KCNB2

Summary

KCNB2 (potassium voltage-gated channel subfamily B member 2, HGNC:6232) is a protein-coding gene on chromosome 8q21.11, encoding Potassium voltage-gated channel subfamily B member 2 (Q92953). Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells.

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shab-related subfamily. This member is a delayed rectifier potassium channel. The gene is expressed in gastrointestinal smooth muscle cells.

Source: NCBI Gene 9312 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 115 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_004770

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6232
Approved symbol	KCNB2
Name	potassium voltage-gated channel subfamily B member 2
Location	8q21.11
Locus type	gene with protein product
Status	Approved
Aliases	Kv2.2
Ensembl gene	ENSG00000182674
Ensembl biotype	protein_coding
OMIM	607738
Entrez	9312

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000523207

RefSeq mRNA: 1 — MANE Select: NM_004770 NM_004770

CCDS: CCDS6209

Canonical transcript exons

ENST00000523207 — 3 exons

Exon	Start	End
ENSE00002091325	72567642	72568313
ENSE00002093880	72935935	72938349
ENSE00002128095	72537225	72537885

Expression profiles

Bgee: expression breadth broad, 94 present calls, max score 83.07.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1287 / max 198.8279, expressed in 245 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89353	0.3583	125
89357	0.3077	110
89356	0.1440	64
89354	0.1171	67
89355	0.0921	54
89359	0.0665	21
89358	0.0267	10
89360	0.0163	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	83.07	gold quality
middle frontal gyrus	UBERON:0002702	82.58	silver quality
endometrium epithelium	UBERON:0004811	81.70	gold quality
buccal mucosa cell	CL:0002336	80.62	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.85	silver quality
Brodmann (1909) area 10	UBERON:0013541	77.52	gold quality
islet of Langerhans	UBERON:0000006	77.51	gold quality
cortical plate	UBERON:0005343	77.01	gold quality
type B pancreatic cell	CL:0000169	74.87	gold quality
olfactory bulb	UBERON:0002264	74.72	gold quality
ganglionic eminence	UBERON:0004023	73.55	gold quality
prefrontal cortex	UBERON:0000451	69.94	gold quality
cerebellar vermis	UBERON:0004720	68.40	gold quality
hair follicle	UBERON:0002073	68.32	gold quality
tongue squamous epithelium	UBERON:0006919	67.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	67.08	gold quality
thymus	UBERON:0002370	66.50	gold quality
frontal cortex	UBERON:0001870	66.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	66.17	gold quality
ventricular zone	UBERON:0003053	65.98	gold quality
neocortex	UBERON:0001950	65.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.10	gold quality
quadriceps femoris	UBERON:0001377	64.98	gold quality
vastus lateralis	UBERON:0001379	64.93	gold quality
diaphragm	UBERON:0001103	64.89	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.85	gold quality
pancreatic ductal cell	CL:0002079	64.83	silver quality
entorhinal cortex	UBERON:0002728	64.55	gold quality
middle temporal gyrus	UBERON:0002771	63.90	silver quality
embryo	UBERON:0000922	63.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2380.14
E-HCAD-30	yes	466.67
E-HCAD-35	yes	64.85
E-GEOD-137537	yes	3.75
E-ANND-3	yes	3.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting KCNB2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-4659A-5P	98.03	66.42	819
HSA-MIR-4659B-5P	98.03	66.84	979
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-5000-5P	97.40	66.11	1055

Literature-anchored findings (GeneRIF, showing 6)

• stromatoxin-1 -sensitive KV2-containing channels are expressed in detrusor smooth muscle (DSM); they control DSM excitability, intracellular Ca2+ levels, and myogenic and nerve-evoked contractions (PMID:22422395)
• The rs2128158 in KCNB2 showed significant associations with MaxDrinks. (PMID:23953852)
• Five de novo mutations were identified in four genes (SCNN1A, KCNJ16, KCNB2, and KCNT1) in three Brugada syndrome patients (PMID:25339316)
• Kv2.1, but not Kv2.2 (KCNB2), forms clusters of 6-12 tetrameric channels at the plasma membrane and facilitates insulin exocytosis (PMID:28607108)
• Kv2 channel-AMIGO beta-subunit assembly modulates both channel function and cell adhesion molecule surface trafficking. (PMID:34137443)
• Protein Kinase C Controls the Excitability of Cortical Pyramidal Neurons by Regulating Kv2.2 Channel Activity. (PMID:34542799)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnb2b	ENSDARG00000088842

Paralogs (31): KCNG1 (ENSG00000026559), KCNQ1 (ENSG00000053918), KCNQ2 (ENSG00000075043), KCND1 (ENSG00000102057), KCNA7 (ENSG00000104848), KCNA1 (ENSG00000111262), KCNC4 (ENSG00000116396), KCNQ4 (ENSG00000117013), KCNS1 (ENSG00000124134), KCNC1 (ENSG00000129159), KCNA5 (ENSG00000130037), KCNC3 (ENSG00000131398), KCNA10 (ENSG00000143105), KCNA6 (ENSG00000151079), KCNS2 (ENSG00000156486), KCNB1 (ENSG00000158445), KCNF1 (ENSG00000162975), KCNV1 (ENSG00000164794), KCNC2 (ENSG00000166006), KCNV2 (ENSG00000168263), KCNG4 (ENSG00000168418), KCNS3 (ENSG00000170745), KCNG3 (ENSG00000171126), KCND3 (ENSG00000171385), KCNA3 (ENSG00000177272), KCNA2 (ENSG00000177301), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNQ3 (ENSG00000184156), KCND2 (ENSG00000184408), KCNQ5 (ENSG00000185760)

Protein

Protein identifiers

Potassium voltage-gated channel subfamily B member 2 — Q92953 (reviewed: Q92953)

Alternative names: Voltage-gated potassium channel subunit Kv2.2

All UniProt accessions (1): Q92953

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells. Channels open or close in response to the voltage difference across the membrane, letting potassium ions pass in accordance with their electrochemical gradient. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB1; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNS1 and KCNS2, creating a functionally diverse range of channel complexes. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells.

Subunit / interactions. Homotetramer or heterotetramer with KCNB1. Heterotetramer with KCNS1 and KCNS2. Interacts (via phosphorylated FFAT motif) with VAPA and VAPB.

Subcellular location. Cell membrane. Perikaryon. Cell projection. Dendrite.

Post-translational modifications. Phosphorylated. Phosphorylation at Ser-608 of the FFAT motif activates interaction with MOSPD2, VAPA and VAPB.

Activity regulation. Inhibited by quinine at micromolar levels. Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP).

Domain organisation. The transmembrane segment S4 functions as a voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region. The FFAT motif is involved in the interaction with VAPA and VAPB and its phosphorylation regulates these interactions.

Similarity. Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.2/KCNB2 sub-subfamily.

RefSeq proteins (1): NP_004761* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR003968	K_chnl_volt-dep_Kv	Family
IPR003973	K_chnl_volt-dep_Kv2	Family
IPR005821	Ion_trans_dom	Domain
IPR005826	K_chnl_volt-dep_Kv2.2	Family
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR028325	VG_K_chnl	Family

Pfam: PF00520, PF02214, PF03521

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (39 total): topological domain 8, region of interest 7, transmembrane region 6, compositionally biased region 6, intramembrane region 2, short sequence motif 2, modified residue 2, sequence variant 2, sequence conflict 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92953-F1	61.23	0.29

Functional residue map

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

Post-translational modifications (2): 448, 608

Glycosylation sites (1): 287

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 111 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, RNGTGGGC_UNKNOWN, AAGCAAT_MIR137, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, AP2_Q3, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, SOX9_B1, GOBP_MUSCLE_CONTRACTION, GATA1_01, MODULE_99

GO Biological Process (9): action potential (GO:0001508), potassium ion transport (GO:0006813), regulation of smooth muscle contraction (GO:0006940), protein homooligomerization (GO:0051260), potassium ion transmembrane transport (GO:0071805), protein localization to plasma membrane (GO:0072659), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (7): delayed rectifier potassium channel activity (GO:0005251), potassium channel regulator activity (GO:0015459), protein heterodimerization activity (GO:0046982), monoatomic ion channel activity (GO:0005216), voltage-gated potassium channel activity (GO:0005249), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (9): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), dendrite (GO:0030425), neuronal cell body membrane (GO:0032809), neuronal cell body (GO:0043025), perikaryon (GO:0043204), monoatomic ion channel complex (GO:0034702), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Potassium Channels	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transport	2
potassium channel activity	2
neuronal cell body	2
regulation of membrane potential	1
metal ion transport	1
regulation of muscle contraction	1
smooth muscle contraction	1
protein complex oligomerization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
protein localization to membrane	1
protein localization to cell periphery	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
voltage-gated potassium channel activity	1
ion channel regulator activity	1
protein dimerization activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
voltage-gated monoatomic cation channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
neuron projection	1
dendritic tree	1
cell body membrane	1
somatodendritic compartment	1
cell body	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

2144 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNB2	KCNAB3	O43448	791
KCNB2	VAPA	Q9P0L0	749
KCNB2	VAPB	O95292	719
KCNB2	KCNS1	Q96KK3	620
KCNB2	STX1A	Q16623	555
KCNB2	CA4	P22748	547
KCNB2	KCNB1	Q14721	525
KCNB2	CACNA1B	Q00975	512
KCNB2	KCNAB2	Q13303	476
KCNB2	KCNA5	P22460	456
KCNB2	CACNG4	Q9UBN1	456
KCNB2	KCNH5	Q8NCM2	449
KCNB2	KCNAB1	Q14722	448
KCNB2	KCNG4	Q8TDN1	447
KCNB2	KCNA2	P16389	447

IntAct

15 interactions, top by confidence:

A	B	Type	Score
KCNS3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
SCRIB	KCNB2	psi-mi:“MI:0915”(physical association)	0.400
GRB2	KCNB2	psi-mi:“MI:0915”(physical association)	0.400
KCNG4	KCNB2	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
GIGYF1	DYNC1I1	psi-mi:“MI:0914”(association)	0.350
TLK2	IGKV1D-13	psi-mi:“MI:0914”(association)	0.350
KCNF1	TRIM13	psi-mi:“MI:0914”(association)	0.350
KCNG1	UBB	psi-mi:“MI:0914”(association)	0.350
BET1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
LAMP1	TRAPPC13	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
SMURF1	HIP1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (73): KCNB2 (Affinity Capture-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), KCNB2 (Proximity Label-MS), CACNA1C (Co-localization), CACNA1D (Co-localization), KCNB2 (Proximity Label-MS)

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

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
KCNB2	“up-regulates quantity”	VAPB	relocalization
KCNB2	“up-regulates quantity”	VAPA	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	90
Likely benign	13
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4680923	NM_004770.3(KCNB2):c.1141A>G (p.Thr381Ala)	Likely pathogenic

SpliceAI

2931 predictions. Top by Δscore:

Variant	Effect	Δscore
8:72621217:A:G	acceptor_gain	1.0000
8:72621423:C:G	donor_gain	1.0000
8:72635314:GATT:G	donor_gain	1.0000
8:72858781:A:T	donor_gain	1.0000
8:72858784:G:GG	donor_gain	1.0000
8:72935933:A:AC	acceptor_loss	1.0000
8:72935933:A:AG	acceptor_gain	1.0000
8:72935934:G:GG	acceptor_gain	1.0000
8:72935934:GA:G	acceptor_gain	1.0000
8:72537678:G:T	donor_gain	0.9900
8:72567641:GCTTT:G	acceptor_gain	0.9900
8:72574320:G:GT	donor_gain	0.9900
8:72607569:G:GG	donor_gain	0.9900
8:72621216:A:AG	acceptor_gain	0.9900
8:72621216:AAGT:A	acceptor_gain	0.9900
8:72621389:G:GT	donor_gain	0.9900
8:72621430:T:TA	donor_gain	0.9900
8:72640861:A:AG	acceptor_gain	0.9900
8:72640862:G:GG	acceptor_gain	0.9900
8:72776479:T:G	acceptor_gain	0.9900
8:72875457:TCC:T	donor_gain	0.9900
8:72935934:GAT:G	acceptor_gain	0.9900
8:72935934:GATC:G	acceptor_gain	0.9900
8:72935934:GATCC:G	acceptor_gain	0.9900
8:72537473:C:T	donor_gain	0.9800
8:72567640:A:AG	acceptor_gain	0.9800
8:72567641:G:GG	acceptor_gain	0.9800
8:72568262:G:GT	donor_gain	0.9800
8:72570586:T:TA	acceptor_gain	0.9800
8:72605909:CAAG:C	acceptor_gain	0.9800

AlphaMissense

6033 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:72567844:T:A	V37D	1.000
8:72567854:T:A	N40K	1.000
8:72567854:T:G	N40K	1.000
8:72567856:T:A	V41E	1.000
8:72567858:G:A	G42R	1.000
8:72567858:G:C	G42R	1.000
8:72567858:G:T	G42W	1.000
8:72567859:G:A	G42E	1.000
8:72567859:G:T	G42V	1.000
8:72567861:G:C	G43R	1.000
8:72567862:G:A	G43D	1.000
8:72567862:G:T	G43V	1.000
8:72567870:C:G	H46D	1.000
8:72567877:T:A	V48D	1.000
8:72567882:T:A	W50R	1.000
8:72567882:T:C	W50R	1.000
8:72567884:G:C	W50C	1.000
8:72567884:G:T	W50C	1.000
8:72567892:T:A	L53Q	1.000
8:72567892:T:C	L53P	1.000
8:72567901:T:C	L56P	1.000
8:72567912:C:A	R60S	1.000
8:72567916:T:A	L61Q	1.000
8:72567916:T:C	L61P	1.000
8:72567916:T:G	L61R	1.000
8:72567918:G:A	G62R	1.000
8:72567918:G:C	G62R	1.000
8:72567919:G:A	G62E	1.000
8:72567919:G:T	G62V	1.000
8:72567925:T:A	L64H	1.000

dbSNP variants (sampled 300 via entrez): RS1000003398 (8:72727347 C>T), RS1000039841 (8:72546860 A>G), RS1000045124 (8:72849442 C>T), RS1000056585 (8:72611192 A>G,T), RS1000066349 (8:72918765 G>A), RS1000070086 (8:72729100 C>T), RS1000072594 (8:72597771 A>G,T), RS1000076033 (8:72721675 C>T), RS1000080836 (8:72906450 TATTTCC>T), RS1000096936 (8:72918476 A>C), RS1000100169 (8:72682793 A>G), RS1000100743 (8:72778677 G>A), RS1000112003 (8:72604258 C>T), RS1000119504 (8:72572337 T>G), RS1000132735 (8:72663821 T>A)

Disease associations

OMIM: gene MIM:607738 | disease phenotypes: MIM:114500

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (2): colorectal cancer (MONDO:0005575), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000110_3	Echocardiographic traits	5.000000e-06
GCST000267_4	Multiple sclerosis (age of onset)	3.000000e-06
GCST000579_53	Cognitive performance	1.000000e-06
GCST001438_7	Crohn’s disease	2.000000e-08
GCST006281_9	Coronary artery disease in type 1 diabetes	6.000000e-06
GCST007576_151	Chronotype	2.000000e-10
GCST008529_15	Tea consumption	3.000000e-08
GCST010118_164	Type 2 diabetes	3.000000e-08
GCST010242_273	HDL cholesterol levels	3.000000e-09
GCST010988_300	Adult body size	7.000000e-20

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004295	left ventricular function
EFO:0004298	cardiovascular measurement
EFO:0004847	age at onset
EFO:0003926	neuropsychological test
EFO:0008328	chronotype measurement
EFO:0010091	tea consumption measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2321618 (SINGLE PROTEIN), CHEMBL2362996 (PROTEIN FAMILY)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Voltage-gated potassium channels (K_v)

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
GxTx-1E	Gating inhibitor	8.6	pKd
ScTx1	Gating inhibitor	7.7	pIC50
RY796	Gating inhibitor	7.1	pIC50
RY785	Gating inhibitor	6.7	pIC50
quinine	Channel blocker	4.9	pIC50
fampridine	Channel blocker	2.8	pIC50
tetraethylammonium	Channel blocker	2.6	pIC50

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	Ki	0.15	nM	CHEMBL5722941
9.74	IC50	0.18	nM	CHEMBL5722941
7.00	IC50	100	nM	CHEMBL2324356

PubChem BioAssay actives

3 with measured affinity, of 40 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(1R,2aS,4S,5aS,8aS,10S,11aR,14aS,16S,17aS,19S,20aS,22S,23aS,25S,26aS,28S,29aS,31R,32aS,35aS,36R,38aS,39S,41aS,42S,44aS,45S,48R,50aS,51S,53aS,54S,56aS,57S,59aS,60S,63S,66S,69S,72S,75S,78S,87R,93S,96S,99S)-17a,20a,23a,53a,63-pentakis(4-aminobutyl)-31-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-16,29a,72,78-tetrakis(2-amino-2-oxoethyl)-14a,26a-bis(3-amino-3-oxopropyl)-2a,38a,66-tribenzyl-28,50a,57-tris[(2S)-butan-2-yl]-4,5a,19,42,45,69-hexakis(3-carbamimidamidopropyl)-51,54-bis(2-carboxyethyl)-56a,99-bis(carboxymethyl)-36-[[(2S,3S)-1-(carboxymethylamino)-3-methyl-1-oxopentan-2-yl]carbamoyl]-39,60-bis[(1R)-1-hydroxyethyl]-75,93-bis(hydroxymethyl)-32a,35a,59a-tris[(4-hydroxyphenyl)methyl]-22-(1H-imidazol-4-ylmethyl)-96-(1H-indol-3-ylmethyl)-41a-methyl-25-(2-methylpropyl)-1a,3,4a,6,7a,9,10a,13a,15,16a,18,19a,21,22a,24,25a,27,28a,30,31a,34a,37a,38,40a,41,43a,44,47,49a,50,52a,53,55a,56,58a,59,61a,62,65,68,71,74,77,80,83,86,89,92,95,98-pentacontaoxo-33,34,63a,64a,67a,68a-hexathia-a,2,3a,5,6a,8,9a,12a,14,15a,17,18a,20,21a,23,24a,26,27a,29,30a,33a,36a,37,39a,40,42a,43,46,48a,49,51a,52,54a,55,57a,58,60a,61,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazapentacyclo[85.74.4.448,111.010,14.0144,148]nonahexacontahectan-8a-yl]propanoic acid	2198828: Binding affinity to KV channel (unknown origin) assessed as inhibition constant	ki	0.0001	uM
2-(dimethylamino)-5-(2-methylpropanoylamino)-N-[(1S)-1-phenylethyl]benzamide	726268: Inhibition of voltage-gated K channel 2.2 (unknown origin) by automated patch clamp assay	ic50	0.1000	uM

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression	2
bisphenol A	decreases methylation	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
4-nonylphenol	affects cotreatment, increases expression	1
4-tert-octylphenol	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	decreases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Estradiol	affects cotreatment, decreases expression	1
Phthalic Acids	increases methylation	1
Aflatoxin B1	decreases methylation	1
Asbestos, Serpentine	increases methylation	1
tert-Butylhydroperoxide	decreases expression	1

ChEMBL screening assays

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

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2328103	Binding	Inhibition of voltage-gated K channel 2.2 (unknown origin) by automated patch clamp assay	Ion channels as therapeutic targets: a drug discovery perspective. — J Med Chem
CHEMBL5522525	Toxicity	Inhibition of human K+ channel by automated electrophysiology	Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	PHASE4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases