KCNIP4

Summary

KCNIP4 (potassium voltage-gated channel interacting protein 4, HGNC:30083) is a protein-coding gene on chromosome 4p15.31-p15.2, encoding Kv channel-interacting protein 4 (Q6PIL6). 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 belong 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. This protein member also interacts with presenilin. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 80333 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_025221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30083
Approved symbol	KCNIP4
Name	potassium voltage-gated channel interacting protein 4
Location	4p15.31-p15.2
Locus type	gene with protein product
Status	Approved
Aliases	CALP, KCHIP4, MGC44947
Ensembl gene	ENSG00000185774
Ensembl biotype	protein_coding
OMIM	608182
Entrez	80333

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000382148, ENST00000382149, ENST00000382150, ENST00000382152, ENST00000447367, ENST00000509207, ENST00000512102, ENST00000515373, ENST00000515786

RefSeq mRNA: 7 — MANE Select: NM_025221 NM_001035003, NM_001035004, NM_001363504, NM_025221, NM_147181, NM_147182, NM_147183

CCDS: CCDS3428, CCDS43215, CCDS43216, CCDS43217, CCDS47035, CCDS87210

Canonical transcript exons

ENST00000382152 — 9 exons

Exon	Start	End
ENSE00001529315	20882608	20882709
ENSE00002028434	20728606	20730129
ENSE00002083383	21948571	21948772
ENSE00003484293	20734628	20734735
ENSE00003532750	20732681	20732785
ENSE00003582303	20758821	20758890
ENSE00003603267	20850543	20850667
ENSE00003613779	20749662	20749732
ENSE00003627411	20732006	20732068

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 97.77.

FANTOM5 (CAGE): breadth broad, TPM avg 4.9776 / max 570.3006, expressed in 264 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51603	3.0648	157
51600	0.4385	82
51583	0.2350	76
51604	0.1648	76
51601	0.1299	55
51602	0.1284	59
51572	0.1210	16
51584	0.1195	47
51574	0.1066	20
51606	0.0803	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	97.77	gold quality
middle temporal gyrus	UBERON:0002771	97.73	gold quality
pons	UBERON:0000988	97.59	gold quality
cerebellar vermis	UBERON:0004720	97.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.84	gold quality
superior frontal gyrus	UBERON:0002661	95.55	gold quality
parietal lobe	UBERON:0001872	95.06	gold quality
superior vestibular nucleus	UBERON:0007227	94.91	gold quality
postcentral gyrus	UBERON:0002581	94.69	gold quality
ventral tegmental area	UBERON:0002691	94.67	gold quality
occipital lobe	UBERON:0002021	94.63	gold quality
endothelial cell	CL:0000115	94.55	gold quality
primary visual cortex	UBERON:0002436	94.29	gold quality
substantia nigra pars compacta	UBERON:0001965	94.15	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.37	gold quality
entorhinal cortex	UBERON:0002728	93.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.98	gold quality
frontal cortex	UBERON:0001870	92.01	gold quality
prefrontal cortex	UBERON:0000451	91.38	gold quality
lateral globus pallidus	UBERON:0002476	91.26	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.21	gold quality
neocortex	UBERON:0001950	91.02	gold quality
cerebral cortex	UBERON:0000956	90.88	gold quality
temporal lobe	UBERON:0001871	90.88	gold quality
right frontal lobe	UBERON:0002810	90.86	gold quality
anterior cingulate cortex	UBERON:0009835	90.69	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.64	gold quality
nucleus accumbens	UBERON:0001882	90.56	gold quality
medulla oblongata	UBERON:0001896	90.04	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	21884.00
E-GEOD-180759	yes	17278.29
E-HCAD-25	yes	10720.76
E-ANND-2	yes	9009.14
E-CURD-119	yes	6885.93
E-GEOD-131882	yes	6664.56
E-HCAD-30	no	14729.27
E-ANND-3	no	3.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, NR4A2

miRNA regulators (miRDB)

83 targeting KCNIP4, 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-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4762-5P	99.57	68.54	1424

Literature-anchored findings (GeneRIF, showing 13)

• cloning and investigation of interaction with presenilin 2 and voltage-gated potassium channel subunit Kv4 (PMID:11847232)
• 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)
• Mutation of KCNIP4 is associated with renal cell carcinoma. (PMID:17981209)
• CALP and calsenilin are involved in the trafficking of Golgi glycosyltransferases. (PMID:18269347)
• 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)
• 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)
• These data demonstrate that PKA phosphorylation of Kv4.2 plays an important role in the trafficking of Kv4.2 through its specific interaction with KChIP4a. (PMID:20045463)
• The synthesis of the variant KCNIP4 isoform is also detrimental to brain physiology, as it results in the concomitant blockade of the fast kinetics of potassium channels. (PMID:21624954)
• genetic association studies in populations in Germany: Data suggest that multiple SNPs in KCNIP4 are associated not only with attention deficit disorder with hyperactivity in children and adults but also with personality disorders. (PMID:22981920)
• Genome-wide association study identifies KCNIP4 as an asthma gene in human and in mouse. (PMID:23457522)
• KChIP4a suppresses A-type Kv4 current via ER retention and enhancement of Kv4 closed-state inactivation. (PMID:23576435)
• Subunit counting by single-molecule imaging revealed that the bound number of KChIP4 in each Kv4.2.KChIP4 complex was dependent on the expression level of KChIP4. (PMID:24811166)
• Results indicate that SNPs in KCNIP4 may modulate ACE inhibitor-induced cough risk. (PMID:26169577)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnip4b	ENSDARG00000037256
mus_musculus	Kcnip4	ENSMUSG00000029088
rattus_norvegicus	Kcnip4	ENSRNOG00000032350
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), KCNIP1 (ENSG00000182132)

Protein

Protein identifiers

Kv channel-interacting protein 4 — Q6PIL6 (reviewed: Q6PIL6)

Alternative names: A-type potassium channel modulatory protein 4, Calsenilin-like protein, Potassium channel-interacting protein 4

All UniProt accessions (3): F5H395, Q6PIL6, Q3YAB7

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Modulates KCND2 channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. Modulates KCND3/Kv4.3 currents. Isoform 4 does not increase KCND2 expression at the cell membrane. Isoform 4 retains KCND3 in the endoplasmic reticulum and negatively regulates its expression at the cell membrane.

Subunit / interactions. Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10. Interacts with KCND2. Interacts with KCND3. Interacts with the C-terminus of PSEN2 and probably PSEN1.

Subcellular location. Cell membrane. Cytoplasm. Peroxisome Endoplasmic reticulum.

Tissue specificity. Predominantly expressed in brain.

Domain organisation. The KIS (K-channel inactivation suppressor) domain is required for converting A-type Kv4 current to a slowly inactivating delayed rectifier potassium current.

Similarity. Belongs to the recoverin family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6PIL6-1	1, KChIP4.1	yes
Q6PIL6-2	2, KChIP4.2
Q6PIL6-3	3, KChIP4bs, KCHIP4.2
Q6PIL6-4	4, KChIP4a, KChIP4.4
Q6PIL6-5	5

RefSeq proteins (7): NP_001030175, NP_001030176, NP_001350433, NP_079497, NP_671710, NP_671711, NP_671712 (=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 (28 total): binding site 13, domain 4, splice variant 4, modified residue 2, sequence conflict 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PIL6-F1	70.52	0.19

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 (13): 144; 169; 171; 173; 175; 180; 217; 219; 221; 228; 133; 135 …

Post-translational modifications (2): 17, 56

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: 136 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, MYAATNNNNNNNGGC_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_MONOATOMIC_CATION_TRANSPORT, TGCTGAY_UNKNOWN, HFH1_01, AACTTT_UNKNOWN, SABATES_COLORECTAL_ADENOMA_DN, CAAGGAT_MIR362, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, TTTNNANAGCYR_UNKNOWN, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (7): regulation of signal transduction (GO:0009966), protein localization to plasma membrane (GO:0072659), 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 (5): potassium channel activity (GO:0005267), calcium ion binding (GO:0005509), potassium channel regulator activity (GO:0015459), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): cytoplasm (GO:0005737), peroxisome (GO:0005777), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), 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
cellular anatomical structure	3
cytoplasm	2
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
protein localization to membrane	1
protein localization to cell periphery	1
regulation of potassium ion transport	1
potassium ion transmembrane 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
binding	1
cation binding	1
intracellular anatomical structure	1
microbody	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

2739 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNIP4	KCNC1	P48547	925
KCNIP4	KCND3	Q9UK17	922
KCNIP4	KCND1	Q9NSA2	920
KCNIP4	KCND2	Q9NZV8	860
KCNIP4	UHMK1	Q8TAS1	777
KCNIP4	PSEN2	P49810	749
KCNIP4	DPP6	P42658	693
KCNIP4	CALML5	Q9NZT1	557
KCNIP4	CALML6	Q8TD86	554
KCNIP4	CALML4	Q96GE6	554
KCNIP4	CALML3	P27482	553
KCNIP4	CFTR	P13569	490
KCNIP4	CTNNB1	P35222	486
KCNIP4	CSMD1	Q96PZ7	445
KCNIP4	KLHL8	Q9P2G9	437

IntAct

38 interactions, top by confidence:

A	B	Type	Score
COL1A2	KCNIP4	psi-mi:“MI:0915”(physical association)	0.720
KCNIP4	ASPH	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	KCNIP4	psi-mi:“MI:0915”(physical association)	0.560
KCNIP4	LITAF	psi-mi:“MI:0915”(physical association)	0.560
TRH	KCNIP4	psi-mi:“MI:0915”(physical association)	0.560
IL17A	KCNIP4	psi-mi:“MI:0915”(physical association)	0.560
ASPH	KCNIP4	psi-mi:“MI:0915”(physical association)	0.560
KCNIP4	GOLGA7	psi-mi:“MI:0915”(physical association)	0.560
KLK4	KCNIP4	psi-mi:“MI:0915”(physical association)	0.400
TFPI	KCNIP4	psi-mi:“MI:0915”(physical association)	0.400
ECE2	KDM1A	psi-mi:“MI:0914”(association)	0.350
KCNIP4	SCGB1D1	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
KCNIP4	MTX1	psi-mi:“MI:0914”(association)	0.350
KCNIP4	FAM120B	psi-mi:“MI:0915”(physical association)	0.000
KCNIP4	KCNIP2	psi-mi:“MI:0915”(physical association)	0.000
KCNIP4		psi-mi:“MI:0915”(physical association)	0.000
KCNIP4	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
LITAF	KCNIP4	psi-mi:“MI:0915”(physical association)	0.000
TRH	KCNIP4	psi-mi:“MI:0915”(physical association)	0.000
COL1A2	KCNIP4	psi-mi:“MI:0915”(physical association)	0.000
KCNIP4	IL17A	psi-mi:“MI:0915”(physical association)	0.000
KCNIP4	GOLGA7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): KCNIP2 (Affinity Capture-MS), KCNIP1 (Affinity Capture-MS), SCGB1D1 (Affinity Capture-MS), MTX1 (Affinity Capture-MS), LACRT (Affinity Capture-MS), ZG16B (Affinity Capture-MS), PRR4 (Affinity Capture-MS), KCNIP2 (Affinity Capture-MS), KCNIP1 (Affinity Capture-MS), MTX1 (Affinity Capture-MS), LACRT (Affinity Capture-MS), SCGB1D1 (Affinity Capture-MS), PRR4 (Affinity Capture-MS), KCNIP4 (Affinity Capture-MS), KCNIP4 (Affinity Capture-MS)

ESM2 similar proteins: A0PJX0, A1L1L6, A4IG32, B1A8Z2, B1H2N3, C7A278, D2HZB0, O88456, P04632, P06813, P07090, P22676, P47728, Q08331, Q0IIL1, Q17QE5, Q1RMX9, Q2HJF8, Q2KI69, Q32L26, Q32LU1, Q3T0E8, Q3ZBY3, Q4R518, Q5PPL2, Q5RDF9, Q5ZM73, Q6NVC5, Q6P6Q9, Q6P8Y1, Q6PHZ8, Q6PIL6, Q8BG51, Q8HYN7, Q8IXI2, Q8R426, Q8VCX5, Q8WWF8, Q99828, Q99MG9

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

1 interactions.

A	Effect	B	Mechanism
KCNIP4	“up-regulates activity”	KCND2	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3103 predictions. Top by Δscore:

Variant	Effect	Δscore
4:20731999:TAC:T	donor_loss	1.0000
4:20732000:ACTT:A	donor_loss	1.0000
4:20732001:CT:C	donor_loss	1.0000
4:20732002:TTACT:T	donor_loss	1.0000
4:20732003:TACTT:T	donor_loss	1.0000
4:20732004:A:AC	donor_gain	1.0000
4:20732005:C:CC	donor_gain	1.0000
4:20732065:TTTT:T	acceptor_gain	1.0000
4:20732069:C:CC	acceptor_gain	1.0000
4:20732074:C:CT	acceptor_gain	1.0000
4:20732075:A:T	acceptor_gain	1.0000
4:20734623:CTTA:C	donor_loss	1.0000
4:20734625:TACCT:T	donor_loss	1.0000
4:20734626:A:AC	donor_gain	1.0000
4:20734627:C:CC	donor_gain	1.0000
4:20734627:CCT:C	donor_gain	1.0000
4:20734731:AAATC:A	acceptor_gain	1.0000
4:20734732:AATC:A	acceptor_gain	1.0000
4:20734733:ATC:A	acceptor_gain	1.0000
4:20734733:ATCC:A	acceptor_gain	1.0000
4:20734734:TC:T	acceptor_gain	1.0000
4:20734734:TCC:T	acceptor_gain	1.0000
4:20734735:CC:C	acceptor_gain	1.0000
4:20734735:CCT:C	acceptor_gain	1.0000
4:20734736:C:CC	acceptor_gain	1.0000
4:20734737:T:G	acceptor_loss	1.0000
4:20749656:GCTTA:G	donor_loss	1.0000
4:20749657:CTTAC:C	donor_loss	1.0000
4:20749658:TTA:T	donor_loss	1.0000
4:20749733:C:CC	acceptor_gain	1.0000

AlphaMissense

1696 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:20732024:G:C	F229L	1.000
4:20732024:G:T	F229L	1.000
4:20732025:A:G	F229S	1.000
4:20732026:A:G	F229L	1.000
4:20732040:A:T	V224D	1.000
4:20732062:C:G	D217H	1.000
4:20732697:A:T	V209D	1.000
4:20732764:C:G	A187P	1.000
4:20734638:A:T	I176N	1.000
4:20734658:G:C	D169E	1.000
4:20734658:G:T	D169E	1.000
4:20734659:T:A	D169V	1.000
4:20734659:T:C	D169G	1.000
4:20734659:T:G	D169A	1.000
4:20734660:C:G	D169H	1.000
4:20734665:A:G	L167P	1.000
4:20734670:A:C	F165L	1.000
4:20734670:A:T	F165L	1.000
4:20734671:A:G	F165S	1.000
4:20734672:A:G	F165L	1.000
4:20734678:A:G	W163R	1.000
4:20734678:A:T	W163R	1.000
4:20734683:A:G	L161P	1.000
4:20734701:C:T	G155E	1.000
4:20734702:C:A	G155W	1.000
4:20734702:C:G	G155R	1.000
4:20734702:C:T	G155R	1.000
4:20734719:A:G	L149P	1.000
4:20749665:G:C	F142L	1.000
4:20749665:G:T	F142L	1.000

dbSNP variants (sampled 300 via entrez): RS1000000708 (4:21703978 G>A,T), RS10000010 (4:21617051 T>C,G), RS1000006926 (4:21687291 C>A,T), RS1000008083 (4:21173111 G>A), RS10000092 (4:21893894 T>C), RS1000011661 (4:21225317 A>G,T), RS1000012898 (4:21740406 C>T), RS1000014665 (4:21519880 A>G,T), RS1000015802 (4:21580590 A>G), RS1000016231 (4:21088230 A>T), RS10000167 (4:21041671 G>A), RS1000019842 (4:21647542 T>C,G), RS1000021210 (4:21540423 T>A,C), RS1000021507 (4:21417781 A>G), RS1000025249 (4:20806285 C>T)

Disease associations

OMIM: gene MIM:608182 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000816_3	Suicidal ideation	3.000000e-06
GCST000917_7	Rheumatoid arthritis	7.000000e-06
GCST001762_201	Obesity-related traits	9.000000e-06
GCST001762_432	Obesity-related traits	9.000000e-06
GCST002778_6	Parkinson disease and lewy body pathology	1.000000e-06
GCST002936_19	Cadmium levels	1.000000e-07
GCST003027_1	Cough in response to angiotensin-converting enzyme inhibitor drugs	2.000000e-09
GCST003264_1098	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST005149_19	Colorectal cancer	2.000000e-06
GCST006479_76	Diverticular disease	9.000000e-07
GCST007251_2	Postburn scar height	9.000000e-06
GCST009188_6	Lingual gyrus volume	1.000000e-06
GCST90000025_261	Appendicular lean mass	1.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004320	suicidal ideation
EFO:0004458	C-reactive protein measurement
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0004713	FEV/FVC ratio
EFO:0009959	diverticular disease
EFO:0007747	postburn hypertrophic scarring severity measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs145489027	Toxicity	3	Ace Inhibitors;Plain
rs1495509	Toxicity	3	Ace Inhibitors;Plain
rs16870989	Toxicity	4	Ace Inhibitors;Plain
rs6838116	Toxicity	3	Ace Inhibitors;Plain
rs7661530	Toxicity	4	Ace Inhibitors;Plain
rs7675300	Toxicity	4	Ace Inhibitors;Plain

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1495509	KCNIP4	3	0.50	1	Ace Inhibitors;Plain
rs6838116	KCNIP4	3	0.00	1	Ace Inhibitors;Plain
rs7661530	KCNIP4	4	-2.00	1	Ace Inhibitors;Plain
rs7675300	KCNIP4	4	-0.75	1	Ace Inhibitors;Plain
rs16870989	KCNIP4	4	-2.00	1	Ace Inhibitors;Plain
rs145489027	KCNIP4	3	0.00	1	Ace Inhibitors;Plain

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
sodium arsenite	affects methylation, decreases expression	2
Copper	decreases expression, affects binding, increases expression, affects cotreatment	2
Valproic Acid	decreases expression	2
bisphenol F	decreases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	increases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Methapyrilene	increases methylation	1
Phenylmercuric Acetate	affects cotreatment, increases expression	1
Rotenone	increases expression	1
Tretinoin	increases expression	1
Cyclosporine	decreases methylation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_YA63	IDG-HEK293T-KCNIP4-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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