ITPKA
protein-codinginositol-trisphosphate 3-kinase A
Gene summary
Regulates inositol phosphate metabolism by phosphorylation of second messenger inositol 1,4,5-trisphosphate to Ins(1,3,4,5)P4. The activity of the inositol 1,4,5-trisphosphate 3-kinase is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling. Both calcium/calmodulin and protein phosphorylation mechanisms control its activity. It is also a substrate for the cyclic AMP-dependent protein kinase, calcium/calmodulin- dependent protein kinase II, and protein kinase C in vitro.[provided by RefSeq, Apr 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ITPKA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002220.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 60 | 1 | 61 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 61 | 1 | 1 | 63 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002211.1 | 7 | MANE Select | |
| Ensembl | ENSP00000260386.5 | 7 | MANE Select | |
| Ensembl | ENSP00000396560.1 | 6 | Standard | |
| Ensembl | ENSP00000637299.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inositol phosphate metabolism - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- Phosphatidylinositol signaling system - Homo sapiens (human)
- Inositol Phosphate Metabolism
- Inositol Metabolism
Biological Process
- inositol metabolic process
- protein phosphorylation
- signal transduction
- actin cytoskeleton organization
- inositol phosphate biosynthetic process
Molecular Function
- calmodulin-dependent protein kinase activity
- calmodulin binding
- ATP binding
- inositol-1,4,5-trisphosphate 3-kinase activity
- Rac GTPase binding
Cellular Component
- cytosol
- dendritic spine
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260386
- Coding exons
- 7
- Length
- 10157
- Individuals with no LoFs
- 125649
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125653
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.57 | 155 | 221 | 0.703 | 0.0000102 | 2919 |
| Missense (PolyPhen) | 42 | 91.283 | 0.46011 | 1066 | ||
| Synonymous | 0.673 | 89 | 97.5 | 0.913 | 0.00000465 | 987 |
| Loss of Function | 3.07 | 3 | 16.4 | 0.183 | 7.99e-7 | 191 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000094 | 0.0000088 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.127
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.764
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |