ITPK1

Summary

ITPK1 (inositol-tetrakisphosphate 1-kinase, HGNC:6177) is a protein-coding gene on chromosome 14q32.12, encoding Inositol-tetrakisphosphate 1-kinase (Q13572). Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. It is a selective cancer dependency (DepMap: 12.2% of cell lines).

This gene encodes an enzyme that belongs to the inositol 1,3,4-trisphosphate 5/6-kinase family. This enzyme regulates the synthesis of inositol tetraphosphate, and downstream products, inositol pentakisphosphate and inositol hexakisphosphate. Inositol metabolism plays a role in the development of the neural tube. Disruptions in this gene are thought to be associated with neural tube defects. A pseudogene of this gene has been identified on chromosome X.

Source: NCBI Gene 3705 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 88 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 12.2% of screened cell lines
• MANE Select transcript: NM_014216

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6177
Approved symbol	ITPK1
Name	inositol-tetrakisphosphate 1-kinase
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100605
Ensembl biotype	protein_coding
OMIM	601838
Entrez	3705

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000267615, ENST00000354313, ENST00000553452, ENST00000553655, ENST00000553695, ENST00000554999, ENST00000555495, ENST00000555553, ENST00000556185, ENST00000556603, ENST00000556954, ENST00000557309, ENST00000906420, ENST00000928428, ENST00000928429, ENST00000945314

RefSeq mRNA: 4 — MANE Select: NM_014216 NM_001142593, NM_001142594, NM_001363707, NM_014216

CCDS: CCDS45157, CCDS86425, CCDS9907

Canonical transcript exons

ENST00000267615 — 11 exons

Exon	Start	End
ENSE00001755227	93076595	93076619
ENSE00002486587	93115772	93115925
ENSE00002707244	93115069	93115305
ENSE00003459355	92951946	92952013
ENSE00003460376	92946331	92946493
ENSE00003469761	92993880	92993997
ENSE00003509622	92962751	92962849
ENSE00003583401	93016676	93016801
ENSE00003604458	92936914	92941904
ENSE00003788000	92962355	92962395
ENSE00003790766	92958201	92958366

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 98.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.2887 / max 266.3273, expressed in 1803 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144628	8.3799	1767
144623	5.8990	1338
144622	2.5880	990
144624	2.5326	1170
144620	1.2171	560
144626	0.7501	471
144625	0.6374	312
144618	0.5500	252
144627	0.3093	135
144617	0.1644	92

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	98.38	gold quality
right frontal lobe	UBERON:0002810	98.27	gold quality
anterior cingulate cortex	UBERON:0009835	97.71	gold quality
cingulate cortex	UBERON:0003027	97.68	gold quality
prefrontal cortex	UBERON:0000451	97.33	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.46	gold quality
lower esophagus	UBERON:0013473	96.42	gold quality
amygdala	UBERON:0001876	96.30	gold quality
nucleus accumbens	UBERON:0001882	96.24	gold quality
cortical plate	UBERON:0005343	96.10	gold quality
sural nerve	UBERON:0015488	96.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.95	gold quality
right coronary artery	UBERON:0001625	95.75	gold quality
tibial nerve	UBERON:0001323	95.73	gold quality
spinal cord	UBERON:0002240	95.73	gold quality
caudate nucleus	UBERON:0001873	95.56	gold quality
gall bladder	UBERON:0002110	95.55	gold quality
monocyte	CL:0000576	95.49	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.41	gold quality
rectum	UBERON:0001052	95.35	gold quality
leukocyte	CL:0000738	95.27	gold quality
mononuclear cell	CL:0000842	95.26	gold quality
popliteal artery	UBERON:0002250	95.25	gold quality
tibial artery	UBERON:0007610	95.23	gold quality
mucosa of stomach	UBERON:0001199	95.06	gold quality
putamen	UBERON:0001874	95.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.68	gold quality
apex of heart	UBERON:0002098	94.60	gold quality
granulocyte	CL:0000094	94.56	gold quality
endocervix	UBERON:0000458	94.47	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-9543	no	2.44
E-ANND-3	no	2.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

78 targeting ITPK1, 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-4692	100.00	67.32	2066
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
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-6764-5P	99.75	67.89	2304
HSA-MIR-7856-5P	99.75	69.99	2901

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• 5/6-kinase modifies TNFalpha-induced apoptosis by interfering with the activation of TNF-R1-associated death domain (PMID:12925536)
• analysis of inositol phosphate signaling pathway integration via human ITPK1 (PMID:17616525)
• HEK293 cells stably expressing acetylated ITPK1 had reduced levels of the higher phosphorylated forms of inositol, compared with the levels seen in cells expressing unacetylated ITPK1 (PMID:22308441)
• Activation of PLC by an endogenous cytokine (GBP) in Drosophila S3 cells and its application as a model for studying inositol phosphate signalling through ITPK1. (PMID:22928859)
• The results suggested that the maternal rs3783903 of ITPK1 might be associated with spina bifida, and the allele G of rs3783903 might affect the binding of AP-1 and the decrease of maternal plasma inositol hexakisphosphate concentration. (PMID:24465924)
• ITPK1 role in the lipid-independent synthesis of inositol phosphates. (PMID:31754032)
• Genetic Effects of ITPK1 Polymorphisms on the Risk of Neural Tube Defects: a Population-Based Study. (PMID:36323916)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	itpk1a	ENSDARG00000013056
danio_rerio	itpk1b	ENSDARG00000070583
mus_musculus	Itpk1	ENSMUSG00000057963
rattus_norvegicus	Itpk1	ENSRNOG00000008051

Protein

Protein identifiers

Inositol-tetrakisphosphate 1-kinase — Q13572 (reviewed: Q13572)

Alternative names: Inositol 1,3,4-trisphosphate 5/6-kinase

All UniProt accessions (5): Q13572, G3V3C0, G3V4M9, G3V588, G3V5A3

UniProt curated annotations — full annotation on UniProt →

Function. Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. Also acts as an inositol polyphosphate phosphatase that dephosphorylates Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain. Plays an important role in MLKL-mediated necroptosis. Produces highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL mediating the release of an N-terminal auto-inhibitory region leading to its activation. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis.

Subunit / interactions. Monomer. Interacts with GPS1/COPS1.

Tissue specificity. Expressed in brain > heart > skeletal muscle = kidney = pancreas = liver = placenta > lung. In brain, it is expressed in cerebellum, cerebral cortex, medulla, spinal cord, occipital lobe, frontal lobe, temporal lobe and putamen.

Post-translational modifications. Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-regulates enzymatic activity. Deacetylated by SIRT1.

Cofactor. Binds 2 magnesium ions per subunit.

Similarity. Belongs to the ITPK1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13572-1	1	yes
Q13572-2	2

RefSeq proteins (4): NP_001136065, NP_001136066, NP_001350636, NP_055031* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008656	Inositol_tetrakis-P_1-kinase	Family
IPR011761	ATP-grasp	Domain
IPR040464	InsP(3)kin_ATP-grasp	Domain
IPR041429	ITPK1_N	Domain

Pfam: PF05770, PF17927

Enzyme classification (BRENDA):

• EC 2.7.1.134 — inositol-tetrakisphosphate 1-kinase (BRENDA: 10 organisms, 33 substrates, 12 inhibitors, 8 Km, 0 kcat entries)
• EC 2.7.1.159 — inositol-1,3,4-trisphosphate 5/6-kinase (BRENDA: 10 organisms, 54 substrates, 7 inhibitors, 4 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.01–1.2	3
MYO-INOSITOL-1,3,4-TRISPHOSPHATE	0.0003–0.2	2
MYO-INOSITOL-3,4,5,6-TETRAKISPHOSPHATE	0.0001–0.0004	2
MYO-INOSITOL-3,4,6-TRISPHOSPHATE	0.0002	1
1D-MYO-INOSITOL 1,3,4,6-TETRAKISPHOSPHATE	0.042	1
1D-MYO-INOSITOL-1,3,4-TRISPHOSPHATE	0.0001	1

Catalyzed reactions (Rhea), 6 shown:

• 1D-myo-inositol 3,4,5,6-tetrakisphosphate + ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ADP + H(+) (RHEA:12452)
• 1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol 1,3,4,5-tetrakisphosphate + ADP + H(+) (RHEA:13253)
• 1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol 1,3,4,6-tetrakisphosphate + ADP + H(+) (RHEA:20940)
• 1D-myo-inositol 1,3,4-trisphosphate + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate = 1D-myo-inositol 3,4,5,6-tetrakisphosphate + 1D-myo-inositol 1,3,4,6-tetrakisphosphate (RHEA:70263)
• 1D-myo-inositol 1,3,4-trisphosphate + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate = 1D-myo-inositol 3,4,5,6-tetrakisphosphate + 1D-myo-inositol 1,3,4,5-tetrakisphosphate (RHEA:70271)
• 1D-myo-inositol 3,4,6-trisphosphate + ATP = 1D-myo-inositol 1,3,4,6-tetrakisphosphate + ADP + H(+) (RHEA:70287)

UniProt features (74 total): mutagenesis site 20, helix 15, binding site 14, strand 13, modified residue 4, turn 3, splice variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2Q7D	X-RAY DIFFRACTION	1.6
2QB5	X-RAY DIFFRACTION	1.8
2ODT	X-RAY DIFFRACTION	2.01
9DN3	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13572-F1	84.48	0.76

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): 236; 281; 295; 295; 297; 297; 18; 106; 157; 167; 188–199; 199 …

Post-translational modifications (4): 340, 383, 396, 410

Mutagenesis-validated functional residues (20):

Position	Phenotype
18	loss of kinase activity.
58	no effect.
59	loss of kinase activity.
106	loss of kinase activity.
157	loss of kinase activity.
162	loss of kinase activity.
163	loss of kinase activity.
163	no effect.
167	loss of kinase activity.
188	no effect.
193	loss of kinase activity.
199	loss of kinase activity.
212	loss of kinase activity.
214	loss of kinase activity.
215	no effect.
281	loss of kinase activity.
295	loss of kinase activity.
297	loss of kinase activity.
297	induces a strong reduction in kinase activity.
301	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1855167	Synthesis of pyrophosphates in the cytosol
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism

MSigDB gene sets: 233 (showing top): FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_WOUND_HEALING, CEBP_Q2, BLALOCK_ALZHEIMERS_DISEASE_UP, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_HEMOSTASIS, GOBP_EMBRYO_DEVELOPMENT, chr14q32

GO Biological Process (5): signal transduction (GO:0007165), blood coagulation (GO:0007596), neural tube development (GO:0021915), inositol trisphosphate metabolic process (GO:0032957), necroptotic process (GO:0070266)

GO Molecular Function (15): magnesium ion binding (GO:0000287), inositol-1,3,4,5-tetrakisphosphate 6-kinase activity (GO:0000825), catalytic activity (GO:0003824), ATP binding (GO:0005524), hydrolase activity (GO:0016787), isomerase activity (GO:0016853), inositol-3,4,5,6-tetrakisphosphate 1-kinase activity (GO:0047325), inositol-1,3,4-trisphosphate 6-kinase activity (GO:0052725), inositol-1,3,4-trisphosphate 5-kinase activity (GO:0052726), inositol-3,4,6-trisphosphate 1-kinase activity (GO:0052835), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (2): cytosol (GO:0005829), apical plasma membrane (GO:0016324)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Inositol phosphate metabolism	2
Hemostasis	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	3
inositol trisphosphate kinase activity	3
inositol tetrakisphosphate kinase activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
hemostasis	1
wound healing	1
coagulation	1
nervous system development	1
tube development	1
chordate embryonic development	1
epithelium development	1
inositol phosphate metabolic process	1
programmed necrotic cell death	1
metal ion binding	1
molecular_function	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
cation binding	1
cytoplasm	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1

Protein interactions and networks

STRING

1168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITPK1	IPMK	Q8NFU5	787
ITPK1	IPPK	Q9H8X2	748
ITPK1	PPIP5K1	Q6PFW1	619
ITPK1	SASH1	O94885	552
ITPK1	IP6K1	Q92551	519
ITPK1	DHRS12	A0PJE2	513
ITPK1	MINPP1	Q9UNW1	512
ITPK1	PRDM11	Q9NQV5	505
ITPK1	MBIP	Q9NS73	505
ITPK1	AADAT	Q8N5Z0	501
ITPK1	FOXE1	O00358	467
ITPK1	CAPNS2	Q96L46	465
ITPK1	COPS5	Q92905	464
ITPK1	CAPZB	P47756	449
ITPK1	SLC17A4	Q9Y2C5	438

IntAct

19 interactions, top by confidence:

A	B	Type	Score
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
ITPK1	CRYZL1	psi-mi:“MI:0915”(physical association)	0.590
TRAC	COCH	psi-mi:“MI:0914”(association)	0.530
ITPK1	CCT6B	psi-mi:“MI:0915”(physical association)	0.400
ITPK1	E7	psi-mi:“MI:0915”(physical association)	0.370
ITPK1	TRAF2	psi-mi:“MI:0915”(physical association)	0.370
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
RAF1	EIF3CL	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
P2RY10	POTEF	psi-mi:“MI:0914”(association)	0.350
TACSTD2	RIMOC1	psi-mi:“MI:0914”(association)	0.350
CDC5L		psi-mi:“MI:0914”(association)	0.350

BioGRID (40): ITPK1 (Affinity Capture-RNA), ITPK1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), ITPK1 (Affinity Capture-MS), TRAF2 (Two-hybrid), DNAAF5 (Co-fractionation), ITPK1 (Co-fractionation), ITPK1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), ITPK1 (Affinity Capture-MS), ITPK1 (Affinity Capture-MS), ITPK1 (Affinity Capture-RNA), ITPK1 (Affinity Capture-RNA), ITPK1 (Affinity Capture-MS), ITPK1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2QC33, A0FKG7, A6H7H7, F1N9S8, O95453, P0C0T1, P42694, P50747, P69341, Q0IIH8, Q0VGM9, Q13572, Q28559, Q4R528, Q5BJZ6, Q5F480, Q5R699, Q5RC51, Q5ZIA0, Q5ZIW7, Q640G7, Q6DDJ3, Q6DFV5, Q6DG88, Q6DJB3, Q6GR37, Q6NYU2, Q6PZ02, Q6PZ03, Q6PZ05, Q7T0P6, Q80UY1, Q80YV4, Q811C2, Q8BGE6, Q8BYN3, Q8C9S8, Q8N4J0, Q8VDG3, Q8WYN0

Diamond homologs: A0JJZ6, A2X4M8, A2Z4C5, A7X657, A7X665, A7X672, A7X680, B8AJL9, B8AR41, O81893, P0C0T1, Q10PL5, Q13572, Q33BI9, Q5F480, Q6K7B8, Q75GI4, Q7XBW0, Q84Y01, Q8BYN3, Q9SBA5, Q9SUG3, Q7SY78, Q7ZU91, O80568, Q9XYQ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3265 predictions. Top by Δscore:

Variant	Effect	Δscore
14:92946326:CTCA:C	donor_loss	1.0000
14:92946329:A:C	donor_loss	1.0000
14:92946489:TCCAG:T	acceptor_gain	1.0000
14:92946490:CCAG:C	acceptor_gain	1.0000
14:92946490:CCAGC:C	acceptor_gain	1.0000
14:92946491:CAG:C	acceptor_gain	1.0000
14:92946491:CAGC:C	acceptor_gain	1.0000
14:92946492:AG:A	acceptor_gain	1.0000
14:92946492:AGC:A	acceptor_loss	1.0000
14:92946493:GCT:G	acceptor_loss	1.0000
14:92946494:C:A	acceptor_loss	1.0000
14:92946494:C:CC	acceptor_gain	1.0000
14:92946495:T:G	acceptor_loss	1.0000
14:92946498:C:CT	acceptor_gain	1.0000
14:92946499:A:T	acceptor_gain	1.0000
14:92946501:C:CT	acceptor_gain	1.0000
14:92946502:A:AC	acceptor_gain	1.0000
14:92946502:A:C	acceptor_gain	1.0000
14:92951941:CCCA:C	donor_loss	1.0000
14:92951942:CCACC:C	donor_loss	1.0000
14:92951943:CACCT:C	donor_loss	1.0000
14:92951944:ACCTC:A	donor_loss	1.0000
14:92951945:C:CT	donor_loss	1.0000
14:92952014:C:CC	acceptor_gain	1.0000
14:92958196:GTTA:G	donor_loss	1.0000
14:92958197:TTA:T	donor_loss	1.0000
14:92958198:TA:T	donor_loss	1.0000
14:92958200:C:CG	donor_loss	1.0000
14:92958362:GCCAT:G	acceptor_gain	1.0000
14:92958363:CCAT:C	acceptor_gain	1.0000

AlphaMissense

2726 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:92941871:A:G	L312P	1.000
14:92941902:A:G	Y302H	1.000
14:92946333:G:T	P300Q	1.000
14:92946334:G:A	P300S	1.000
14:92946341:A:C	N297K	1.000
14:92946341:A:T	N297K	1.000
14:92946343:T:C	N297D	1.000
14:92946347:G:C	D295E	1.000
14:92946347:G:T	D295E	1.000
14:92946348:T:A	D295V	1.000
14:92946348:T:G	D295A	1.000
14:92946351:A:T	I294N	1.000
14:92946354:A:T	V293D	1.000
14:92946389:G:C	D281E	1.000
14:92946389:G:T	D281E	1.000
14:92946390:T:A	D281V	1.000
14:92946390:T:C	D281G	1.000
14:92946390:T:G	D281A	1.000
14:92946391:C:A	D281Y	1.000
14:92946391:C:G	D281H	1.000
14:92951988:G:C	S232R	1.000
14:92951988:G:T	S232R	1.000
14:92951990:T:G	S232R	1.000
14:92951994:G:C	F230L	1.000
14:92951994:G:T	F230L	1.000
14:92951996:A:G	F230L	1.000
14:92958220:G:C	N217K	1.000
14:92958220:G:T	N217K	1.000
14:92958235:C:A	R212S	1.000
14:92958235:C:G	R212S	1.000

dbSNP variants (sampled 300 via entrez): RS1000027459 (14:92994963 G>C,T), RS1000036731 (14:92988412 C>G), RS1000096331 (14:93033417 A>T), RS1000097100 (14:93067078 C>G), RS1000098864 (14:93082608 C>T), RS1000118312 (14:93082304 C>T), RS1000128665 (14:93042080 C>T), RS1000133665 (14:93104450 G>GAA), RS1000150147 (14:93066701 C>A), RS1000176788 (14:93036332 T>C), RS1000177240 (14:92960836 T>C), RS1000187765 (14:93026780 C>T), RS1000204095 (14:93105941 G>A), RS1000214846 (14:92967065 A>C), RS1000230370 (14:93073118 T>C)

Disease associations

OMIM: gene MIM:601838 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001337_42	Platelet count	1.000000e-10
GCST001856_21	Thyroid hormone levels	2.000000e-09
GCST001856_5	Thyroid hormone levels	3.000000e-06
GCST001894_15	Endometriosis	3.000000e-06
GCST003720_2	Migraine	8.000000e-09
GCST003986_15	Migraine	4.000000e-09
GCST004607_100	Plateletcrit	2.000000e-12
GCST005951_7	Body mass index	4.000000e-08
GCST007692_32	Chronic obstructive pulmonary disease	2.000000e-08
GCST008839_428	Height	2.000000e-12
GCST010396_289	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-08
GCST010653_84	Thyroid stimulating hormone levels	2.000000e-42
GCST90002393_491	Monocyte count	2.000000e-16
GCST90002400_141	Plateletcrit	1.000000e-35
GCST90002402_194	Platelet count	6.000000e-23
GCST90002407_581	White blood cell count	3.000000e-10
GCST90016667_24	Spleen volume	9.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004730	hormone measurement
EFO:0007985	platelet crit
EFO:0004340	body mass index
EFO:0007874	gut microbiome measurement
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1938220 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, increases expression	4
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	3
bisphenol A	increases methylation, decreases methylation, increases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases expression	2
bisphenol S	increases methylation, affects cotreatment, increases expression	2
Estradiol	increases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression	1
afimoxifene	decreases response to substance	1
manganese chloride	increases abundance, increases expression	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
pinostrobin	increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
(+)-JQ1 compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cycloheximide	increases activity, increases cleavage, increases reaction, increases response to substance, affects cotreatment (+1 more)	1
Dexamethasone	increases expression, affects cotreatment	1
Diethylstilbestrol	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1942463	Binding	Inhibition of human ITPK1 in HL-60 cells lysate assessed as reduction of labeling of acyl-phosphate ATP probe at 100 nM	6-Position optimization of tricyclic 4-quinolone-based inhibitors of glycogen synthase kinase-3β: discovery of nitrile derivatives with picomolar potency. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7SS	Ubigene A-549 ITPK1 KO	Cancer cell line	Male
CVCL_D8NJ	Ubigene HCT 116 ITPK1 KO	Cancer cell line	Male
CVCL_D9HJ	Ubigene HEK293 ITPK1 KO	Transformed cell line	Female
CVCL_E0FN	Ubigene HeLa ITPK1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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