELECTRON MICROSCOPY	2.57
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
6V22	ELECTRON MICROSCOPY	3.2
6V35	ELECTRON MICROSCOPY	3.5
9CZK	ELECTRON MICROSCOPY	3.5
9CZJ	ELECTRON MICROSCOPY	3.54
5Y7L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W47-F1	87.07	0.54

Functional residue map

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

Glycosylation sites (2): 53, 90

Mutagenesis-validated functional residues (8):

Position	Phenotype
11	suppresses its effect on kcnma1 channel activation and on deactivation kinetics; when associated with e-17 and e-210.
17	suppresses the effect of okadaic acid and increases activation time constant; when associated with a-11 and a-210.
17	suppresses its effect on kcnma1 channel activation and on deactivation kinetics; when associated with d-11 and e-210.
53	loss of n-glycosylation and reduced protection against charybdotoxin; when associated with a-90.
90	loss of n-glycosylation and reduced protection against charybdotoxin; when associated with a-53.
210	suppresses the effect of okadaic acid and increases activation time constant; when associated with a-11 and a-17.
210	suppresses its effect on kcnma1 channel activation and on deactivation kinetics; when associated with d-11 and e-17.
11	suppresses the effect of okadaic acid and increases activation time constant; when associated with a-17 and a-210.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1296052	Ca2+ activated K+ channels
R-HSA-418457	cGMP effects
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

MSigDB gene sets: 197 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_POTASSIUM_CHANNELS, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_RESPONSE_TO_METAL_ION, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, BLALOCK_ALZHEIMERS_DISEASE_UP, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_REGULATION_OF_NEUROTRANSMITTER_TRANSPORT, GOBP_SECRETION

GO Biological Process (11): action potential (GO:0001508), detection of calcium ion (GO:0005513), potassium ion transport (GO:0006813), chemical synaptic transmission (GO:0007268), neuronal action potential (GO:0019228), regulation of vasoconstriction (GO:0019229), regulation of neurotransmitter secretion (GO:0046928), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), potassium ion transmembrane transport (GO:0071805), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (4): calcium-activated potassium channel activity (GO:0015269), potassium channel regulator activity (GO:0015459), voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099508), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Potassium Channels	1
Nitric oxide stimulates guanylate cyclase	1
Neuronal System	1
Platelet homeostasis	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of membrane potential	2
potassium channel activity	2
detection of chemical stimulus	1
response to calcium ion	1
metal ion transport	1
anterograde trans-synaptic signaling	1
action potential	1
transmission of nerve impulse	1
vasoconstriction	1
blood vessel diameter maintenance	1
regulation of blood circulation	1
neurotransmitter secretion	1
modulation of chemical synaptic transmission	1
regulation of neurotransmitter transport	1
regulation of secretion by cell	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
calcium-activated cation channel activity	1
ion channel regulator activity	1
voltage-gated monoatomic ion channel activity	1
presynaptic membrane	1
regulation of presynaptic membrane potential	1
binding	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNMB4	KCNMA1	Q12791	954
KCNMB4	KCNN3	Q9UGI6	830
KCNMB4	KCNN4	O15554	761
KCNMB4	KCNN2	Q9H2S1	655
KCNMB4	KCNU1	A8MYU2	636
KCNMB4	LRRC26	Q2I0M4	591
KCNMB4	KCNT1	Q5JUK3	549
KCNMB4	LRRC52	Q8N7C0	535
KCNMB4	KCNMB1	P78475	533
KCNMB4	LRRC38	Q5VT99	492
KCNMB4	SNRNP25	Q9BV90	479
KCNMB4	LRRC55	Q6ZSA7	461
KCNMB4	KCNQ5	Q9NR82	429
KCNMB4	KCNAB2	Q13303	422
KCNMB4	BHLHE23	Q8NDY6	397

IntAct

9 interactions, top by confidence:

A	B	Type	Score
MAL	KCNMB4	psi-mi:“MI:0915”(physical association)	0.560
MS4A13	KCNMB4	psi-mi:“MI:0915”(physical association)	0.560
MFSD12	SNAP23	psi-mi:“MI:0914”(association)	0.350
STXBP1	KCNMB4	psi-mi:“MI:0915”(physical association)	0.000
MAL	KCNMB4	psi-mi:“MI:0915”(physical association)	0.000
MS4A13	KCNMB4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): MAL (Two-hybrid), MS4A13 (Two-hybrid), KCNMB4 (Proximity Label-MS), KCNMB4 (Affinity Capture-RNA), KCNMB4 (Two-hybrid), KCNMB4 (Affinity Capture-MS)

ESM2 similar proteins: A2AGL3, A5HK05, B0LPN4, E9PZQ0, F1LMY4, O09172, O75031, P30957, P42694, P48507, P48508, Q15413, Q28C34, Q2T9W7, Q2T9Y6, Q3MHH0, Q3SZM3, Q3T0J1, Q3TYS2, Q3UX43, Q4R7G8, Q5RCC7, Q5RCR8, Q6AYA6, Q6DFV5, Q6NRD0, Q6NTT6, Q6NYU2, Q6P4H8, Q7SXV1, Q7ZUV0, Q80YV4, Q811Q0, Q86W47, Q8CHQ0, Q8L7N4, Q8N6S4, Q8VCM5, Q92736, Q969V5

Diamond homologs: A7VL23, O46372, P97678, Q16558, Q28067, Q28266, Q811Q0, Q86W47, Q8CAE3, Q98855, Q9CZM9, Q9ESK8, Q9JIN6, Q9NPA1, Q9Y691

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

618 predictions. Top by Δscore:

Variant	Effect	Δscore
12:70367067:CAAGG:C	donor_loss	1.0000
12:70367068:AAGG:A	donor_loss	1.0000
12:70367069:AGG:A	donor_loss	1.0000
12:70367070:GGTA:G	donor_loss	1.0000
12:70367071:G:GG	donor_gain	1.0000
12:70367071:GTAAG:G	donor_loss	1.0000
12:70367072:T:G	donor_loss	1.0000
12:70400207:A:AG	acceptor_gain	1.0000
12:70400207:AGTG:A	acceptor_loss	1.0000
12:70400208:G:GG	acceptor_gain	1.0000
12:70400208:G:GT	acceptor_loss	1.0000
12:70400208:GT:G	acceptor_gain	1.0000
12:70400336:GGTA:G	donor_loss	1.0000
12:70400337:G:GG	donor_gain	1.0000
12:70400337:GT:G	donor_loss	1.0000
12:70400338:T:G	donor_loss	1.0000
12:70367069:AG:A	donor_gain	0.9900
12:70367070:GG:G	donor_gain	0.9900
12:70369131:G:GT	donor_gain	0.9900
12:70400203:T:TA	acceptor_gain	0.9900
12:70400207:AGT:A	acceptor_gain	0.9900
12:70400208:GTG:G	acceptor_gain	0.9900
12:70400208:GTGC:G	acceptor_gain	0.9900
12:70400208:GTGCT:G	acceptor_gain	0.9900
12:70400334:AAG:A	donor_gain	0.9900
12:70409598:T:TA	donor_gain	0.9900
12:70409599:A:AA	donor_gain	0.9900
12:70430483:A:AG	acceptor_gain	0.9900
12:70430484:G:GA	acceptor_gain	0.9900
12:70430484:GACCA:G	acceptor_gain	0.9900

AlphaMissense

1386 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:70366896:C:G	C54W	0.998
12:70430546:T:A	W176R	0.998
12:70430546:T:C	W176R	0.998
12:70430570:G:C	G184R	0.998
12:70366894:T:A	C54S	0.997
12:70366895:G:C	C54S	0.997
12:70400209:T:A	C113S	0.997
12:70400209:T:C	C113R	0.997
12:70400210:G:C	C113S	0.997
12:70400314:T:A	C148S	0.997
12:70400314:T:C	C148R	0.997
12:70400315:G:C	C148S	0.997
12:70400316:C:G	C148W	0.997
12:70366795:G:C	G21R	0.996
12:70366816:G:C	G28R	0.996
12:70366817:G:A	G28D	0.996
12:70366894:T:C	C54R	0.996
12:70366895:G:A	C54Y	0.996
12:70366942:T:C	F70L	0.996
12:70366944:C:A	F70L	0.996
12:70366944:C:G	F70L	0.996
12:70400315:G:A	C148Y	0.996
12:70430571:G:A	G184D	0.996
12:70366985:G:A	C84Y	0.995
12:70367035:C:G	H101D	0.995
12:70366796:G:A	G21D	0.994
12:70366936:T:A	C68S	0.994
12:70366937:G:C	C68S	0.994
12:70366984:T:C	C84R	0.994
12:70366986:C:G	C84W	0.994

dbSNP variants (sampled 300 via entrez): RS1000037660 (12:70427277 G>A), RS1000061193 (12:70384477 A>G), RS1000102618 (12:70386570 T>G), RS1000124437 (12:70372402 T>C), RS1000139521 (12:70432513 C>T), RS1000162624 (12:70422086 A>G), RS1000221644 (12:70414307 C>A,T), RS1000272899 (12:70425874 C>T), RS1000280634 (12:70365444 C>T), RS1000297048 (12:70378198 TGCCTGCCTTG>T), RS1000304619 (12:70421615 T>C), RS1000328984 (12:70420886 G>A), RS1000410341 (12:70427547 T>C), RS1000440434 (12:70371733 A>T), RS1000443563 (12:70421121 A>C,G)

Disease associations

OMIM: gene MIM:605223 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST009391_1031	Metabolite levels	2.000000e-06
GCST009391_555	Metabolite levels	2.000000e-06
GCST012488_15	L1-L4 bone mineral density x serum urate levels interaction	7.000000e-06
GCST90000025_978	Appendicular lean mass	1.000000e-10
GCST90007004_1	Gut microbiota relative abundance (unassigned genus belonging to family Clostridiales)	3.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009775	threonine measurement
EFO:0009769	histidine measurement
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density
EFO:0004980	appendicular lean mass
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523376 (SINGLE PROTEIN), CHEMBL4523613 (PROTEIN COMPLEX)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.22	IC50	602	nM	CHEMBL4516172

PubChem BioAssay actives

1 with measured affinity, of 19 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
(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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	9
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	4
potassium chromate(VI)	decreases expression, increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
deoxynivalenol	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	increases expression	1
chromium hexavalent ion	affects expression	1
cylindrospermopsin	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
NSC 689534	decreases expression, affects binding	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Panobinostat	affects cotreatment, affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4357418	Binding	Binding affinity to NT-495 fluorophore reagent labelled human BK beta4 (45 to 166 residues) incubated for 30 mins by microscale thermophoresis assay	Selective Blockade of Neuronal BK (α + β4) Channels Preventing Epileptic Seizure. — J Med Chem

Clinical trials (associated diseases)

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