ITPKC

Summary

ITPKC (inositol-trisphosphate 3-kinase C, HGNC:14897) is a protein-coding gene on chromosome 19q13.2, encoding Inositol-trisphosphate 3-kinase C (Q96DU7). Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis.

This gene encodes a member of the inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase family of enzymes that catalyze the phosphorylation of inositol 1,4,5-trisphosphate to 1,3,4,5-tetrakisphosphate. The encoded protein is localized to the nucleus and cytoplasm and has both nuclear import and nuclear export activity. Single nucleotide polymorphisms in this gene are associated with Kawasaki disease.

Source: NCBI Gene 80271 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 145 total
• MANE Select transcript: NM_025194

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14897
Approved symbol	ITPKC
Name	inositol-trisphosphate 3-kinase C
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	IP3KC, IP3-3KC
Ensembl gene	ENSG00000086544
Ensembl biotype	protein_coding
OMIM	606476
Entrez	80271

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 nonsense_mediated_decay

ENST00000263370, ENST00000597003, ENST00000699488, ENST00000699489, ENST00000699490

RefSeq mRNA: 2 — MANE Select: NM_025194 NM_001411098, NM_025194

CCDS: CCDS12563, CCDS92621

Canonical transcript exons

ENST00000263370 — 7 exons

Exon	Start	End
ENSE00000707569	40725340	40725439
ENSE00000707574	40729202	40729415
ENSE00000842326	40733160	40733364
ENSE00001281412	40739357	40740860
ENSE00001281420	40717112	40718290
ENSE00003483226	40736986	40737087
ENSE00003655119	40737698	40737769

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9520 / max 483.9928, expressed in 1766 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175887	8.9100	1610
175885	1.5075	934
208814	1.0527	718
175886	0.4819	252

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.59	gold quality
esophagus mucosa	UBERON:0002469	95.50	gold quality
skin of leg	UBERON:0001511	93.09	gold quality
tongue squamous epithelium	UBERON:0006919	92.81	gold quality
amniotic fluid	UBERON:0000173	92.52	gold quality
skin of abdomen	UBERON:0001416	92.45	gold quality
cervix squamous epithelium	UBERON:0006922	92.23	gold quality
left uterine tube	UBERON:0001303	91.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.60	gold quality
esophagus	UBERON:0001043	91.39	gold quality
squamous epithelium	UBERON:0006914	90.91	gold quality
right lung	UBERON:0002167	90.79	gold quality
epithelium of esophagus	UBERON:0001976	90.77	gold quality
mucosa of stomach	UBERON:0001199	90.76	gold quality
upper lobe of left lung	UBERON:0008952	90.68	gold quality
esophagus squamous epithelium	UBERON:0006920	90.54	gold quality
ectocervix	UBERON:0012249	90.53	gold quality
pancreatic ductal cell	CL:0002079	90.08	silver quality
upper lobe of lung	UBERON:0008948	89.85	gold quality
minor salivary gland	UBERON:0001830	89.83	gold quality
omental fat pad	UBERON:0010414	89.68	gold quality
zone of skin	UBERON:0000014	89.65	gold quality
peritoneum	UBERON:0002358	89.62	gold quality
gall bladder	UBERON:0002110	89.31	gold quality
gingival epithelium	UBERON:0001949	89.20	gold quality
mouth mucosa	UBERON:0003729	89.20	gold quality
tibial nerve	UBERON:0001323	89.06	gold quality
vagina	UBERON:0000996	88.90	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.41	gold quality
saliva-secreting gland	UBERON:0001044	87.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	54.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting ITPKC, 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-9-5P	100.00	72.28	2361
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-1227-5P	98.65	65.32	1549

Literature-anchored findings (GeneRIF, showing 24)

• results highlight the potential role of the three isoforms of InsP3 3-kinase as direct InsP3 metabolizing enzymes and direct regulators of Ca2+ responses to extracellular signals (PMID:12747803)
• ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. (PMID:18084290)
• A statistically significant association was not found between the ITPKC gene single-nucleotide polymorphism rs28493229 and Kawasaki disease or coronary artery lesions in Taiwanese children. (PMID:20045869)
• Single nucleotide polymorphism rs28493229 in ITPKC contributes to Kawasaki disease susceptibility through induced hyperimmune function reflected in the BCG reactivation. (PMID:20805785)
• results indicated that C-allele of ITPKC SNP rs28493229 is associated with the susceptibility and aneurysm formation in KD patients in a Taiwanese population (PMID:21533171)
• Functional single-nucleotide polymorphisms in ITPKC and CASP3 are associated with susceptibility to Kawasaki’s disease (KD). (PMID:21987091)
• The study failed to prove any association between SNP rs28493229 of ITPKC gene and Kawasaki disease/coronary artery lesions in Chinese patients. (PMID:22161096)
• The C allele of the ITPKC gene rs2290692 is linked to a significantly higher risk for KD in the Han Chinese population studied. (PMID:22361738)
• ITPKC susceptibility in Kawasaki syndrome is related to its synergy with environmental triggers, such as thimerosal, which alter calcium homeostasis and promote oxidative stress. (PMID:22498790)
• It was found the G/G genotype and G allele of the inositol 1,4,5-trisphosphate 3-kinase rs28493229 polymorphism may contribute to the risk of cervical squamous cell carcinoma in Taiwanese women. (PMID:22610085)
• the functional polymorphism rs28493229 in ITPKC significantly contributes to the risk of Kawasaki disease. (PMID:23065250)
• functional studies demonstrated that PPP3CC positively influences the protein level of ITPKC, likely by inhibiting phosphorylation of ITPKC and consequently preventing ITPKC from ubiquitin-mediated protein degradation (PMID:23747857)
• a combinatorial association between ITPKC (rs28493229) and CASP3 (rs113420705) was found in coronary artery lesion formation (P = 0.0227, OR: 3.06)in Taiwanese population (PMID:23894522)
• SNP rs7251246 in ITPKC is associated with the severity of Kawasaki disease (PMID:24621571)
• Our results identify a novel polymorphism for renal function and highlight the importance of ITPKC as a key molecule to regulate calcium signaling. (PMID:24800221)
• ITPKC polymorphisms are associated with Kawasaki disease. (PMID:24903211)
• this study shows that the KD-associated genetic polymorphism in inositol-triphosphate 3-kinase C (ITPKC) (rs28493229) has important functional consequences, governing ITPKC protein levels and thereby intracellular calcium, which in turn regulates NLRP3 expression and production of IL-1beta and IL-18. (PMID:27694492)
• Genetic variants of ITPKC may have a potential association with HSCR (Hirschsprung disease) susceptibility and/or developmental diseases related to enteric nervous system development. (PMID:28664405)
• This study identified several important polymorphisms in the ITPKC and SLC11A1 genes in Koreans. (PMID:29214786)
• Our findings suggest that ITPKC is a susceptibility gene for bone mineral density (BMD), and rs2607420 may play an important role in the regulation of this gene (PMID:30355649)
• Immune-related genes STIM1, ITPKC and PELI1 polymorphisms are associated with risk of colorectal cancer. (PMID:33470690)
• Association of ITPKC gene polymorphisms rs28493229 and rs2290692 in North Indian children with Kawasaki disease. (PMID:34952936)
• Inositol-Triphosphate 3-Kinase C and DNA Methylation Involvement in NLRP3 Inflammasome Activation in Kawasaki Disease. (PMID:35353363)
• ITPKC polymorphism (rs7251246 T > C), coronary artery aneurysms, and thrombosis in patients with Kawasaki disease in a Southern Han Chinese population. (PMID:37404818)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	itpkca	ENSDARG00000002994
danio_rerio	itpkcb	ENSDARG00000067741
mus_musculus	Itpkc	ENSMUSG00000003752
rattus_norvegicus	Itpkc	ENSRNOG00000013945
drosophila_melanogaster	IP3K1	FBGN0032147
drosophila_melanogaster	Ip6k	FBGN0034644
caenorhabditis_elegans	lfe-2	WBGENE00002979
caenorhabditis_elegans	F30A10.3	WBGENE00009262

Paralogs (6): IP6K2 (ENSG00000068745), ITPKA (ENSG00000137825), ITPKB (ENSG00000143772), IPMK (ENSG00000151151), IP6K3 (ENSG00000161896), IP6K1 (ENSG00000176095)

Protein

Protein identifiers

Inositol-trisphosphate 3-kinase C — Q96DU7 (reviewed: Q96DU7)

Alternative names: Inositol 1,4,5-trisphosphate 3-kinase C

All UniProt accessions (4): Q96DU7, A0A8V8TNF9, A0A8V8TPP3, M0R2L7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis. Can phosphorylate inositol 2,4,5-triphosphate to inositol 2,4,5,6-tetraphosphate.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in pancreas, skeletal muscle, liver, placenta and weakly in kidney and brain.

Activity regulation. Activated by calcium/calmodulin. Inhibited by high concentrations of the substrate Ins(1,2,4)P3, and allosterically activated by the product Ins(1,3,4,5)P4.

Similarity. Belongs to the inositol phosphokinase (IPK) family.

RefSeq proteins (2): NP_001398027, NP_079470* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005522	IPK	Family
IPR038286	IPK_sf	Homologous_superfamily

Pfam: PF03770

Enzyme classification (BRENDA):

• EC 2.7.1.127 — inositol-trisphosphate 3-kinase (BRENDA: 14 organisms, 87 substrates, 104 inhibitors, 42 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1D-MYO-INOSITOL 1,4,5-TRISPHOSPHATE	0.0002–0.011	21
ATP	0.033–2.5	13
1D-MYO-INOSITOL 2,4,5-TRISPHOSPHATE	0.0015–0.005	2
INSP3	0.0002–0.0017	2

Catalyzed reactions (Rhea), 1 shown:

• 1D-myo-inositol 1,4,5-trisphosphate + ATP = 1D-myo-inositol 1,3,4,5-tetrakisphosphate + ADP + H(+) (RHEA:11020)

UniProt features (52 total): helix 11, strand 10, binding site 9, compositionally biased region 7, region of interest 4, modified residue 4, turn 3, chain 1, mutagenesis site 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2A98	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DU7-F1	59.57	0.33

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): 431; 471–473; 484; 486; 507–513; 534–541; 558; 638; 641

Post-translational modifications (4): 127, 162, 336, 404

Mutagenesis-validated functional residues (1):

Position	Phenotype
486	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism

MSigDB gene sets: 179 (showing top): CREL_01, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_RESPONSE_TO_METAL_ION, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, AP1_Q4_01, KOYAMA_SEMA3B_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (3): inositol phosphate biosynthetic process (GO:0032958), phosphatidylinositol phosphate biosynthetic process (GO:0046854), cellular response to calcium ion (GO:0071277)

GO Molecular Function (8): inositol hexakisphosphate kinase activity (GO:0000828), calmodulin binding (GO:0005516), ATP binding (GO:0005524), inositol-1,4,5-trisphosphate 3-kinase activity (GO:0008440), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), inositol phosphate kinase activity (GO:0180030)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Inositol phosphate metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
inositol phosphate metabolic process	1
polyol biosynthetic process	1
organophosphate biosynthetic process	1
glycerophospholipid biosynthetic process	1
response to calcium ion	1
cellular response to metal ion	1
phosphotransferase activity, phosphate group as acceptor	1
inositol phosphate kinase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
inositol trisphosphate kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
kinase activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITPKC	BLK	P51451	668
ITPKC	CASP3	P42574	650
ITPKC	FCGR2A	P12318	574
ITPKC	FAM167A	Q96KS9	559
ITPKC	IPMK	Q8NFU5	515
ITPKC	ORAI1	Q96D31	514
ITPKC	NAALADL2	Q58DX5	494
ITPKC	PPP3CC	P48454	489
ITPKC	ACTMAP	Q5BKX5	479
ITPKC	RAB4B	P22750	474
ITPKC	CD40LG	P29965	472
ITPKC	LRRC59	Q96AG4	448
ITPKC	CD40	P25942	448
ITPKC	ITPR3	Q14573	438
ITPKC	TMEM64	Q6YI46	431

IntAct

18 interactions, top by confidence:

A	B	Type	Score
ERP44	MEX3A	psi-mi:“MI:0914”(association)	0.530
AURKA	WDR62	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
PPP3CC	ITPKC	psi-mi:“MI:0915”(physical association)	0.370
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
AURKA	WDR62	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
CFAP184	TARS3	psi-mi:“MI:0914”(association)	0.350
COQ3	TARS3	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCDC71	SUPT5H	psi-mi:“MI:0914”(association)	0.350
RAMP1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
RARRES1	ZNF609	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS), ITPKC (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YX57, A1A5P9, A2A368, A2A9R3, A8MXT2, B2KFW1, O15479, O15480, O15481, O15553, P0C6Y7, P10073, P17040, P25233, P43355, P43356, P43357, P43358, P43360, P43362, P43363, P43364, P43366, Q13342, Q16666, Q4R998, Q5PPP4, Q5RD14, Q6AY37, Q6PCZ4, Q8BQR7, Q8IWY8, Q8IX06, Q8N660, Q8N7X4, Q8TD90, Q96DU7, Q96LZ2, Q96M61, Q99608

Diamond homologs: P17105, P23677, P27987, P42335, Q7TS72, Q80ZG2, Q8R071, Q95Q62, Q96DU7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

667 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40725339:GAGC:G	acceptor_gain	1.0000
19:40725436:GCTG:G	donor_gain	1.0000
19:40725437:CTGG:C	donor_loss	1.0000
19:40725439:GGTA:G	donor_loss	1.0000
19:40725440:G:GA	donor_loss	1.0000
19:40725441:T:A	donor_loss	1.0000
19:40729195:C:G	acceptor_gain	1.0000
19:40729201:GGGA:G	acceptor_gain	1.0000
19:40729201:GGGAA:G	acceptor_gain	1.0000
19:40729357:G:GT	donor_gain	1.0000
19:40729405:A:G	donor_gain	1.0000
19:40733149:T:TA	acceptor_gain	1.0000
19:40733151:T:TA	acceptor_gain	1.0000
19:40733153:T:TA	acceptor_gain	1.0000
19:40733156:TCA:T	acceptor_loss	1.0000
19:40733157:CAG:C	acceptor_loss	1.0000
19:40733158:A:AG	acceptor_gain	1.0000
19:40733158:AGG:A	acceptor_loss	1.0000
19:40733159:G:GA	acceptor_gain	1.0000
19:40733362:AAGG:A	donor_loss	1.0000
19:40733363:AGG:A	donor_loss	1.0000
19:40733364:GGT:G	donor_loss	1.0000
19:40733365:GTGAG:G	donor_loss	1.0000
19:40733366:T:A	donor_loss	1.0000
19:40736972:ACCCT:A	acceptor_gain	1.0000
19:40736983:CA:C	acceptor_loss	1.0000
19:40736984:A:AG	acceptor_gain	1.0000
19:40736985:G:GT	acceptor_gain	1.0000
19:40736985:GA:G	acceptor_gain	1.0000
19:40736985:GAA:G	acceptor_gain	1.0000

AlphaMissense

4457 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40729239:A:C	K431N	0.998
19:40729239:A:T	K431N	0.998
19:40729404:G:C	K486N	0.998
19:40729404:G:T	K486N	0.998
19:40733285:T:A	V532D	0.998
19:40729238:A:T	K431I	0.997
19:40733345:T:C	F552S	0.997
19:40739366:A:C	S620R	0.997
19:40739368:C:A	S620R	0.997
19:40739368:C:G	S620R	0.997
19:40739421:A:T	D638V	0.997
19:40739422:C:A	D638E	0.997
19:40739422:C:G	D638E	0.997
19:40733292:G:C	K534N	0.996
19:40733292:G:T	K534N	0.996
19:40729207:T:C	F421L	0.995
19:40729208:T:C	F421S	0.995
19:40729209:C:A	F421L	0.995
19:40729209:C:G	F421L	0.995
19:40729237:A:G	K431E	0.995
19:40729398:C:A	D484E	0.995
19:40729398:C:G	D484E	0.995
19:40733344:T:C	F552L	0.995
19:40733346:C:A	F552L	0.995
19:40733346:C:G	F552L	0.995
19:40733348:G:C	R553P	0.995
19:40739379:T:C	F624S	0.995
19:40739421:A:C	D638A	0.995
19:40739421:A:G	D638G	0.995
19:40725415:T:A	W411R	0.994

dbSNP variants (sampled 300 via entrez): RS1000178257 (19:40721826 C>T), RS1000209241 (19:40732354 C>A), RS1000243964 (19:40722551 G>A), RS1000334948 (19:40721239 G>A), RS1000350065 (19:40734270 A>T), RS1000455571 (19:40728026 G>A,T), RS1000458646 (19:40716383 G>A), RS1000569443 (19:40727063 G>A), RS1000576383 (19:40721067 T>G), RS1000684885 (19:40732795 C>T), RS1000840430 (19:40739193 C>T), RS1000895924 (19:40732479 G>A,C), RS1000984921 (19:40739209 C>T), RS1001014331 (19:40738929 C>T), RS1001191181 (19:40726745 A>T)

Disease associations

OMIM: gene MIM:606476 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST001322_2	Kawasaki disease	2.000000e-12
GCST003847_2	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) level)	6.000000e-08
GCST003849_1	Caffeine metabolism (plasma 3,7-dimethylxanthine (theobromine) level)	4.000000e-06
GCST003851_10	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	5.000000e-12
GCST003851_11	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	8.000000e-09
GCST003851_12	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-10
GCST003851_13	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-22
GCST003851_14	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-10
GCST003851_15	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-11
GCST003851_16	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-09
GCST003851_17	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-11
GCST003851_18	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-08
GCST003851_19	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-11
GCST003851_20	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-09
GCST003851_21	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-09
GCST003851_22	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-08
GCST003851_23	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-08
GCST003851_26	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	5.000000e-12
GCST003851_27	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-08
GCST003851_9	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	6.000000e-09
GCST009921_7	Carotid intima media thickness (mean)	1.000000e-10
GCST010979_5	Kawasaki disease	1.000000e-14
GCST90013537_1	Kawasaki disease	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007872	caffeine metabolite measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs28493229	COQ8B, ITPKC		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Inositol 1,4,5-trisphosphate 3-kinases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
GNF362	Inhibition	7.72	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	increases expression	2
Testosterone	increases expression, affects cotreatment	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
nutlin 3	increases expression, affects cotreatment	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
gardiquimod	increases expression, decreases reaction	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Calcitriol	increases expression, affects cotreatment	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	increases expression	1

Clinical trials (associated diseases)

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