KCNMB1

Summary

KCNMB1 (potassium calcium-activated channel subfamily M regulatory beta subunit 1, HGNC:6285) is a protein-coding gene on chromosome 5q35.1, encoding Calcium-activated potassium channel subunit beta-1 (Q16558). 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 product of this gene, the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits.

Source: NCBI Gene 3779 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 2 total
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_004137

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6285
Approved symbol	KCNMB1
Name	potassium calcium-activated channel subfamily M regulatory beta subunit 1
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	hslo-beta
Ensembl gene	ENSG00000145936
Ensembl biotype	protein_coding
OMIM	603951
Entrez	3779

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000274629, ENST00000521859, ENST00000962422

RefSeq mRNA: 1 — MANE Select: NM_004137 NM_004137

CCDS: CCDS4373

Canonical transcript exons

ENST00000274629 — 4 exons

Exon	Start	End
ENSE00000973135	170385314	170385471
ENSE00000973136	170383679	170383850
ENSE00001287209	170374671	170378973
ENSE00002111410	170389259	170389367

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 97.22.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2202 / max 136.9812, expressed in 385 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64814	0.8109	163
64818	0.6898	226
64813	0.4656	152
64815	0.1802	48
64816	0.0444	23
64817	0.0292	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	97.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.47	gold quality
lower esophagus	UBERON:0013473	96.40	gold quality
cauda epididymis	UBERON:0004360	95.94	gold quality
popliteal artery	UBERON:0002250	95.78	gold quality
tibial artery	UBERON:0007610	95.77	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.69	gold quality
right coronary artery	UBERON:0001625	95.52	gold quality
aorta	UBERON:0000947	95.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.06	gold quality
seminal vesicle	UBERON:0000998	94.97	gold quality
saphenous vein	UBERON:0007318	94.76	gold quality
thoracic aorta	UBERON:0001515	94.63	gold quality
ascending aorta	UBERON:0001496	94.56	gold quality
descending thoracic aorta	UBERON:0002345	94.18	gold quality
myometrium	UBERON:0001296	94.02	gold quality
left coronary artery	UBERON:0001626	93.32	gold quality
mucosa of stomach	UBERON:0001199	93.14	gold quality
coronary artery	UBERON:0001621	93.07	gold quality
body of uterus	UBERON:0009853	92.84	gold quality
urethra	UBERON:0000057	91.76	gold quality
superficial temporal artery	UBERON:0001614	90.21	gold quality
left uterine tube	UBERON:0001303	89.47	gold quality
smooth muscle tissue	UBERON:0001135	88.32	gold quality
sigmoid colon	UBERON:0001159	88.23	gold quality
decidua	UBERON:0002450	87.94	gold quality
prostate gland	UBERON:0002367	87.14	gold quality
buccal mucosa cell	CL:0002336	86.44	gold quality
urinary bladder	UBERON:0001255	86.35	gold quality
mammary duct	UBERON:0001765	86.33	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	1747.78
E-MTAB-10287	yes	50.99
E-HCAD-11	yes	8.04
E-ANND-3	yes	5.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, HIF1A, SP1, SRF

miRNA regulators (miRDB)

47 targeting KCNMB1, 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-4481	100.00	66.42	1669
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4745-5P	99.98	65.95	1028
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-6825-5P	99.96	69.81	3431
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4742-5P	98.89	68.41	1542

Literature-anchored findings (GeneRIF, showing 37)

• Phosphorylation-dependent functional coupling of hSlo and its hbeta 4 subunit (PMID:11790768)
• have a reset baroreflex. Variants in the gene (KCNMB1) coding for the BK beta1 subunit are associated with baroreflex function. (PMID:12011654)
• 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)
• mesangial cells contain hbeta1, a BK accessory protein, which confers activation of BK by cGMP kinase. (PMID:12670831)
• Beta1 subunits facilitate gating of BK channels by acting through the Ca2+, but not the Mg2+, activating mechanisms. (PMID:12893878)
• We conclude that transient membrane current is generated by a mechanism related to the deactivation, and level of prior activation, of glioma BK channels. (PMID:12962281)
• 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)
• Hemoxygenase-2 is part of the BK channel complex and enhances channel activity in normoxia (PMID:15528406)
• results reveal the molecular regions in the beta1 and beta2 subunits that determine their differential functional coupling with the pore-forming alpha-subunit (PMID:16446507)
• identified and characterized single nucleotide polymorphisms in the exons, intron/exon junctions, upstream region and 3’ untranslated regions of KCNMB1 using denaturing high-performance liquid chromatography combined with direct DNA sequencing (PMID:17496725)
• The protective effect of KCNMB1 E65K against hypertension is restricted to blood pressure treatment with beta-blockade. (PMID:18418400)
• African American male asthmatics carrying the KCNMB1 818T allele (10% of population) are potentially at risk for greater airway obstruction and increased asthma morbidity. (PMID:18535015)
• The findings suggest that the KCNMB1 Glu65Lys polymorphism associates with reduced systolic and diastolic blood pressure in middle-aged men. (PMID:18854753)
• The KCNMB1 E65K variant is associated with reduced central pulse pressure. (PMID:19050450)
• maxi-K(+) beta1-subunit could contribute to vascular dysregulation in severe obstructive sleep apnea syndrome patients. Leukocyte beta1 expression may be independent readout of hypoxemia that could be useful as molecular marker for impending hypertension. (PMID:19057512)
• Report beta subunit (KNMB1-4)-specific modulations of BK channel function by a Slo1 mutation associated with epilepsy and dyskinesia. (PMID:19204046)
• Cell membrane stretch and cell volume sensitivity are independently regulated by KCNMB1 (BK) and KCNQ1 channels, respectively. (PMID:19289549)
• genetic polymorphism shows sex-specific association with asthma severity in male african population (PMID:19295429)
• The expressed hSloalpha + beta1 subunit complex demonstrated to be fully functional for its typical single-channel traces, Ca(2+)-sensitivity, voltage-dependency, high conductance (151 +/- 7 pS), and its pharmacological activation and inhibition. (PMID:19430934)
• Results reveal the first ion channel subunit as a direct target of SRF-MYOCD transactivation, providing further insight into the role of MYOCD as a master regulator of the SMC contractile phenotype. (PMID:19801679)
• In transfected HEK293 cells, activation of cloned BK(Ca) channel induced apoptosis, whereas inhibition of cloned BK(Ca) channel decreased apoptosis. (PMID:20457834)
• Here we found that KCNMB1 common variant Glu65Lys influences glomerular filtration rate across multiple populations of different clinical characteristics and biogeographic ancestries. (PMID:20861615)
• downregulation of vascular BK-beta(1) expression in diabetes and in high-glucose culture conditions was associated with FOXO-3a/FBXO-dependent increase in BK-beta(1) degradation. (PMID:20966391)
• Cloned BK(Ca) channel directly regulated apoptosis and proliferation of HEK293 cell under hyperglycemia condition. (PMID:21413024)
• HIF-1alpha increases KCNMB1 expression in response to hypoxia in human pulmonary artery smooth muscle cells by binding to two hypoxia response elements located at -3,540 to -3,311 of the KCNMB1 promoter (PMID:22114151)
• The results indicate that the beta1-subunit can form a tripartite complex with TP and MaxiKalpha, has the ability to associate with each protein independently. (PMID:23255603)
• In large-conductance calcium-dependent potassium channels, beta1 and beta2 subunits alter the voltage sensing domain-cytosolic domain interface. (PMID:23825428)
• Bisphenol A activates BK alpha via an extracellular site and that Bisphenol A-sensitivity is increased by the beta1 subunit. (PMID:24476761)
• N-terminal isoforms of the large-conductance Ca(2)-activated K channel are differentially modulated by the auxiliary beta1-subunit. (PMID:24569989)
• The study demonstrates that both transmembrane domains of BKbeta1 are required to provide the characteristic ion current phenotype of beta1-containing BK channels. (PMID:25275635)
• To determine the relationship between atherosclerosis and KCNMB1, we studied some atherogenic factors affecting vascular tone. Blood of atherosclerotic patients shows increased concentration of 7-ketocholesterol, possibly a harmful lipid to blood vessels. (PMID:25576871)
• Data show that two lysine residues that are unique to the N terminus of calcium-activated potassium channel subunit beta-1 were identified to be sufficient for voltage-sensor modulation. (PMID:25825713)
• By introducing lanthanide binding tags in the extracellular region of the alpha- or beta1-subunit, we determined (i) a basic extracellular map of the BK channel, (ii) beta1-subunit-induced rearrangements of the voltage sensor in alpha-subunits, and (iii) the relative position of the beta1-subunit within the alpha/beta1-subunit complex. (PMID:27217576)
• Expression of vascular large-conductance calcium-activated potassium channel Kcnmb1 is regulated by Nrf2 signaling. (PMID:28429615)
• These results provide further insights into the mechanism of modulation of the different N-terminal regions of the BKCa channel by beta-subunits. (PMID:28750098)
• Decreased protein expression and altered intrinsic properties of BKbeta1 channels mediates abnormal vasodilation in the coronary microvasculature of type 2 diabetics. (PMID:29850792)
• that epigenetic upregulation of KCNMB1 contributes to increased large-conductance (Big) potassium channel activity in idiopathic pulmonary fibrosis fibroblasts (PMID:31486669)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kcnmb1	ENSMUSG00000020155
rattus_norvegicus	Kcnmb1	ENSRNOG00000005465

Paralogs (3): KCNMB4 (ENSG00000135643), KCNMB3 (ENSG00000171121), KCNMB2 (ENSG00000197584)

Protein

Protein identifiers

Calcium-activated potassium channel subunit beta-1 — Q16558 (reviewed: Q16558)

Alternative names: BK channel subunit beta-1, Calcium-activated potassium channel, subfamily M subunit beta-1, Charybdotoxin receptor subunit beta-1, K(VCA)beta-1, Maxi K channel subunit beta-1, Slo-beta-1

All UniProt accessions (1): Q16558

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. Increases the apparent Ca(2+)/voltage sensitivity of the KCNMA1 channel. It also modifies KCNMA1 channel kinetics and alters its pharmacological properties. It slows down the activation and the deactivation kinetics of the channel. Acts as a negative regulator of smooth muscle contraction by enhancing the calcium sensitivity to KCNMA1. Its presence is also a requirement for internal binding of the KCNMA1 channel opener dehydrosoyasaponin I (DHS-1) triterpene glycoside and for external binding of the agonist hormone 17-beta-estradiol (E2). Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1 peptide blocker by increasing the CTX association rate and decreasing the dissociation rate.

Subunit / interactions. Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB1 per KCNMA1 tetramer.

Subcellular location. Membrane.

Tissue specificity. Abundantly expressed in smooth muscle. Low levels of expression in most other tissues. Within the brain, relatively high levels found in hippocampus and corpus callosum.

Post-translational modifications. N-glycosylated.

Polymorphism. Genetic variation in KCNMB1 can influence the severity of diastolic hypertension.

Similarity. Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16558-1	1	yes
Q16558-2	2

RefSeq proteins (1): NP_004128* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003930	K_chnl_Ca-activ_BK_bsu	Family

Pfam: PF03185

UniProt features (12 total): topological domain 3, sequence variant 2, transmembrane region 2, glycosylation site 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16558-F1	84.09	0.31

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): 80, 142

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: 181 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, MODULE_274, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, REACTOME_POTASSIUM_CHANNELS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_RESPONSE_TO_METAL_ION, SRF_01, PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN, SRF_C, JAZAG_TGFB1_SIGNALING_DN, GOBP_SYNAPTIC_SIGNALING

GO Biological Process (6): detection of calcium ion (GO:0005513), potassium ion transport (GO:0006813), chemical synaptic transmission (GO:0007268), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), potassium ion transmembrane transport (GO:0071805)

GO Molecular Function (3): calcium-activated potassium channel activity (GO:0015269), potassium channel regulator activity (GO:0015459), 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-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
potassium channel activity	2
detection of chemical stimulus	1
response to calcium ion	1
metal ion transport	1
anterograde trans-synaptic signaling	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
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

0 interactions, top by confidence (×1000):

IntAct

2 interactions, top by confidence:

A	B	Type	Score
EWSR1	KCNMB1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (9): KCNMB1 (Two-hybrid), KCNMB1 (Co-fractionation), STX8 (Two-hybrid), KCNMB1 (Affinity Capture-RNA), KCNMB1 (Two-hybrid), PCM1 (Cross-Linking-MS (XL-MS)), KCNMA1 (Affinity Capture-Western), KCNMB1 (Affinity Capture-Western), TBXA2R (Affinity Capture-Western)

ESM2 similar proteins: A2A6C4, A4D0V7, A6H684, A6NH21, A7VL23, A8WCG0, E9PY61, O70397, O73698, O75631, P0C8N6, P38574, P49653, P97678, Q15904, Q16558, Q1HG43, Q28067, Q28266, Q28705, Q2T9K0, Q2YDJ2, Q498W5, Q52LC2, Q5R8Q2, Q5XK03, Q5ZJY9, Q60409, Q6P5F7, Q6PRD1, Q811Q0, Q86XJ0, Q8CAE3, Q8CB65, Q8CIP5, Q8CJ26, Q8IUH8, Q8K3P1, Q8K5A9, Q8VE49

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

653 predictions. Top by Δscore:

Variant	Effect	Δscore
5:170383677:AC:A	donor_loss	1.0000
5:170383678:C:CT	donor_loss	1.0000
5:170383678:CCTG:C	donor_gain	1.0000
5:170383847:CACG:C	acceptor_gain	1.0000
5:170383851:C:CC	acceptor_gain	1.0000
5:170383861:C:CT	acceptor_gain	1.0000
5:170383861:C:T	acceptor_gain	1.0000
5:170385308:CAGTA:C	donor_loss	1.0000
5:170385310:GTACC:G	donor_loss	1.0000
5:170385311:TACC:T	donor_loss	1.0000
5:170385312:A:C	donor_loss	1.0000
5:170385313:C:A	donor_loss	1.0000
5:170385467:CATTT:C	acceptor_gain	1.0000
5:170385468:ATTT:A	acceptor_gain	1.0000
5:170385469:TTT:T	acceptor_gain	1.0000
5:170385470:TT:T	acceptor_gain	1.0000
5:170385471:TC:T	acceptor_loss	1.0000
5:170385472:C:CA	acceptor_loss	1.0000
5:170385472:C:CC	acceptor_gain	1.0000
5:170385473:T:C	acceptor_loss	1.0000
5:170385479:C:CT	acceptor_gain	1.0000
5:170385479:C:T	acceptor_gain	1.0000
5:170378706:A:AC	donor_gain	0.9900
5:170378707:C:CC	donor_gain	0.9900
5:170378709:T:TA	donor_gain	0.9900
5:170378974:C:CC	acceptor_gain	0.9900
5:170382797:T:TA	donor_gain	0.9900
5:170383846:ACACG:A	acceptor_gain	0.9900
5:170383847:CACGC:C	acceptor_gain	0.9900
5:170383848:ACG:A	acceptor_gain	0.9900

AlphaMissense

1232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:170383827:C:G	C53S	0.983
5:170383828:A:T	C53S	0.983
5:170378972:C:G	C103S	0.980
5:170378973:A:T	C103S	0.980
5:170378875:G:C	C135W	0.975
5:170383828:A:G	C53R	0.974
5:170378973:A:G	C103R	0.973
5:170383755:A:G	L77P	0.971
5:170378876:C:G	C135S	0.966
5:170378877:A:T	C135S	0.966
5:170383758:C:G	C76S	0.963
5:170383759:A:T	C76S	0.963
5:170383826:G:C	C53W	0.961
5:170378876:C:T	C135Y	0.956
5:170383757:G:C	C76W	0.956
5:170383759:A:G	C76R	0.956
5:170378793:A:G	W163R	0.955
5:170378793:A:T	W163R	0.955
5:170385390:C:G	G20R	0.955
5:170385389:C:T	G20D	0.953
5:170383716:A:T	L90Q	0.952
5:170383844:C:A	W47C	0.952
5:170383844:C:G	W47C	0.952
5:170378877:A:G	C135R	0.948
5:170383749:A:T	V79D	0.947
5:170383758:C:T	C76Y	0.946
5:170378768:C:T	G171D	0.942
5:170383827:C:T	C53Y	0.942
5:170383846:A:G	W47R	0.941
5:170383846:A:T	W47R	0.941

dbSNP variants (sampled 300 via entrez): RS1000096729 (5:170379889 C>T), RS1000279566 (5:170385879 G>A), RS1000625256 (5:170376277 C>T), RS1000680260 (5:170384771 A>G), RS1000729329 (5:170385132 G>A), RS1000880052 (5:170387096 T>A,C), RS1000997185 (5:170376082 G>A,T), RS1001047400 (5:170381033 C>A), RS1001099779 (5:170381325 C>G), RS1001194180 (5:170380643 G>C), RS1001863910 (5:170375363 G>A), RS1002117432 (5:170386191 T>C), RS1002418214 (5:170376461 C>T), RS1002771182 (5:170376831 C>A,T), RS1002826620 (5:170387248 C>T)

Disease associations

OMIM: gene MIM:603951 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0005117	Elevated diastolic blood pressure

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002481_3	Acne (severe)	3.000000e-06
GCST005859_3	Liver transplant-free survival in primary sclerosing cholangitis (time to event)	7.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3038495 (PROTEIN COMPLEX), CHEMBL5078 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11739136	Efficacy	3	verapamil	Hypertension
rs2301149	Efficacy	3	verapamil	Coronary Artery Disease;Hypertension

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2301149	KCNIP1, KCNMB1	3	2.50	1	verapamil
rs11739136	KCNIP1, KCNMB1	3	5.50	1	verapamil
rs703505	KCNIP1, KCNMB1		0.00	0

Binding affinities (BindingDB)

1 measured of 2 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SR 147778	KI	1000 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lithocholic Acid	affects cotreatment, increases response to substance, increases activity, affects binding, increases reaction (+1 more)	2
Smoke	decreases expression, decreases reaction, increases expression	2
bisphenol A	increases expression	1
sodium bichromate	decreases expression	1
NS 1619	affects binding, decreases expression, decreases reaction, decreases activity	1
abrine	increases expression	1
Decitabine	decreases expression, decreases reaction	1
Calcium	affects cotreatment, increases transport, increases reaction	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Glucose	decreases activity, increases reaction, affects binding, decreases expression, decreases reaction	1
Methyl Methanesulfonate	decreases expression	1
Tamoxifen	affects binding, increases activity, decreases expression, decreases reaction, decreases activity	1
Triclosan	decreases expression	1
Verapamil	affects response to substance	1
Vincristine	increases expression	1
Aflatoxin B1	increases methylation	1
Tetraethylammonium	affects binding, decreases activity, increases reaction	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

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

Clinical trials (associated diseases)

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