ITPK1

inositol-tetrakisphosphate 1-kinase

Basic information

Region (hg38): 14:92936913-93116320

Links

ENSG00000100605 ∙ NCBI:3705 ∙ OMIM:601838 ∙ HGNC:6177 ∙ Uniprot:Q13572 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITPK1 gene.

• Inborn genetic diseases (23 variants)
• not specified (1 variants)
• not provided (1 variants)

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		1
missense			21	3		24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	21	4	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)
14-92941668-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)
14-92941806-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)
14-92951982-G-C		not specified	Uncertain significance (Aug 03, 2022)
14-92958251-T-C		not specified	Uncertain significance (Dec 14, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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