KCNIP2

Summary

KCNIP2 (potassium voltage-gated channel interacting protein 2, HGNC:15522) is a protein-coding gene on chromosome 10q24.32, encoding A-type potassium channel modulatory protein KCNIP2 (Q9NS61). Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels.

This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belongs to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified from this gene.

Source: NCBI Gene 30819 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 31 total
• Druggable target: yes
• MANE Select transcript: NM_173191

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15522
Approved symbol	KCNIP2
Name	potassium voltage-gated channel interacting protein 2
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	KCHIP2
Ensembl gene	ENSG00000120049
Ensembl biotype	protein_coding
OMIM	604661
Entrez	30819

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 30 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000239117, ENST00000343195, ENST00000348850, ENST00000353068, ENST00000355657, ENST00000356640, ENST00000358038, ENST00000370046, ENST00000434163, ENST00000460388, ENST00000461105, ENST00000472764, ENST00000483385, ENST00000642874, ENST00000853594, ENST00000853595, ENST00000945923, ENST00000945924, ENST00000945925, ENST00000945926, ENST00000945927, ENST00000945928, ENST00000945929, ENST00000945930, ENST00000945931, ENST00000945932, ENST00000945933, ENST00000945934, ENST00000945935, ENST00000945936, ENST00000945937, ENST00000945938, ENST00000945939, ENST00000945940

RefSeq mRNA: 7 — MANE Select: NM_173191 NM_014591, NM_173191, NM_173192, NM_173193, NM_173194, NM_173195, NM_173197

CCDS: CCDS41562, CCDS7521, CCDS7522, CCDS7523, CCDS7524, CCDS7525, CCDS7526

Canonical transcript exons

ENST00000356640 — 10 exons

Exon	Start	End
ENSE00001843586	101843496	101843800
ENSE00003325773	101829844	101829897
ENSE00003461669	101828389	101828459
ENSE00003507889	101827689	101827751
ENSE00003513367	101825974	101827400
ENSE00003520934	101831072	101831167
ENSE00003568130	101828627	101828696
ENSE00003610123	101829075	101829199
ENSE00003625121	101828151	101828258
ENSE00003634061	101827889	101827993

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 98.92.

FANTOM5 (CAGE): breadth broad, TPM avg 7.8512 / max 699.4029, expressed in 383 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111114	5.3844	241
111115	1.3589	172
111112	0.7767	215
111116	0.2194	81
111113	0.1118	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.92	gold quality
right atrium auricular region	UBERON:0006631	98.91	gold quality
cardiac atrium	UBERON:0002081	98.54	gold quality
nucleus accumbens	UBERON:0001882	98.43	gold quality
caudate nucleus	UBERON:0001873	98.15	gold quality
putamen	UBERON:0001874	96.85	gold quality
right frontal lobe	UBERON:0002810	96.84	gold quality
heart left ventricle	UBERON:0002084	96.76	gold quality
cardiac ventricle	UBERON:0002082	96.61	gold quality
anterior cingulate cortex	UBERON:0009835	95.80	gold quality
cingulate cortex	UBERON:0003027	95.61	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.91	gold quality
amygdala	UBERON:0001876	94.70	gold quality
heart	UBERON:0000948	94.51	gold quality
cerebellar hemisphere	UBERON:0002245	94.37	gold quality
cerebellar cortex	UBERON:0002129	94.24	gold quality
adipose tissue	UBERON:0001013	94.19	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.10	gold quality
omental fat pad	UBERON:0010414	94.08	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.05	gold quality
peritoneum	UBERON:0002358	94.00	gold quality
prefrontal cortex	UBERON:0000451	93.73	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.49	gold quality
heart right ventricle	UBERON:0002080	93.31	gold quality
telencephalon	UBERON:0001893	92.72	gold quality
neocortex	UBERON:0001950	92.61	gold quality
frontal cortex	UBERON:0001870	92.56	gold quality
Ammon’s horn	UBERON:0001954	92.51	gold quality
connective tissue	UBERON:0002384	92.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, THRA

miRNA regulators (miRDB)

125 targeting KCNIP2, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-3910	99.95	71.13	2227

Literature-anchored findings (GeneRIF, showing 26)

• Regulation of Kv4.3 current by KChIP2 splice variants (PMID:12135940)
• Analysis with chimeric proteins between KChIP2 and NCS-1 reveals that the three regions of KChIP2 are necessary and sufficient for its effective binding to Kv4.3 protein (PMID:12928444)
• Kv4.2 and K+ channel-interacting protein 2 make up a complex of Ito channels (PMID:14623880)
• Data show that KChIP1, KChIP2.1, and KChIP2.2 could form homo- as well as hetero-oligomers, and that this oligomerization did not perturb their interaction with Kv4.2 potassium channel. (PMID:15358149)
• Both Kv4.3 and KChIP2 may contribute to epicardial-endocardial gradients in the transient outward current in normal and failing hearts. (PMID:15498806)
• Co-expression of SGK1, but not of SGK2 or SGK3, increased Kv 4.3/KChIP2b channel currents. [KChIP2b; AH010566] (PMID:15578212)
• KChIP-2 is a Ca2+-dependent repressor of the immune response. (PMID:16177826)
• the C-terminal domain of Kv4.2 plays a critical role in voltage-dependent activation and functional expression that is mediated by direct interaction between the Kv4.2 C terminus and KChIP2 (PMID:16820361)
• The conformational change with metal-bound KChIP4.1 is crucial for its interaction with Kv channel but not for KChIP2.2, and that the Mg2+- and Ca2+-binding properties of KChIP2.2 and KChIP4.1 have different effects on their molecular structure. (PMID:16951992)
• These results reveal a new role for KChIP3 in the regulation of calcium regulated secretion and also suggest that the functions of each of the KChIPs may be more specialized than previously appreciated. (PMID:18393943)
• KChIP2c and KCNE2 simultaneously participate in recapitulation of the electrophysiological properties of transient outward current in cardiac myocytes (PMID:18501111)
• KChIP4a, KChIP2x, and KChIP3x comprise a novel class of KChIP isoforms characterized by an unusual transmembrane domain at their N termini that modulates Kv4 channel gating and trafficking. (PMID:18957440)
• Down-regulated atrial KChIP2 and Kv4.3 mRNA expressions in rheumatic heart disease patients with chronic atrial fibrillation might be one of the molecular bases responsible for the down-regulation of the I(to) current density of AF. (PMID:19927631)
• N-linked glycosylation of DPP10 plays an important role in modulating Kv4.3 channel/KCHIP2 complex activities. (PMID:20354865)
• The cytoplasmic accessory subunit KChIP2 also assembles with Kv4.2 to increase peak current, shift V1/2 ~5mV, slow time to peak ~10%, slow inactivation ~100%, and speed recovery from inactivation ~250% without overshoot. (PMID:20498229)
• The I(to) activator NS5806 modified Kv4.3/KChIP2 gating in several ways that inhibit current. (PMID:20649599)
• KChIP2 differentially regulates total and cell surface Kv4.2 protein expression and Kv4 current densities. (PMID:20709747)
• The “structurally minimal” isoform KChIP2d modulates recovery of K(v)4.3 N-terminal deletion mutant Delta2-39. (PMID:21422811)
• A novel KCNQ1-G229D mutation identified in a juvenile-onset AF patient altered the IKs activity and kinetics, thereby increasing the arrhythmogenicity to AF. (PMID:24096004)
• mutations cause a gainoffunction of KV4.3/KChIP2encoded channels by increasing membrane protein expression and slowing channel inactivation. (PMID:26016905)
• although there is a baseline presence of KChIP2 in the nucleus both in vivo and in vitro, KChIP2 does not directly regulate transcriptional activity. Moreover, the nuclear transport of KChIP2 is not dependent on Ca(2+). Thus, KChIP2 does not function as a conventional transcription factor in the heart. (PMID:27349185)
• Results identify the KChIP2/miR-34 axis as a central regulator in developing cardiac electrical dysfunction. (PMID:28263709)
• Binding of Ca(2+) to KChIP2 EF-hands can acutely modulate Kv4.3/KChIP2 channel inactivation gating. (PMID:28735419)
• Our results do not support the notion that accessory KChIP2 binding is a prerequisite for dendritic trafficking and functional surface expression of Kv4.2 channels, however, accessory KChIP2 binding may play a potential role in Kv4.2 modulation during intrinsic plasticity processes. (PMID:29385176)
• polybasic motif in alternatively spliced KChIP2 isoforms prevents Ca(2+) regulation of Kv4 channels (PMID:30622142)
• The palmitoylation status of KChIP2 determines its subcellular distribution in cardiac myocytes. Stress promotes nuclear entry of KChIP2, diverting it from ion channel modulation at the plasma membrane to other functions in the nuclear compartment. (PMID:31362018)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnip2	ENSDARG00000075846
danio_rerio		ENSDARG00000113766
mus_musculus	Kcnip2	ENSMUSG00000025221
rattus_norvegicus	Kcnip2	ENSRNOG00000018018
drosophila_melanogaster	CG7646	FBGN0036926
drosophila_melanogaster	CG5890	FBGN0039380
caenorhabditis_elegans	ncs-2	WBGENE00003564
caenorhabditis_elegans		WBGENE00015867

Paralogs (14): CLXN (ENSG00000034239), GUCA1A (ENSG00000048545), NCALD (ENSG00000104490), NCS1 (ENSG00000107130), RCVRN (ENSG00000109047), GUCA1B (ENSG00000112599), KCNIP3 (ENSG00000115041), HPCAL1 (ENSG00000115756), HPCAL4 (ENSG00000116983), HPCA (ENSG00000121905), GUCA1C (ENSG00000138472), VSNL1 (ENSG00000163032), KCNIP1 (ENSG00000182132), KCNIP4 (ENSG00000185774)

Protein

Protein identifiers

A-type potassium channel modulatory protein KCNIP2 — Q9NS61 (reviewed: Q9NS61)

Alternative names: Cardiac voltage-gated potassium channel modulatory subunit, Kv channel-interacting protein 2, Potassium channel-interacting protein 2

All UniProt accessions (4): A0A2R8Y6D7, A6NFF4, Q9NS61, Q3YAC7

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Modulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. Involved in KCND2 and KCND3 trafficking to the cell surface. May be required for the expression of I(To) currents in the heart.

Subunit / interactions. Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10. The KCND2-KCNIP2 channel complex contains four KCND2 and four KCNIP2 subunits. Interacts with KCND2. Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. At least isoform 2 and isoform 3 can self-associate to form homodimers and homotetramers. Isoform 3 interacts with KCNIP1 in a calcium-dependent manner. Interacts with KCND3; each KCNIP2 monomer interacts with two adjacent KCND3 subunits, through both the N-terminal inactivation ball of a KCND3 subunit and a C-terminal helix from the adjacent KCND3 subunit, clamping them together; this interaction modulates the channel gating kinetics.

Subcellular location. Cell membrane Cell membrane Cell membrane.

Tissue specificity. Expressed in brain. Colocalizes with KCND2 in excitatory neurons including cortical and hippocampal CA1 pyramidal cells. Isoform 3 is expressed in heart and in umbilical vein endothelial cells. Not expressed in fetal heart.

Post-translational modifications. Palmitoylated. Palmitoylation enhances association with the plasma membrane.

Similarity. Belongs to the recoverin family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q9NS61-1	1, KChIP2a, KChIP2b, KCHIP2.4, KCHIP2L	yes
Q9NS61-2	2, 3, KChIP2.1, KChIP2b
Q9NS61-3	3, 2, KChIP2.2, KChIP2c, KCHIP2S
Q9NS61-4	4
Q9NS61-5	5
Q9NS61-6	6, KCHIP4.2
Q9NS61-7	7
Q9NS61-8	8, KCHIP2.6
Q9NS61-9	9, KCHIP2.5

RefSeq proteins (7): NP_055406, NP_775283, NP_775284, NP_775285, NP_775286, NP_775287, NP_775289 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR028846	Recoverin	Family

Pfam: PF13499, PF13833

UniProt features (59 total): binding site 14, splice variant 10, helix 10, sequence conflict 9, strand 5, domain 4, lipid moiety-binding region 2, region of interest 2, chain 1, modified residue 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7UKH	ELECTRON MICROSCOPY	2.33
7W6S	ELECTRON MICROSCOPY	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS61-F1	70.02	0.28

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 (14): 157; 159; 164; 189; 191; 193; 195; 200; 237; 239; 241; 248 …

Post-translational modifications (3): 9, 45, 46

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5576894	Phase 1 - inactivation of fast Na+ channels
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 211 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, TGGTGCT_MIR29A_MIR29B_MIR29C, FXR_IR1_Q6, BENPORATH_ES_WITH_H3K27ME3, MYOGENIN_Q6, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEURON_MATURATION, SP3_Q3, MAZ_Q6, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_POTASSIUM_ION_TRANSPORT, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT

GO Biological Process (18): action potential (GO:0001508), detection of calcium ion (GO:0005513), potassium ion transport (GO:0006813), muscle contraction (GO:0006936), signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), regulation of heart contraction (GO:0008016), regulation of signal transduction (GO:0009966), clustering of voltage-gated potassium channels (GO:0045163), regulation of membrane repolarization (GO:0060306), membrane repolarization (GO:0086009), membrane repolarization during cardiac muscle cell action potential (GO:0086013), regulation of potassium ion transmembrane transport (GO:1901379), regulation of potassium ion export across plasma membrane (GO:1903764), positive regulation of potassium ion export across plasma membrane (GO:1903766), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), potassium ion transmembrane transport (GO:0071805)

GO Molecular Function (10): potassium channel activity (GO:0005267), calcium ion binding (GO:0005509), potassium channel regulator activity (GO:0015459), identical protein binding (GO:0042802), transmembrane transporter binding (GO:0044325), protein-containing complex binding (GO:0044877), ER lumen protein retrieval receptor activity (GO:0046923), A-type (transient outward) potassium channel activity (GO:0005250), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): cytoplasm (GO:0005737), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), dendrite (GO:0030425), synapse (GO:0045202), Kv4.2-KChIP2 channel complex (GO:0071193), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cardiac conduction	1
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of membrane potential	3
potassium ion export across plasma membrane	2
protein binding	2
binding	2
cellular anatomical structure	2
detection of chemical stimulus	1
response to calcium ion	1
metal ion transport	1
muscle system process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anterograde trans-synaptic signaling	1
heart contraction	1
regulation of blood circulation	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
neuronal ion channel clustering	1
regulation of biological process	1
membrane repolarization	1
cardiac muscle cell action potential	1
membrane repolarization during action potential	1
cardiac muscle cell membrane repolarization	1
regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
regulation of potassium ion transmembrane transport	1
positive regulation of potassium ion transmembrane transport	1
regulation of potassium ion export across plasma membrane	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1

Protein interactions and networks

STRING

2697 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNIP2	KCND3	Q9UK17	999
KCNIP2	KCND2	Q9NZV8	991
KCNIP2	KCNC1	P48547	984
KCNIP2	KCNA4	P22459	902
KCNIP2	KCNA5	P22460	815
KCNIP2	DPP6	P42658	814
KCNIP2	UHMK1	Q8TAS1	737
KCNIP2	KCND1	Q9NSA2	708
KCNIP2	SCN5A	Q14524	664
KCNIP2	KCNQ1	P51787	624
KCNIP2	KCNH2	Q12809	624
KCNIP2	CACNA1C	Q13936	615
KCNIP2	KCNE3	Q9Y6H6	614
KCNIP2	KCNJ3	P48549	613
KCNIP2	KCNE2	Q9Y6J6	611

IntAct

13 interactions, top by confidence:

A	B	Type	Score
KCND2	KCNIP2	psi-mi:“MI:0915”(physical association)	0.550
KCNIP2	KCND2	psi-mi:“MI:0915”(physical association)	0.550
WBP1	EXTL3	psi-mi:“MI:0914”(association)	0.530
STK17B	KCNIP2	psi-mi:“MI:0915”(physical association)	0.400
KCNIP4	SCGB1D1	psi-mi:“MI:0914”(association)	0.350
KCNIP2	S100A7	psi-mi:“MI:0914”(association)	0.350
REEP2	KCNIP4	psi-mi:“MI:0914”(association)	0.350
KCNIP4	ANKRD13A	psi-mi:“MI:0914”(association)	0.350
KCNIP2	ANKRD13A	psi-mi:“MI:0914”(association)	0.350
KCNIP4	MTX1	psi-mi:“MI:0914”(association)	0.350
KCNIP4	KCNIP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): KCNIP2 (Affinity Capture-MS), KCNIP1 (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), S100A7 (Affinity Capture-MS), KCNIP2 (Affinity Capture-MS), KCNIP2 (Affinity Capture-MS), KCNIP2 (Affinity Capture-MS), KCNIP1 (Affinity Capture-MS), KCNIP2 (Affinity Capture-MS), KCNIP2 (Affinity Capture-MS), KCNIP2 (Affinity Capture-MS), S100A7 (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), KCNIP2 (Affinity Capture-RNA), KCNIP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6A2H6, A2VEI2, A4IG32, A4IHK8, A5D7A0, D2HZB0, D4A1F2, E9Q4Z2, F1MF74, O00763, O08874, O14795, O94851, P23092, Q05AA6, Q08BI9, Q13474, Q17QM6, Q3TWN3, Q4FZY0, Q4KUS2, Q4V8B2, Q5E9V1, Q5R9G1, Q5RDI4, Q5U2P1, Q5ZJT0, Q62768, Q62769, Q69ZT9, Q6DFA1, Q86XE3, Q8BHD4, Q8BML1, Q8IWE4, Q8K0V2, Q8WN03, Q96C19, Q9BQI0, Q9BUP0

Diamond homologs: A9JTH1, B3DLU1, B3VSB7, B5FZ84, O73761, O73762, O73763, O95843, P21457, P22728, P25296, P29104, P29105, P31227, P34057, P35243, P35332, P36608, P36609, P37235, P37236, P42322, P42324, P42325, P43080, P43081, P46065, P51177, P61601, P61602, P62166, P62167, P62168, P62748, P62749, P62758, P62759, P62760, P62761, P62762

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1694 predictions. Top by Δscore:

Variant	Effect	Δscore
10:101827762:G:GC	acceptor_gain	1.0000
10:101827767:C:CT	acceptor_gain	1.0000
10:101827768:A:T	acceptor_gain	1.0000
10:101827771:C:CT	acceptor_gain	1.0000
10:101827772:A:T	acceptor_gain	1.0000
10:101827780:C:CT	acceptor_gain	1.0000
10:101827781:A:T	acceptor_gain	1.0000
10:101827788:A:AC	acceptor_gain	1.0000
10:101827788:A:C	acceptor_gain	1.0000
10:101827792:C:CT	acceptor_gain	1.0000
10:101827793:A:T	acceptor_gain	1.0000
10:101827887:AC:A	donor_loss	1.0000
10:101827888:C:A	donor_loss	1.0000
10:101827902:T:A	donor_gain	1.0000
10:101827912:C:A	donor_gain	1.0000
10:101827989:ATTTC:A	acceptor_gain	1.0000
10:101827990:TTTC:T	acceptor_gain	1.0000
10:101827991:TTC:T	acceptor_gain	1.0000
10:101827992:TC:T	acceptor_gain	1.0000
10:101827993:CC:C	acceptor_gain	1.0000
10:101827994:C:CA	acceptor_loss	1.0000
10:101827994:C:CC	acceptor_gain	1.0000
10:101827997:T:TC	acceptor_gain	1.0000
10:101828003:C:CT	acceptor_gain	1.0000
10:101828003:C:T	acceptor_gain	1.0000
10:101828004:A:T	acceptor_gain	1.0000
10:101828152:T:TA	donor_gain	1.0000
10:101828153:C:A	donor_gain	1.0000
10:101828621:CCTCA:C	donor_loss	1.0000
10:101828622:CTCAC:C	donor_loss	1.0000

AlphaMissense

1804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:101827707:G:C	F249L	1.000
10:101827707:G:T	F249L	1.000
10:101827708:A:G	F249S	1.000
10:101827709:A:G	F249L	1.000
10:101827723:A:T	V244E	1.000
10:101828161:A:T	I196N	1.000
10:101828182:T:G	D189A	1.000
10:101828188:A:G	L187P	1.000
10:101828193:G:C	F185L	1.000
10:101828193:G:T	F185L	1.000
10:101828194:A:G	F185S	1.000
10:101828195:A:G	F185L	1.000
10:101828201:A:G	W183R	1.000
10:101828201:A:T	W183R	1.000
10:101828206:A:G	L181P	1.000
10:101828399:A:T	V160D	1.000
10:101828431:G:C	F149L	1.000
10:101828431:G:T	F149L	1.000
10:101828433:A:G	F149L	1.000
10:101828435:A:G	L148P	1.000
10:101828444:G:T	A145D	1.000
10:101828637:A:C	F136L	1.000
10:101828637:A:T	F136L	1.000
10:101828639:A:G	F136L	1.000
10:101828662:A:G	F128S	1.000
10:101828677:A:T	V123D	1.000
10:101828683:C:T	G121E	1.000
10:101829078:C:A	K115N	1.000
10:101829078:C:G	K115N	1.000
10:101829081:G:C	F114L	1.000

dbSNP variants (sampled 300 via entrez): RS1000017419 (10:101827192 G>A), RS1000049837 (10:101826893 C>A,G), RS1000283419 (10:101840513 G>A), RS1000521020 (10:101835839 A>G), RS1000616254 (10:101838959 C>T), RS1001101254 (10:101828885 A>G), RS1001416278 (10:101840915 G>A), RS1001487153 (10:101834661 G>A), RS1001597455 (10:101827584 G>A,T), RS1001626420 (10:101834451 C>T), RS1001717448 (10:101826998 A>G), RS1002150886 (10:101840067 G>A,C,T), RS1002212531 (10:101841692 CA>C), RS1002362003 (10:101839683 T>C), RS1002523106 (10:101839888 G>A,C)

Disease associations

OMIM: gene MIM:604661 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010138_11	Raw vegetable consumption	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2189164 (SINGLE PROTEIN), CHEMBL3885598 (PROTEIN COMPLEX)

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Nickel	decreases expression	2
triphenyl phosphate	affects expression	1
methylparaben	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
gallium arsenide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases expression	1
prothioconazole	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Ethanol	increases expression	1
Cisplatin	decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Ozone	increases abundance, affects expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Urethane	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Raloxifene Hydrochloride	affects cotreatment, decreases activity	1

ChEMBL screening assays

12 unique, capped per target: 7 binding, 4 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4378228	Binding	Inhibition of human KvChIP2 expressed in CHOK1 cells at < 33 uM at -90 mV holding potential by Ionwork-based analysis	Discovery of the Oral Leukotriene C4 Synthase Inhibitor (1S,2S)-2-({5-[(5-Chloro-2,4-difluorophenyl)(2-fluoro-2-methylpropyl)amino]-3-methoxypyrazin-2-yl}carbonyl)cyclopropanecarboxylic Acid (AZD9898) as a New Treatment for Asthma. — J Med Chem
CHEMBL4393838	ADMET	Inhibition of human KChip2.2 by Ion-work electrophysiology assay	Discovery and Early Clinical Development of an Inhibitor of 5-Lipoxygenase Activating Protein (AZD5718) for Treatment of Coronary Artery Disease. — J Med Chem
CHEMBL5258223	Toxicity	Inhibition of Kv4.3/KChIP2 (unknown origin) at 10 uM	Discovery of VU2957 (Valiglurax): An mGlu4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson’s Disease. — ACS Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0Y5	B’SYS CHO Kv4.3/KChiP2	Spontaneously immortalized cell line	Female
CVCL_D1K7	PrecisION hKv4.2/KCHiP2-CHO	Spontaneously immortalized cell line	Female
CVCL_D1K9	PrecisION hKv4.3/KChiP2-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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