ITPK1
inositol-tetrakisphosphate 1-kinase
Basic information
Region (hg38): 14:92936914-93116320
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITPK1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 28 | 32 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 28 | 5 | 0 |
Variants in ITPK1
This is a list of pathogenic ClinVar variants found in the ITPK1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-92938488-C-T | not specified | Uncertain significance (Nov 08, 2022) | ||
| 14-92941568-G-A | not specified | Uncertain significance (Oct 03, 2022) | ||
| 14-92941583-G-A | not specified | Uncertain significance (Oct 12, 2021) | ||
| 14-92941592-G-A | not specified | Uncertain significance (Oct 03, 2023) | ||
| 14-92941617-G-A | not specified | Uncertain significance (Feb 22, 2023) | ||
| 14-92941623-C-T | not specified | Likely benign (Jun 21, 2022) | ||
| 14-92941626-C-T | not specified | Likely benign (Jan 03, 2024) | ||
| 14-92941652-G-A | not specified | Uncertain significance (Aug 02, 2022) | ||
| 14-92941662-C-T | not specified | Uncertain significance (Apr 15, 2024) | ||
| 14-92941668-C-T | not specified | Likely benign (Jan 27, 2022) | ||
| 14-92941671-C-T | not specified | Uncertain significance (Dec 01, 2022) | ||
| 14-92941674-C-T | not specified | Uncertain significance (Mar 14, 2023) | ||
| 14-92941719-C-T | not specified | Likely benign (Oct 03, 2022) | ||
| 14-92941737-C-T | not specified | Uncertain significance (Feb 13, 2024) | ||
| 14-92941754-C-T | not specified | Uncertain significance (Sep 29, 2023) | ||
| 14-92941769-G-A | not specified | Likely benign (Mar 19, 2024) | ||
| 14-92941806-C-T | not specified | Uncertain significance (Jun 07, 2023) | ||
| 14-92941827-T-C | not specified | Uncertain significance (Jun 07, 2023) | ||
| 14-92946355-C-T | not specified | Uncertain significance (Aug 15, 2023) | ||
| 14-92946358-C-T | not specified | Uncertain significance (Oct 12, 2021) | ||
| 14-92946388-T-C | not specified | Uncertain significance (Mar 04, 2024) | ||
| 14-92946415-G-T | not specified | Uncertain significance (Jan 19, 2022) | ||
| 14-92946432-C-T | not specified | Uncertain significance (Jul 19, 2023) | ||
| 14-92946457-C-T | not specified | Uncertain significance (Jul 09, 2021) | ||
| 14-92946465-C-T | not specified | Uncertain significance (Aug 02, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ITPK1 | protein_coding | protein_coding | ENST00000267615 | 10 | 179407 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.994 | 0.00611 | 125736 | 0 | 6 | 125742 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.17 | 214 | 268 | 0.798 | 0.0000178 | 2685 |
| Missense in Polyphen | 30 | 66.61 | 0.45039 | 736 | ||
| Synonymous | -0.641 | 140 | 131 | 1.07 | 0.0000104 | 821 |
| Loss of Function | 3.89 | 1 | 19.6 | 0.0511 | 9.20e-7 | 219 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000623 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000466 | 0.0000440 |
| Middle Eastern | 0.0000623 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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 dephosphorylate 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-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain (PubMed:11909533, PubMed:12925536, PubMed:17616525). 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 (PubMed:17616525). {ECO:0000269|PubMed:11909533, ECO:0000269|PubMed:12925536, ECO:0000269|PubMed:17616525}.;
- Pathway
- Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Inositol Phosphate Metabolism;Inositol Metabolism;Factors involved in megakaryocyte development and platelet production;D-<i>myo</i>-inositol (3,4,5,6)-tetrakisphosphate biosynthesis;1D-<i>myo</i>-inositol hexakisphosphate biosynthesis II (mammalian);Metabolism;superpathway of inositol phosphate compounds;Synthesis of IP3 and IP4 in the cytosol;D-<i>myo</i>-inositol (1,4,5,6)-tetrakisphosphate biosynthesis;Synthesis of pyrophosphates in the cytosol;Hemostasis;Inositol phosphate metabolism;1D-<i>myo</i>-inositol hexakisphosphate biosynthesis V (from Ins(1,3,4)P3)
(Consensus)
Recessive Scores
- pRec
- 0.115
Intolerance Scores
- loftool
- 0.154
- rvis_EVS
- -0.45
- rvis_percentile_EVS
- 24.33
Haploinsufficiency Scores
- pHI
- 0.211
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.606
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.956
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Itpk1
- Phenotype
- embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- signal transduction;blood coagulation;dephosphorylation;neural tube development;inositol trisphosphate metabolic process;inositol phosphate metabolic process;inositol phosphorylation;necroptotic process
- Cellular component
- cytoplasm;cytosol;apical plasma membrane
- Molecular function
- magnesium ion binding;inositol tetrakisphosphate 6-kinase activity;catalytic activity;ATP binding;isomerase activity;inositol tetrakisphosphate 1-kinase activity;inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity;inositol-1,3,4-trisphosphate 6-kinase activity;inositol-1,3,4-trisphosphate 5-kinase activity;inositol-1,3,4,5,6-pentakisphosphate 1-phosphatase activity;inositol-1,3,4,6-tetrakisphosphate 6-phosphatase activity;inositol-1,3,4,6-tetrakisphosphate 1-phosphatase activity;inositol-3,4,6-trisphosphate 1-kinase activity