KCNIP1

Summary

KCNIP1 (potassium voltage-gated channel interacting protein 1, HGNC:15521) is a protein-coding gene on chromosome 5q35.1, encoding A-type potassium channel modulatory protein KCNIP1 (Q9NZI2). Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels.

This gene encodes a member of the family of cytosolic voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the neuronal calcium sensor (NCS) family of the calcium binding EF-hand proteins. They associate with Kv4 alpha subunits to form native Kv4 channel complexes. The encoded protein may regulate rapidly inactivating (A-type) currents, and hence neuronal membrane excitability, in response to changes in the concentration of intracellular calcium. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 30820 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 66 total — 1 pathogenic
• MANE Select transcript: NM_014592

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15521
Approved symbol	KCNIP1
Name	potassium voltage-gated channel interacting protein 1
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	KCHIP1
Ensembl gene	ENSG00000182132
Ensembl biotype	protein_coding
OMIM	604660
Entrez	30820

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000328939, ENST00000377360, ENST00000411494, ENST00000434108, ENST00000517344, ENST00000518527, ENST00000520740, ENST00000636734

RefSeq mRNA: 5 — MANE Select: NM_014592 NM_001034837, NM_001034838, NM_001278339, NM_001278340, NM_014592

CCDS: CCDS34285, CCDS34286, CCDS4374, CCDS64312, CCDS64313

Canonical transcript exons

ENST00000328939 — 8 exons

Exon	Start	End
ENSE00001304556	170721833	170721903
ENSE00001306119	170732800	170732904
ENSE00001311831	170733836	170733898
ENSE00001326623	170722713	170722820
ENSE00001628615	170504020	170504633
ENSE00001642927	170720321	170720390
ENSE00001805476	170735759	170736632
ENSE00003650445	170718758	170718882

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 91.77.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2775 / max 83.0521, expressed in 385 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60155	1.1261	306
60158	0.4492	131
60148	0.2120	43
60151	0.1725	74
60156	0.0941	65
60159	0.0815	59
60150	0.0683	42
60157	0.0627	45
60149	0.0111	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	91.77	gold quality
anterior cingulate cortex	UBERON:0009835	91.24	gold quality
cingulate cortex	UBERON:0003027	91.07	gold quality
caudate nucleus	UBERON:0001873	90.09	gold quality
amygdala	UBERON:0001876	89.89	gold quality
cortical plate	UBERON:0005343	88.83	gold quality
right frontal lobe	UBERON:0002810	88.78	gold quality
prefrontal cortex	UBERON:0000451	87.80	gold quality
hypothalamus	UBERON:0001898	87.14	gold quality
putamen	UBERON:0001874	87.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.57	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	85.69	gold quality
neocortex	UBERON:0001950	84.43	gold quality
frontal cortex	UBERON:0001870	83.50	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.32	gold quality
telencephalon	UBERON:0001893	83.12	gold quality
cerebral cortex	UBERON:0000956	81.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.27	gold quality
forebrain	UBERON:0001890	80.60	gold quality
cerebellar cortex	UBERON:0002129	80.37	gold quality
cerebellar hemisphere	UBERON:0002245	80.37	gold quality
spinal cord	UBERON:0002240	79.78	gold quality
brain	UBERON:0000955	79.41	gold quality
temporal lobe	UBERON:0001871	79.26	gold quality
Ammon’s horn	UBERON:0001954	78.92	gold quality
cerebellum	UBERON:0002037	78.14	gold quality
islet of Langerhans	UBERON:0000006	77.39	gold quality
substantia nigra	UBERON:0002038	77.27	gold quality
ganglionic eminence	UBERON:0004023	77.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	33.42
E-ANND-3	no	3.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting KCNIP1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-609	99.82	64.26	505
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325

Literature-anchored findings (GeneRIF, showing 12)

• 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)
• X-ray crystallographic and small-angle X-ray scattering data that show that the KChIP1-Kv4.3 N-terminal cytoplasmic domain complex is a cross-shaped octamer bearing two principal interaction sites. (PMID:17057713)
• 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)
• EF-hands 3 and 4 of KChIP1 are functionally involved in a specific association with PS on the membrane (PMID:19550036)
• our findings suggest that KChIP1 interacts with Kv4.3 in interneurons at the stratum lacunosum-moleculare/radiatum junction (PMID:21129448)
• Protein aggregation due to nsSNP resulting in P56S VABP protein is associated with amyotrophic lateral sclerosis (PMID:24681403)
• V234I-VAPB induces ubiquitin aggregation followed by cell death; proposed that V234I-VAPB exhibits the characteristics of amyotrophic lateral sclerosis in spite of not having the typical aggregation property of different mutations in various neurodegenerative diseases (PMID:24792378)
• KCNIP1 from copy number variations study might function as a type 2 diabetes susceptibility gene whose dysregulation alters insulin production. (PMID:24886904)
• These studies showed that a common copy number variation in KCNIP1 gene is a genetic predictor of atrial fibrillation risk possibly pointing to a functional pathway. (PMID:26831368)
• Study shows that the VAPB-PTPIP51 tethers regulate autophagy and demonstrates that overexpression of VAPB or PTPIP51 to tighten endoplasmic reticulum-mitochondria contacts impairs, whereas small interfering RNA-mediated loss of VAPB or PTPIP51 to loosen contacts stimulates, autophagosome formation. (PMID:28132811)
• the current study provides evidence that genetic variants of Kv accessory proteins may contribute to the susceptibility of Attention-deficit/hyperactivity disorder. (PMID:29176790)
• This is the first copy number variation association study of the KCNIP1 gene in Chinese population, and these data indicated that KCNIP1 might function as a type 2 diabetes-susceptibility gene whose dysregulation alters insulin production. (PMID:29491224)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnip1b	ENSDARG00000034808
		ENSDARG00000102210
mus_musculus	Kcnip1	ENSMUSG00000053519
rattus_norvegicus	Kcnip1	ENSRNOG00000005365
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), KCNIP2 (ENSG00000120049), HPCA (ENSG00000121905), GUCA1C (ENSG00000138472), VSNL1 (ENSG00000163032), KCNIP4 (ENSG00000185774)

Protein

Protein identifiers

A-type potassium channel modulatory protein KCNIP1 — Q9NZI2 (reviewed: Q9NZI2)

Alternative names: Kv channel-interacting protein 1, Potassium channel-interacting protein 1, Vesicle APC-binding protein

All UniProt accessions (3): Q9NZI2, A0A1B0GTZ7, E5RJY5

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Regulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND1/Kv4.1 and KCND2/Kv4.2 currents. Increases the presence of KCND2 at the cell surface.

Subunit / interactions. Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10. Part of a heterooctamer composed of the tetrameric channel and four KCNIP1 chains. Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. Self-associates to form homodimers and homotetramers. Interacts with KCNIP2 isoform 3 in a calcium-dependent manner. Interacts with Naja atra venom CTX3. Interacts with KCND2; this interaction mediates the capture of both the N- and C-terminus of KCND2, thus preventing KCND2 N-type inactivation and modulates the channel gating kinetics. Interacts with KCND3; each KCNIP1 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 stabilizes the tetrameric form and modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation.

Subcellular location. Cell membrane. Cytoplasm. Cell projection. Dendrite.

Tissue specificity. Isoform 1 and isoform 2 are expressed in brain and kidney. Isoform 1 is also expressed in liver, pancreas, skeletal muscle, small intestine and testis. Isoform 2 is also expressed in lung, pancreas, leukocytes, prostate and thymus.

Similarity. Belongs to the recoverin family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9NZI2-1	1, KCHIP1b, KCNIP1-Ib	yes
Q9NZI2-2	2, KCHIP1a, KCNIP1-IbdeltaII
Q9NZI2-3	3
Q9NZI2-4	4, KCNIP1-IadeltaII
Q9NZI2-5	5

RefSeq proteins (5): NP_001030009, NP_001030010, NP_001265268, NP_001265269, NP_055407* (*=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 (40 total): helix 12, binding site 9, strand 8, domain 4, splice variant 4, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
1S1E	X-RAY DIFFRACTION	2.3
7E83	ELECTRON MICROSCOPY	3.1
7E84	ELECTRON MICROSCOPY	3.1
7F3F	ELECTRON MICROSCOPY	3.1
2NZ0	X-RAY DIFFRACTION	3.2
2I2R	X-RAY DIFFRACTION	3.35
7W6N	ELECTRON MICROSCOPY	3.4
7W6T	ELECTRON MICROSCOPY	3.85
7E8E	ELECTRON MICROSCOPY	3.9
7E8H	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZI2-F1	78.28	0.37

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 (9): 157; 194; 196; 198; 205; 146; 148; 150; 152

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: 143 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_MUSCLE_CONTRACTION, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_SYSTEM_PROCESS, AACTTT_UNKNOWN, GOBP_HEART_PROCESS, GOBP_MUSCLE_SYSTEM_PROCESS, GOCC_NEURON_PROJECTION, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_MEMBRANE_REPOLARIZATION, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (11): muscle contraction (GO:0006936), chemical synaptic transmission (GO:0007268), regulation of heart contraction (GO:0008016), regulation of signal transduction (GO:0009966), membrane repolarization (GO:0086009), potassium ion export across plasma membrane (GO:0097623), regulation of potassium ion transmembrane transport (GO:1901379), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220), potassium ion transmembrane transport (GO:0071805)

GO Molecular Function (6): potassium channel activity (GO:0005267), calcium ion binding (GO:0005509), potassium channel regulator activity (GO:0015459), transmembrane transporter binding (GO:0044325), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (10): cytoplasm (GO:0005737), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), cytoplasmic side of plasma membrane (GO:0009898), dendrite (GO:0030425), synapse (GO:0045202), Kv4.3-KChIP1 channel complex (GO:0071196), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702), cell projection (GO:0042995)

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
cellular anatomical structure	3
potassium ion transmembrane transport	2
muscle system process	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
regulation of membrane potential	1
export across plasma membrane	1
regulation of potassium ion transport	1
regulation of monoatomic cation transmembrane transport	1
transport	1
metal ion 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
metal ion binding	1
potassium channel activity	1
ion channel regulator activity	1
protein binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
plasma membrane	1
cytoplasmic side of membrane	1
neuron projection	1
dendritic tree	1
cell junction	1
voltage-gated potassium channel complex	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

2617 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNIP1	KCND3	Q9UK17	998
KCNIP1	KCNC1	P48547	995
KCNIP1	KCND2	Q9NZV8	981
KCNIP1	KCND1	Q9NSA2	863
KCNIP1	RMDN3	Q96TC7	823
KCNIP1	DPP6	P42658	790
KCNIP1	HABP2	Q14520	774
KCNIP1	VAPB	O95292	742
KCNIP1	UHMK1	Q8TAS1	730
KCNIP1	DPP10	Q8N608	639
KCNIP1	GUF1	Q8N442	554
KCNIP1	CAV3	P56539	548
KCNIP1	KCNA2	P16389	539
KCNIP1	KCNAB1	Q14722	476
KCNIP1	VAPA	Q9P0L0	457

IntAct

25 interactions, top by confidence:

A	B	Type	Score
Kcnd3	KCNIP1	psi-mi:“MI:0407”(direct interaction)	0.620
KCNIP1	KCND3	psi-mi:“MI:0915”(physical association)	0.540
KCNIP1	KCND3	psi-mi:“MI:0407”(direct interaction)	0.540
KCND3	KCNIP1	psi-mi:“MI:0407”(direct interaction)	0.540
KCNIP1	KCNIP2	psi-mi:“MI:0407”(direct interaction)	0.520
KCND2	KCNIP2	psi-mi:“MI:0914”(association)	0.520
KCNIP1	KCND2	psi-mi:“MI:0407”(direct interaction)	0.520
KCNIP2	KCNIP1	psi-mi:“MI:0407”(direct interaction)	0.520
KCNIP1	KCNIP2	psi-mi:“MI:0914”(association)	0.520
	KCNIP1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNIP1		psi-mi:“MI:0915”(physical association)	0.370
CTXN1	ABCC4	psi-mi:“MI:0914”(association)	0.350
KCNIP4	SCGB1D1	psi-mi:“MI:0914”(association)	0.350
KCNIP2	S100A7	psi-mi:“MI:0914”(association)	0.350
OR14J1	BST1	psi-mi:“MI:0914”(association)	0.350
TBC1D28	CAPS	psi-mi:“MI:0914”(association)	0.350
LOXL1	KLHDC10	psi-mi:“MI:0914”(association)	0.350
KCNIP1	ATRAID	psi-mi:“MI:0914”(association)	0.350
KCNIP2	ANKRD13A	psi-mi:“MI:0914”(association)	0.350
UBAC1	KCNIP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): KCNIP1 (Affinity Capture-MS), KCNIP1 (Affinity Capture-MS), KCND3 (Co-crystal Structure), KCND3 (Reconstituted Complex), KCNIP1 (Affinity Capture-MS), KCNIP1 (Affinity Capture-MS), KCNIP1 (Two-hybrid), KCNIP1 (Two-hybrid), KCNIP1 (Two-hybrid), KCNIP1 (Two-hybrid), KCNIP1 (Two-hybrid), KCNIP1 (Two-hybrid), KCNIP1 (Two-hybrid), LITAF (Two-hybrid), NIF3L1 (Two-hybrid)

ESM2 similar proteins: A0AVX7, A2VEI2, F4J0W4, O43745, O70200, O73761, O73762, P04354, P04467, P05937, P07171, P12658, P22728, P41044, P43080, P43081, P46065, P51177, P55008, P61022, P61023, P79880, P81076, Q0V9B1, Q1LWZ0, Q298L5, Q3KQ77, Q3SYS6, Q3T024, Q4R760, Q4V7T8, Q5R4V1, Q5R7F0, Q5TM25, Q5U554, Q5ZM44, Q6P8Y1, Q810D1, Q8IMX7, Q8R426

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	47
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1217228	NM_014592.4(KCNIP1):c.328G>A (p.Asp110Asn)	Pathogenic

SpliceAI

2821 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
5:170718749:T:TA	acceptor_gain	1.0000
5:170718750:G:A	acceptor_gain	1.0000
5:170718753:TCCA:T	acceptor_loss	1.0000
5:170718754:CCAG:C	acceptor_loss	1.0000
5:170718755:CAGAT:C	acceptor_loss	1.0000
5:170718756:A:AG	acceptor_gain	1.0000
5:170718756:AGATA:A	acceptor_loss	1.0000
5:170718757:G:GA	acceptor_gain	1.0000

AlphaMissense

1458 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:170718854:T:C	L64P	1.000
5:170718875:T:C	F71S	1.000
5:170718879:A:C	K72N	1.000
5:170718879:A:T	K72N	1.000
5:170720340:T:A	V80D	1.000
5:170721848:C:A	A102D	1.000
5:170722776:T:C	F142L	1.000
5:170722778:T:A	F142L	1.000
5:170722778:T:G	F142L	1.000
5:170733879:T:C	F206S	1.000
5:170718839:T:C	F59S	0.999
5:170718863:T:C	L67P	0.999
5:170718865:T:G	Y68D	0.999
5:170718869:G:C	R69P	0.999
5:170718874:T:C	F71L	0.999
5:170718876:C:A	F71L	0.999
5:170718876:C:G	F71L	0.999
5:170718877:A:G	K72E	0.999
5:170720324:T:C	C75R	0.999
5:170720334:G:A	G78D	0.999
5:170720355:T:C	F85S	0.999
5:170720375:T:C	F92L	0.999
5:170720377:T:A	F92L	0.999
5:170720377:T:G	F92L	0.999
5:170720378:T:C	F93L	0.999
5:170720380:C:A	F93L	0.999
5:170720380:C:G	F93L	0.999
5:170721857:T:C	L105P	0.999
5:170721859:T:C	F106L	0.999
5:170721861:C:A	F106L	0.999

dbSNP variants (sampled 300 via entrez): RS1000012806 (5:170550140 G>A,T), RS1000020909 (5:170453838 G>C), RS1000021363 (5:170576833 C>T), RS1000028668 (5:170368083 T>C), RS1000034242 (5:170729444 A>G), RS1000035395 (5:170505140 A>G), RS1000053243 (5:170663942 C>T), RS1000069037 (5:170704653 G>A,C), RS1000086423 (5:170735318 T>C), RS1000096729 (5:170379889 C>T), RS1000103670 (5:170460183 T>C), RS1000105199 (5:170664294 G>A), RS1000107995 (5:170448427 T>A,C), RS1000116452 (5:170558180 G>A), RS1000131082 (5:170358640 A>T)

Disease associations

OMIM: gene MIM:604660 | disease phenotypes: MIM:600669

GenCC curated gene-disease

Mondo (1): idiopathic generalized epilepsy (MONDO:0005579)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000268_2	Normalized brain volume	9.000000e-06
GCST002481_3	Acne (severe)	3.000000e-06
GCST005844_6	Placental abruption	5.000000e-06
GCST005859_3	Liver transplant-free survival in primary sclerosing cholangitis (time to event)	7.000000e-08
GCST007471_10	Short-term memory (digit-span task)	4.000000e-06
GCST008758_30	Pre-treatment viral load in HIV-1 infection	1.000000e-16
GCST009305_11	California verbal learning test score	9.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004335	short-term memory
EFO:0010125	viral load
EFO:0004874	memory performance

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562694	Epilepsy, Idiopathic Generalized (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
Ethinyl Estradiol	decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
aminomethylphosphonic acid (AMPA)	increases expression	1
lasiocarpine	decreases expression	1
bisphenol A	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	affects methylation	1
ochratoxin A	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
Acetaminophen	decreases expression	1
Glyphosate	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Formaldehyde	decreases expression	1
Methapyrilene	increases methylation	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Triclosan	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_D1K8	PrecisION hKv4.3/KCHiP1-CHO	Spontaneously immortalized cell line	Female
CVCL_YA62	IDG-HEK293T-KCNIP1-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03590197	PHASE4	COMPLETED	Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy
NCT03940326	PHASE4	COMPLETED	Levetiracetam Versus Valproate in Idiopathic Generalized Tonic-clonic Seizures
NCT00150735	PHASE3	COMPLETED	Monotherapy With Levetiracetam in Newly Diagnosed Patients Suffering From Epilepsy
NCT00150748	PHASE3	COMPLETED	Long Term Follow up Treatment With Levetiracetam in Subjects of 4 Years and Older With Generalized Epilepsy
NCT03678753	PHASE3	COMPLETED	Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures
NCT05147571	PHASE3	ACTIVE_NOT_RECRUITING	RNS System NAUTILUS Study
NCT06908356	PHASE2	RECRUITING	An Open Label Trial to Evaluate the Efficacy and Safety of PRAX-628 in Adults With Focal Onset or Tonic-Clonic Seizures
NCT06425159	PHASE2/PHASE3	TERMINATED	A Study to Determine if BHV-7000 is Effective and Safe in Adults With Idiopathic Generalized Epilepsy With Generalized Tonic-clonic Seizures
NCT00001325	Not specified	COMPLETED	Metabolic Abnormalities in Children With Epilepsy
NCT00916903	Not specified	TERMINATED	Genetic Disease Gene Identification
NCT01311440	Not specified	COMPLETED	Modified Atkins Diet Treatment for Adults With Drug-resistant Epilepsy
NCT01432821	Not specified	COMPLETED	Blinking and Yawning in Epilepsy: The Role of Dopamine
NCT03368469	Not specified	WITHDRAWN	Transcranial Direct Current Stimulation (tDCS) in Children and Adolescents With Epilepsy and Depression
NCT03457961	Not specified	UNKNOWN	Post-market Study of AMPA Receptor Antagonists for Epilepsy Patients in Hong Kong
NCT03955432	Not specified	TERMINATED	Long-term Cardiac Monitoring in Epilepsy
NCT04252846	Not specified	COMPLETED	A Study to Investigate Dosage, Effectiveness, and Safety of Perampanel When Used as First Add-on Therapy in Participants >=12 Years With Partial Onset Seizures With or Without Secondary Generalization or With Primary Generalized Tonic-Clonic Seizures Associated With Idiopathic Generalized Epilepsy
NCT04965571	Not specified	COMPLETED	Clinical Features and Outcome of Wilson’s Disease With Generalized Epilepsy in Chinese Patients
NCT05374928	Not specified	ACTIVE_NOT_RECRUITING	Human Epilepsy Project 3
NCT05530109	Not specified	TERMINATED	Study of Attentional Disorders in Patients Suffering From Idiopathic Generalized Epilepsy.
NCT06388174	Not specified	RECRUITING	Idiopathic Generalized Epilepsy Syndromes
NCT06797791	Not specified	COMPLETED	Assessment of Multifocal Continuous Theta Burst Transcranial Magnetic Stimulation (cTBS) Effects in Generalized Epilepsy Patients.